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Guidelines (JSH 2014)

Chapter 3. Principles of treatment

Subjects

POINT 3a

  1. 1

    Antihypertensive treatment should be performed to prevent the occurrence of cardiovascular disease due to sustained high blood pressure/progression/recurrence-related mortality and a reduction in the quality of life (QOL). (Recommendation grade A) (I)

  2. 2

    Antihypertensive treatment should be indicated for all hypertensive patients with a blood pressure of 140/90 mm Hg or above. These patients are stratified into three groups: low-, moderate- and high-risk groups, based on the blood pressure level, risk factors other than blood pressure and presence or absence of hypertensive organ damage.

  3. 3

    Antihypertensive treatment consists of lifestyle modifications (step 1) and antihypertensive drug therapy (step 2). The starting point of this therapy should be determined on the basis of the risk level of individual patients.

  4. 4

    The risk increases from the level of high-normal blood pressure. Progression from high-normal blood pressure to hypertension should be prevented by modifying the lifestyle. (Recommendation grade B) (II)

  5. 5

    The goal of antihypertensive treatment is to reduce blood pressure to <140/90 mm Hg. However, among diabetics and chronic kidney disease (CKD) patients with proteinuria, treatment should be performed in those with a blood pressure of 130/80 mm Hg or more. The target blood pressure is <130/80 mm Hg. In late-phase elderly persons, the target blood pressure is <150/90 mm Hg. If tolerance is present, a blood pressure of <140/90 mm Hg should be targeted. (Recommendation grade A) (I)

  6. 6

    In principle, antihypertensive drug therapy should be started with a low dose of a long-acting drug once a day. If the dose must be increased, twice-daily administration may be considered. Appropriate combination therapy with antihypertensive drugs should be administered to prevent adverse effects and enhance antihypertensive effects. Combination therapy should be considered from the outset for grade II or more severe hypertension. (Recommendation grade B) (III)

  7. 7

    Reducing the number of tablets and the frequency of dosing is useful for improving adherence. (Recommendation grade A) (I)

  8. 8

    Home blood pressure measurement is useful not only for the diagnosis of white coat hypertension and masked hypertension but also for evaluating the antihypertensive effects or for improving patients’ adherence/concordance. (Recommendation grade A) (I)

  9. 9

    Sufficient communication, information and consideration for QOL/adverse effects aid in improving adherence, achieving better blood pressure control and preventing cardiovascular disease. (Recommendation grade B) (Consensus IVa)

  10. 10

    For treatment, the attending physician must eventually determine a therapeutic strategy after establishing concordance involving the results of epidemiological and clinical studies, clinical background of the patient, pharmacological actions of antihypertensive drugs, health expenditure and cost-effectiveness. (Recommendation grade C1) (VI)

1. OBJECTIVES OF TREATMENT

The objectives of antihypertensive treatment are to prevent the occurrence/progression/recurrence of cardiovascular disease related to sustained high blood pressure, reduce mortality and help patients with hypertension lead their lives as normally as do healthy people.

According to a meta-analysis of previous clinical studies, a 10-mm Hg decrease in systolic blood pressure and a 5-mm Hg decrease in diastolic blood pressure reduce the risks of stroke and coronary artery disease by 40 (33–48%) and 20% (17–27%), respectively.226 In patients with a higher blood pressure level or at a more advanced age, antihypertensive drug therapy more markedly reduces these risks.123,227 An analysis of the results of a study involving patients with systolic hypertension also showed that a 10-mm Hg decrease in systolic blood pressure reduced the risk of stroke by 30% or more and that of coronary artery disease by 20% or more.123,227229

In Japan, the profiles of cardiovascular diseases differ from that in Europe and the United States. In men, the incidence of stroke is 3–6 times higher than that of myocardial infarction. In women, it is 4–12 times higher than that of myocardial infarction.7 Therefore, the preventative effects of antihypertensive drug therapy on cardiovascular events may be more potent than in international studies.16,17,230235

The effects of hypertension treatment increase with the risk of cardiovascular disease.236,237 Therefore, clinical studies involving higher-risk patients more strongly suggest the usefulness of treatment. The results of large-scale, placebo-controlled, randomized comparative studies in foreign countries have shown that antihypertensive drug therapy has many beneficial effects in patients with hypertension, and that it reduces the incidence and mortality rate of cardiovascular disease.238240

The results of an analysis regarding the preventative effects of antihypertensive drug therapy on cardiovascular disease indicated that there was no gender difference in a treatment-related decrease in the risk for cardiovascular disease.16,241243

2. PATIENTS TO BE TREATED

Antihypertensive treatment should be indicated for hypertensive patients of all ages. The HYVET study244 involving patients aged over 80 years showed that antihypertensive drug therapy decreased stroke-related mortality, cardiovascular morbidity, such as heart failure, and total mortality.

In patients with masked hypertension, such as morning hypertension, hypertension in the presence of stress and nighttime hypertension, antihypertensive treatment should be performed (see Chapter 2, Measurement and clinical evaluation of blood pressure). Basically, drug therapy is not performed in those with white coat hypertension, and the possibility that the condition may progress to hypertension in the future should be explained. Physicians must instruct patients to measure home blood pressure and improve their lifestyle. Periodic follow-up should be performed (see Chapter 2, Measurement and clinical evaluation of blood pressure).

3. RISK STRATIFICATION FOR PROGNOSIS ASSESSMENT AND MANAGEMENT PLANS

1) Risk factors for cardiovascular disease/organ damage

Hypertension is a primary risk factor for cardiovascular disease. In particular, it is the most important risk factor for stroke. Not only hypertension but also risk factors other than hypertension and the degree of organ damage such as hypertension-associated brain/heart/kidney diseases are closely involved in the prognosis of hypertensive patients (Table 3-1).241 Therefore, in hypertension treatment, it is important to evaluate the blood pressure level, risk factors for cardiovascular disease (Table 3-1) and the presence or absence of organ damage/cardiovascular disease (Table 3-1).

Table 1 Prognostic factors to be used for risk stratification for planning of hypertension management

As risk factors for cardiovascular disease other than blood pressure level, smoking, diabetes mellitus, dyslipidemia, obesity (especially visceral fat-type obesity), CKD, advanced age, and a family history of juvenile cardiovascular disease are important. Diabetes mellitus is an independent, strong risk factor. It is particularly important in comparison with other risk factors, as presented in Table 3-1. CKD and albuminuria are risk factors for cardiovascular disease, and are also classified as indicators of hypertensive organ damage.32,245254

Obese (especially visceral fat-type obesity) patients with a high-normal or higher blood pressure level, a fasting blood glucose level of 110 mg dl−1 or more, or 2 or 3 of three factors comprising dyslipidemia are regarded as having metabolic syndrome (MetS). As indicators of hypertensive organ damage or cardiovascular disease, the presence or absence of brain/heart/kidney/vascular/eyeground lesions should be evaluated (Table 3-1).

2) Risk stratification

In the Guidelines, hypertensive patients are stratified into three groups—low-, moderate- and high-risk groups—on the basis of the hypertensive level, primary risk factors (diabetes mellitus and other risk factors) and presence or absence of hypertensive organ damage/cardiovascular disease, as shown in Table 3-2. In the JSH2009 Guidelines, risk stratification was also expressed with respect to patients with a high-normal blood pressure of 130–139/85–89 mm Hg. However, in the Guidelines, the column expression of high-normal blood pressure was eliminated. As emphasized in other sections, the risk in patients with a high-normal blood pressure is markedly higher than in those with an optimal blood pressure. In particular, patients with diabetes mellitus, CKD, MetS meeting all four items, three or more risk factors, organ damage or cardiovascular disease are regarded as high-risk patients. However, the category of high-normal blood pressure consists of a condition in which the target level of blood pressure control is <140/90 mm Hg and that in which it is <130/80 mm Hg. Descriptions based on the differentiation of these conditions may be complex, causing unnecessary confusion. In the Guidelines, a conventional target level of 130/85 mm Hg for young and middle-aged persons was abandoned, and there is no group with this level. On the basis of these, the JSH2014-Preparing Committee decided to prepare figures and tables regarding risk stratification and planning of hypertension management at the initial examination only in patients diagnosed with hypertension to promote the clinical application of the Guidelines. Table 3-2 shows risk stratification in hypertensive patients. Figure 3-1 shows planning of hypertension management at initial examination in these patients. Thus, hypertension-specified figures and tables may help physicians understand the Guidelines.

Table 2 Stratification of the risk of cardiovascular disease based on clinic blood pressure
Figure 3-1
figure1

Planning of hypertension management at the initial examination. A full color version of this figure is available at the Hypertension Research journal online.

As the risk of cerebro-/cardiovascular diseases increases with the number of items meeting diagnostic criteria (see Chapter 7, Hypertension complicated by other diseases), MetS meeting three items (visceral fat-type obesity, high blood pressure and impaired glucose or lipid metabolism) was classified as Risk II, and MetS meeting all four items as Risk III.

When diabetes mellitus or CKD is present among risk factors, the risk is particularly high.252,253 On the basis of the results of many interventional studies,246,255259antihypertensive treatment is recommended in many guidelines.77,112,260

In the 2013 ESH/ESC Guidelines,120 the risk is stratified into four categories—low, moderate, high and super high—in accordance with risk factors, as described in the 2007 ESH-ESC Guidelines.260 However, therapeutic strategies are similar between high- and super-high-risk patients.

In the Japan Atherosclerosis Society Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012, a risk chart from NIPPON DATA is used with respect to the absolute risk of myocardial infarction-related mortality.261 The influence of hypertension on stroke is more marked than that on myocardial infarction among cardiovascular diseases. The Hisayama Study and Tanno-Sobetsu Study have also indicated that the JSH2009 risk stratification reflects the occurrence of cardiovascular disease in Japan;262,263 it may be clinically available. Considering the degree of recognition and availability in clinicians, the use of the conventional risk stratification table is recommended as the JSH2014-Preparing Committee's agreement.

In elderly persons in whom the absolute risk is high, the risk-reducing effects of therapeutic intervention are relatively clear.123,227 However, in young and middle-aged hypertensive patients, the relative risk is higher, but the absolute risk is lower than in normotensive individuals of the same age. Therefore, the absolute risk-reducing effects of treatment do not appear. Long-term follow-up may be necessary.

4. PLANNING OF HYPERTENSION MANAGEMENT AT THE INITIAL EXAMINATION

If blood pressure is high at the initial examination, it is usually measured several times on another day to confirm a high blood pressure level.119,135,264270 In addition, the patient is instructed to measure home blood pressure to confirm the presence or absence of white coat hypertension, white coat phenomenon and masked hypertension. The overall risk of the patient developing cardiovascular disease, including blood pressure, is assessed by investigating the presence or absence and degree of organ damage and risk factors for cardiovascular disease other than hypertension while eliminating secondary hypertension.

If home blood pressure or ABP differs widely from clinic blood pressure, it may be appropriate to determine a therapeutic strategy based on home blood pressure or ABP.119,135,264270

After evaluating the overall risk of cardiovascular disease in hypertensive patients, the evaluation contents, therapeutic strategy and target control levels of clinic and home blood pressures should be explained to the patient until the patient understands them. In low-risk patients with a blood pressure of 140–159/90–99 mm Hg (grade I hypertension) at the initial examination but no other risk factors, organ damage or cardiovascular disease, the lifestyle should be modified, and blood pressure should be measured again after a certain period (within 3 months). Risk is stratified by blood pressure on additional measurement, and a therapeutic strategy is determined according to Figure 3-1. Therefore, even in low-risk patients, if blood pressure is not reduced to <140/90 mm Hg through lifestyle modifications alone, antihypertensive drug therapy is started after a certain period (within 3 months). On the other hand, even when blood pressure at the initial examination is classed as grade I hypertension, a therapeutic strategy matched to the risk should be established and executed according to Figure 3-1 if the risk is judged to be moderate or high on the basis of the number of risk factors for cardiovascular disease other than hypertension as well as on the basis of the presence or absence of organ damage, including MetS, diabetes mellitus, and CKD, or cardiovascular disease. If blood pressure at the initial examination is 160-179/100–109 mm Hg (grade II), having excluded white coat hypertension or white coat phenomenon by measuring home blood pressure, and if the overall risk is judged to be moderate by risk assessment, antihypertensive drug therapy should be initiated after a period of lifestyle modification (within 1 month). Antihypertensive drug therapy should be initiated immediately if the risk is judged to be high even in patients showing grade II hypertension at the initial examination (Figure 3-1). If blood pressure is 180/110 mm Hg (grade III) at the initial examination, the risk is judged to be high and antihypertensive drug therapy must be initiated immediately (within a few days). These strategies should be applied in accordance with individual conditions. In particular, individualized strategies are required for elderly persons (see Chapter 8, Hypertension in the elderly).

In individuals with a high-normal blood pressure, progression to hypertension should be prevented by modifying their lifestyle. This reduces the risk for cardiovascular disease.271 In particular, patients with organ damage or other diseases such as diabetes mellitus, CKD, MetS meeting all items, cerebrovascular disorders and heart disease are judged to be at high risk even if their blood pressure is <140/90 mm Hg. In addition to guidance for lifestyle modifications (see Chapter 4, Lifestyle modifications), strict antihypertensive drug therapy should be promptly performed according to the target levels of blood pressure control matched to individual conditions (see Chapters 5, Treatment with antihypertensive drugs, Chapter 6, Hypertension associated with organ damage and Chapter 7, Hypertension complicated by other diseases).

5. TARGET LEVELS OF BLOOD PRESSURE CONTROL

On the basis of the results of interventional studies such as the MRC,272 HOT273 and FEVER,274 the target level of blood pressure control should be established as <140/90 mm Hg (Table 3-3). In young/middle-aged, low-risk patients with hypertension, the target level of blood pressure control had been established as <130/85 mm Hg in the JSH2009 Guidelines or earlier. This was similar to that described in the WHO-ISH1999 Guidelines.118 This target level was set on the basis of the results of the HOT Study,273 in which the cardiovascular prognosis was examined by classifying the target level of diastolic blood pressure into 90, 85 and 80 mm Hg or less (three groups): there was no increase in cardiovascular risk in the lowest target level group, although there were no significant differences among the three groups. In addition, as the diastolic blood pressure level at which the incidence of cardiovascular disease reached a minimum in the subjects of the HOT Study overall was 82.6 mm Hg, the target level of blood pressure control has been established as optimal to normal blood pressure. As a result, until the JSH2009 Guidelines, there had been a gap between criteria for the start of antihypertensive drug therapy and the target level of blood pressure control. In the JSH2014 Guidelines, recommendations were decided on the basis of the results of comparative studies. As a result, a target level of <140/90 mm Hg may achieve a further blood pressure fall-related decrease in the relative risk for cardiovascular disease in young and middle-aged individuals.17 However, there are few interventional studies supporting a target blood pressure of <140/90 mm Hg with significance;275 therefore, the target level of blood pressure control was established as <140/90 mm Hg.

Table 3 Target levels of blood pressure control

In diabetics and CKD patients with proteinuria in whom the risk for cardiovascular disease is high, the target level of blood pressure control is <130/80 mm Hg (see Chapter 6, Hypertension associated with organ damage and Chapter 7, Hypertension complicated by other diseases). In those with stroke or coronary artery disease, it is <140/90 mm Hg (see Chapter 6, Hypertension associated with organ damage). In late-phase elderly persons, in whom organ damage is frequently observed, the target level of blood pressure control should be established as <150/90 mm Hg, and antihypertensive treatment must be carefully performed while monitoring changes in symptoms and laboratory data, considering the possibility of blood flow disturbance in important organs. Even in late-phase elderly persons, the final target level of blood pressure control is <140/90 mm Hg.

Although evidence regarding home blood pressure-based interventional studies is not sufficient, the target levels of blood pressure control are <135/85 mm Hg in hypertensive patients and <125/75 mm Hg in hypertensive patients with diabetes mellitus according to the Ohasama Study277,278 and observational studies with HOMED BP.279,280 Concerning other conditions, there is no evidence, but the target levels of home systolic and diastolic blood pressures are established as being 5-mm Hg lower than clinic systolic and diastolic blood pressures, considering differences in blood pressure on the home blood pressure-based diagnosis of hypertension.

With respect to the lower limit of the target level of blood pressure control, a further fall in blood pressure should be avoided in the presence of conditions281286 in which excessive blood pressure fall-related increases in the stroke-/myocardial infarction-/kidney hypofunction-related mortality rates were shown by a subanalysis of interventional studies involving high-risk hypertensive patients. Internationally, a meta-analysis287 of 61 prospective studies regarding the relationship between blood pressure and cardiovascular mortality indicated that cardiovascular mortality increased with an increase in blood pressure not only in hypertensive but also in normotensive individuals aged 40–89 years. However, it is unclear whether the incidence of cardiovascular disease further decreases at a blood pressure level of <115/75 mm Hg. Treatment should be performed, considering that no interventional study has demonstrated an improvement in prognosis through a decrease in blood pressure to an optimal level.

6. SELECTION OF TREATMENTS

Several genetic and environmental factors are involved in the occurrence and progression of essential hypertension. Therefore, treatment always includes the correction of lifestyle (non-drug therapy), which comprises the greater portion of environmental factors. However, few patients achieve the target of blood pressure control through lifestyle modifications alone, and drug therapy is necessary in most cases. In individual patients, the risk should be stratified by comprehensively evaluating the blood pressure level, risk factors for cardiovascular disease and presence of cardiovascular disease, and a treatment plan must be established according to the stratification (Figure 3-1).

1) Lifestyle modifications

Hypertension is a lifestyle-related disease. Lifestyle modifications may prevent hypertension and exhibit blood pressure-decreasing effects.288290 All patients with a high-normal or high blood pressure must undergo a change in lifestyle. In particular, when other lifestyle-related diseases such as dyslipidemia, diabetes mellitus, MetS and obesity are concomitantly present, lifestyle modifications are very important as a treatment method, and it is possible to simultaneously reduce these risk factors with safety at a low cost. To maintain the blood pressure-decreasing effects of lifestyle modifications, it is necessary for both physicians and patients to continue efforts over a long period.291

Although many hypertensive patients fail to achieve the target of blood pressure control through lifestyle modifications alone, it is possible to decrease the number and doses of antihypertensive drugs by enhancing their effects. Therefore, even after the start of antihypertensive drug therapy, the importance of lifestyle modifications does not change.292,293 The contents of lifestyle improvement are described in Chapter 4, Lifestyle modifications.

2) Antihypertensive drug therapy

Many patients with hypertension require drug therapy. Major antihypertensive drugs that are currently used include Ca antagonists, renin–angiotensin system inhibitors (angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors and renin inhibitors), diuretics (thiazide and thiazide-like diuretics, loop diuretics and K-sparing diuretics) and β-blockers. In accordance with the condition, α-blockers and central sympathetic nerve inhibitors (methyldopa, clonidine and guanabenz) are additionally administered. The action mechanisms and adverse effects of respective antihypertensive drugs are characteristic. On the basis of evidence on prognosis improvement from large-scale clinical studies, diuretics, Ca antagonists, ACE inhibitors and ARBs are selected as first-choice drugs (Chapter 5, Treatment with antihypertensive drugs).

For the administration of antihypertensive drugs, (1) a drug to be administered once a day should be selected; (2) drug therapy should be started at a low dose (in particular, commence therapy with a thiazide diuretic using half of the tablet); (3) when a 20-/10-mm Hg or greater decrease in blood pressure is targeted, combination therapy should be considered in the initial phase; (4) to enhance the depressor effects of drugs without adverse effects, drugs should be combined appropriately; (5) if a drug shows only a weak depressor effect or is poorly tolerated, it must be switched to another drug with a different action mechanism; and (6) positive indication should be considered in accordance with concomitant diseases or conditions, and antihypertensive drugs should be selected, considering contraindications/careful administration and interactions with combined drugs other than antihypertensive drugs.

7. OTHER POINTS REQUIRING ATTENTION

1) Long-term treatment

The objective of long-term treatment is to prevent cardiovascular disease and target organ damage by maintaining a target blood pressure level over a long period and comprehensively managing risk factors other than blood pressure.

As hypertension does not cause any marked symptoms, and as treatment continues over a long period, some patients may stop visiting medical facilities. An antihypertensive drug-related decrease in blood pressure is misunderstood as the cure for hypertension, and treatment is discontinued in some cases.294 Attending physicians should perform patient-involved treatment by sufficiently explaining the condition of hypertension, treatment methods, expected effects of treatment and adverse effects of antihypertensive drugs that may occur, through close communication with patients. In addition, it is important to make efforts/devise measures so that patients may observe lifestyle modifications and continue hospital visits and taking drugs. A good physician (hospital)–patient relationship must be maintained, and much attention should be paid so that antihypertensive treatment may not affect the patient's daily living or social activities. The sufficiency of communication with the physician and the degree of patient satisfaction with the medical staff markedly affect the patient's QOL.295

2) Attention to the QOL

Hypertensive patients’ QOL is objectively and comprehensively evaluated on the basis of generalized comfort, physical symptoms, sexual activity, working efficiency, emotional state, intellectual functions, satisfaction with their lives, and social activities.296 Although the influence of hypertension on the QOL is less marked than that of other serious diseases, the QOL is impaired by being conscious of hypertension.297,298 Problems with emotional responses, home life, social activities, sleep and heart and digestive functions appear with increases in blood pressure.299 Furthermore, the QOL reduces with age, and there are marked individual differences among elderly persons.300

Although treatment for hypertension improves the QOL,301,302 the adverse effects of antihypertensive drugs reduce it.303 As treatment for hypertension continues over a long period, it is important to maintain a favorable QOL for the continuation of treatment.

3) Concordance/adherence

The term ‘compliance’ (meaning obedience/acceptance) has been used to express the patient taking a drug and continuing treatment according to the physician's instructions. However, this means simply obeying regulations/orders and does not reflect what hypertension treatment should be. The entity ‘adherence’ (meaning support/attachment) or ‘concordance’ (meaning agreement/harmony) was introduced.304,305 Adherence refers to the patient understanding the disease and necessity of treatment and continuing treatment spontaneously and positively, which is more desirable. In addition, the term concordance involves continuing to determine a therapeutic strategy based on an agreement through a partnership between the physician and the patient on the assumption that the patient has sufficient knowledge of the disease and treatment. If the physician continues treatment from force of habit without sufficiently understanding the risk of hypertension or advantages and disadvantages of antihypertensive treatment, it may prevent the establishment of concordance. A supporting system by the medical staff, as a team, should be established through favorable communication between the physician (hospital) and the patient. Table 3-4 shows the ways through which to approach such adherence-/concordance-based medical practice.

Table 4 Methods for the medical staff and patient to establish a partnership and continue concordance-based medical practice

Adherence to antihypertensive treatment is related to favorable/unfavorable blood pressure control and the development/prognosis of cardiovascular disease.306310 To achieve favorable concordance, it is necessary for the physician and the patient to understand the condition of hypertension, the objective of treatment (prevention of target organ damage and cardiovascular disease), treatment methods (lifestyle modifications and drug therapy), expected effects and adverse effects of treatment, and health expenditure.311314 The appearance of adverse effects related to antihypertensive drugs affects adherence to antihypertensive treatment.315 When the number of tablets to be taken and frequency of dosing are smaller, adherence improves.307,316 In this sense, the use of a mixed preparation decreases the number of tablets to be taken and reduces drug expenses, improving adherence/concordance.317 Generic drugs approved through drug elution and biological equivalence studies (changes in the blood concentration of a drug after administration) may also improve adherence/concordance as drug expenses can be reduced.

4) Blood pressure management in hypertensive patients taking antithrombotic drugs

POINT 3b

Blood pressure management in hypertensive patients taking antithrombotic drugs

1. As hypertension is a risk factor for intracranial hemorrhage during therapy with antithrombotic drugs (antiplatelet drugs and anticoagulants), strict blood pressure control should be performed in patients taking these drugs. (Recommendation grade B) (II)

Recently, antiplatelet drugs have been increasingly used for the secondary prevention of arteriosclerotic disorders (transient cerebral ischemic attacks, cerebral infarction, coronary artery disease, peripheral arteriosclerotic disease and carotid sclerosis), and oral anticoagulants for the prevention of cardiogenic cerebral embolism/deep venous thrombosis. Treatment with these antithrombotic drugs increases the incidence of hemorrhagic complications, especially intracranial hemorrhage.318,319 After treatment with a drug-eluting stent, combination therapy with two antiplatelet drugs such as aspirin and clopidogrel is administered for a long period. To treat atherosclerotic disorders with atrial fibrillation, an antiplatelet drug is often combined with an oral anticoagulant. Such combination therapy with antithrombotic drugs further increases the risk of hemorrhage.319323

As hypertension is a risk factor for intracranial hemorrhage during treatment with antithrombotic drugs, strict blood pressure management is important. The PROGRESS subanalysis involving patients taking antithrombotic drugs showed that the mean blood pressure in the antihypertensive drug group was 8.9/4.0 mm Hg lower than that in the placebo group, and that the incidence of intracranial hemorrhage decreased by 46%.324 In the BAT prospective observational study involving Japanese patients taking antiplatelet drugs/Warfarin, there was a correlation between the blood pressure level during therapy and incidence of intracranial hemorrhage, and the cutoff value of blood pressure for predicting the onset of intracranial hemorrhage was 130/81 mm Hg.325 Although evidence on the target level of blood pressure control to prevent hemorrhagic complications during therapy with antithrombotic drugs is not sufficient, blood pressure control should be further promoted carefully, considering a target level of 130/80 mm Hg, if possible, aiming at <130/80 mm Hg, while monitoring ischemic symptoms/findings of important organs such as the brain/heart/kidney, in order to prevent intracranial hemorrhage in hypertensive patients taking antithrombotic drugs (with respect to patients with cerebral infarction, see Section 1 of Chapter 6, CEREBROVASCULAR DISEASE).

5) Cost-effectiveness of antihypertensive treatment

POINT 3c

1. The cost-effectiveness of home blood pressure-based antihypertensive therapy with ARBs, ACE inhibitors, Ca antagonists or diuretics, which are routinely used in Japan, is encouraging.

As economic burdens are required for chronic disease treatment, short-/long-term personal/social economic burdens must be considered in addition to the effects of treatment in clinical practice. Cost-effectiveness analyses based on the results of large-scale clinical studies in Japan and other countries, as well as those using a model for predicting the prognosis, such as the Markov model, are useful.

As a method of cost-effectiveness analysis, the acquisition of 1QALY (quality-adjusted life year: survival in complete health status for 1 year) is used as a parameter of efficacy.326 In cost-effectiveness analyses, the results are commonly expressed using the incremental cost-effectiveness ratio (ICER)—that is, an additional cost required for test therapy in comparison with control therapy to obtain specific effects. When the ICER per 1QALY is 50000 dollars in the United States, 20,000 to 30,000 pounds in England and 5,000,000 yen in Japan, the cost-effectiveness is regarded as favorable.327,328 Expenses include not only those for antihypertensive drugs but also those for consultations, examinations and treatment for hypertension-related cardiovascular complications and concomitant diseases such as new-onset diabetes mellitus.

Additional home blood pressure measurement329 and ABPM330 make it possible to rule out white coat hypertension in comparison with hypertension diagnosis based on clinic blood pressure alone. Therefore, their cost-effectiveness is favorable. According to the LIFE results on antihypertensive drug therapy, treatment with losartan as a first-choice drug was more effective than that with atenolol, reducing the cost. This treatment method was dominant.331

According to the results of the ASCOT-BPLA Study, combination therapy with amlodipine and perindopril, as a first-choice regimen, was more cost-effective than combination therapy with atenolol and bendroflumethiazide.332 According to the ALLHAT results, treatment with amlodipine, as a first-choice drug, was more cost-effective than therapy with chlortalidone.333

In an analytical model on the prognosis of Japanese patients with essential hypertension using the Markov model,334 the cost-effectiveness of four treatment methods, ARBs (Ca antagonists were combined in some patients), ARBs (diuretics were combined in some patients), Ca antagonists (ARBs were combined in some patients) and diuretics (ARBs were combined in some patients), was analyzed. Assuming that their antihypertensive effects were similar, there were no marked differences in the cost or life-year among the four treatment methods in the absence of diabetes mellitus at the start of treatment. However, when diabetes mellitus was present at the start of treatment, ARBs (Ca antagonists were combined in some patients) exhibited maximal effects at a minimal cost.335 In a cost-effectiveness analysis of four treatment methods, monotherapy with ARBs, monotherapy with Ca antagonists, combination therapy with ARBs and Ca antagonists, and no antihypertensive drug,336 combination therapy with ARBs and Ca antagonists showed the greatest QALY in men without diabetes mellitus, followed by monotherapy with ARBs, monotherapy with Ca antagonists and the absence of treatment, as their antihypertensive effects differed. On the other hand, the cost was the lowest in untreated patients, followed by those receiving monotherapy with Ca antagonists, combination therapy with ARBs and Ca antagonists, and monotherapy with ARBs. The ICER of combination therapy with ARBs and Ca antagonists to the absence of treatment was 200,000 yen/QALY. It was concluded that the cost-effectiveness of this combination therapy was favorable.337 In men with diabetes mellitus, this combination therapy showed the greatest QALY at a minimal cost. It was the most cost-effective among the four treatment methods.

In a study comparing a fixed combination drugs therapy with respective drugs a difference in adherence was observed. The fixed combination drugs entailed a lower cost of treatment.338 Thus, home blood pressure-based antihypertensive therapy with ARBs, ACE inhibitors, Ca antagonists or diuretics, which are routinely used in Japan, is cost-effective.

Citation Information

We recommend that any citations to information in the Guidelines are presented in the following format:

The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH2014). Hypertens Res 2014; 37: 253–392.

Please refer to the title page for the full list of authors.

References

  1. 7

    Ueshima H . Explanation for the Japanese paradox: prevention of increase in coronary heart disease and reduction in stroke. J Atheroscler Thromb 2007; 14: 278 –286. E-III

    Article  Google Scholar 

  2. 16

    Arima H, Tanizaki Y, Yonemoto K, Doi Y, Ninomiya T, Hata J, Fukuhara M, Matsumura K, Iida M, Kiyohara Y . Impact of blood pressure levels on different types of stroke: the Hisayama study. J Hypertens 2009; 27: 2437 –2443. E-Ib

    Article  CAS  Google Scholar 

  3. 17

    Lawes CM, Rodgers A, Bennett DA, Parag V, Suh I, Ueshima H, MacMahon S, Asia Pacific Cohort Studies Collaboration. Blood pressure and cardiovascular disease in the Asia Pacific region. J Hypertens 2003; 21: 707 –716. E-Ia

    Article  CAS  PubMed  Google Scholar 

  4. 32

    Ninomiya T, Kiyohara Y, Tokuda Y, Doi Y, Arima H, Harada A, Ohashi Y, Ueshima H, Japan Arteriosclerosis Longitudinal Study Group. Impact of kidney disease and blood pressure on the development of cardiovascular disease: an overview from the Japan Arteriosclerosis Longitudinal Study. Circulation 2008; 118: 2694 –2701. E-Ia

    Article  Google Scholar 

  5. 77

    The Japanese Society of Hypertension. Guidelines Subcommittees of the Japanese Society of Hypertension Guidelines for the Management of Hypertension JSH2009 (in Japanese). Life Science Publishing Co, Ltd: Tokyo. 2009. GL

  6. 112

    The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Arch Intern Med 1997; 157: 2413 –2446. GL

  7. 118

    Guidelines Subcommittee. 1999 World Health Organization-International Society of Hypertension Guidelines for the Management of Hypertension. J Hypertens 1999; 17: 151 –183. GL

    Google Scholar 

  8. 119

    Kikuya M, Hansen TW, Thijs L, Björklund-Bodegård K, Kuznetsova T, Ohkubo T, Richart T, Torp-Pedersen C, Lind L, Ibsen H, Imai Y, Staessen JA, International Database on Ambulatory blood pressure monitoring in relation to Cardiovascular Outcomes Investigators. Diagnostic thresholds for ambulatory blood pressure monitoring based on 10-year cardiovascular risk. Circulation 2007; 115: 2145 –2152. E-Ia

    Article  PubMed  Google Scholar 

  9. 120

    Mancia G, Fagard R, Narkiewicz K, Redón J, Zanchetti A, Böhm M, Christiaens T, Cifkova R, De Backer G, Dominiczak A, Galderisi M, Grobbee DE, Jaarsma T, Kirchhof P, Kjeldsen SE, Laurent S, Manolis AJ, Nilsson PM, Ruilope LM, Schmieder RE, Sirnes PA, Sleight P, Viigimaa M, Waeber B, Zannad F . The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 2013; 31: 1281–1357 GL

    Article  CAS  Google Scholar 

  10. 123

    Staessen JA, Gasowski J, Wang JG, Thijs L, Den Hond E, Boissel JP, Coope J, Ekbom T, Gueyffier F, Liu L, Kerlikowske K, Pocock S, Fagard RH . Risks of untreated and treated isolated systolic hypertension in the elderly: meta-analysis of outcome trials. Lancet 2000; 355: 865 –872. I

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. 135

    Bobrie G, Chatellier G, Genes N, Clerson P, Vaur L, Vaisse B, Menard J, Mallion JM . Cardiovascular prognosis of’masked hypertension’detected by blood pressure self-measurement in elderly treated hypertensive patients. JAMA 2004; 291: 1342 –1349. E-Ib

    CAS  Article  Google Scholar 

  12. 226

    Law MR, Morris JK, Wald NJ . Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies . BMJ 2009 ; 338 : b1665.I .

    Article  Google Scholar 

  13. 227

    Bejan-Angoulvant T, Saadatian-Elahi M, Wright JM, Schron EB, Lindholm LH, Fagard R, Staessen JA, Gueyffier F . Treatment of hypertension in patients 80 years and older: the lower the better? A meta-analysis of randomized controlled trials . J Hypertens 2010 ; 28 : 1366 – 1372. I .

    Article  CAS  PubMed  Google Scholar 

  14. 228

    Asayama K, Ohkubo T, Yoshida S, Suzuki K, Metoki H, Harada A, Murakami Y, Ohashi Y, Ueshima H, Imai Y, Japan Arteriosclerosis Longitudinal Study (JALS) group . Stroke risk and antihypertensive drug treatment in the general population: the Japan arteriosclerosis longitudinal study . J Hypertens 2009 ; 27 : 357 – 364 . E-Ia .

    Article  CAS  PubMed  Google Scholar 

  15. 229

    Inoue R, Ohkubo T, Kikuya M, Metoki H, Asayama K, Obara T, Hirose T, Hara A, Hoshi H, Hashimoto J, Totsune K, Satoh H, Kondo Y, Imai Y . Stroke risk in systolic and combined systolic and diastolic hypertension determined using ambulatory blood pressure. The Ohasama study . Am J Hypertens 2007 ; 20 : 1125 – 1131 . E-Ib .

    Article  PubMed  Google Scholar 

  16. 230

    Barengo NC, Hu G, Kastarinen M, Antikainen R, Tuomilehto J . The effects of awareness, treatment and control of hypertension on future stroke incidence in a community-based population study in Finland . J Hypertens 2009 ; 27 : 1459 – 1465 . E-Ib .

    Article  CAS  PubMed  Google Scholar 

  17. 231

    Barengo NC, Kastarinen M, Antikainen R, Nissinen A, Tuomilehto J . The effects of awareness, treatment and control of hypertension on cardiovascular and all-cause mortality in a community-based population . J Hum Hypertens 2009 ; 23 : 808 – 816 . E-Ib .

    Article  CAS  PubMed  Google Scholar 

  18. 232

    Arima H, Chalmers J, Woodward M, Anderson C, Rodgers A, Davis S, Macmahon S, Neal B, PROGRESS Collaborative Group . Lower target blood pressures are safe and effective for the prevention of recurrent stroke: the PROGRESS trial . J Hypertens 2006 ; 24 : 1201 – 1208 . III .

    Article  CAS  PubMed  Google Scholar 

  19. 233

    Ishikawa S, Kario K, Kayaba K, Gotoh T, Nago N, Nakamura Y, Tsutsumi A, Kajii E, Jichi Medical School (JMS) Cohort Study Group . Continued high risk of stroke in treated hypertensives in a general population: the Jichi Medical School Cohort study . Hypertens Res 2008 ; 31 : 1125 – 1133 . E-Ib .

    Article  CAS  PubMed  Google Scholar 

  20. 234

    Okayama A, Kadowaki T, Okamura T, Hayakawa T, Ueshima H, NIPPON DATA80 Research Group . Age-specific effects of systolic and diastolic blood pressures on mortality due to cardiovascular diseases among Japanese men (NIPPON DATA80) . J Hypertens 2006 ; 24 : 459 – 462 . E-Ib .

    Article  CAS  PubMed  Google Scholar 

  21. 235

    Shimamoto K, Fujita T, Ito S, Naritomi H, Ogihara T, Shimada K, Tanaka H, Yoshiike N, J-HEALTH Study Committees . Impact of blood pressure control on cardiovascular events in 26,512 Japanese hypertensive patients: the Japan Hypertension Evaluation with Angiotensin II Antagonist Losartan Therapy (J-HEALTH) study, a prospective nationwide observational study . Hypertens Res 2008 ; 31 : 469 – 478 . E-Ib .

    Article  PubMed  Google Scholar 

  22. 236

    Lever AF, Ramsay LE . Treatment of hypertension in the elderly . J Hypertens 1995 ; 13 : 571 – 579 . VI .

    Article  CAS  PubMed  Google Scholar 

  23. 237

    ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group . The Antihypertensive and Lipid-Lowering Treatment t o Prevent Heart Attack Trial. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT) . JAMA 2002 ; 288 : 2981 – 2997 . II .

    Article  Google Scholar 

  24. 238

    Moser M, Hebert PR . Prevention of disease progression, left ventricular hypertrophy and congestive heart failure in hypertension treatment trials . J Am Coll Cardiol 1996 ; 27 : 1214 – 1218. I .

    Article  CAS  Google Scholar 

  25. 239

    Psaty BM, Smith NL, Siscovick DS, Koepsell TD, Weiss NS, Heckbert SR, Lemaitre RN, Wagner EH, Furberg CD . Health outcomes associated with antihypertensive therapies used as first-line agents. A systematic review and meta-analysis . JAMA 1997 ; 277 : 739 – 745. I .

    Article  CAS  Google Scholar 

  26. 240

    Verdecchia P, Staessen JA, Angeli F, de Simone G, Achilli A, Ganau A, Mureddu G, Pede S, Maggioni AP, Lucci D, Reboldi G, Cardio-Sis investigators . Usual versus tight control of systolic blood pressure in non-diabetic patients with hypertension (Cardio-Sis): an open-label randomised trial . Lancet 2009 ; 374 : 525 – 533 . II .

    Article  PubMed  Google Scholar 

  27. 241

    Gueyffier F, Boutitie F, Boissel JP, Pocock S, Coope J, Cutler J, Ekbom T, Fagard R, Friedman L, Perry M, Prineas R, Schron E . Effect of antihypertensive drug treatment on cardiovascular outcomes in women and men. A meta-analysis of individual patient data from randomized, controlled trials. The INDANA Investigators . Ann Intern Med 1997 ; 126 : 761 – 767 . III .

    Article  CAS  PubMed  Google Scholar 

  28. 242

    Sairenchi T, Iso H, Irie F, Fukasawa N, Yamagishi K, Kanashiki M, Saito Y, Ota H, Nose T . Age-specific relationship between blood pressure and the risk of total and cardiovascular mortality in Japanese men and women . Hypertens Res 2005 ; 28 : 901 – 909 . E-Ib .

    Article  PubMed  Google Scholar 

  29. 243

    Conen D, Ridker PM, Buring JE, Glynn RJ . Risk of cardiovascular events among women with high normal blood pressure or blood pressure progression: prospective cohort study . BMJ 2007 ; 335 : 432 . E-Ib .

    Article  PubMed  PubMed Central  Google Scholar 

  30. 244

    Beckett NS, Peters R, Fletcher AE, Staessen JA, Liu L, Dumitrascu D, Stoyanovsky V, Antikainen RL, Nikitin Y, Anderson C, Belhani A, Forette F, Rajkumar C, Thijs L, Banya W, Bulpitt CJ, HYVET Study Group . Treatment of hypertension in patients 80 years of age or older . New Engl J Med 2008 ; 358 : 1887 – 1898 . II .

    Article  CAS  PubMed  Google Scholar 

  31. 245

    Ninomiya T, Kiyohara Y, Kubo M, Tanizaki Y, Doi Y, Okubo K, Wakugawa Y, Hata J, Oishi Y, Shikata K, Yonemoto K, Hirakata H, Iida M . Chronic kidney disease and cardiovascular disease in a general Japanese population: the Hisayama Study . Kidney Int 2005 ; 68 : 228 – 236 . E-Ib .

    Article  PubMed  Google Scholar 

  32. 246

    Rahman M, Ford CE, Cutler JA, Davis BR, Piller LB, Whelton PK, Wright Jr JT, Barzilay JI, Brown CD, Colon Sr PJ, Fine LJ, Grimm Jr RH, Gupta AK, Baimbridge C, Haywood LJ, Henriquez MA, Ilamaythi E, Oparil S, Preston R, ALLHAT Collaborative Research Group . Long-term renal and cardiovascular outcomes in Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants by baseline estimated GFR . Clin J Am Soc Nephrol 2012 ; 7 : 989 – 1002 . IVa .

    Article  PubMed  PubMed Central  Google Scholar 

  33. 247

    Arnlöv J, Evans JC, Meigs JB, Wang TJ, Fox CS, Levy D, Benjamin EJ, D’Agostino RB, Vasan RS . Low-grade albuminuria and incidence of cardiovascular disease events in nonhypertensive and nondiabetic individuals: the Framingham Heart Study . Circulation 2005 ; 112 : 969 – 975 . E-Ib .

    Article  CAS  PubMed  Google Scholar 

  34. 248

    Nakayama M, Metoki H, Terawaki H, Ohkubo T, Kikuya M, Sato T, Nakayama K, Asayama K, Inoue R, Hashimoto J, Totsune K, Hoshi H, Ito S, Imai Y . Kidney dysfunction as a risk factor for first symptomatic stroke events in a general Japanese population—the Ohasama study . Nephrol Dial Transplant 2007 ; 22 : 1910 – 1915 . E-Ib .

    Article  PubMed  Google Scholar 

  35. 249

    Irie F, Iso H, Sairenchi T, Fukasawa N, Yamagishi K, Ikehara S, Kanashiki M, Saito Y, Ota H, Nose T . The relationships of proteinuria, serum creatinine, glomerular filtration rate with cardiovascular disease mortality in Japanese general population . Kidney Int 2006 ; 69 : 1264 – 1271 . E-Ib .

    Article  CAS  PubMed  Google Scholar 

  36. 250

    Hallan SI, Matsushita K, Sang Y, Mahmoodi BK, Black C, Ishani A, Kleefstra N, Naimark D, Roderick P, Tonelli M, Wetzels JF, Astor BC, Gansevoort RT, Levin A, Wen CP, Coresh J, Chronic Kidney Disease Prognosis Consortium . Age and association of kidney measures with mortality and end-stage renal disease . JAMA 2012 ; 308 : 2349 – 2360 . E-Ia .

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. 251

    Asayama K, Ohkubo T, Sato A, Hara A, Obara T, Yasui D, Metoki H, Inoue R, Kikuya M, Hashimoto J, Hoshi H, Satoh H, Imai Y . Proposal of a risk-stratification system for the Japanese population based on blood pressure levels: the Ohasama study . Hypertens Res 2008 ; 31 : 1315 – 1322 . E-Ib .

    Article  PubMed  Google Scholar 

  38. 252

    Mahmoodi BK, Matsushita K, Woodward M, Blankestijn PJ, Cirillo M, Ohkubo T, Rossing P, Sarnak MJ, Stengel B, Yamagishi K, Yamashita K, Zhang L, Coresh J, de Jong PE, Astor BC, Chronic Kidney Disease Prognosis Consortium . Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without hypertension: a meta-analysis . Lancet 2012 ; 380 : 1649 – 1661 . E-Ia .

    Article  PubMed  PubMed Central  Google Scholar 

  39. 253

    Fox CS, Matsushita K, Woodward M, Bilo HJ, Chalmers J, Heerspink HJ, Lee BJ, Perkins RM, Rossing P, Sairenchi T, Tonelli M, Vassalotti JA, Yamagishi K, Coresh J, de Jong PE, Wen CP, Nelson RG, Chronic Kidney Disease Prognosis Consortium . Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis . Lancet 2012 ; 380 : 1662 – 1673 . E-Ia .

    Article  PubMed  PubMed Central  Google Scholar 

  40. 254

    de Leeuw PW, Ruilope LM, Palmer CR, Brown MJ, Castaigne A, Mancia G, Rosenthal T, Wagener G . Clinical significance of renal function in hypertensive patients at high risk: results from the INSIGHT trial . Arch Intern Med 2004 ; 164 : 2459 – 2464 . III .

    Article  PubMed  Google Scholar 

  41. 255

    Turnbull F, Neal B, Algert C, Chalmers J, Chapman N, Cutler J, Woodward M, MacMahon S, Blood Pressure Lowering Treatment Trialists’ Collaboration . Effects of different blood pressure-lowering regimens on major cardiovascular events in individuals with and without diabetes mellitus: results of prospectively designed overviews of randomized trials . Arch Intern Med 2005 ; 165 : 1410 – 1149. I .

    Article  PubMed  Google Scholar 

  42. 256

    PROGRESS Collaborative Group . Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or ransient ischaemic attack . Lancet 2001 ; 358 : 1033 – 1041 . II .

    Article  Google Scholar 

  43. 257

    UK Prospective Diabetes Study Group . Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38 . BMJ 1998 ; 317 : 703 – 713 . II .

    Article  PubMed Central  Google Scholar 

  44. 258

    Bangalore S, Kumar S, Lobach I, Messerli FH . Blood pressure targets in subjects with type 2 diabetes mellitus/impaired fasting glucose: observations from traditional and bayesian random-effects meta-analyses of randomized trials . Circulation 2011 ; 123 : 2799 – 27810 . I .

    Article  CAS  PubMed  Google Scholar 

  45. 259

    Casas JP, Chua W, Loukogeorgakis S, Vallance P, Smeeth L, Hingorani AD, MacAllister RJ . Effect of inhibitors of the renin–angiotensin system and other antihypertensive drugs on renal outcomes: systematic review and meta-analysis . Lancet 2005 ; 366 : 2026 – 2033 . I .

    Article  CAS  PubMed  Google Scholar 

  46. 260

    Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, Grassi G, Heagerty AM, Kjeldsen SE, Laurent S, Narkiewicz K, Ruilope L, Rynkiewicz A, Schmieder RE, Boudier HA, Zanchetti A, Vahanian A, Camm J, De Caterina R, Dean V, Dickstein K, Filippatos G, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL, Erdine S, Kiowski W, Agabiti-Rosei E, Ambrosioni E, Lindholm LH, Viigimaa M, Adamopoulos S, Agabiti-Rosei E, Ambrosioni E, Bertomeu V, Clement D, Erdine S, Farsang C, Gaita D, Lip G, Mallion JM, Manolis AJ, Nilsson PM, O’Brien E, Ponikowski P, Redon J, Ruschitzka F, Tamargo J, van Zwieten P, Waeber B, Williams B . Management of Arterial Hypertension of the European Society of Hypertension, European Society of Cardiology. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management o f Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) . J Hypertens 2007 ; 25 : 1105 – 1187 GL .

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. 261

    Japan Atherosclerosis Society (JAS) . Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases (in Japanese) . 2012 GL .

  48. 262

    Onishi H, Saito S, Akasaka K, Miura T, Shimamoto K . Examination regarding the ability of risk stratification in the JSH2009 Guidelines to predict cardiovascular events in the regional general population: Tanno-Sobetsu Study . J Clin Exp Med 2013 ; 245 : 675 – 676 . Japanese. E-II .

    Google Scholar 

  49. 263

    Ninomiya T, Kiyohara H. . Prognostic factors to be used for risk stratification and reassessment of these factors, (1) Metabolic syndrome, Clinical Hypertension Workbook—-Next approach beyond evidence—-2nd volume, Risk stratificati on in hypertensive patients Edited by Tsuchihashi T, Oya Y, and Kario N, Osaka, Iyaku (Medicine and Drug) Journal 2012 pp 58 – 64 Japanese. VI .

  50. 264

    Dolan E, Stanton A, Thijs L, Hinedi K, Atkins N, McClory S, Den Hond E, McCormack P, Staessen JA, O’Brien E . Superiority of ambulatory over clinic blood pressure measurement in predicting mortality: the Dublin outcome study . Hypertension 2005 ; 46 : 156 – 161 . E-Ib .

    Article  CAS  Google Scholar 

  51. 265

    Hansen TW, Jeppesen J, Rasmussen S, Ibsen H, Torp-Pedersen C . Ambulatory blood pressure and mortality: a population-based study . Hypertension 2005 ; 45 : 499 – 504 . E-Ib .

    Article  CAS  Google Scholar 

  52. 266

    Hansen TW, Kikuya M, Thijs L, Björklund-Bodegård K, Kuznetsova T, Ohkubo T, Richart T, Torp-Pedersen C, Lind L, Jeppesen J, Ibsen H, Imai Y, Staessen JA, IDACO Investigators . Prognostic superiority of daytime ambulatory over conventional blood pressure in four populations: a meta-analysis of 7,030 individuals . J Hypertens 2007 ; 25 : 1554 – 1564 . E-Ia .

    Article  CAS  PubMed  Google Scholar 

  53. 267

    Hodgkinson J, Mant J, Martin U, Guo B, Hobbs FD, Deeks JJ, Heneghan C, Roberts N, McManus RJ . Relative effectiveness of clinic and home blood pressure monitoring compared with ambulatory blood pressure monitoring in diagnosis of hypertension: systematic review . BMJ 2011 ; 342 : d3621 .E-Ia .

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. 268

    Ingelsson E, Björklund-Bodegård K, Lind L, Arnlöv J, Sundström J . Diurnal blood pressure pattern and risk of congestive heart failure . JAMA 2006 ; 295 : 2859 – 2866 . E-Ib .

    Article  CAS  Google Scholar 

  55. 269

    Niiranen TJ, Hänninen MR, Johansson J, Reunanen A, Jula AM . Home-measured blood pressure is a stronger predictor of cardiovascular risk than office blood pressure: the Finn-Home study . Hypertension 2010 ; 55 : 1346 – 1351 . E-Ib .

    Article  CAS  PubMed  Google Scholar 

  56. 270

    Ishikawa J, Carroll DJ, Kuruvilla S, Schwartz JE, Pickering TG . Changes in home versus clinic blood pressure with antihypertensive treatments: a meta-analysis . Hypertension 2008 ; 52 : 856 – 864 . E-Ia .

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. 271

    Appel LJ, Champagne CM, Harsha DW, Cooper LS, Obarzanek E, Elmer PJ, Stevens VJ, Vollmer WM, Lin PH, Svetkey LP, Stedman SW, Young DR, Writing Group of the PREMIER Collaborative Research Group . Effects of comprehensive lifestyle modification on blood pressure control: main results of the PREMIER clinical trial . JAMA 2003 ; 289 : 2083 – 2093 . II .

    PubMed  PubMed Central  Google Scholar 

  58. 272

    Medical Research Council Working Party . MRC trial of treatment of mild hypertension: principal results . Br Med J (Clin Res Ed) 1985 ; 291 : 97 – 104 . II .

    Article  Google Scholar 

  59. 273

    Hansson L, Zanchetti A, Carruthers SG, Dahlöf B, Elmfeldt D, Julius S, Ménard J, Rahn KH, Wedel H, Westerling S, HOT Study Group . Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial . Lancet 1998 ; 351 : 1755 – 1762 . II .

    Article  CAS  Google Scholar 

  60. 274

    Liu L, Zhang Y, Liu G, Li W, Zhang X, Zanchetti A, FEVER Study Group . The Felodipine Event Reduction (FEVER) Study: a randomized long-term placebo-controlled trial in Chinese hypertensive patients . J Hypertens 2005 ; 23 : 2157 – 2172 . II .

    Article  CAS  PubMed  Google Scholar 

  61. 275

    Zanchetti A, Grassi G, Mancia G . When should antihypertensive drug treatment be initiated and to what levels should systolic blood pressure be lowered? A critical reappraisal . J Hypertens 2009 ; 27 : 923 – 934 . IVa .

    Article  CAS  PubMed  Google Scholar 

  62. 276

    Berry JD, Dyer A, Cai X, Garside DB, Ning H, Thomas A, Greenland P, Van Horn L, Tracy RP, Lloyd-Jones DM . Lifetime risks of cardiovascular disease . New Engl J Med 2012 ; 366 : 321 – 329 . IVa .

    Article  CAS  PubMed  Google Scholar 

  63. 277

    Yasui D, Asayama K, Ohkubo T, Kikuya M, Kanno A, Hara A, Hirose T, Obara T, Metoki H, Inoue R, Totsune K, Hoshi H, Satoh H, Imai Y . Stroke risk in treated hypertension based on home blood pressure: the Ohasama study . Am J Hypertens 2010 ; 23 : 508 – 514 . IVa .

    Article  PubMed  PubMed Central  Google Scholar 

  64. 278

    Yasui D, Asayama K, Takada N, Ohkubo T, Kikuya M, Hara A, Hirose T, Obara T, Metoki H, Inoue R, Totsune K, Hoshi H, Satoh H, Staessen JA, Imai Y . Evaluating home blood pressure in treated hypertensives in comparison with the referential value of casual screening of blood pressure: the Ohasama study . Blood Press Monit 2012 ; 17 : 89 – 95 . IVb .

    Article  PubMed  PubMed Central  Google Scholar 

  65. 279

    Asayama K, Ohkubo T, Metoki H, Obara T, Inoue R, Kikuya M, Thijs L, Staessen JA, Imai Y, Hypertension Objective Treatment Based on Measurement by Electrical Devices of Blood Pressure (HOMED-BP) . Cardiovascular outcomes in the first trial of antihypertensive therapy guided by self-measured home blood pressure . Hypertens Res 2012 ; 35 : 1102 – 1110 . II .

    Article  PubMed  PubMed Central  Google Scholar 

  66. 280

    Noguchi Y, Asayama K, Staessen JA, Inaba M, Ohkubo T, Hosaka M, Satoh M, Kamide K, Awata T, Katayama S, Imai Y, the HOMED-BP study group . Predictive power of home blood pressure and clinic blood pressure in hypertensive patients with impaired glucose metabolism and diabetes . J Hypertens 2013 ; 31 : 1593 – 1602 . IVa .

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. 281

    Messerli FH, Mancia G, Conti CR, Hewkin AC, Kupfer S, Champion A, Kolloch R, Benetos A, Pepine CJ . Dogma disputed: can aggressively lowering blood pressure in hypertensive patients with coronary artery disease be dangerous? Ann Intern Med 2006 ; 144 : 884 – 893 . E-Ib .

    Article  PubMed  PubMed Central  Google Scholar 

  68. 282

    Rothwell PM, Howard SC, Spence JD, Carotid Endarterectomy Trialists’ Collaboration . Relationship between blood pressure and stroke risk in patients with symptomatic carotid occlusive disease . Stroke 2003 ; 34 : 2583 – 2590 . E-Ia .

    Article  CAS  PubMed  Google Scholar 

  69. 283

    Ueshima H . NIPPON DATA 80 . J Blood Pressure 2000 ; 7 : 421 – 426 . Japanese. VI .

    Google Scholar 

  70. 284

    Sleight P, Redon J, Verdecchia P, Mancia G, Gao P, Fagard R, Schumacher H, Weber M, Böhm M, Williams B, Pogue J, Koon T, Yusuf S, ONTARGET investigators . Prognostic value of blood pressure in patients with high vascular risk in the Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial study . J Hypertens 2009 ; 27 : 1360 – 1369 . III .

    Article  CAS  PubMed  Google Scholar 

  71. 285

    Cushman WC, Evans GW, Byington RP, Goff Jr DC, Grimm Jr RH, Cutler JA, Simons-Morton DG, Basile JN, Corson MA, Probstfield JL, Katz L, Peterson KA, Friedewald WT, Buse JB, Bigger JT, Gerstein HCIsmail-Beigi F, ACCORD Study Group . Effects of intensive blood-pressure control in type 2 diabetes mellitus . New Engl J Med 2010 ; 362 : 1575 – 1585 . II] .

    Article  CAS  PubMed  Google Scholar 

  72. 286

    Cooper-DeHoff RM, Gong Y, Handberg EM, Bavry AA, Denardo SJ, Bakris GL, Pepine CJ . Tight blood pressure control and cardiovascular outcomes among hypertensive patients with diabetes and coronary artery disease . JAMA 2010 ; 304 : 61 – 68 . IVa .

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. 287

    Lewington S, Clarke R, Qizilbash N, Peto R, Collins R, Prospective Studies Collaboration . Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies . Lancet 2002 ; 360 : 1903 – 1913 . E-Ia .

    Article  Google Scholar 

  74. 288

    Appel LJ, Moore TJ, Obarzanek E, Vollmer WM, Svetkey LP, Sacks FM, Bray GA, Vogt TM, Cutler JA, Windhauser MM, Lin PH, Karanja N, DASH Collaborative Research Group . A clinical trial of the effects of dietary patterns on blood pressure . New Engl J Med 1997 ; 336 : 1117 – 1124 . II .

    Article  CAS  PubMed  Google Scholar 

  75. 289

    Whelton PK, Appel LJ, Espeland MA, Applegate WB, Ettinger Jr WH, Kostis JB, Kumanyika S, Lacy CR, Johnson KC, Folmar S, Cutler JA, TONE Collaborative Research Group . Sodium reduction and weight loss in the treatment of hypertension in older persons: a randomized controlled trial of nonpharmacologic interventions in the elderly (TONE) . JAMA 1998 ; 279 : 839 – 846 . II .

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. 290

    Hayashi T, Tsumura K, Suematsu C, Okada K, Fujii S, Endo G . Walking to work and the risk for hypertension in men: the Osaka Health Survey . Ann Intern Med 1999 ; 131 : 21 – 26 . IVa .

    Article  CAS  Google Scholar 

  77. 291

    Svetkey LP, Pollak KI, Yancy Jr WS, Dolor RJ, Batch BC, Samsa G, Matchar DB, Lin PH . Hypertension improvement project: randomized trial of quality improvement for physicians and lifestyle modification for patients . Hypertension 2009 ; 54 : 1226 – 1233 . II .

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. 292

    Neaton JD, Grimm Jr RH, Prineas RJ, Stamler J, Grandits GA, Elmer PJ, Cutler JA, Flack JM, Schoenberger JA, McDonald R, Lewis CE, Liebson PR, Treatment of Mild Hypertension Study Research Group . Treatment of Mild Hypertension Study. Final results . JAMA 1993 ; 270 : 713 – 724 . II .

    Article  CAS  PubMed  Google Scholar 

  79. 293

    Singer DR, Markandu ND, Cappuccio FP, Miller MA, Sagnella GA, MacGregor GA . Reduction of salt intake during converting enzyme inhibitor treatment compared with addition of a thiazide . Hypertension 1995 ; 25 : 1042 – 1044 . II .

    Article  CAS  PubMed  Google Scholar 

  80. 294

    Saito I, Saruta T . Effect of education through a periodic newsletter on persistence with antihypertensive therapy . Hypertens Res 2003 ; 26 : 159 – 162 . III .

    Article  PubMed  Google Scholar 

  81. 295

    Yoshida K, Matsuoka H, Omae T, Fujii J . Patient-hospital relationship and quality of life in elderly patients with hypertension . Hypertens Res 1995 ; 18 : 77 – 83 . IVb .

    Article  CAS  PubMed  Google Scholar 

  82. 296

    Croog SH, Levine S, Testa MA, Brown B, Bulpitt CJ, Jenkins CD, Klerman GL, Williams GH . The effects of antihypertensive therapy on the quality of life . New Engl J Med 1986 ; 314 : 1657 – 1664 . II .

    Article  CAS  PubMed  Google Scholar 

  83. 297

    Kaplan NM . Anxiety-induced hyperventilation. A common cause of symptoms in patients with hypertension . Arch Intern Med 1997 ; 157 : 945 – 948 . V .

    Article  CAS  Google Scholar 

  84. 298

    Mena-Martin FJ, Martin-Escudero JC, Simal-Blanco F, Carretero-Ares JL, Arzua-Mouronte D, Herreros-Fernandez V . Health-related quality of life of subjects with known and unknown hypertension: results from the population-based Hortega study . J Hypertens 2003 ; 21 : 1283 – 1289 . IVb .

    Article  CAS  PubMed  Google Scholar 

  85. 299

    Dimenäs ES, Wiklund IK, Dahlöf CG, Lindvall KG, Olofsson BK, De Faire UH . Differences in the subjective well-being and symptoms of normotensives, borderline hypertensives and hypertensives . J Hypertens 1989 ; 7 : 885 – 890 . IVb .

    Article  PubMed  Google Scholar 

  86. 300

    Mikami H, Ogihara T . Quality of life in the pharmacologically treated elderly patients . Jpn J Geriat 1999 ; 7 : 1657 – 1664 . Japanese. VI .

    Google Scholar 

  87. 301

    Grimm Jr RH, Grandits GA, Cutler JA, Stewart AL, McDonald RH, Svendsen K, Prineas RJ, Liebson PR . Relationships of quality-of-life measures to long-term lifestyle and drug treatment in the Treatment of Mild Hypertension Study . Arch Intern Med 1997 ; 157 : 638 – 648 . II .

    Article  PubMed  Google Scholar 

  88. 302

    Degl’Innocenti A, Elmfeldt D, Hofman A, Lithell H, Olofsson B, Skoog I, Trenkwalder P, Zanchetti A, Wiklund I . Health-related quality of life during treatment of elderly patients with hypertension: results from the Study on COgnition and Prognosis in the Elderly (SCOPE) . J Hum Hypertens 2004 ; 18 : 239 – 2345 . II .

    Article  PubMed  Google Scholar 

  89. 303

    Bremner AD . Antihypertensive medication and quality of life—silent treatment of a silent killer? Cardiovasc Drugs Ther 2002 ; 16 : 353 – 364 . VI .

    Article  PubMed  Google Scholar 

  90. 304

    Bane C, Hughes CM, Cupples ME, McElnay JC . The journey to concordance for patients with hypertension: a qualitative study in primary care . Pharm World Sci 2007 ; 29 : 534 – 540 . IVb .

    Article  PubMed  Google Scholar 

  91. 305

    Saito I . Factors and strategies: Adherence . J Blood Pressure 2010 ; 17 : 217 – 219 . Japanese. VI .

    Google Scholar 

  92. 306

    Ashida T . White coat hypertension, Therapeutic strategies for poor compliance . Cardioangiology 2003 ; 53 : 236 – 244 . Japanese. VI .

    Google Scholar 

  93. 307

    Saito I . Compliance and blood pressure control, Influence of the number of antihypertensive drugs on compliance . J Blood Pressure 2006 ; 13 : 1019 – 1025 . Japanese. IVb .

    Google Scholar 

  94. 308

    Ho PM, Bryson CL, Rumsfeld JS . Medication adherence: its importance in cardiovascular outcomes . Circulation 2009 ; 119 : 3028 – 3035 . VI .

    Article  PubMed  Google Scholar 

  95. 309

    Mazzaglia G, Ambrosioni E, Alacqua M, Filippi A, Sessa E, Immordino V, Borghi C, Brignoli O, Caputi AP, Cricelli C, Mantovani LG . Adherence to antihypertensive medications and cardiovascular morbidity among newly diagnosed hypertensive patients . Circulation 2009 ; 120 : 1598 – 15605 . IVa .

    Article  CAS  PubMed  Google Scholar 

  96. 310

    Grassi G, Seravalle G, Mancia G . Cardiovascular consequences of poor compliance to antihypertensive therapy . Blood Press 2011 ; 20 : 196 – 203 . VI .

    Article  PubMed  Google Scholar 

  97. 311

    Roumie CL, Elasy TA, Greevy R, Griffin MR, Liu X, Stone WJ, Wallston KA, Dittus RS, Alvarez V, Cobb J, Speroff T . Improving blood pressure control through provider education, provider alerts, and patient education: a cluster randomized trial . Ann Intern Med 2006 ; 145 : 165 – 175 . II .

    Article  PubMed  Google Scholar 

  98. 312

    Lee JK, Grace KA, Taylor AJ . Effect of a pharmacy care program on medication adherence and persistence, blood pressure, and low-density lipoprotein cholesterol: a randomized controlled trial . JAMA 2006 ; 296 : 2563 – 2571 . II .

    Article  CAS  PubMed  Google Scholar 

  99. 313

    Hill MN, Miller NH, Degeest S, Materson BJ, Black HR, Izzo Jr JL, Oparil SWeber MA, American Society of Hypertension Writing Group . Adherence and persistence with taking medication to control high blood pressure . J Am Soc Hypertens 2011 ; 5 : 56 – 63 . VI .

    Article  PubMed  Google Scholar 

  100. 314

    Marshall IJ, Wolfe CD, McKevitt C . Lay perspectives on hypertension and drug adherence: systematic review of qualitative research . BMJ 2012 ; 345 : e3953 . I .

    Article  PubMed  PubMed Central  Google Scholar 

  101. 315

    Burnier M . Medication adherence and persistence as the cornerstone of effective antihypertensive therapy . Am J Hypertens 2006 ; 19 : 1190 – 1196 . VI .

    Article  PubMed  Google Scholar 

  102. 316

    Schroeder K, Fahey T, Ebrahim S . How can we improve adherence to blood pressure-lowering medication in ambulatory care? Systematic review of randomized controlled trials . Arch Intern Med 2004 ; 164 : 722 – 732 . E-Ia .

    Article  Google Scholar 

  103. 317

    Bangalore S, Kamalakkannan G, Parkar S, Messerli FH . Fixed-dose combinations improve medication compliance: a meta-analysis . Am J Med 2007 ; 120 : 713 – 719 . I .

    Article  PubMed  Google Scholar 

  104. 318

    Antithrombotic Trialists’ Collaboration . Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients . BMJ 2002 ; 324 : 71 – 86 . I .

    Article  Google Scholar 

  105. 319

    Hart RG, Tonarelli SB, Pearce LA . Avoiding central nervous system bleeding during antithrombotic therapy: recent data and ideas . Stroke 2005 ; 36 : 1588 – 1593 . VI .

    Article  PubMed  Google Scholar 

  106. 320

    Diener HC, Bogousslavsky J, Brass LM, Cimminiello C, Csiba L, Kaste M, Leys D, Matias-Guiu J, Rupprecht HJ, MATCH investigators . Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial . Lancet 2004 ; 364 : 331 – 337 . II .

    Article  CAS  PubMed  Google Scholar 

  107. 321

    Bhatt DL, Fox KA, Hacke W, Berger PB, Black HR, Boden WE, Cacoub P, Cohen EA, Creager MA, Easton JD, Flather MD, Haffner SM, Hamm CW, Hankey GJ, Johnston SC, Mak KH, Mas JL, Montalescot G, Pearson TA, Steg PG, Steinhubl SR, Weber MA, Brennan DM, Fabry-Ribaudo L, Booth J, Topol EJ, CHARISMA Investigators . Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events . New Engl J Med 2006 ; 354 : 1706 – 1717 . II .

    Article  CAS  PubMed  Google Scholar 

  108. 322

    Dentali F, Douketis JD, Lim W, Crowther M . Combined aspirin-oral anticoagulant therapy compared with oral anticoagulant therapy alone among patients at risk for cardiovascular disease: a meta-analysis of randomized trials . Arch Intern Med 2007 ; 167 : 117 – 124 . I .

    Article  CAS  PubMed  Google Scholar 

  109. 323

    Toyoda K, Yasaka M, Iwade K, Nagata K, Koretsune Y, Sakamoto T, Uchiyama S, Gotoh J, Nagao T, Yamamoto M, Takahashi JC, Minematsu K, Bleeding with Antithrombotic Therapy (BAT) Study Group . Dual antithrombotic therapy increases severe bleeding events in patients with stroke and cardiovascular disease: a prospective, multicenter, observational study . Stroke 2008 ; 39 : 1740 – 1745 . E-Ib .

    Article  PubMed  Google Scholar 

  110. 324

    Arima H, Anderson C, Omae T, Woodward M, MacMahon S, Mancia G, Bousser MG, Tzourio C, Rodgers A, Neal B, Chalmers J, Perindopril Protection Against Recurrent Stroke Study (PROGRESS) Collaborative Group . Effects of blood pressure lowering on intracranial and extracranial bleeding in patients on antithrombotic therapy: the PROGRESS trial . Stroke 2012 ; 43 : 1675 – 1677 . III .

    Article  PubMed  Google Scholar 

  111. 325

    Toyoda K, Yasaka M, Uchiyama S, Nagao T, Gotoh J, Nagata K, Koretsune Y, Sakamoto T, Iwade K, Yamamoto M, Takahashi JC, Minematsu K, Bleeding with Antithrombotic Therapy (BAT) Study Group . Blood pressure levels and bleeding events during antithrombotic therapy: the Bleeding with Antithrombotic Therapy (BAT) Study . Stroke 2010 ; 41 : 1440 – 1444 . V .

    Article  PubMed  Google Scholar 

  112. 326

    Ikeda S . Cost-effectiveness of hypertension (examination/treatment) Hypertension Therapeutics Edited by Imaizumi T, Osaka, Nagai Shoten 2010 pp 327 – 332 . Japanese. VI .

  113. 327

    Okubo I . Basis of clinical economics (10) . Jpn J Publ Health 2008 ; 55 : 254 – 255 . VI .

    Google Scholar 

  114. 328

    Shiroiwa T, Sung YK, Fukuda T, Lang HC, Bae SC, Tsutani K . International survey on willingness-to-pay (WTP) for one additional QALY gained: what is the threshold of cost effectiveness? Health Econ 2010 ; 19 : 422 – 437 . IVb .

    Article  PubMed  Google Scholar 

  115. 329

    Fukunaga H, Ohkubo T, Kobayashi M, Tamaki Y, Kikuya M, Obara T, Nakagawa M, Hara A, Asayama K, Metoki H, Inoue R, Hashimoto J, Totsune K, Imai Y . Cost-effectiveness of the introduction of home blood pressure measurement in patients with office hypertension . J Hypertens 2008 ; 26 : 685 – 690 . IVb .

    Article  CAS  PubMed  Google Scholar 

  116. 330

    Lovibond K, Jowett S, Barton P, Caulfield M, Heneghan C, Hobbs FD, Hodgkinson J, Mant J, Martin U, Williams B, Wonderling D, McManus RJ . Cost-effectiveness of options for the diagnosis of high blood pressure in primary care: a modelling study . Lancet 2011 ; 378 : 1219 – 1230 . IVb .

    Article  PubMed  Google Scholar 

  117. 331

    Jönsson B, Carides GW, Burke TA, Dasbach EJ, Lindholm LH, Dahlöf B, LIFE Study Group . Cost effectiveness of losartan in patients with hypertension and LVH: an economic evaluation for Sweden of the LIFE trial . J Hypertens 2005 ; 23 : 1425 – 1431 . III .

    Article  PubMed  Google Scholar 

  118. 332

    Lindgren P, Buxton M, Kahan T, Poulter NR, Dahlöf B, Sever PS, Wedel H, Jönsson B, ASCOT trial investigators . Economic evaluation of ASCOT-BPLA:antihypertensive treatment with an amlodipine-based regimen is cost effective compared with an atenolol-based regimen . Heart 2008 ; 94 : e4 . III .

    Article  CAS  PubMed  Google Scholar 

  119. 333

    Heidenreich PA, Davis BR, Cutler JA, Furberg CD, Lairson DR, Shlipak MG, Pressel SL, Nwachuku C, Goldman L . C ost-effectiveness of chlorthalidone, amlodipine, and lisinopril as first-step treatment for patients with hypertension: an analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) . J Gen Intern Med 2008 ; 23 : 509 – 5016 . III .

    Article  PubMed  PubMed Central  Google Scholar 

  120. 334

    Saito I, Kobayashi M, Saruta T . Economic analysis of antihypertensive agents in treating patients with essential hypertension . J Clin Ther Med 2003 ; 19 : 777 – 788 . Japanese. VI .

    Google Scholar 

  121. 335

    Saito I, Kobayashi M, Matsushita Y, Saruta T . Pharmacoeconomical evaluation of combination therapy for lifetime hypertension treatment in Japan . Jpn Med Assoc J 2006 ; 48 : 574 – 585 . VI .

    Google Scholar 

  122. 336

    Saito I, Kobayashi M, Matsushita Y, Mori A, Kawasugi K, Saruta T . Cost-utility analysis of antihypertensive combination therapy in Japan by a Monte Carlo simulation model . Hypertens Res 2008 ; 31 : 1373 – 1383 . IVb .

    Article  CAS  PubMed  Google Scholar 

  123. 337

    Saito I, Kobayashi M, Saruta T . Hypertension Treatment in Japan from the perspective of medical economics . Prog Med 2009 ; 29 : 376 – 385 . Japanese. IVb .

    Google Scholar 

  124. 338

    Taylor AA, Shoheiber O . Adherence to antihypertensive therapy with fixed-dose amlodipine besylate/benazepril HCl versus comparable component-based therapy . Congest Heart Fail 2003 ; 9 : 324 – 332 . IVb .

    Article  CAS  PubMed  Google Scholar 

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Chapter 3. Principles of treatment. Hypertens Res 37, 279–285 (2014). https://doi.org/10.1038/hr.2014.6

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