The efficacy and safety of blood pressure lowering in patients with heart failure with preserved ejection fraction (HFpEF) remain unknown. We systematically searched PubMed/Medline, ICHUSHI, EMBASE, and the Cochrane Central Library database for randomized controlled trials (RCTs) assessing the efficacy and safety of blood pressure lowering in patients with HFpEF that were published from January 1996 to July 2017. Our study included a total of 10 RCTs involving 13,091 patients with HFpEF that compared all-cause mortality, cardiovascular mortality, heart failure hospitalization, renal dysfunction, and/or hypotension between drug intervention and control groups. Then, we analyzed systolic blood pressure (SBP) before and during trials using the SBP from the RCTs data. SBP decreased in the intervention group (134.7–130.2 mmHg) more than that in the control group (134.4–133.3 mmHg), and heart failure hospitalization was reduced in the intervention group compared to that in the control group [RR 0.89 (0.82–0.97), P = 0.006]. There was no effect of treatment on all-cause mortality, cardiovascular mortality, and hypotension. However, in the studies that compared renal function, SBP decreased in the intervention group (134.3–129.6 mmHg) more than that in the control group (134.0–132.8 mmHg), and the occurrence of renal dysfunction increased in the intervention group compared to that in the control group [RR 1.52 (1.31–1.76), P < 0.00001)]. Blood pressure lowering that achieves SBP levels of ~130 mmHg may be related to the reduction in heart failure hospitalization in patients with HFpEF, but it also possibly leads to an increased risk of renal dysfunction.
Subscribe to Journal
Get full journal access for 1 year
only $24.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, et al. American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2013 update: a report from the American Heart Association. Circulation. 2013;127:e6–e245.
Hogg K, Swedberg K, McMurray J. Heart failure with preserved left ventricular systolic function; epidemiology, clinical characteristics, and prognosis. J Am Coll Cardiol. 2004;43:317–27.
Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006;355:251–9.
Shah SJ, Kitzman DW, Borlaug BA, van Heerebeek L, Zile MR, Kass DA, et al. Phenotype-specific treatment of heart failure with preserved ejection fraction: a multiorgan roadmap. Circulation. 2016;134:73–90.
Yancy CW, Lopatin M, Stevenson LW, De Marco T, Fonarow GC. Clinical presentation, management, and in-hospital outcomes of patients admitted with acute decompensated heart failure with preserved systolic function: a report from the Acute Decompensated Heart Failure National Registry (ADHERE) Database. J Am Coll Cardiol. 2006;47:76–84.
McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M, Dickstein K, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2012;14:803–69.
Lee DS, Gona P, Vasan RS, Larson MG, Benjamin EJ, Wang TJ, et al. Relation of disease pathogenesis and risk factors to heart failure with preserved or reduced ejection fraction: insights from the framingham heart study of the national heart, lung, and blood institute. Circulation. 2009;119:3070–7.
Levy D, Larson MG, Vasan RS, Kannel WB, Ho KK. The progression from hypertension to congestive heart failure. JAMA. 1996;275:1557–62.
Shimamoto K, Ando K, Fujita T, Hasebe N, Higaki J, Horiuchi M, et al. The Japanese society of hypertension guidelines for the management of hypertension (JSH 2014). Hypertens Res. 2014;37:253–390.
Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Colvin MM, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017;136:e137–e161.
Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535.
Yusuf S, Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, et al. CHARM Investigators and Committees. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. Lancet. 2003;362:777–81.
Zi M, Carmichael N, Lye M. The effect of quinapril on functional status of elderly patients with diastolic heart failure. Cardiovasc Drugs Ther. 2003;17:133–9.
Cleland JG, Tendera M, Adamus J, Freemantle N, Polonski L, Taylor J. PEP-CHF Investigators. The perindopril in elderly people with chronic heart failure (PEP-CHF) study. Eur Heart J. 2006;27:2338–45.
Yip GW, Wang M, Wang T, Chan S, Fung JW, Yeung L, et al. The Hong Kong diastolic heart failure study: a randomised controlled trial of diuretics, irbesartan and ramipril on quality of life, exercise capacity, left ventricular global and regional function in heart failure with a normal ejection fraction. Heart. 2008;94:573–80.
Massie BM, Carson PE, McMurray JJ, Komajda M, McKelvie R, Zile MR, et al. I-PRESERVE Investigators. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med. 2008;359:2456–67.
Deswal A, Richardson P, Bozkurt B, Mann DL. Results of the randomized aldosterone antagonism in heart failure with preserved ejection fraction trial (RAAM-PEF). J Card Fail. 2011;17:634–42.
Yamamoto K, Origasa H, Hori M. J-DHF Investigators. Effects of carvedilol on heart failure with preserved ejection fraction: the Japanese Diastolic Heart Failure Study (J-DHF). Eur J Heart Fail. 2013;15:110–8.
Edelmann F, Wachter R, Schmidt AG, Kraigher-Krainer E, Colantonio C, Kamke W, et al. Aldo-DHF Investigators. Effect of spironolactone on diastolic function and exercise capacity in patients with heart failure with preserved ejection fraction: the Aldo-DHF randomized controlled trial. JAMA. 2013;309:781–91.
Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B, et al. TOPCAT Investigators. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014;370:1383–92.
Miura M, Sakata Y, Miyata S, Shiba N, Takahashi J, Nochioka K, et al. SUPPORT Trial Investigators. influence of left ventricular ejection fraction on the effects of supplemental use of angiotensin receptor blocker olmesartan in hypertensive patients with heart failure. Circ J. 2016;80:2155–64.
Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39:3021–3104.
SPRINT Research Group, Wright JT Jr, Williamson JD, Whelton PK, Snyder JK, Sink KM, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373:2103–16.
Solomon SD, Verma A, Desai A, Hassanein A, Izzo J, Oparil S, et al. Exforge intensive control of hypertension to evaluate efficacy in diastolic dysfunction investigators. Effect of intensive versus standard blood pressure lowering on diastolic function in patients with uncontrolled hypertension and diastolic dysfunction. Hypertension. 2010;55:241–8.
Bangalore S, Toklu B, Gianos E, Schwartzbard A, Weintraub H, Ogedegbe G, et al. Optimal systolic blood pressure target after SPRINT: insights from a network meta-analysis of randomized trials. Am J Med. 2017;130:707–19. e8.
Tsimploulis A, Lam PH, Arundel C, Singh SN, Morgan CJ, Faselis C, et al. Systolic blood pressure and outcomes in patients with heart failure with preserved ejection fraction. JAMA Cardiol. 2018;3:288–97.
Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013;128:e240–327.
Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37:2129–2200.
Conflict of interest
Dr. HK has received honoraria from Daiichi Sankyo Co., Mitsubishi Tanabe Pharma Co., Shionogi & Co., Dainippon Sumitomo Pharma Co., and Takeda Pharmaceutical Co. Dr. RS received honoraria from Medtronic Co., Boehringer Ingelheim Co., Eli Lilly & Co. and Mitsubishi Tanabe Pharma Co. Dr. TO received honoraria from Sanwa Kagaku Kenkyusho Co. Dr. KM received honoraria from Daiichi Sankyo Co., MSD KK., Actelion Pharmaceuticals Japan,and Nippon Boehringer Ingelheim Co. Dr. KM received research support from Bayer Co., Eisai Co., Bristol-Myers Squibb Co., Astellas Pharma Inc., MSD KK., Daiichi-Sankyo Co., Actelion Pharmaceuticals Japan., Teijin Pharma and Nippon Boehringer Ingelheim Co. The remaining authors declare they have no conflicts of interest.
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Kawano, H., Fujiwara, A., Kai, H. et al. Effects of blood pressure lowering in patients with heart failure with preserved ejection fraction: a systematic review and meta-analysis. Hypertens Res 42, 504–513 (2019). https://doi.org/10.1038/s41440-019-0216-8
- heart failure with preserved ejection fraction
The Korean Journal of Internal Medicine (2020)
Highlights of the 2019 Japanese Society of Hypertension Guidelines and perspectives on the management of Asian hypertensive patients
The Journal of Clinical Hypertension (2020)
Hypertension Research (2019)