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HYPERTENSION

Assessing hypertension therapies: randomization or confounding by indication?

Findings from a large, international study comprising 4.9 million people with mild hypertension suggest that thiazide and thiazide-like diuretics might be more effective and safer than other first-line antihypertensive drugs. However, the study was not randomized, and the findings might be explained by a phenomenon known as ‘confounding by indication’.

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Fig. 1: One pill daily for first-line treatment of hypertension.

References

  1. Suchard, M. A. et al. Comprehensive comparative effectiveness and safety of first-line antihypertensive drug classes: a systematic, multinational, large-scale analysis. Lancet 394, 1816–1826 (2019).

    Article  Google Scholar 

  2. Whelton, P. K. et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 138, e426–e483 (2018).

    PubMed  Google Scholar 

  3. Williams, B. et al. 2018 Practice guidelines for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). Blood Press. 27, 314–340 (2018).

    Article  Google Scholar 

  4. Wing, L. M. H. et al. A comparison of outcomes with angiotensin-converting–enzyme inhibitors and diuretics for hypertension in the elderly. N. Engl. J. Med. 348, 583–592 (2003).

    Article  CAS  Google Scholar 

  5. The ONTARGET Investigators. Telmisartan, ramipril or both in patients with high risk for vascular events. N. Engl. J. Med. 358, 1547–1559 (2008).

    Article  Google Scholar 

  6. Dahlöf, B. et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 359, 995–1003 (2002).

    Article  Google Scholar 

  7. Julius, S. et al. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet 363, 2022–2031 (2004).

    Article  CAS  Google Scholar 

  8. Hansson, L. et al. Randomised trial of effects of calcium antagonists compared with diuretics and β-blockers on cardiovascular morbidity and mortality in hypertension: the Nordic Diltiazem (NORDIL) study. Lancet 356, 359–365 (2000).

    Article  CAS  Google Scholar 

  9. Brown, M. J. et al. Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT). Lancet 356, 366–372 (2000).

    Article  CAS  Google Scholar 

  10. Kjeldsen, S. E., Westheim, A. S. & Os, I. INSIGHT and NORDIL. International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment. Nordic Diltiazem Study. Lancet 356, 1929–1930 (2000).

    Article  CAS  Google Scholar 

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Correspondence to Sverre E. Kjeldsen.

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Competing interests

S.E.K. has received lecture honoraria from Merck KGaA, Merck & Co., Sanofi and Takeda, and consulting honoraria from Takeda. I.O. declares no competing interests.

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Kjeldsen, S.E., Os, I. Assessing hypertension therapies: randomization or confounding by indication?. Nat Rev Cardiol 17, 73–74 (2020). https://doi.org/10.1038/s41569-019-0313-z

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