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’.
This is a preview of subscription content, access via your institution
Subscribe to Nature+
Get immediate online access to Nature and 55 other Nature journal
Subscribe to Journal
Get full journal access for 1 year
only $6.58 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
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).
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).
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).
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).
The ONTARGET Investigators. Telmisartan, ramipril or both in patients with high risk for vascular events. N. Engl. J. Med. 358, 1547–1559 (2008).
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).
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).
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).
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).
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).
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.
About this article
Cite this article
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