Research in context
Evidence before this study
2017 American College of Cardiology/American Heart Association Blood Pressure Treatment Guidelines recommend initiating monotherapy for hypertension with any primary agent among five first-line drug classes based on a systematic review of randomised trials. Similar non-specificity emerges from the 2018 European Society of Cardiology/European Society of Hypertension Guidelines. The largest such trial, ALLHAT, enrolled patients more than two decades ago, only evaluated three representative agents, and a majority of participants had been previously treated for hypertension. We lack contemporary knowledge of the real-world comparative effectiveness of common antihypertensive drugs with respect to outcomes and the safety trade-offs among these class options for treatment initiation.
Added value of this study
Our study uses state-of-the-art methods to control for residual confounding, publication bias, and p-hacking in real-world evidence studies, and shows generally comparable effectiveness between drug classes across nine international health databases. However, effectiveness and safety benefits suggest initiating with a thiazide or thiazide-like diuretic over an angiotensin converting-enzyme inhibitor, the most common initiating monotherapy across databases. Non-dihydropyridine calcium channel blockers are also inferior to thiazide or thiazide-like diuretics, angiotensin converting-enzyme inhibitors, angiotensin receptor blockers, and dihydropyridine calcium channel blockers.
Implications of all the available evidence
Initiating with a thiazide instead of an angiotensin converting-enzyme inhibitor carries potential to avoid many major cardiovascular events and warrants further study.