Diuretics may be superior to ACE inhibitors for initial hypertension monotherapy

Angiotensin-converting enzyme (ACE) inhibitors appeared only modestly less effective than thiazide or thiazide-like diuretics, but the effect of initial monotherapy with the latter across the whole population could be substantial, the study authors concluded.


Thiazide or thiazide-like diuretics appear superior to angiotensin-converting enzyme (ACE) inhibitors for initial monotherapy in patients with hypertension, according to a recent analysis.

Researchers applied a comprehensive framework to observational data from previously published studies to estimate effectiveness and safety outcomes associated with all first-line drug classes for hypertension. Six administrative claims databases and three electronic health record databases were used. Acute myocardial infarction, heart failure hospitalization, and stroke were the primary end points, while cardiovascular events, ischemic stroke, hemorrhagic stroke, heart failure, sudden cardiac death, and unstable angina were the secondary cardiovascular outcomes. Data from 4.9 million patients who initiated treatment from July 1996 to March 2018 were included, and 22,000 propensity-score-adjusted hazard ratios comparing all drug classes and outcomes were generated. The results of the study, which was partially funded by industry, were published Oct. 24 by The Lancet.

ACE inhibitors were the most commonly prescribed drug (48%), followed by thiazide or thiazide-like diuretics (17%), dihydropyridine calcium-channel blockers (16%), angiotensin-receptor blockers (15%), and nondihydropyridine calcium-channel blockers (3%). Most of the drug classes did not appear to differ for any of the measured outcomes. Primary effectiveness was better with thiazide or thiazide-like diuretics, however, than with ACE inhibitors. Hazard ratios were 0.84 (95% CI, 0.75 to 0.95) for acute myocardial infarction, 0.83 (95% CI, 0.74 to 0.95) for heart failure hospitalization, and 0.83 (95% CI, 0.74 to 0.95) for stroke in patients receiving initial hypertension treatment. Thiazide and thiazide-like diuretics also had better safety profiles than ACE inhibitors. Nondihydropyridine calcium-channel blockers appeared to be significantly inferior to the other four drug classes for effectiveness outcomes.

Among other limitations, some of the databases did not include information on blood pressure measurements, and choice of drug class can be affected by blood pressure at baseline, the authors said. However, they concluded that although most drug classes for hypertension monotherapy appear equivalent, nondihydropyridine calcium-channel blockers appear to be inferior to the other four classes, while thiazide or thiazide-like diuretics appear superior to ACE inhibitors. “Although our results suggest angiotensin-converting enzyme inhibitors are only modestly less effective than thiazide or thiazide-like diuretics, the effect of monotherapy with thiazide or thiazide-like diuretics across the whole population could be substantial,” the authors wrote.

The authors of an accompanying comment said the study provides evidence that thiazide and thiazide-like diuretics are more effective and underused as initial monotherapy for hypertension. However, they noted that questions about risks and benefits in groups underrepresented in randomized controlled trials remain unanswered. “More importantly, the study describes a unique method for future analysis of large quantities of observational data gathered from real-world health-care settings,” the comment authors wrote. “Going forward, use of this analytical technique in this scenario might allow new insights and clarify otherwise unanswerable questions to empower clinicians to practise evidence-based medicine.”