Los Angeles—Angiotensin-converting enzyme (ACE) inhibitors might be widely prescribed for initial treatment of extremely high blood pressure, but a new study suggests that doesn’t mean that the drug class is the best choice.

A study in The Lancet provides information about the relative safety and effectiveness of different hypertension drugs to help pharmacists and other healthcare professionals make the best treatment decisions.

Nearly 5 million patients were involved in the study led by UCLA researchers. The authors point out that ACE inhibitors, the most popular first-line treatment for hypertension, are not as effective and cause more side effects compared with thiazide diuretics. The study demonstrated that patients prescribed thiazide diuretics had 15% fewer cardiovascular events than those prescribed ACE inhibitors and suggested that about 3,100 major cardiovascular events could have been avoided had first-time patients been prescribed thiazides instead of ACE inhibitors.

“Uncertainty remains about the optimal monotherapy for hypertension, with current guidelines recommending any primary agent among the first-line drug classes thiazide or thiazide-like diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, dihydropyridine calcium channel blockers, and non-dihydropyridine calcium channel blockers, in the absence of comorbid indications,” researchers write, adding that randomized trials have not further refined the choice.

The study team developed a comprehensive framework for real-world evidence that enables comparative effectiveness and safety evaluation across many drugs and outcomes from observational data encompassing millions of patients, while minimizing inherent bias. That framework was then employed for a systematic, large-scale study to estimate the relative risks of three primary outcomes—acute myocardial infarction, hospitalization for heart failure, and stroke—as well as six secondary effectiveness and 46 safety outcomes comparing all first-line classes. Used for comparison were a global network of six administrative claims and three electronic health record databases.

Resulting estimates generally showed no effectiveness differences between classes. The exception, however, was that thiazide or thiazide-like diuretics showed better primary effectiveness than ACE inhibitors in terms of risks for acute myocardial infarction (hazard ratio [HR] 0.84; 95% CI, 0.75-0.95), hospitalization for heart failure (HR 0.83; 95% CI, 0.74-0.95), and stroke (HR 0.83; 95% CI, 0.74-0.95) risk while on initial treatment.

“Safety profiles also favored thiazide or thiazide-like diuretics over angiotensin-converting enzyme inhibitors,” the authors note. “The non-dihydropyridine calcium channel blockers were significantly inferior to the other four classes.”

“This is a remarkable, massive, multinational study that has provided insights that can inform patient choices about hypertension treatment,” said coauthor Harlan Krumholz, MD, SM, of the Yale School of Medicine. “What is distinctive is not only the size, but the advanced methods that optimize the trustworthiness of the results.”

Researchers estimated that their use of big data revealed patterns that would otherwise have taken 22,000 typical observational studies to detect.

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