Thiazides best first line drugs for treating high BP, finds Lancet study

Current guidelines from the American College of Cardiology and the American Heart Association recommend starting antihypertensive therapy with any drug from five different classes of medications, including thiazide diuretics, ACE inhibitors, angiotensin II receptor blockers (ARBs), dihydropyridine calcium channel blockers, and non-dihydropyridine calcium channel blockers. But there is no clarity about the optimal monotherapy for hypertension.

A new multinational study appearing in The Lancet has found that ACE inhibitors, the most popular first-line treatment for hypertension, are not as effective and cause more side effects compared with thiazide diuretics. Patients prescribed thiazide diuretics had 15% fewer cardiovascular events than those prescribed ACE inhibitors. For initiating monotherapy thiazide or thiazide-like diuretics safer and superior to angiotensin-converting enzyme inhibitors, is the bottom line of study.

The researchers, including Columbia's George Hripcsak, MD, and Patrick Ryan, PhD, analyzed electronic health records and claims data from nearly 5 million patients who had begun drug treatment for hypertension. They found that patients who were first prescribed thiazide diuretics had 15% fewer heart attacks, strokes, and hospitalizations for heart failure, compared to those who were prescribed ACE inhibitors. Patients who began with thiazides also experienced fewer side effects.

The researchers estimated that approximately 3,100 major cardiovascular events among the patients who first took ACE inhibitors could have been avoided had they first been treated with a thiazide diuretic.

Little Evidence to Guide Drug Selection

But there is little evidence to help physicians decide which drug class to start with: the literature contains data from randomized, controlled clinical trials encompassing just 31,000 patients--and none of them were just beginning antihypertensive treatment. As a result, most clinical guidelines are based on expert opinion rather than data.

"Randomized clinical trials demonstrate a drug's effectiveness and safety in a highly defined patient population," says George Hripcsak, MD, chair of biomedical informatics at Columbia University Vagelos College of Physicians and Surgeons and an author of the study. "But they're not good at making comparisons among multiple drug classes in a diverse group of patients that you would encounter in the real world."

Observational studies can be used to detect effects that might not have been apparent in randomized trials. But many are too small to draw meaningful conclusions or suffer from other types of distortion.

"Unintentionally or not, journals and authors tend to publish studies that have exciting results, and researchers may even select analytical methods that are best suited to getting the results that fit their hypotheses," says Hripcsak. "It comes down to a cherry-picking exercise, which makes the results less reliable."

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DOI:https://doi.org/10.1016/S0140-6736(19)32317-7