Most-prescribed hypertension medicine less effective, causes more side effects: Study

Over 3,000 heart attacks and strokes could have been prevented had first-time patients been prescribed alternative drugs, say researchers


                            Most-prescribed hypertension medicine less effective, causes more side effects: Study

The most popular first-line treatment for hypertension is less effective and has more side-effects than an alternative that is prescribed much less often, according to a study.

Approximately 3,100 major cardiovascular events — heart attacks, strokes and hospitalizations — could have been avoided had first-time patients been prescribed thiazides instead of the most prescribed blood pressure drug, ACE inhibitors, according to a multi-national study involving nearly five million patients. The researchers analyzed electronic health records and claims data from patients who had begun drug treatment for hypertension.

"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," says the analysis by researchers from Columbia University Irving Medical Center. The findings — which compare outcomes in newly treated patients with hypertension — have been published in The Lancet.

Little evidence to guide the selection of medicine

According to the research team, current guidelines from the American College of Cardiology and the American Heart Association recommend starting anti-hypertensive therapy with any drug from five different classes of medications. This includes ACE inhibitors, angiotensin II receptor blockers (ARBs), thiazide diuretics, dihydropyridine calcium channel blockers, and non-dihydropyridine calcium channel blockers.

However, experts say there is not much proof that can help physicians decide which drug class to start with. The literature, says the study, contains data from randomized, controlled clinical trials covering just 31,000 patients, and none of them were just beginning anti-hypertensive treatment. Hence, explain researchers, most clinical guidelines are based on expert opinion rather than data.

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. (Getty Images)

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

The research team says while observational studies can be used to detect effects that might not have been apparent in randomized trials, 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. It comes down to a cherry-picking exercise, which makes the results less reliable," says Hripcsak.

Research attempts to address limitations

To address limitations, the researchers analyzed data from millions of patient health records. The method, known as Large-Scale Evidence Generation and Evaluation across a Network of Databases, or LEGEND, was pioneered by a consortium of scientists participating in the Observational Health Data Science Initiative (OHDSI) network. 

The team analyzed insurance claims and electronic health records from 4.9 million patients in four countries who were starting anti-hypertensive therapy with a single drug. The researchers used a complex algorithm to identify the number of heart attacks, hospitalizations for heart failure, strokes, and nearly 50 medication side effects occurring in patients who took any of the first-line anti-hypertensive drugs. They employed multiple techniques designed to minimize bias, and account for about 60,000 different variables.

The researchers found that ACE inhibitors were the first anti-hypertensive drug prescribed to 48% of patients, compared with 17% of patients who were first prescribed thiazide diuretics.

"Yet patients who were first treated with thiazide diuretics had 15% fewer heart attacks, hospitalizations for heart failure, and strokes compared with those treated with other first-line therapies. Besides, patients first treated with ACE inhibitors had higher rates of 19 side effects compared with thiazide users," the findings state.

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