With Antihypertensives, BP Reduction Matters More Than Drug Class

The different first-line antihypertensive medications are equally good at reducing heart attack, stroke, and cardiovascular mortality after accounting for their effect on blood pressure, according to a new systematic review.

"Among hypertensive patients who have not experienced recent cardiovascular events, each 10-mm Hg reduction in systolic blood pressure and 5-mm Hg reduction in diastolic blood pressure, regardless of which class of antihypertension medication was used, was significantly associated with a lower risk of cardiovascular death, stroke, and overall cardiovascular events," said Dr. Jingkai Wei of George Washington University in Washington, D.C., the first author of the study.

"This suggests that reducing blood pressure matters more than taking a specific class of medications," he told Reuters Health by email.

Just one network meta-analysis, published in 2003, has been done to investigate the comparative effectiveness of blood pressure drugs, Dr. Wei and his colleagues note in JAMA Network Open.

In the new research, the team analyzed data from 46 clinical trials including more than 248,000 patients and 28,000 cardiovascular events. Fifteen trials were of angiotensin-converting enzyme (ACE) inhibitors, 23 of dihydropyridine calcium-channel blockers (DH CCBs), four of non-DH CCBs, eight of beta-blockers, 12 of angiotensin-receptor blockers (ARBs) and 13 of thiazide diuretics.

Follow-up lasted a mean 3.7 years. Overall, participants had mean reductions of 18.0 mm/Hg in systolic blood pressure and 10.1 mm/Hg in diastolic pressure. The risk of cardiovascular events was 11.5%.

Risk of cardiovascular death was reduced by 15%-22% with ACE inhibitors, DH CCBs, ARBs and diuretics. ACE inhibitors, DH CCBs and beta-blockers reduced MI risk by 20%-28%. All classes of medications were associated with a 19%-39% reduced risk of stroke.

Diuretics reduced revascularization risk by 33%, and each medication class was linked to a 17%-29% lower risk of overall cardiovascular events.

Adverse effects occurred in up to 17% of patients, depending on medication class.

"Clinicians should work with their patients to identify and use the medication and lifestyle modification regimen that is most well tolerated and sustainable to prevent cardiovascular events," Dr. Wei said.

"Future studies should compare the effectiveness of combinations of antihypertension medications in reducing cardiovascular events. Very few studies looked at combinations of antihypertension medications, so we were unable to include them in our analysis," Dr. Wei said. "Also, we need more studies from South Asia and Africa as most of the studies in this meta-analysis were from North America and Europe. Further studies in patients with existing heart failure and chronic kidney disease are also needed."

Another recent study comparing monotherapies for hypertension (https://bit.ly/2vn6r9Z) found similar effectiveness for most cardiovascular outcomes across drug classes. But that analysis showed thiazide and thiazide-like diuretics were more effective than ACE inhibitors for preventing acute MI, heart failure hospitalization, and stroke. The diuretics also had a better safety profile than ACE inhibitors, while non-DH CCBs were inferior to all other drug classes.

The 2019 study is part of the Observational Health Data Sciences and Informatics (OHDSI) collaborative's Large-Scale Evidence Generation and Evaluation across a Network of Databases (LEGEND) project, which uses high-level analytics to perform observational studies using millions of patient records.

Dr. George Hripcsak, a professor at Columbia University and co-author of the LEGEND hypertension study, noted that there were several differences between the two studies.

"LEGEND considered only first users of anti-hypertension medications, whereas the Wei study does not," he told Reuters Health email. "The LEGEND study used real-world practice, which may differ from behavior in strict study protocols."

He added: "This study's confidence intervals are fairly wide, so the two sets of results may actually overlap for most results. And note that a network meta-analysis is not a randomized experiment; the indirect comparisons are a form of observational research that is subject to bias such as differences in populations and, perhaps more important, differences in how the underlying trials are designed and executed."

—Anne Harding

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