Is it safe to take olmesartan in combination therapy for advanced hypertension?

Use of olmesartan in combination practice is safe and results in similar cardiovascular composite outcomes, including myocardial infarction (MI), when compared with active comparators in hypertensive patients who need more than two antihypertensive medications, reports a study.

“Our findings support the cardiovascular efficacy and safety of olmesartan in patients with advanced hypertension receiving the combination therapy,” the researchers said.

In this multicentre retrospective study, the researchers obtained data from the Korea University Medical Centre database, built from electronic health records (EHRs). They then followed-up patients prescribed at least two antihypertensive drugs as a combined therapy for 3 years.

A composite of all-cause mortality, MI, stroke, and hospitalization for heart failure served as the primary outcome. Propensity score (PS) matching was used to compare the adjusted outcomes.

A total of 24,806 patients were identified, of whom 4,050 (16.3 percent, mean age 64 years, 45 percent women, 41 percent had diabetes) were using olmesartan between January 2017 and December 2018. Olmesartan users were younger and less likely to have diabetes mellitus or chronic kidney disease. [J Hypertens 2023;41:1578-1584]

In PS-matched cohort, cumulative incidence of the composite outcome at 3 years was similar between treatment groups (p=0.91). Specifically, the 3-year cumulative incidence of MI was 1.4 percent in olmesartan users (4.8 per 1,000 person-years) and 1.5 percent in active comparators (5.2 per 1,000 person-years; p=0.74).

Additionally, olmesartan demonstrated comparable safety profiles, including acute kidney injury and newly started dialysis.

Retrospective studies

Previous retrospective studies provided further postmarketing evidence using claims or EHR data, and the results suggested no association between olmesartan use and an increased cardiovascular death in different study samples and populations other than those with diabetes. [Pharmacoepidemiol Drug Saf 2014;23:331-339; Hypertension 2014;63:968-976; Pharmacoepidemiol Drug Saf 2014;23:348-356]

“However, patients prescribed olmesartan are generally younger and healthier than those receiving other antihypertensive medications, and these retrospective studies did not adjust for the most important confounder, blood pressure (BP),” the researchers said. [Pharmacoepidemiol Drug Saf 2014;23:348-356; JAMA 2007;297:278-285; JAMA 2007;297:278-285]

“Our study included baseline BP in the thorough PS-matching process, and the on-treatment BP during the follow-up period was similar between the two groups, suggesting that minimal residual confounding existed in the matched cohort,” they added.

Angiotensin receptor blocker

Olmesartan, an angiotensin receptor blocker (ARB) with a favourable tolerability profile, is safe when used in combination with hydrochlorothiazide and amlodipine. [J Am Soc Hypertens 2012;6:132-141; J Am Soc Hypertens 2012;6:132-141; J Am Soc Hypertens 2012;6:132-141]

Olmesartan also has a more potent effect in terms of reducing BP, as well as a prolonged half-life, when compared with other ARBs. [J Cardiovasc Pharmacol 2005;46:585-593; J Cardiovasc Pharmacol 2005;46:585-593; J Cardiovasc Pharmacol 2005;46:585-593; J Cardiovasc Pharmacol 2005;46:585-593]

“However, previous randomized studies examining the efficacy of olmesartan in patients with diabetes mellitus have shown unexpected numerical imbalances in cardiovascular mortality compared with those in the placebo group, and the United States Food and Drug Administration has discouraged the use of olmesartan to help delay or prevent renal disease,” the researchers said. [N Engl J Med 2011;364:907-917; Diabetologia 2011;54:2978-2986]