Combination therapy with olmesartan safe, effective in advanced hypertension

Use of olmesartan in a combination therapy for advanced hypertension results in similar cardiovascular outcomes, including myocardial infarction (MI), relative to active comparators, according to a study. Additionally, there is no convincing evidence that olmesartan is harmful to patients with hypertension.

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

Data from electronic health records (EHR) from the Korea University Medical Center databases were used in this multicentre retrospective study. The research team followed-up patients prescribed two or more antihypertensive medications 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. Finally, propensity score (PS) matching was used to compare the adjusted outcomes.

Overall, 24,806 patients (mean age 64 years, 45 percent women, 41 percent had diabetes) were included in the study, of whom 4,050 (16.3 percent) were treated with olmesartan between January 2017 and December 2018. Olmesartan users were usually younger and less likely to have diabetes or chronic kidney disease. [J Hypertens 2023;41:1578-1584]

In the PS-matched cohort, similar cumulative incidences of cardiovascular outcomes were observed between olmesartan users and active comparators at 3 years (p=0.91). Specifically for MI, the 3-year cumulative incidence 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).

Notably, olmesartan had similar safety profiles, including acute kidney injury and newly initiated dialysis.

Other studies

In earlier retrospective studies using claims or EHR data, use of olmesartan showed no association with greater cardiovascular mortality in different samples and populations other than those with diabetes. However, patients treated with olmesartan were generally younger and healthier than those treated with other antihypertensive medications. [Pharmacoepidemiol Drug Saf 2014;23:331-339; Hypertension 2014;63:968-976; Pharmacoepidemiol Drug Saf 2014;23:348-356]

In addition, some of these studies did not adjust for a critical confounder: blood pressure. [Hypertension 2014;63:977-983; Pharmacoepidemiol Drug Saf 2014;23:340-347; 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,” the researchers said.

Furthermore, a large meta-analysis of individual patient-level data provided evidence showing that the difference in adverse cardiovascular events between olmesartan group and placebo or active comparators was not clinically relevant and did not achieve statistical significance. [Am J Cardiovasc Drugs 2016;16:427-437]

“Thus, regarding the cardiovascular outcomes, there is no conclusive evidence that olmesartan use is harmful,” the researchers said. “Our study also showed no differences in safety outcomes of new-onset hypotension, hypertensive crisis, new-onset atrial fibrillation, newly started dialysis, or new-onset dementia or Alzheimer’s disease.”

Olmesartan is an angiotensin receptor blocker used to treat hypertension. It has a favourable tolerability profile and is safe to use when combined with hydrochlorothiazide and amlodipine. [J Am Soc Hypertens 2012;6:132-141; J Hum Hypertens 2010;24:730-738; Postgrad Med 2013;125:124-134]