Australia: Meta-analysis on Antihypertensives

A new meta-analysis published in JAMA Cardiology has suggested that low-dose combinations (LDCs) with 3 or 4 antihypertensives are an effective and well-tolerated treatment option for the early management of hypertension.

"The polypills containing low doses of three or four antihypertensive agents are better at blood pressure (BP) lowering than monotherapy, usual care, or placebo," the study stated. The investigators reported that fixed-dose combinations led to a significantly higher mean reduction in systolic blood pressure than placebo (18.0-mm Hg more significant reduction) and monotherapy or usual care (7.4-mm Hg more substantial reduction).

Patients who received polypills were more likely to have their blood pressure controlled to below 140/90 mm Hg early on (66% versus 46%) and at 6-12 months (72% versus 59%) than those treated with standard care/monotherapy. Also, they were more likely to be controlled than placebo-treated patients in the first 4 to 12 weeks (54% vs 18%).

Low-dose combination antihypertensives comprising 3 or 4 BP–lowering drugs have emerged as a potentially necessary treatment for initial hypertension management. Therefore, Nelson Wang, University of New South Wales, Sydney, New South Wales, Australia, and colleagues aimed to assess the safety and efficacy of LDC therapies for hypertension management.

For this purpose, the researchers searched online databases from inception until September 2022. The meta-analysis included randomized clinical trials (RCTs) comparing low-dose combinations of 3 or 4 BP-lowering drugs to usual care, monotherapy, or placebo.

Two independent authors did data extraction and synthesized the data from fixed-effects and random models using risk ratios for mean differences and binary outcomes for continuous outcomes.

Study Findings

• Seven trials with 1918 patients (mean [mean range] age, 59 years; 38% female) were included.
• Four trials involved triple-component low-dose combinations, and three involved quadruple-component LDC.
• LDC was associated with a more significant mean reduction in systolic BP than initial monotherapy or usual care (mean reduction, 7.4 mm Hg) and placebo (mean reduction, 18.0 mm Hg) at 4 to 12 weeks follow-up.
• LDC was tied to a higher proportion of participants achieving blood pressure below 140/90 mm Hg at 4 to 12 weeks versus usual care or monotherapy (66% vs 46%; RR, 1.40) and placebo (54% vs 18%; RR, 3.03).
• There was no remarkable heterogeneity between trials enrolling patients with and without baseline BP-lowering therapy.
• Findings from two trials indicated LDC was superior to usual care or monotherapy at 6 to 12 months.
• LDC was linked with more dizziness (14% vs 11%; RR 1.28) but no other adverse effects nor treatment withdrawal.

"The study's findings revealed that LDCs with 3 or 4 antihypertensives were a well-tolerated and effective BP-lowering treatment option for the early or initial hypertension management," the authors conclude.

Reference

Wang N, Rueter P, Atkins E, et al. Efficacy and Safety of Low-Dose Triple and Quadruple Combination Pills vs Monotherapy, Usual Care, or Placebo for the Initial Management of Hypertension: A Systematic Review and Meta-analysis. JAMA Cardiol. Published online April 26, 2023. doi:10.1001/jamacardio.2023.0720