Low-Dose Combinations With 3 or 4 Blood Pressure-Lowering Medications for the Treatment of Hypertension

Low-dose combinations (LDCs) of 3 or 4 blood pressure (BP)-lowering drugs as a single pill show promise for initial treatment of hypertension.

The purpose of this study was to assess the efficacy and safety of single pill LDC therapies compared to placebo, monotherapy, or usual care.

A systematic search for randomized trials comparing LDC consisting of 3 or 4 BP-lowering drugs all at ≤0.5 standard dose, compared to placebo, monotherapy, or usual care. Mean BP reductions, proportions achieving BP <140/90 mm Hg, and risk of adverse events were summarized using random effects meta-analyses.

Twelve trials (N = 2,581) were included which contributed to 12 comparisons of LDCs vs placebo, 6 for LDCs vs monotherapy, and 4 for LDCs vs usual care. LDC reduced BP by 14/6 mm Hg vs placebo at 4 to 12 weeks, with larger systolic BP reductions at higher pretreatment systolic BP. Compared to monotherapy, LDC reduced BP by 7/6 mm Hg and increased the proportion achieving BP <140/90 mm Hg at first follow-up (67% vs 46%). Compared to usual care, LDC-based care was superior for BP reduction (7/4 mm Hg) and BP control (80% vs 65%) over an average 29 weeks; and results were similar whether patients were initially untreated or on monotherapy. LDC was not associated with significant increase in withdrawals due to adverse events compared to placebo (3% vs 2%), monotherapy (1% vs 0%), or usual care (3% vs 4%).

Single pill LDCs are effective and safe as an initial treatment option for hypertension. The degree of BP reduction depends strongly on pretreatment BP level.