Low-Dose Combinations With 3 or 4 Blood Pressure–Lowering Medications for the Treatment of Hypertension
Nelson Wang, Phidias Rueter, Abdul Salam, Mark D. Huffman, Emily Atkins, Dike Ojji, Asita de Silva, Ruth Webster, Clara K Chow, Paul K. Whelton, Aletta E. Schutte, Anthony Rodgers
Abstract
BACKGROUND: Low-dose combinations (LDCs) of 3 or 4 blood pressure (BP)-lowering drugs as a single pill show promise for initial treatment of hypertension. OBJECTIVES: The purpose of this study was to assess the efficacy and safety of single pill LDC therapies compared to placebo, monotherapy, or usual care. METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.