The efficacy and safety of low-dose triple combination for hypertension treatment: a systematic review and meta-analysis of randomized controlled trials

Abstract

Recently, Low-dose triple single-pill combinations (LDTC) have become a promising option for managing hypertension. This review evaluates LDTC’s effectiveness and safety versus standard care, monotherapy, and placebo for blood pressure (BP) control. A systematic review and meta-analysis of randomized controlled trials retrieved from PubMed, EMBASE, WOS, Scopus, and Cochrane from inception to September 2024. The analysis presented risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI). PROSPERO ID: CRD42024595331. We identified five eligible trials with a total of 1,709 patients. LDTC had a higher rate of achieving BP < 140/90 at 4 to 6 weeks (wk) (RR: 1.56; CI: 1.41, 1.72; p < 0.01) and at 8 to 12 wk (RR: 1.43; CI: 1.31, 1.57; P < 0.01). Additionally, LDTC significantly reduced the automated office systolic BP at 4 to 6 wk (MD: -8.80; CI: -10.16, -7.44; p < 0.01), 8 to 12 wk (MD: -8.30; CI: -11.18, -5.42; P < 0.01), and at 24 wk (MD: -6.94; CI: -10.56, -3.32; P < 0.01). However, LDTC indicated an increased rate of hypokalemia (RR: 2.25; CI: 1.50, 3.38; P < 0.01), with no difference between both groups in total adverse events (AEs) ( P = 0.44), serious AEs ( P = 0.79), treatment discontinuation due to AEs ( P = 0.91), and the AEs of special interest ( P = 0.54). LDTC therapy is effective and safe for hypertension management but poses potassium depletion. Further large-scale studies are essential to confirm its clinical benefits. Graphical Abstract

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