ESC Congress 2026 Abstract · Oct 26, 2026

Initial triple low-dose combination therapy improves blood pressure control without increased adverse events: a systematic review and meta-analysis

By Jang J, Lee MY, Park JS et al.

Background/Introduction: Single-pill triple low-dose combination (triple-LDC) antihypertensive drugs have become available for clinical use as an alternative initial therapy for hypertension, expanding the range of validated treatment strategies beyond established monotherapies. Purpose: We hypothesized that initial triple-LDC therapy would achieve superior blood pressure (BP) reduction compared with placebo and standard-dose monotherapy, with preserved tolerability. Methods: This systematic review and meta-analysis were conducted according to a prespecified PROSPERO-registered protocol and PRISMA guidelines. Randomized controlled trials comparing triple-LDC therapy (<=50% of the standard dose per component) with placebo or standard-dose monotherapy were identified through MEDLINE, EMBASE, and CENTRAL. Pooled estimates were calculated using random-effects inverse-variance models with restricted maximum likelihood, applying the Hartung–Knapp–Sidik–Jonkman (HKSJ) method for primary inference and Wald-type confidence intervals for sensitivity analyses. Within-study pooling was performed for multi-arm trials, and robustness was assessed using leave-one-out analyses. Results: Eight randomized controlled trials from seven publications (1,749 participants) were included. Compared with placebo, triple-LDC therapy significantly reduced systolic BP by -13.76 mmHg (95% CI, -19.28 to -8.23) and diastolic BP by -7.45 mmHg (95% CI, -10.85 to -4.04), with more than a twofold increase in BP control rates (risk ratio [RR] 2.27, 95% CI, 1.37 to 3.75). Compared with standard-dose monotherapy, triple-LDC therapy achieved an additional systolic BP reduction of -3.65 mmHg (95% CI, -7.40 to 0.11). Although not statistically significant in the primary HKSJ model, the effect was significant in Wald-based sensitivity analyses (95% CI, -6.53 to -0.77). Diastolic BP reduction was numerically greater but did not reach statistical significance (-1.39 mmHg; 95% CI, -3.35 to 0.58). BP control rates were higher with triple-LDC therapy (RR 1.25, 95% CI, 1.00 to 1.56). Findings were robust in sensitivity and leave-one-out analyses. Treatment-emergent adverse events and withdrawal rates were comparable between treatment groups. Conclusion: Triple-LDC therapy provides substantial BP reduction compared with placebo and modest additional benefit over standard-dose monotherapy without increased adverse events, supporting its role as an effective initial treatment strategy for hypertension.ESC2026_triple_ldc_meta_forest.jpg

doi.org/10.1093/eurheartj/ehag785.3043Open accessInterventions