Triple drug antihypertensive single-pill combinations included as WHO essential medicines: an overview of efficacy, safety, and cost

Abstract

Globally, only about one in five of the 1.4 billion people with hypertension achieve blood pressure (BP) control to <140/90 mmHg, despite strong evidence and clear guideline recommendations for optimal management. Many patients require three or more antihypertensive medicines, yet real-world barriers, including limited access, poor adherence and health system complexities, prevent them from achieving optimal BP control. Single pill combinations (SPCs) improve adherence, simplify treatment, and enhance efficacy with favourable safety through complementary pharmacological mechanisms at lower, better-tolerated doses. The World Health Organization in 2025 added triple drug antihypertensive SPCs to the 24 th Model Essential Medicines List, building on the 2019 inclusion of dual drug SPCs. This paper reviews the clinical trial and real-world evidence supporting the inclusion of triple drug SPCs as essential medicines—their efficacy, safety, cost, and role in current guideline recommendations. Randomized control trials show that triple drug SPCs achieve greater BP reduction (~5.4/3.2 mmHg) and higher control than dual therapy. Low-dose triple drug SPCs further improve adherence, accelerate BP control, and enhance real-world effectiveness in primary care. Economic analyses suggest that SPCs are often cost-saving due to reduced pill burden, fewer clinic visits, and improved outcomes, though affordability varies across settings. The inclusion of triple drug SPCs in the Essential Medicines List signals their global priority. However, translation to population-level benefit will depend on inclusion in national formularies, standardized treatment protocols, and deliberate strategies to improve access in low- and middle-income countries where treatment gaps are widest.