One Pill to Rule Them All: The Role of Single-Pill Combinations in Optimizing Blood Pressure Control

Hypertension control in the United States (U.S.) remains suboptimal, perpetuating preventable risk for primary and secondary cardiovascular events. Single-pill combinations (SPCs) that contain two or more agents have improved adherence and outcomes in conditions such as human immunodeficiency virus (HIV) and heart failure, yet remain underused in hypertension care. Based on evidence of improved adherence and reductions in cardiovascular events and all-cause mortality, the recent AHA/ACC High Blood Pressure (BP) Guideline strongly recommends initiating SPC therapy for patients with stage 2 hypertension. However, translating recommendations into clinical practice remains challenging. Concerns regarding agent selection, safety, tolerability, cost, and long-term management, coupled with clinical inertia and workflow constraints, may limit uptake. In this Perspective, we review the evidence supporting SPC use and focus on implementation considerations relevant to primary care, highlighting strategies and evidence gaps that must be addressed to integrate SPCs into routine hypertension management and achieve population-level BP control.