Challenges and Perspectives in Optimising the Treatment of Arterial Hypertension: Role of the Ramipril-Amlodipine-Hydrochlorothiazide Single-Pill Combination

Globally, hypertension remains inadequately controlled, despite the availability of effective therapies and guideline recommendations. This narrative review synthesises current evidence on the clinical rationale, efficacy and implementation of single-pill combination (SPC) therapy to control blood pressure (BP), with a focus on an SPC containing ramipril, amlodipine and hydrochlorothiazide. These agents offer complementary mechanisms of action and a favourable tolerability profile, supporting their use in dual and triple SPCs to overcome therapeutic inertia (failure to intensify therapy when BP goals are unmet) and improve BP control. Clinical trial and real-world data demonstrate that combination therapy leads to faster, more sustained reductions in BP, with better cardiovascular and renal outcomes compared with monotherapy. SPCs also improve adherence and persistence, reduce visit-to-visit BP variability and lower healthcare costs. The "LESS is BETTER" framework, advocating for Lower BP targets, Earlier BP control, Stronger therapy with SPCs for greater efficacy and Simpler regimens to improve adherence to therapy, provides a pragmatic approach for translating current guidelines into practice. However, barriers can hinder SPC adoption, such as physicians' limited attitudes to implement major international guideline recommendations, misconceptions about SPCs, limited use of ambulatory BP monitoring and suboptimal patient engagement. Strategies to overcome these barriers include clinician education, communication tools, flexible dose options and supportive healthcare policies. Taken together, the evidence supports broader adoption of the ramipril-amlodipine-hydrochlorothiazide SPC as an effective therapeutic approach to contemporary hypertension management.