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Fixed-dose combinations have been strongly endorsed by European guidelines for first-line and second-line treatment of hypertension. Among recommended combinations, that of an angiotensin-converting enzyme inhibitor and a calcium channel blocker stands out because the mechanisms of action of these two therapeutic classes are complementary, leading to enhanced efficacy. In the large multicentre ASCOT-BPLA trial, treatment based on the combination of amlodipine and perindopril significantly reduced the risk of cardiovascular and all-cause death, stroke, coronary events and procedures, new-onset diabetes, and new-onset renal impairment in a wide range of patients with hypertension and other cardiovascular risk factors, when compared with atenolol/thiazide–based therapy. The perindopril/amlodipine single-pill combination was developed based on guideline recommendations for combination treatment, the indications of each component, and ASCOT-BPLA trial data. Several studies in real-life settings show that a wide range of hypertensive patients, including everyday hypertensives with common risk factors, would benefit from the perindopril/amlodipine combination.