The comparative effects of S-amlodipine versus racemic amlodipine on long-term cardiovascular outcomes in subjects with hypertension: a nationwide population-based cohort study

Although S-amlodipine is known to have similar effects in lowering blood pressure and fewer side effects compared to amlodipine (= mixture of S- and R-amlodipine), there are no available data on its impact on long-term cardiovascular prognosis. This retrospective cohort study analyzed claims data from Korean subjects with hypertension treated with either S-amlodipine or amlodipine from 2010 to 2020. Subjects with prior history of cardiovascular disease or stroke were excluded. The composite endpoints of all-cause death, myocardial infarction, and stroke as 3P-major adverse cardiovascular event (MACE) and the composite endpoints of 3P-MACE and heart failure hospitalization as 4P-MACE were assessed. The study included 1:2 propensity score-matched groups of subjects taking S-amlodipine (n = 15,709) and amlodipine (n = 29,951). The mean clinical follow-up duration was 4.9 ± 0.3 years (median 5.0 years). After adjusting for clinical factors, S-amlodipine was associated with a reduced incidence of 3P-MACE (adjusted hazard ratio aHR, 0.87; 95% confidence interval CI, 0.81-0.94; P < 0.001), and 4P-MACE (aHR, 0.86; 95% CI, 0.80-0.93; P < 0.001) compared to amlodipine. The better impact of S-amlodipine compared to amlodipine on 3P-MACE and 4P-MACE was also observed in the subgroup analysis based on various clinical factors. S-amlodipine showed better adherence than amlodipine (proportions of days covered ≥ 0.8: 96.7% vs . 91.8%; P < 0.001). In conclusion, S-amlodipine appears to potentially reduce the risk of long-term MACE compared to amlodipine in patients with hypertension who have no history of cardiovascular disease. However, these findings should be interpreted with caution and confirmed through further prospective studies.