Effectiveness of Indapamide Prolonged‐Release and Perindopril Versus Perindopril Monotherapy for Treated Uncontrolled Hypertension: A Target Trial Emulation

OBJECTIVE: To assess the effectiveness of indapamide prolonged release and perindopril in combination using blood pressure (BP) records collected in routine practice. METHODS: Using a target trial emulation framework, an observational retrospective cohort study was conducted. The data source was the United Kingdom's CPRD Aurum general practice database. Adults with systolic BP (SBP) ≥ 145 mmHg treated with perindopril 4/5 mg for ≥ 4 weeks at a stable dose who either added indapamide 1.5 mg to perindopril (n = 193) or continued on perindopril monotherapy (n = 14 571) were included. Balance between treatment arms was achieved with propensity score matching; results were explored in additional analyses using different eligibility criteria and alternative statistical methodologies. The primary outcome was change in SBP from baseline to Week 8 between indapamide added to perindopril versus perindopril monotherapy. RESULTS: In the primary analysis, indapamide added to perindopril yielded an additional SBP reduction of -6.3 mmHg (95% confidence interval [CI] -8.7 to -3.9) over perindopril monotherapy at Week 8. Results of additional analyses were consistent with the main analysis, but effect estimates varied due to diverse underlying assumptions. CONCLUSIONS: Target trial emulation allowed assessment of antihypertensive treatment effectiveness, and indapamide plus perindopril yielded clinically meaningful decreases in SBP over perindopril monotherapy. Secondary and sensitivity analyses support that these findings were robust.