(155) Comparative effectiveness and prescribing trends of modified-release versus immediate-release indapamide in patients with hypertension: a cohort study in the UK

Background: Indapamide is a thiazide-like diuretic available in modified-release (MR) and immediate-release (IR) formulations. Previous trial has demonstrated preferable pharmacokinetic properties of the MR formulation. Yet no study has directly compared the long-term effectiveness of MR versus IR indapamide. The current prescribing practice for MR and IR indapamide in the United Kingdom (UK) is also unknown.

Objectives: To investigate the prescribing trends and long-term comparative effectiveness of MR versus IR indapamide.

Methods: Population-based cohort study using the IQVIA Medical Research Data-UK database. Patients with hypertension who were initiated on MR or IR indapamide between 2005 and 2020 were included. We described the monthly prescribing trends of MR and IR indapamide and conducted a target trial emulation to compare the risk of composite cardiovascular events (myocardial infarction and stroke), and death, between MR and IR indapamide. We estimated the intention-to-treat and per-protocol effects in hazard ratios (HRs) and five-year absolute risk differences (ARDs) using pooled logistic regression models. Confounding and selection bias were accounted by multivariable adjustments and inverse probability weights.

Results: 1,904,289 patients with hypertension were identified. There was a greater increase in the proportion of IR indapamide users (0.43% to 2.31%), than MR indapamide (0.71% to 0.79%) from 2005 to 2020 in the UK. 30,021 and 56,367 patients initiated MR and IR indapamide were included in the target trial emulation. There was a lower risk of composite cardiovascular event with MR indapamide (HR=0.81, 95% CI, 0.68-0.98; ARD=-0.39%) compared to IR indapamide in the per-protocol analysis during a median follow-up time of 12 months, but no difference in the intention-to-treat analysis (HR=0.99, 95% CI, 0.90-1.08; ARD=-0.03%). No difference in the risk of death was observed in both analyses.

Conclusions: In the UK, there was a substantial increase in prescribing of IR indapamide after the NICE guideline change in 2011, but not for MR indapamide. In patients treated for hypertension with indapamide, sustained treatment with MR preparations may lower the risk of cardiovascular events but not all-cause mortality, compared to IR preparations.