Benefit of treatment based on indapamide mostly combined with perindopril on mortality and cardiovascular outcomes: a pooled analysis of four trials

J Hypertens. 2023 Mar 1;41(3):508-515. doi: 10.1097/HJH.0000000000003368. Epub 2023 Jan 19.

Abstract

Objective: The aim of this study was to assess the reduction in all-cause death and cardiovascular outcomes associated with the administration of the thiazide-like diuretic indapamide monotherapy or in combination with perindopril as a blood pressure lowering drug in randomized controlled trials (RCTs).

Method: Aggregate data from four published RCTs conducted versus matching placebo were pooled: PATS, a 2-year study (indapamide), and PROGRESS, a 4-year study (indapamide and perindopril), both in patients with a history of stroke or transient ischemic attack; ADVANCE, a 4-year study in patients with type 2 diabetes and cardiovascular risk factor (single-pill combination perindopril/indapamide) and HYVET, a 2-year study in very elderly hypertensive individuals (indapamide and an option of perindopril). The pooled effect (fixed and random) estimate (hazard ratio) was reported with corresponding 95% confidence intervals and P values. Treatment discontinuations were also analysed to assess the net benefit of the treatment.

Results: The population involved 24 194 patients (active: 12 113, placebo: 12 081). The fixed-effects meta-analysis of the three mortality endpoints found low statistical heterogeneity ( I2 = 0). Statistically significant risk reductions in the indapamide with or without perindopril-treated patients as compared to placebo were observed for all-cause death (-15%), cardiovascular death (-21%), fatal stroke (-36%) and all strokes (-27%). Other cardiovascular outcomes were improved (risk reduction, 22 to 36%). As expected, discontinuation rates for safety (two studies) were higher in the active group (6.4 vs. 3.9%), while they were similar when discontinuation for any reason is concerned (18.4 vs. 18.0%).

Conclusion: Across medium to high cardiovascular risk population, long-term indapamide, mostly combined with perindopril-based treatment, provided evidence of benefit on mortality and morbidity.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antihypertensive Agents
  • Blood Pressure
  • Drug Combinations
  • Humans
  • Hypertension* / complications
  • Indapamide* / therapeutic use
  • Perindopril / therapeutic use
  • Randomized Controlled Trials as Topic
  • Stroke* / epidemiology

Substances

  • Perindopril
  • Indapamide
  • Antihypertensive Agents
  • Drug Combinations