Page 9 - hypertension_newsletter4_Final

REFLECTIONS
Hypertension
Hypertension Global Newsletter #4 2023

CLICK HERE Hypertension
FOR THE LINK TO FULL ARTICLE

WATCH A QUICK TAKE VIDEO SUMMARY
OF THE ARTICLE HERE (2 MIN 7 SEC).

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

Chalmers J, et al. J Hypertens. 2023 Apr 1;41(4):527-544.

Among the diuretics recommended for antihypertensive treatment, some guidelines preferentially recommend the thiazide-like
diuretics chlorthalidone and indapamide, because of their longer duration of action and greater BP-lowering ability compared to
thiazide diuretics, such as hydrochlorothiazide. Some thiazide-like diuretics (e.g., chlorthalidone) have been associated with a
greater risk of side effects, leading to treatment discontinuation. Indapamide has been used in large-scale clinical trials, both as
monotherapy and in combination with other BP-lowering agents, such as ACEi, perindopril.

The study aimed to assess the reduction in all-cause death and CV outcomes associated with using indapamide monotherapy
or in combination with perindopril in randomized controlled trials. Pooling results from four large trials has never been done
before, although previous meta-analyses have presented some partial results with indapamide.

Features of the studies

PATS (1995) PROGRESS (2001) ADVANCE (2007) HYVET (2008)
Secondary prevention Primary prevention
Countries (centres) China 10 countries; Asia, Australasia, 20 countries: Europe, China, Asia, 13 countries: Europe, China,
and Europe Australasia, and Canada Australasia, and Tunisia

Inclusion criteria Poststroke (stroke or TIA) Poststroke (stroke or TIA) with T2DM, age ≥55 years ± risk factor Very elderly (>80 years old)
with or without HTN or without HTN with or without HTN + HTN
2-week placebo with 6-week with low-dose perindopril/ 8-week placebo with cessation
Run-in period cessation of any BPL 4-week with perindopril indapamide of any BPL
Perindopril 4mg alone or + SPC perindopril
Intervention group Indapamide 2.5 mg indapamide 2.5 mg (2 mg in Japan) 4 mg/indapamide 1.25 mg + Indapamide SR 1.5 mg ±
+ standard additional therapy standard additional therapy perindopril (2 or 4 mg)

Comparator group Matching placebo Matching placebo + standard Matching placebo + standard Matching placebo
additional therapy additional therapy
BP-lowering Additional Tx authorized Additional Tx authorized No additional Tx authorized
treatment Not to be modified
Composite endpoint: Major
Stroke recurrence Stroke recurrence
Primary endpoint microvascular and major Any stroke (fatal or non-fatal)
(fatal or non-fatal) (fatal or non-fatal) macrovascular events*
Years of follow-up 2 years, median (0–3.8) 3.9 years, mean (0–4.5) 4.3 years, mean (0–5.6) 1.8 years, median (0–6.5)
(range)

*Composite: Major macrovascular and microvascular events, defined as death from CVD, non-fatal stroke or non-fatal MI, and new or worsening renal or diabetic eye disease.
BP, blood pressure; BPL, blood pressure lowering; CVD, cardiovascular disease; HTN, hypertension; MI, myocardial infraction; SPC, single-pill combination; SR, sustained release; T2DM,
type 2 diabetes mellitus; TIA, transient ischemic attack; Tx, open-label treatment.

TABLE OF CONTENTS