Cerebrovasc Dis. 2026 May 25:1-13. doi: 10.1159/000552671. Online ahead of print.
ABSTRACT
INTRODUCTION: The benefits of long-term blood pressure (BP) lowering for the prevention of recurrent stroke and other serious cardiovascular (CV) events in patients who suffer an acute spontaneous intracerebral hemorrhage (ICH) is well established. However, there is uncertainty as to whether the treatment effect varies according to certain patient characteristics and across various CV and non-CV outcomes, and the timing of when the benefits manifest over time. We aim to pool individual participant data (IPD) from randomised controlled trials (RCTs) that included patients with a history of ICH to determine the efficacy of BP lowering for the secondary prevention of major CV events.
METHODS AND ANALYSIS: A systematic review was undertaken according to the Preferred Reporting Items for Systematic review and Meta-Analysis of Individual Participant Data (PRISMA-IPD) Statement. A search of multiple databases from inception to 25 January 2026 was conducted to identify RCTs of BP-lowering therapy for secondary prevention after ICH that enrolled at least 100 participants with ICH. We will undertake an IPD meta-analysis, with TRIDENT (Triple therapy prevention of Recurrent Intracerebral Disease EveNts Trial) serving as our anchor study, and three other major RCTs of BP lowering treatment for secondary prevention with a subgroup of at least 100 ICH patients: ESPRIT (Effects of Intensive Systolic Blood Pressure Lowering Treatment in Reducing Risk of Vascular Events) trial, PROGRESS (Perindopril Protection Against Recurrent Stroke Study), and RESPECT (Recurrent Stroke Prevention Clinical Outcome) Study. The primary CV outcome is the time to first recurrent stroke of any type. Secondary outcomes include major adverse cardiovascular events (MACE): non-fatal stroke, non-fatal myocardial infarction, or cardiovascular death; each component of MACE, stroke subtypes, and all-cause death. The safety outcome is any serious adverse event. All analyses will be performed on the intention-to-treat dataset from each trial using a one-stage approach. The effect of the intervention will be estimated as the cause-specific hazard ratio and 95% confidence intervals (CI) obtained from a Cox proportional hazard model, adjusting for age, sex, history of hypertension, and history of diabetes mellitus. A sensitivity analysis will treat death as a competing risk. The time to benefit of BP lowering will also be estimated according to specific absolute risk reduction thresholds.
PMID:42184233 | DOI:10.1159/000552671