Abstract Body: Background: Elevated blood pressure (BP) is common after Intracerebral Hemorrhage (ICH) and is linked with increased morbidity and mortality, partly due to hematoma expansion. We conducted a systematic review and meta-analysis to determine the effect of BP lowering within 6 hours of ICH onset on functional outcome at 90 days, including a subgroup analysis of undifferentiated stroke patients.
Methods: We searched PubMed, Embase, Cochrane Central, Google Scholar, and Clinicaltrials.gov for randomized controlled trials (RCTs). Odds ratio (ORs) with 95% CI were pooled across trials using a random-effects model for the outcomes of 1) change in modified Rankin Scale (mRS) score at 90 days; 2) 90-day death; 3) combined death or disability (mRS>2); 4) significant hematoma expansion (>6ml or >33% of baseline) and 4) serious adverse events (SAEs). The above analyses were replicated in the patients with undifferentiated (radiologically unconfirmed) stroke who recieved pre-hospital BP lowering. Trial sequential analysis (TSA) was performed to determine cumulative evidence strength.
Results: We included 9 RCTs with 11,773 patients; 5884 (49.9%) of whom received early BP control within 6 hours of ICH onset. Early BP lowering therapy was associated with a favorable change in 90-day mRS scores (OR 0.88; 95% CI 0.78-0.98; Fig.1A), a reduced risk of death (OR 0.86; 95% CI 0.75-0.98; Fig.1B), a lower risk of death or disability (OR 0.85; 95% CI 0.73-0.99; Fig.2A) and reduced risk of significant hematoma expansion (OR 0.74; 95% CI 0.58-0.95; Fig.2B) in larger trials. On pooling the results of smaller RCTs (<100 patients) with those from larger trials, none of the above outcomes were significant. The same was true for prehospital BP management in undifferentiated stroke. No increased risk of SAEs was observed. TSA indicated that the current evidence is inconclusive to reach definitive conclusions for both the 90-day death outcome and the combined death or disability at 90 days in the primary analysis.
Conclusion: Early BP lowering within 6 hours ICH of onset had no increased risk of SAE and is associated with improved 90-day mRS scores, reduced mortality, lower combined death or disability rates, and reduced risk of hematoma expansion in larger trials, which becomes non-significant on pooled analysis of larger and smaller trials. TSA indicated the need for additional trials with larger sampling sizes to confirm these findings.