Early lowering of blood pressure after acute intracerebral haemorrhage: a systematic review and meta-analysis of individual patient data

Objective To summarise evidence of the effects of blood pressure (BP)-lowering interventions after acute spontaneous intracerebral haemorrhage (ICH). Methods A prespecified systematic review of the Cochrane Central Register of Controlled Trials, EMBASE and MEDLINE databases from inception to 23 June 2020 to identify randomised controlled trials that compared active BP-lowering agents versus placebo or intensive versus guideline BP-lowering targets for adults <7 days after ICH onset. The primary outcome was function (distribution of scores on the modified Rankin scale) 90 days after randomisation. Radiological outcomes were absolute (>6 mL) and proportional (>33%) haematoma growth at 24 hours. Meta-analysis used a one-stage approach, adjusted using generalised linear mixed models with prespecified covariables and trial as a random effect. Results Of 7094 studies identified, 50 trials involving 11 494 patients were eligible and 16 (32.0%) shared patient-level data from 6221 (54.1%) patients (mean age 64.2 [SD 12.9], 2266 [36.4%] females) with a median time from symptom onset to randomisation of 3.8 hours (IQR 2.6-5.3). Active/intensive BP-lowering interventions had no effect on the primary outcome compared with placebo/guideline treatment (adjusted OR for unfavourable shift in modified Rankin scale scores: 0.97, 95% CI 0.88 to 1.06; p=0.50), but there was significant heterogeneity by strategy (p(interaction)=0.031) and agent (p(interaction)<0.0001). Active/intensive BP-lowering interventions clearly reduced absolute (>6 ml, adjusted OR 0.75, 95%CI 0.60 to 0.92; p=0.0077) and relative (>= 33%, adjusted OR 0.82, 95%CI 0.68 to 0.99; p=0.034) haematoma growth. Interpretation Overall, a broad range of interventions to lower BP within 7 days of ICH onset had no overall benefit on functional recovery, despite reducing bleeding. The treatment effect appeared to vary according to strategy and agent. PROSPERO registration number CRD42019141136.