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

Abstract

ObjectiveTo summarise evidence of the effects of blood pressure (BP)-lowering interventions after acute spontaneous intracerebral haemorrhage (ICH).MethodsA 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.ResultsOf 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 (pinteraction=0.031) and agent (pinteraction<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.InterpretationOverall, 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 numberCRD42019141136.

Blood Pressure Management After Intracerebral and Subarachnoid Hemorrhage: The Knowns and Known Unknowns

“…In the aforementioned IPD meta-analysis of 16 RCTs, there was heterogeneity in the treatment effect according to BP lowering strategy: ICH patients with titration of treatment to a systolic BP target appeared to have better outcomes than patients treated with a fixed agent without a specified target. 10 These data support the pooled IPD analysis of INTERACT2 and ATACH-II of potential benefits to systolic levels as low as 120 to 130 mm Hg. 22 However, a one-size-fits-all approach to up-, down-, or cross-titrate BP lowering to achieve an effective target, at the lowest dose, and without causing hypotension and other side effects, is often challenging in practice.…”

“…There may be heterogeneity in the effects (and safety) of various BP lowering agents, according to those most frequently used in the treatment group of 16 RCTs in the IPD meta-analysis. 10 Patients who received α- and β-adrenoreceptor blockers appeared to have better outcomes from active/intensive BP lowering, compared with patients who had renin-angiotensin system blockers, calcium channel blockers, nitrates, and magnesium sulfate. These findings suggest that α- and β-adrenoreceptor blockers may benefit from blocking the autonomic response that has been shown to drive the hypertensive response from critical illness.…”

“…A recent post hoc subgroup analysis of the ATACH-II trial showed that intensive BP lowering (systolic target, 110–139 mm Hg) with intravenous nicardipine delivered within 2 hours of ICH onset was associated with reduced hematoma growth and improved functional outcome. 26 However, there was no heterogeneity in the effect of BP lowering treatment according to time to randomization in a broader IPD meta-analysis of 16 RCTs; 10 but this included a substantial number of ICH patients (N=145) who received a glyceryl trinitrate (GTN) patch as part of a large prehospital ambulance-initiated treatment RCT (RIGHT-2) in patients with suspected acute stroke, and where subgroup analysis showed patients treated with GTN had greater hematoma growth and poorer outcomes than sham-GTN controls. 27 These data suggest that very early use of GTN might promote vasodilation or disrupt hemostatic mechanisms in ICH, and this may have modified the signal for potential benefits from other BP lowering interventions delivered within 2 hours of ICH onset in the IPD meta-analysis.…”

“…2022;53:1065-1073. DOI: 10.1161/STROKEAHA.121.036139 individual participant data (IPD) meta-analysis of RCTs of BP control in acute ICH, 10 we aim to provide guidance for clinical practice and future research.…”

European Stroke Organisation (ESO) guidelines on mobile stroke units for prehospital stroke management

“…48 Also, the quicker identification of an ICH as underlying cause of the symptoms and the emergency site management by specialised teams can lead to an earlier individualised blood pressure management, which has been shown to influence haematoma expansion and subsequent clinical outcome. 35,[74][75][76][77] Another advantage of the prehospital patient assessment is the possibility of emergency site reversal of anticoagulants to control haematoma volume in patients with anticoagulant-related ICH. 36,78,79 All-cause mortality of ICH patients at 7 and 90 days was not different in MSU treated compared to standard care patients.…”