Intensive BP-lowering a no-go after reperfusion in ischaemic stroke

An intensive blood pressure target (<120 mm Hg) should be avoided in patients who have undergone endovascular thrombectomy for acute ischaemic stroke (AIS) for large-vessel occlusion (LVO), results of the phase III ENCHANTED2/MT* trial showed.

“In people who have successfully reached reperfusion, the 120 [mm Hg] target led to worse functional outcomes compared to a less intensive target,” presented study investigator Dr Craig Anderson from The George Institute for Global Health, University of New South Wales, Sydney, Australia, at WSC 2022.

This multicentre (44 tertiary hospitals in China), open-label trial involved 821 adults (mean age 67 years, 38 percent female, median NIHSS** score=15) who had persistent hypertension (two successive measurements of systolic blood pressure [SBP] ≥140 mm Hg for >10 minutes) within 3 hours of reperfusion with endovascular thrombectomy for AIS due to any intracranial LVO. They were randomized 1:1 to receive a more intensive (SBP target <120 mm Hg) or less intensive (SBP target 140–180 mm Hg) BP-lowering treatment regimen, with targets to be achieved within 1 hour and lasting 72 hours.

At 90 days, poor functional outcome, based on worse scores on the modified Rankin scale (mRS), was more commonly observed in the more intensive vs less intensive treatment group (common odds ratio [OR], 1.37, 95 percent confidence interval [CI], 1.07–1.76; p=0.01). [WSC 2022, abstract LB011; Lancet 2022;doi:10.1016/S0140-6736(22)01882-7]

The results were consistent across the prespecified subgroups, noted Anderson.

Death or neurological deterioration at 7 days was more common in the more vs less intensive treatment groups (OR, 1.53, 95 percent CI, 1.18–1.97; p=0.001).

“The early increase in neurological deterioration supports the hypothesis that more intensive treatment compromised perfusion of the cerebral microcirculation,” the authors said.

Death or disability (mRS score 3–6) was also more frequent in the more vs less intensive treatment groups at 90 days (53 percent vs 39 percent; OR, 1.85, 95 percent CI, 1.36–2.51; p<0.0001). This latter outcome was consistent when the comparison was restricted to major disability in survivors at 90 days (mRS score 3–5; 43 percent vs 28 percent; OR, 2.07, 95 percent CI, 1.47–2.93; p<0.0001).

Patients in the more vs less intensive treatment groups had significantly worse patient-reported physical subcategories of health-related quality of life. All-cause mortality incidence was comparable between groups at 90 days (16 percent vs 15 percent; OR, 1.14; p=0.53), as was incidence of symptomatic intracranial haemorrhage (6 percent each; OR, 0.93; p=0.80).

“[This last finding] suggests that the less intensive treatment group derived some benefit from BP lowering, and that the optimum target for SBP after mechanical thrombectomy might be within the range of 120–140 mm Hg,” the authors added.

Serious adverse event rate was also similar between the more vs less intensive treatment groups (28 percent vs 27 percent; OR, 1.06; p=0.71). Post-hoc analysis showed no between-group difference with regard to recurrent ischaemic stroke incidence at 90 days (6 percent vs 5 percent; OR 1.32; p=0.38), and there were no recorded incidents of severe hypotension. Duration of hospitalization did not differ between patients in the more vs less intensive treatment groups (median 12 vs 11 days; p=0.25).

The trial was stopped early due to “persistent efficacy and safety concerns,” noted the authors.

According to Anderson and co-authors, the risk of reperfusion injury remains elevated despite the established used of thrombectomy for LVO-related AIS.

“There is a lot of uncertainty about whether modification of BP will reduce the adverse outcomes [in this population] or worsen them because of the unstable state in the brain in the context of acute ischaemic injury,” said Anderson.

Despite the findings, the optimum BP level following reperfusion for AIS is yet to be determined and requires exploration in further trials, the authors concluded.