SOURCES: Mistry EA, Hart KW, Davis LT, et al. Blood pressure management after endovascular therapy for acute ischemic stroke. The BEST-II randomized clinical trial. JAMA 2023;330:821-831.
Nam HS, Kim YD, Heo J, et al. Intensive vs conventional blood pressure lowering after endovascular thrombectomy in acute ischemic stroke: The OPTIMAL–BP randomized clinical trial. JAMA 2023;330:832-842.
Endovascular thrombectomy has had a dramatic effect on acute ischemic stroke treatment. Of those who have large vessel occlusion, an 80% rate of successful vessel recanalization can be achieved. For every four patients treated, one additional patient will achieve functional independence. However, approximately 50% of patients who undergo endovascular therapy for ischemic stroke still have a severe impairment or will die within 90 days. Therefore, additional interventions are being investigated to improve overall outcome.
Peri-procedure treatments have been investigated, and the one of greatest concern has been the management of hypertension. Current guidelines from the American Heart Association suggest maintaining systolic blood pressure below 180 mmHg for patients who were treated both with intravenous thrombolysis and endovascular thrombectomy.
However, a number of centers around the world have tried different systolic blood pressure thresholds ranging from 120 mmHg to 160 mmHg. Many of these studies have been single-center or small non-randomized studies and have not been designed to get a definitive answer.
Mistry et al designed a randomized, open-label, blinded endpoint, Phase II trial with a futility endpoint, to try to understand what the best systolic blood pressure range for patients might be immediately after endovascular therapy. Three large academic medical centers participated, one in the Northeast, one in the South, and one in the Midwest. The prespecified primary endpoints, which could lead to an assessment of harm, were follow-up infarct volume at 36 hours and utility-weighted modified Rankin Scale score at 90 days. Secondary endpoints included any intracerebral hemorrhage on a 36-hour computed tomography or magnetic resonance imaging, symptomatic intracerebral hemorrhage on a 36-hour imaging study, and neurological worsening that was associated with any given antihypertensive treatment. Although perfusion scores with an ischemic penumbra were considered, they were removed as a secondary outcome because of the difficulties in the logistics of obtaining such studies.
A total of 120 patients were randomized in this trial, and 94% completed the study. There were three treatment arms for the study. Forty patients were enrolled in a group with a target systolic blood pressure < 140 mmHg, 40 were assigned to a group with a target blood pressure < 160 mmHg, and 40 were assigned to a group with a target blood pressure < 180 mmHg. Treatment was initiated within 60 minutes of recanalization and blood pressure treatment was maintained for 24 hours. There were no significant differences across the groups on the follow-up infarct volume of each blood pressure group. The investigators estimated that the probability of success for a future trial to study this problem was less than 25% to compare the 140 mmHg and 160 mmHg groups to the standard recommendation of maintaining systolic blood pressure below 180 mmHg.
The investigators concluded that this pilot trial did not meet any of the prespecified criteria for futility, but that a future study would be unlikely to provide a definitive answer. Although the authors did not discuss recommendations for blood pressure management, the implication is that the current practice recommendations of keeping systolic blood pressure below a target of 180 mmHg should be continued.
In a related study published in the same issue of JAMA, Nam et al investigated the optimal blood pressure after successful reperfusion following endovascular thrombectomy for acute ischemic stroke. This study was performed in South Korea and conducted across 19 stroke centers from 2020 until 2022. It included 306 patients with large vessel occlusion treated with endovascular thrombectomy who had partial or complete reperfusion.
Patients were randomly assigned to two treatment groups. One group received intensive blood pressure management with a targeted systolic blood pressure < 140 mmHg and the second group was a conventional management group with a target of systolic blood pressure between 140 mmHg and 180 mmHg. Treatments were maintained for 24 hours after enrollment. The primary outcome measurement was functional independence at three months, as documented by a modified Rankin Scale score of 0-2. The primary safety outcome was intracerebral hemorrhage within 36 hours or death related to the stroke within three months.
The trial was terminated early based on an interim analysis of the data and safety monitoring board, which noted safety concerns. A total of 302 patients completed the trial, with a mean age of 73 years, and 40% were women. The intensive blood pressure management group achieved a lower proportion of functional independence (39.4%) than the conventional management group (54.4%), which was a significant risk difference of -15.1% and adjusted odds ratio of 0.56%, P = 0.03. The rate of symptomatic intracerebral hemorrhage was 9% in the intensive group and 8.1% in the conventional group (P = 0.82, nonsignificant). Death rate related to the stroke within three months occurred in 7.7% of the intensive group and 5.4% of the conventional group. This was not a statistically significant difference in mortality. The investigators concluded that, among patients who were successfully reperfused with endovascular thrombectomy, intensive blood pressure management with lowering of systolic blood pressure < 140 mmHg led to a worse functional outcome at three months compared to conventional blood pressure management and supported maintaining the current recommended standards for blood pressure management following endovascular thrombectomy.
