A Randomised Trial of Intensive versus Standard Blood-Pressure Control in Patients with a History of Stroke: The RESPECT Study

Background: Lowering of blood pressure after stroke reduces the risk of recurrent stroke, but the optimum target blood pressure level is unknown. We evaluated the effects of intensive versus standard blood-pressure-lowering regimen on the rate of recurrent stroke in patients with recent stroke. Methods: This randomised open-label trial included eligible patients in Japan who had recent, CT- or MRI-defined symptomatic ischaemic or haemorrhagic stroke. Patients were recruited between October 2010 and December 2015, and were randomly assigned 1:1 to blood pressure control to less than 140/90 mmHg, standard treatment, or to levels of less than 120/80 mmHg, intensive treatment, according to a parallel design. The primary endpoint was stroke including ischaemic stroke and intracerebral haemorrhage. Analysis was done by intention to treat. Findings: The trial was stopped early because of cessation of funding after the enrolment of 1263 out of the planned 2000 patients. Of these patients, 630 in the standard-treatment group and 633 in the intensive-treatment group were followed up for a mean of 3.9 (SD 1.5) years. Mean age was 67 (SD 8.8) years. After 1 year, the mean blood pressure was 132.0/77.5 mmHg (95% CI 130.9-133.0/76.6-78.3) in the standard target group and 123.7/72.8 mmHg (95% CI 122.6-124.8/72.0-73.7) in the intensive target group. Ninety-one first recurrent strokes occurred. Non-significant rate reductions were seen for all cases of stroke (hazard ratio 0.73, 95% CI 0.49-1.11, p=0.145); however, when this finding was pooled with the results of prior trials of intensive blood pressure lowering for secondary stroke prevention, the pooled risk ratio favoured intensive blood pressure control (relative risk 0.78, 95% CI 0.64-0.96, p= 0.016). Interpretation: Intensive blood pressure lowering does not significantly reduce stroke recurrence. The non-significant findings might be attributable to insufficient statistical power due to early termination of the trial or the modest difference in blood pressure level between groups. Nevertheless, the updated meta-analysis including this trial supports the target blood pressure of less than 130/80 mmHg in the secondary prevention of stroke. Clinical Trial Number: This study was registered with ClinicalTrials.gov, number NCT01198496. Funding Statement: Merck and Co. Inc., Bristol-Myers Squibb Company, Towa Pharmaceutical Co., Ltd, and Omron Corporation. Declaration of Interests: KK reports grants and personal fees from Daiichi Sankyo, grants and personal fees from Bayer Inc., grants and personal fees from Takeda Pharmaceutical, grants and personal fees from Nippon Boehringer Ingelheim, grants and personal fees from Kyowa Hakko Kirin, grants and personal fees from Sumitomo Dainippon Pharma, grants and personal fees from Astellas Pharma, grants and personal fees from Sanofi, outside the submitted work; YY has nothing to disclose; HA reports personal fees from Bayer, personal fees from Daiichi Sankyo, personal fees from Fukuda Denshi, personal fees from Kyowa Kirin, personal fees from Takeda, outside the submitted work; TM has nothing to disclose; NS has nothing to disclose; TK has nothing to disclose; KM has nothing to disclose; KeKa has nothing to disclose; KM reports personal fees from Bayer Yakuhin, personal fees from Otsuka Pharmaceutical, personal fees from Boehringer-Ingelhaeim, personal fees from AstraZeneca, personal fees from Pfizer, personal fees from Mitsubishi Tanabe Pharma Cooperation, personal fees from Japan Stryker, personal fees from Kowa, personal fees from Nihon Medi-Physics Co., personal fees from BM from Bayer Yakuhin, grants and personal fees from Kyowa Hakko Kirin, grants and personal fees from Mochida Pharmaceutical, grants and personal fees from Nippon Boehringer Ingelheim, grants and personal fees from Takeda Pharmaceutical, grants from Mitsubishi Tanabe Pharma, grants from Novartis Pharma, grants from Otsuka Pharmaceutical, grants from Pfizer Japan, grants from Shionogi & Co, grants from Teijin Pharma, outside the submitted work; YO reports grants and personal fees from Takeda Pharma, grants and personal fees from Daiichi-Sankyo, grants from Novartis Pharma, grants from Asterasu, personal fees from Dainippon-Sumitomo, personal fees from MSD, grants and personal fees from Bayer, grants and personal fees from Pfizer, grants and personal fees from Bohelinger, outside the submitted work; TK has nothing to disclose; YaOk has nothing to disclose; NT has nothing to disclose; GK has nothing to disclose; SaUm reports grants from Dainippon-Sumitomo, grants from Asteras, grants from Pfizer, grants from Nippon Boehringer Ingelheim, grants from Daiichi-Sankyo, grants from Takeda, personal fees from Nippon Boehringer Ingelheim, personal fees from Takeda, outside the submitted work; MM reports personal fees from Kowa Pharmaceutical Co Ltd, personal fees from Takeda Pharmaceutical Co Ltd, personal fees from Bayer Yakuhin, Ltd, personal fees from Sanofi KK, personal fees from Daiichi Sankyo Co0 Ltd, personal fees from Otsuka Pharmaceutical Co Ltd, personal fees from Astellas Pharma Inc, personal fees from Astra Zeneca KK, personal fees from Mochida Pharmaceutical Co, Ltd, personal fees from Sumitomo Dainippon Pharma Co Ltd, personal fees from Amgen Astellas BioPharma KK, personal fees from Esai Co, Ltd, personal fees from Pfizer Japan Inc, outside the submitted work; KS reports personal fees from Takeda, personal fees from Sumitomo Dainippon Pharma Co. Ltd., personal fees from MSD, personal fees from Astellas Pharma, personal fees from Boehringer-Ingelheim, personal fees from Bayer Yakuhin, outside the submitted work; SI reports personal fees from MSD, during the conduct of the study; grants and personal fees from Daiichi Sankyo, grants and personal fees from Takeda, grants and personal fees from Astellas, personal fees from Boehilinger-Ingerhaim, outside the submitted work; TS has nothing to disclose; KS reports personal fees from Dainippon-Sumitomo LTD, and Daiichi-Sankyo. Ethics Approval Statement: Participation required written informed consent, and approval was provided by the local ethics committees for human research.