An interview with Prof. Kazuo Kitagawa, MD, PhD, Department of Neurology, Tokyo Women’s Medical University, Tokyo, Japan, about the optimal blood pressure goal for secondary stroke prevention.
Interviewed by Dr. Mohammad Anadani, MD, neurocritical care fellow, Washington University, St. Louis, MO.
They will be discussing the article “Effect of Standard vs Intensive Blood Pressure Control on the Risk of Recurrent Stroke: A Randomized Clinical Trial and Meta-analysis,” published in JAMA Neurology.
Dr. Anadani: First, I want to thank Prof. Kitagawa for agreeing to the interview. Prof. Kitagawa is the lead investigator of the RESPECT trial, which investigated the optimal blood pressure goal for secondary stroke prevention.
Could you please share with the readers the rationale behind the RESPECT trial and summarize the key findings of the trial?
Dr. Kitagawa: Although the SPRINT trial recently demonstrated that a systolic blood pressure (BP) target of <120 mmHg was superior to <140 mmHg for preventing vascular events, no evidence was published about what is the optimal blood pressure target in the secondary stroke prevention.
In the RESPECT Study that included 1263 patients with a history of stroke, intensive blood pressure control to less than 120/80 mmHg tended to reduce stroke recurrence compared with standard blood pressure control (<140/90 mmHg). When this finding was pooled with the results of prior trials of intensive blood pressure control for secondary stroke prevention in an updated systematic review, intensive blood pressure treatment significantly reduced stroke recurrence by 22%. In conclusion, intensive blood pressure control to less than 130/80 mmHg is recommended for secondary stroke prevention.
Dr. Anadani: Interestingly, only 31% of patients in the intensive group achieved the blood pressure target, which highlights the difficulty of achieving intensive blood pressure control in outpatient settings. Why do you think only a third of patients achieved blood pressure goals? Do you think that this factor affected trial results? Would you expect the achievement rate to be higher or lower in routine practice?
Dr. Kitagawa: We had set up step-wise titration for control of blood pressure in the protocol. During the study, we always encouraged each investigator to control blood pressure based on the assigned group. However, the clinical guideline in our country during the period of the RESPECT Study (Shimamoto K, Ando K, Fujita T et al., The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2014). Hypertens Res. 2014;37:253-390) recommended less than 150/90 mmHg as an initial target level in elderly people. Because mean age of our patients were 67 years old, the statement of the guideline might make physicians unwilling to lower blood pressure aggressively in elderly people.
I think small difference of blood pressure (6.5/3.3 mmHg) between two groups would result in only non-significant difference.
The target blood pressure in the intensive group was less than 120/80 mmHg; however, based on meta-analysis which included other trials of target BP 130/80 mmHg, we concluded target BP is less than 130/80 mmHg for secondary stroke prevention. Once evidence was published, I think blood pressure in most patients with a history of stroke would be controlled to less than 130/80 mmHg.
Dr. Anadani: The trial showed a possible benefit of intensive blood pressure control in the prevention of hemorrhagic strokes, but not ischemic strokes. Was the etiology of hemorrhagic stroke recorded? Was the benefit of intensive blood pressure control similar across hemorrhagic stroke etiologies?
Dr. Kitagawa: In our country, the etiology of hemorrhagic stroke is mostly hypertensive. In other words, we have few hemorrhagic patients with cerebral amyloid angiopathy (less than 10% in all hemorrhagic stroke).
Dr. Anadani: The RESPECT trial proved that intensive blood pressure control is safe with no increased risk of cerebrovascular events or kidney injury. I was surprised, however, to see that pneumonia rate was significantly higher in the intensive group (2.8% vs. 1.1%, P=0.04). Do you have any explanation for this finding?
Dr. Kitagawa: Actually, we observed more patients with pneumonia in the intensive treatment group than in the standard treatment group. However, this record was only picked up in serious adverse events; therefore, we do not have enough information about the etiology of pneumonia, for example, aspiration pneumonia or not. We might need to be more careful about pneumonia in future trial for patients with a history of stroke.
Dr. Anadani: The RESPECT trial excluded patients with stroke (ischemic or hemorrhagic) less than 30 days from randomization. Could you please share with the readers the rationale behind excluding those patients?
Dr. Kitagawa: When the RESPECT Study was started, clinical international guideline did not recommend blood pressure lowering in acute stage of ischemic stroke. That is why we excluded patients with stroke less than 30 days from randomization.
Dr. Anadani: The RESPECT trial included only Japanese centers. Does this affect the generalizability of its findings?
Dr. Kitagawa: As we mentioned in the Discussion of the paper, we enrolled only Japanese patients. The percentage of hemorrhagic stroke in Japan and Asian countries is higher than that in western countries. Intensive blood pressure lowering seems to be more beneficial in prevention of hemorrhagic stroke than in ischemic stroke. Thus, intensive blood pressure lowering might be more beneficial in Asian people than in Caucasian people.
Dr. Anadani: How do you think the RESPECT trial could change the current clinical practice?
Dr. Kitagawa: Once the RESPECT Study was published, evidence of BP target to less than 130/80 mmHg for secondary stroke prevention is proved. Most physicians will start to control blood pressure to less than 130/80 mmHg in patients with a history of stroke.
Dr. Anadani: What advice do you have for investigators interested in further investigating the field of blood pressure and stroke research?
Dr. Kitagawa: Target of blood pressure might be different among stroke subtypes. Therefore, future clinical trial might focus on each stroke subtype for more aggressive lowering of blood pressure. For example, we do not know how we manage blood pressure in patients with cerebral small vessel disease, or cerebral aneurysm. I think more aggressive treatment (not <130/80 mmHg, but <120/80 mmHg) would be beneficial in such patients.