The blood pressure paradox in acute ischaemic stroke “lies in the modifying effect of reperfusion”

Xin Cheng and Dr. Dong

The relationship between blood pressure and outcomes is highly dependent on reperfusion, conclude Lang Hong (Fudan University, Shanghai, China) and colleagues on behalf of the INSPIRE group. Recently published in Annals of Neurology, the study denotes that “active blood pressure-lowering treatment may be inappropriate in acute ischaemic stroke patients prior to reperfusion treatment”. Through these findings, the authors shed light on why rapidly lowering blood pressure beyond recommendations—outlined in the ENCHANTED trial (see above)—failed to limit post-stroke disability.

The authors noted that thus far, positive, negative, and even U-shaped correlations between blood pressure and outcome have all been described. “Especially [in patients] with large vessel occlusion or a proximal stenosis, higher blood pressure may help sustain collateral perfusion […], yet high blood pressure may also increase the risk of complications”, write the authors.

Aiming to depolarise expert opinion on the matter, Hong et al set out to investigate the association between post-stroke baseline blood pressure, collateral flow, infarct growth, and clinical outcomes in acute ischaemic stroke patients with large vessel occlusion or stenosis, using baseline CT perfusion to measure collateral flow.

Patients presenting within 12 hours of symptom onset from seven medical centres based in China, Australia, and Canada between 2011 and 2017 were prospectively recruited for the International Stroke Perfusion Imaging Registry (INSPIRE). In total, 306 patients (mean age: 69.5 [60–79]; median baseline NIHSS: 12 [7–16]; 59.8% male) that identified with large vessel occlusion/stenosis with baseline multimodal CT, follow-up imaging and complete clinical profiles were included.

Through a multivariate analysis, the authors observed that with every increase of 10mmHg in baseline systolic blood pressure, the odds of achieving an excellent functional outcome decreased by 12% (OR= 0.88; 95% CI: 0.78, 0.995; p=0.048). In contrast, increased baseline blood pressure was associated with better collateral flow, where every 10mmHg increase was associated with an increase in the delay time ratio.

Lastly, the paper detailed a subgroup analysis carried out on patients with major reperfusion, where Hong et al report that in such patients: “Higher baseline blood pressure was associated with decreased infarct growth and a better clinical outcome.”

Providing an explanation for the “paradox”—high blood pressure leading to smaller infarct core in acute ischaemic stroke, the authors write that it “lies in the modifying effect of reperfusion”. They add: “Initially, higher baseline blood pressure may improve collateral flow to sustain penumbra and prevent the core from expanding. Patients with good collaterals are likely to be ‘slow infarct core growers’”.

Yet, Hong and colleagues acknowledge that in patients with good collateral flow, “if there is subsequent reperfusion, there may be smaller infarct volume, and hence better clinical outcomes. However, if the occlusion persists and reperfusion does not occur, eventually the infarct core will grow […], leading to a worse clinical outcome”.

With these findings in mind, co-corresponding author Xin Cheng (Fudan University, Shanghai, China) provided an explanation for why the recent ENCHANTED trial failed to demonstrate superiority to guideline-recommended blood pressure-lowering: “In ENCHANTED, intensive blood pressure lowering was initiated a median 20 minutes after the administration of intravenous thrombolysis, where tissue perfusion status was unknown and, indeed, presence of vessel occlusion was only documented in 9%”.

Speaking to NeuroNews, Cheng commented: “ENCHANTED and our recent study raised the intriguing hypothesis that in patients with acute large vessel occlusion, maintaining higher blood pressure to sustain collateral flow before reperfusion therapy, but then aggressively lowering blood pressure to prevent haemorrhagic transformation may be beneficial. To test this hypothesis, we need a well-designed randomised trial, which must include pre-treatment perfusion imaging of reperfusion status.”


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