Guidelines on Rapid BP Reduction in Stroke Challenged

New findings challenge the practice of rapidly lowering blood pressure (BP) in acute ischemic stroke to allow for speedy thrombolysis.

The observational cluster study showed that patients treated in hospitals that followed the guideline-recommended practice of rapidly reducing BP did no better — and actually showed a trend toward worse outcomes — than those treated in hospitals that did not lower BP, even though this meant fewer patient received thrombolysis. 

“We found insufficient evidence to recommend active blood pressure lowering in patients with ischemic stroke who have blood pressure levels exceeding the guidelines but are otherwise eligible for thrombolytic therapy,” senior study author, Nyika Kruyt, MD, PhD, Leiden University Medical Center, the Netherlands, concluded. 

“Our results suggest that if the blood pressure is too high for thrombolysis, then it is best to wait and only treat with thrombolysis if the blood pressure drops spontaneously,” Kruyt told Medscape Medical News.

The findings were presented at the European Stroke Organisation Conference (ESOC) Annual Meeting and also published online on May 16 in The Lancet Neurology. 

Guidelines Without Evidence?

Owing to concerns about high BP increasing the risk for intracerebral hemorrhage after thrombolysis, the original trials evaluating thrombolysis in stroke set an arbitrary threshold of 185/110 mm Hg, which has been incorporated into stroke guidelines. These trials cautioned against lowering BP rapidly, which is not included in guidelines. 

Most stroke centers therefore tend to rapidly lower BP in patients who have values> 185/110 mm Hg and who are otherwise eligible for thrombolysis, investigators noted. Because thrombolysis is more effective the earlier it is administered, there is some urgency to reduce the BP quickly when patients first arrive at the hospital. 

“But there has never been any evidence for the lowering of blood pressure with IV [intravenous] antihypertensives before thrombolysis, and some centers have never adopted this approach because of concerns that a rapid decline in blood pressure may reduce perfusion of the brain at a time when there is already ischemia present,” Kruyt noted. 

However, if BP is lowered quickly, there is a greater chance that patients will not be able to receive thrombolysis because the 4.5-hour time limit could be exceeded.

For the prospective, observational TRUTH study, researchers compared outcomes in 853 patients treated at 27 stroke centers in the Netherlands with an active BP-lowering strategy vs 199 patients treated at 10 hospitals with no such strategy. 

Baseline characteristics of participants in the two groups were similar. 

Results showed a strong trend toward worse outcomes in participants whose BP was lowered, with an adjusted odds ratio (aOR) for a shift toward a worse 90-day functional outcome on the modified Rankin Scale of 1.27 (95% CI, 0.96-1.68). 

This was despite the fact that many more patients whose BP was reduced received thrombolysis (94% vs 52% of those with no BP lowering) and had shorter times to treatment, with average door-to-needle times of 35 minutes (vs 47 minutes among those with no BP lowering). 

Symptmatic intracranial hemorrhage occurred in 5% of the active BP-lowering group vs 3% of those who did not have their BP lowered (aOR, 1.28; 95% CI, 0.62-2.62).

Reconsider Guidelines?

These results are consistent with those from the INTERACT4 trial, which was also presented at the ESOC 2024 meeting. That trial showed a harmful effect of lowering BP in the ambulance in patients with acute ischemic stroke, but a beneficial effect in patients with hemorrhagic stroke. 

“I think the guidelines need to be reconsidered after these studies and we should refrain from active blood pressure–lowering in patients with acute ischemic stroke,” Kruyt said. 

But he acknowledged that not rapidly lowering BP will mean fewer patients will be able to receive thrombolysis within the 4.5-hour treatment window.

Kruyt estimated that the combination of being eligible for thrombolysis, with the only exclusion criterion being BP> 185/110 mm Hg, applies to about 10%-15% of patients. 

“If we have a watch-and-wait policy, then about half of those patients will still get treated with thrombolysis within in the 4.5-hour limit but later than if blood pressure was reduced with IV antihypertensives,” he added. 

Kruyt noted that there has never been a randomized trial on the practice of BP lowering in order to be able to administer thrombolysis. 

“The 185/110 mmHg blood pressure level is an arbitrary threshold that was chosen for the original thrombolysis stroke trials,” he said. “I believe we need trials to investigate whether we can give thrombolysis safely to patients with higher blood pressure levels than this, without needing to rapidly reduce the pressure.”

Caution Advised

Discussing the TRUTH study at the ESOC meeting, Guillaume Turc, MD, professor of neurology at Sainte-Anne Hospital, Paris, said he thought the findings were “very thought provoking.”

Simona Sacco, MD, professor of neurology at the University of L’Aquila, Italy, said the result was surprising, but she advised caution in acting on this finding. 

“I don’t think this study can change practice or guidelines as it is not a randomized trial. Yes, it can generate a hypothesis, but we need more research before changing clinical practice,” she commented. 

In an accompanying editorial, Verónica Olavarría, MD, Clínica Alemana Universidad del Desarrollo, Santiago, Chile, also suggested the trial should be interpreted cautiously because there was “insufficient evidence for a definitive conclusion.”

But Kruyt noted that even though the TRUTH study was not a randomized trial, the results are in line with those of recent randomized trials such as INTERACT4.

He added that the ENCHANTED trial also showed no benefit of intensive BP management immediately after thrombolysis in mild to moderate stroke and even suggested harm in severe stroke. And other trials (OPTIMAL-BP and ENCHANTED2/MT) have shown worse outcomes with BP lowering in patients with acute ischemic stroke undergoing thrombectomy. 

“All these studies are showing similar signals throughout the whole timeline in acute ischemic stroke. The results are very much in line with each other. I think this strengthens our findings,” Kruyt said. 

“With this data, I think the guidelines should be revised, and until randomized data become available showing that reducing blood pressure in acute ischemic stroke patients in order for them to receive early thrombolysis is beneficial, then we should refrain from doing so,” he added.

INTERACT4 investigator Craig Anderson, MD, George Institute for Global Health, Sydney, New South Wales, Australia, agreed. 

“The TRUTH study gives the same message as INTERACT4. They are completely in line with each other, both suggesting harm with blood pressure lowering in acute ischemic stroke. These two together are going to rattle the cage around blood pressure control in acute ischemic stroke patients,” Anderson said. 

The TRUTH study was funded by a grant from Fonds NutsOhra. Kruyt reported no relevant financial disclosures. Olavarría reported receiving a grant from Boehringer Ingelheim for the RECCA registry and honoraria from Novo Nordisk.

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