New findings challenge the practice of rapidly lowering blood pressure in acute ischemic stroke to allow rapid thrombolysis.[1]
The observational group study showed that patients treated in hospitals that followed the guideline-recommended practice of rapidly lowering blood pressure did not have better outcomes (and in fact showed a trend toward worse outcomes) than those treated in hospitals that did not reduce blood pressure. blood pressure, although that meant fewer patients received thrombolysis.
“We found insufficient evidence to recommend active blood pressure reduction in ischemic stroke patients who have blood pressure levels that exceed guidelines but who are otherwise eligible for thrombolytic therapy,” said the study’s lead author, Dr. Nyika Kruyt, Ph. D., from Leiden University Medical Center, the Netherlands.
“Our results suggest that if the blood pressure is too high for thrombolysis, then it is better to wait and treat with this process only if the blood pressure falls spontaneously,” Dr. Kruyt told Medscape Medical News.
The findings were presented at the annual meeting of the European Stroke Organization Conference (ESOC) and were also published online on May 16 in The Lancet Neurology.[1]
Guide without evidence?
Because of concerns that high blood pressure increases the risk of intracerebral hemorrhage after thrombolysis, the original trials evaluating thrombolysis in stroke established an arbitrary threshold of 185/110 mm Hg, which has been incorporated into guidelines on ictus. These trials warned against rapidly lowering blood pressure, which is not included in the guidelines.
Therefore, most stroke centers tend to rapidly reduce blood pressure in patients who have values >185/110 mm Hg and who are otherwise eligible for thrombolysis, the researchers noted. Because thrombolysis is more effective the sooner it is given, there is some urgency to quickly reduce blood pressure when patients first arrive at the hospital.
“But there has never been any evidence of blood pressure reduction with intravenous antihypertensives before thrombolysis, and some centers have never adopted this approach because of concerns that a rapid decrease in blood pressure could reduce brain perfusion to the bloodstream. same time that ischemia is already present,” Dr. Kruyt noted.
However, if blood pressure is reduced rapidly, 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, the researchers compared the outcomes of 853 patients treated at 27 stroke centers in the Netherlands with an active blood pressure-lowering strategy, versus 199 patients treated at 10 hospitals without such a strategy.
The baseline characteristics of the participants in the two groups were similar.
The results showed a strong trend toward worse outcomes in participants whose blood pressure was reduced, with a odds ratio adjusted (aOR) for a change towards a worse functional outcome at 90 days on the modified Rankin scale of 1.27 (confidence interval [IC] 95%: 0.96 to 1.68).
This was despite the fact that many more patients whose blood pressure was reduced received thrombolysis (94% vs. 52% of those without blood pressure reduction) and had shorter treatment times, with average door-to-needle times of 35 minutes (vs. to 47 minutes among those without blood pressure reduction).
Symptomatic intracranial hemorrhage occurred in 5% of the active blood pressure lowering group versus 3% of those whose blood pressure was not lowered (aOR: 1.28; 95% CI: 0.62 to 2.62 ).
Reconsider clinical guidelines?
These results are consistent with those of the INTERACT4 trial, which was also presented at the European Stroke Organization Conference 2024. That trial showed a harmful effect of lowering blood pressure in the ambulance in patients with acute ischemic stroke, but a beneficial effect in patients with hemorrhagic stroke.
“I think clinical guidelines need to be reconsidered after these studies and we should refrain from actively lowering blood pressure in patients with acute ischemic stroke,” Dr. Kruyt said.
However, he acknowledged that not rapidly reducing blood pressure will mean that fewer patients will be able to receive thrombolysis within the 4.5-hour treatment period.
Dr. Kruyt estimated that the combination of being eligible for thrombolysis with the only exclusion criterion of blood pressure >185/110 mm Hg applies to approximately 10% to 15% of patients.
“If we have a watch-and-wait policy, then about half of those patients will still be treated with thrombolysis within the 4.5-hour limit, but later than if blood pressure was lowered with intravenous antihypertensives,” he added.
Dr. Kruyt noted that there has never been a randomized trial on the practice of lowering blood pressure so thrombolysis can be administered.
“The blood pressure level of 185/110 mmHg is an arbitrary threshold that was chosen for the original thrombolysis and stroke trials,” he said. “I think we need trials to investigate whether we can safely give thrombolysis to patients with blood pressure levels higher than this, without needing to rapidly lower the pressure.”
Caution is advised
Discussing the TRUTH study at the European Stroke Organization Conference, Dr. Guillaume Turc, professor of neurology at Sainte-Anne Hospital, Paris, France, said he thought the findings were “very striking.”
Dr. Simona Sacco, a professor of neurology at the University of L’Aquila, Italy, called the result surprising but 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 we change clinical practice,” he said.
In an accompanying editorial, Dr. Verónica Olavarría, Clínica Alemana Universidad del Desarrollo, Santiago, Chile, also suggested that the trial should be interpreted with caution, because there was “insufficient evidence for a definitive conclusion.”[2]
Either way, Dr. Kruyt noted that although 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 from intensive blood pressure control 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 results with blood pressure reduction in acute ischemic stroke patients undergoing thrombectomy.
“All of these studies show similar signals along the entire acute ischemic stroke timeline. The results are very consistent with each other. I think this reinforces our findings,” Dr. Kruyt said.
“With these data, I think the guidelines should be revised, and until randomized data are available showing that it is beneficial to lower blood pressure in patients with acute ischemic stroke so that they receive early thrombolysis, we should refrain from doing so,” he added.
INTERACT4 researcher Dr. Craig Anderson, 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 and both suggest harm with lowering blood pressure in acute ischemic stroke. These two together are going to shake the cage around blood pressure control in patients with acute ischemic stroke,” Dr. Anderson said.
The TRUTH study was funded by a grant from Fonds NutsOhra. Dr. Kruyt has declared that he has no relevant financial relationships. Dr. Olavarría reported receiving a grant from Boehringer Ingelheim for the RECCA registry and honoraria from Novo Nordisk.
This content was originally published in the edition in English from Medscape.