Guidelines for rapid blood pressure reduction in stroke patients

New discovery questions the practice of rapidly lowering blood pressure (BP) during the acute phase Ischemic stroke Allows rapid thrombolysis.

A cluster observational study showed that patients treated at hospitals that followed guideline-recommended practices for rapid blood pressure reduction did not do better than patients treated at hospitals that did not lower blood pressure and showed a trend toward worse outcomes. Patients received thrombolytic therapy.

“We found that there is insufficient evidence to recommend aggressive blood pressure lowering for ischemic stroke patients whose blood pressure levels exceed guidelines but who are otherwise eligible for blood pressure lowering.” . Thrombolytic therapy“Concluded lead study author Nika Kluyt, MD, PhD, from Leiden University Medical Center in the Netherlands.

“Our results suggest that if blood pressure is too high for thrombolytic therapy, it is best to wait and treat with thrombolytic therapy only when blood pressure falls spontaneously.” Clute said. Medscape Medical News.

The findings were presented at the following conference: European Stroke Organization Congress (ESOC) Annual Meeting and again Publish online on may 16th lancet neurology.

Guidelines without evidence?

There is concern that high blood pressure increases the risk of disease. intracerebral hemorrhage After thrombolysis, the first trials evaluating thrombolysis in stroke set an arbitrary threshold of 185/110 mmHg, which has been incorporated into stroke guidelines. These trials warned against rapid blood pressure drops, which are not included in the guidelines.

Therefore, most stroke centers tend to rapidly lower blood pressure in patients who have values ​​above 185/110 mmHg and would otherwise be candidates for thrombolytic therapy, the researchers noted. Because thrombolytic therapy is more effective the sooner it is administered, it is imperative that blood pressure be lowered quickly when the patient first arrives at the hospital.

“But there has never been any evidence that IV fluids lower blood pressure.” [intravenous] Antihypertensive drugs must be administered before thrombolytic therapy, and some institutions do so because of concerns that a sudden drop in blood pressure when ischemia is already present may reduce cerebral perfusion. We are not taking this approach,” Kruyt said.

However, if blood pressure falls rapidly, the 4.5-hour time limit may be exceeded, increasing the likelihood that the patient will not receive thrombolytic therapy.

In the prospective observational TRUTH study, researchers studied 853 patients treated with aggressive blood pressure-lowering strategies at 27 Dutch stroke centers and without such strategies at 10 hospitals. Outcomes of 199 patients were compared.

Baseline characteristics of participants in the two groups were similar.

Results showed a strong trend towards worse outcomes in participants with reduced blood pressure, with adjusted odds ratios (aORs) trending towards worse 90-day functional outcomes. Modified Rankine Scale 1.27 (95% CI, 0.96-1.68).

This means that more patients whose blood pressure drops receive thrombolytic therapy (94% vs. 52% of patients whose blood pressure does not drop) and the average door-to-needle time is 35 minutes (vs. 47 minutes) and treatment This was despite the fact that the time was reduced. among those whose blood pressure did not fall).

have symptoms intracranial hemorrhage It occurred in 5% of the group that actively lowered blood pressure and 3% of the group that did not lower blood pressure (aOR, 1.28; 95% CI, 0.62-2.62).

Revisit the guidelines?

These results are INTERACT4 trial version, which was also presented at the ESOC 2024 conference. The trial showed that lowering blood pressure in the ambulance for acute ischemic stroke patients had a detrimental effect, but a beneficial effect for stroke patients. hemorrhagic stroke.

“These studies warrant a reexamination of guidelines, and we believe that aggressive blood pressure lowering should be discouraged in patients with acute ischemic stroke,” Kluyt said.

However, he acknowledged that unless blood pressure is lowered quickly, fewer patients will be able to receive thrombolytic therapy within the 4.5-hour treatment window.

Kruyt estimated that the combination of eligibility for thrombolytic therapy and the only exclusion criterion of blood pressure >185/110 mmHg applies to about 10% to 15% of patients.

“If we had a wait-and-see policy, about half of the patients would still receive thrombolytic therapy within the 4.5-hour limit, but it would be slower than if they lowered their blood pressure with intravenous antihypertensives.” he added.

Kluyt pointed out that no randomized trials have ever been conducted on the practice of lowering blood pressure in order to administer thrombolytic therapy.

“Blood pressure levels of 185/110 mmHg are the arbitrary thresholds chosen in the original thrombolytic stroke trial,” he said. “I think we need trials to see if thrombolytic therapy can be safely administered to patients with higher blood pressure levels without lowering the pressure too rapidly.”

Caution is required

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

Dr Simona Sacco, professor of neurology at the University of L'Aquila in Italy, said the results were surprising, but advised caution when acting on the findings.

“This study is not a randomized trial, so I don't think it can change practice or guidelines. Yes, it can generate a hypothesis, but more research is needed before changing clinical practice,” she said. I commented.

in accompanying editorialDr. Veronica Olavarria of the Universidad Alemana del Desarrollo clinic in Santiago, Chile, also suggested that the trial should be interpreted with caution as there was “insufficient evidence to draw a final conclusion.”

However, Kruyt noted that although the TRUTH study was not a randomized trial, the results are consistent with those of recent randomized trials such as INTERACT4.

He added: Enchanted The trial also showed no benefit of intensive blood pressure control immediately after thrombolysis in mild to moderate stroke, and even suggested harm in severe stroke. and other trials (optimal blood pressure and Enchanted 2/MT) It has been shown that lowering blood pressure in patients with acute ischemic stroke undergoing thrombectomy worsens outcome.

“All of these studies show similar signs throughout the entire course of acute ischemic stroke. The results are very consistent with each other, and we think this confirms our findings,” Kluyt said. he said.

“In light of this data, I think the guidelines should be revised. Until randomized data are available that show there is a benefit to lowering blood pressure and getting earlier thrombolytic therapy in patients with acute ischemic stroke, we should refrain from lowering blood pressure,” he added.

Craig Anderson, MD, PhD, an INTERACT4 researcher at the George Institute for Global Health in Sydney, New South Wales, Australia, agreed.

“The TRUTH study gives the same message as INTERACT4. They are completely consistent, and both suggest harm from lowering blood pressure in acute ischemic stroke. It's going to shake the cage around blood pressure control in patients,'' Anderson said.

The TRUTH study was funded by a grant from Fonds NutsOhra. Mr. Crute has not reported any relevant financial disclosures. Mr. Olavarria reported that he received grants for the RECCA registry from Boehringer Ingelheim and honoraria from Nordisk.