Correcting Hypertension Cuts Poststroke Deaths


NEW ORLEANS — Treatment of dangerously high blood pressure in the period immediately following an acute stroke was associated with significantly reduced 3-month mortality in the randomized, placebo-controlled Control of Hypertension and Hypotension Immediately Post-Stroke trial.

Patients in the CHHIPS pilot trial did not immediately benefit from antihypertensive medications because the trial's primary end point—the rate of death and dependency at 2 weeks after the stroke—was no different between treated and placebo patients, even though the patients who received antihypertensive drugs had significantly greater decline in systolic blood pressure (SBP) within the first 24 hours than did those who received placebo, Dr. John Potter reported at International Stroke Conference 2008.

“We know that elevated blood pressure levels are important in predicting primary and secondary [stroke] prevention, but we don't know much about the relationship in the acute situation,” said Dr. Potter of the University of East Anglia, Norwich, England.

Current guidelines on the early management of adult acute ischemic stroke patients advise the use of antihypertensive medications in patients who are eligible for tissue plasminogen activator when their blood pressure is greater than 185 mm Hg/110 mm Hg and in other patients when their blood pressure is above 220 mm Hg/120 mm Hg (Stroke 2007;38:1655–711).

To determine if antihypertensive treatment would benefit acute stroke patients with a SBP greater than 160 mm Hg, Dr. Potter and his colleagues randomized 179 patients to receive the β-blocker labetalol, the ACE inhibitor lisinopril, or placebo.

The investigators enrolled patients older than 18 years with a stroke onset within 36 hours and stroke symptoms lasting more than 60 minutes. The patients had not previously been taking antihypertensive medications and had undergone neuroimaging within 72 hours of stroke onset. They excluded any patients who were undergoing thrombolysis as well as those who had impaired consciousness, hypertensive encephalopathy, prestroke dependency (a modified Rankin score of more than 3), any coexisting cardiac or vascular emergencies, contraindications to the study medications, or a primary intracerebral hemorrhage with a SBP greater than 200 mm Hg and/or a diastolic blood pressure greater than 120 mm Hg.

CT scans revealed that about 60% of patients in all groups had an ischemic stroke and about 15% had a primary intracerebral hemorrhage. No relevant abnormality could be seen in the other 25%.

The patients in all groups had a mean National Institutes of Health Stroke Severity score of 11. More than 90% of the patients had no history of stroke or transient ischemic attack. Nearly half of the patients in all groups were dysphagic.

After randomization, patients who could swallow oral medications received 5 mg lisinopril, 50 mg labetalol, or oral placebo. If after 4 hours, their SBP had not dropped to a target range of 145–155 mm Hg or decreased by at least 15%, then the investigators gave another round of the same doses. This was repeated at 8 hours if necessary. During the next 13 days, patients received 5–15 mg lisinopril, 50–150 mg labetalol, or placebo.

For dysphagic patients, the investigators combined sublingual lisinopril with an intravenous placebo, oral labetalol with sublingual placebo, or sublingual and intravenous placebos. Between days 1 and 5, dysphagic patients were switched to oral medications or received their medications through a nasogastric or percutaneous endoscopic gastrostomy tube. Lisinopril is not approved for use as a sublingual preparation, Dr. Potter noted.

Although the active treatment groups had a significantly greater mean decline in SBP than did placebo-treated patients within the first 24 hours (21 mm Hg vs. 11 mm Hg) and at 2 weeks (31 mm Hg vs. 24 mm Hg), there was no difference between the treatment groups in the rate of death and dependency at 2 weeks (61% vs. 59%). Dependency was defined as a modified Rankin score of more than 3.

Patients who received labetalol or lisinopril reached the target SBP outcomes in significantly higher proportions than did placebo patients at 4 and 8 hours after stroke, but not at 24 hours. There were no differences in neurological status between groups at 72 hours post stroke.

However, patients who received placebo had a 2.2 times higher risk of dying by 3 months than did actively treated patients, based on 12 deaths in the placebo group and 11 deaths in the active treatment groups, Dr. Potter said at the conference, which was sponsored by the American Stroke Association.

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