CHIPPS: Immediate Blood Pressure Lowering After Stroke May Reduce Mortality

Caroline Cassels

February 25, 2008

February 25, 2008 (New Orleans, Louisiana) — Blood pressure lowering in the 60% to 70% of patients who become hypertensive immediately following acute stroke reduces 3-month mortality without serious adverse effects or increasing stroke severity, a randomized pilot study suggests.

Late-breaking scientific results from the hypertension cohort of the Control of Hypertension and Hypotension Immediately Post Stroke (CHIPPS) study, presented here at the American Stroke Association's (ASA's) International Stroke Conference 2008, showed patients who received active blood pressure–lowering treatment — either lisinopril or labetalol — had lower mortality at 3 months compared with subjects in the placebo group.

The study, which included 179 randomized patients, found those in the placebo group were more than twice as likely to die 3 months after stroke compared than those on active treatment.

"These are very small numbers, and I don't want to hang too much on these results. Nonetheless, I think it's a very encouraging result that will allow us to go forward and do a much larger phase 3 study to see whether the benefits seen in this phase 2 study can be replicated," principal investigator John Potter, DM, from the University of East Anglia, in the United Kingdom, said at a press conference.

Treatment Gamble

According to Dr. Potter, the current ASA guidelines suggest a systolic blood pressure of 200 to 220 mm Hg following acute stroke should be treated if patients are stable within 24 hours of the event. In the United Kingdom, said Dr. Potter, treatment is much more of a "gamble" and largely left to the discretion of the individual physician.

The study included 179 adult patients who had suffered a hemorrhagic or ischemic stroke within the previous 36 hours and had hypertension, defined as a systolic blood pressure greater than 160 mm Hg.

Nondysphagic patients received titrated doses of oral lisinopril (an ACE inhibitor), labetalol (an alpha beta blocker), or matching placebo. Target systolic blood pressure was 145 to 155 mm Hg or a drop in systolic blood pressure of 15 mm Hg or greater.

Dysphagic patients received similar titrated doses of sublingual lisinopril, intravenous labetalol, or placebo. According to Dr. Potter, this study marks the first time sublingual lisinopril has been used as an antihypertensive treatment — either in a stroke or nonstroke population.

The study's primary outcome was death or dependence at 2 weeks, with the secondary outcome of 3-month mortality.

Clinical Recommendations Premature

The active treatment group experienced a greater drop in systolic blood pressure within the first 24 hours compared with placebo – 21 mm Hg vs 11 mm Hg. Similarly, patients on active treatment also had a significantly greater fall in systolic blood pressure at 2 weeks than the placebo group (31 mm Hg vs 24 mm Hg).

At 2 weeks poststroke, death and dependence were similar among the active treatment and placebo groups, at 61% and 59%, respectively, and not statistically significant.

At 3 months, the active treatment group had much lower mortality, with a hazard ratio of 2.2 for increased risk of death in the placebo group.

In addition, said Dr. Potter the active treatment had a very good adverse-effect profile, with no difference in discontinuation rates between active treatment and placebo groups. In addition, and most important, active treatment did not cause an early increase in stroke severity.

However, he added, it is premature to make any clinical recommendations regarding blood pressure lowering immediately following stroke based on these results.

Falling Through the Cracks

Philip Gorelick, MD, from the University of Illinois College of Medicine, in Chicago, and spokesperson for the ASA, agreed with Dr. Potter's conclusion. However, he added, if these results can be replicated in a larger phase 3 study, the findings could have a major impact on stroke guidelines.

Dr. Gorelick pointed out that treating high blood pressure is 1 of the most important aspects of preventing primary and secondary stroke. However, he added, no one knows for sure what to do about hypertension following ischemic stroke.

"The concern is that if you suddenly drop blood pressure, the perfusion will drop and you may lose brain tissue. So we have been quite liberal about letting it remain high after an acute stroke," he told Medscape Neurology & Neurosurgery.

The finding that it is safe to initiate or resume blood pressure–lowering medications immediately following stroke may help maintain a continuum of care, which is an issue with many stroke patients.

"This study is important because many doctors are concerned about lowering blood pressure in the early period following stroke. As a result, a considerable number of patients end up falling through the cracks and do not receive antihypertensive medications for extended periods of time, which puts them at increased risk of secondary stroke and, in many cases, cardiac events," Dr. Gorelick told Medscape Neurology & Neurosurgery.

"This exploratory study has provided us with good basis for a larger and more definitive trial. If it's dangerous, we won't do it. If it's not dangerous, then let's start treating patients early on in the controlled hospital setting, which will allow us to fine-tune their [blood pressure] levels, get them on treatment, and provide them with education so they don't fall through the cracks," he added.

The study investigators report no disclosures.

International Stroke Conference 2008: Abstract LB2. Presented February 22, 2008.

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