ARTICLE IN BRIEF
Athough the differences were not signicant in a randomized, open-label trial, there were 13 percent fewer subsequent lacunar strokes and 63 percent fewer intracerebral hemorrhages among patients who lowered their blood pressure to 130 mm Hg or lower. Moreover, there was an overall reduction of 19 percent in all secondary strokes in the lower target arm.
Small vessel stroke patients who reduce their systolic blood pressure below 130 mm Hg may significantly protect themselves against a subsequent intracerebral hemorrhage or another lacunar stroke, according to a randomized, open-label study conducted in North America, South America, and Europe. The findings, initially presented at the American Stroke Association's International Stroke Conference last February, were published in the Aug. 10 issue of The Lancet.
In the Secondary Prevention of Small Subcortical Strokes (SPS3) Trial, researchers divided 3,020 patients into two target groups of blood pressure control — a lower target of systolic blood pressure below 130 mm Hg and a higher target of between 130 mm Hg and 149 mm Hg.
Although there was no statistically significant difference in the likelihood of any secondary strokes among patients in either group, there were 13 percent fewer subsequent lacunar strokes and 63 percent fewer intracerebral hemorrhages among patients who lowered their blood pressure to 130 mm Hg or lower. Moreover, there was an overall reduction of 19 percent in all secondary strokes in the lower target arm.
After one year, patients in the lower blood pressure group had an average systolic blood pressure of 126.8 mm Hg while those in the higher target group averaged 137.8 mm Hg.
The findings may provide physicians with more definitive blood pressure targets for patients with lacunar strokes, according to lead investigator Oscar Benavente, MD, professor and research director of stroke at the University of British Columbia in Vancouver, British Columbia, Canada.
“We well understand that reducing blood pressure can protect individuals against first stroke and recurrent events, but until now we have not known how low it needs to go. Our study has provided some answers,” he told Neurology Today in a telephone interview.
The study enrolled patients who had previously suffered a small subcortical or lacunar stroke, and at the start of the study, the two treatment groups had similar systolic blood pressure. However 75 percent of the subjects had a history of high blood pressure, 37 percent had a history of diabetes, and 20 percent were tobacco users. The average follow-up lasted about 3.7 years.
There were 277 first recurrent strokes during follow-up. Among these were 243 ischemic events (86 percent) of which 173, or 71 percent, were recurrent lacunar strokes and 14 percent were intracranial hemorrhages, including intracerebral, subdural or epidural, and subarachnoid events.
The annualized rate of recurrent strokes in the higher target group was 2.7 percent per patient year, compared with 2.2 percent in the lower-target group, a finding that was not statistically significant. Nonetheless, Dr. Benavente told Neurology Today that it was feasible to achieve the trial's blood pressure targets, and that treatment was both safe and well tolerated, although patients in the lower target group had more fainting episodes.
“Achieving a systolic target of 135 mm Hg may not be enough,” he said. “Getting the level down to 130 mm Hg may offer greater clinical benefits. I would tell my patients who had this type of stroke to get their BP below 130,” he said.
Although the study was not designed to analyze differences in the blood pressure-lowering medicines, patients in the lower target group took more medications, especially beta blockers, and the distribution of medications were not the same between the groups.
Subcortical stroke accounts for an estimated 25 percent of all ischemic strokes and occurs when small arteries deep within the brain are affected.
The National Institutes of Health-National Institute of Neurological Disorders and Stroke provided funding for the trial.
“The SPS 3 trial shows that reduction of systolic blood pressure to a target of less than 130 mm Hg in the weeks after lacunar stroke is well tolerated, safe, and effective in reducing the rate of recurrent stroke, particularly hemorrhagic stroke,” wrote Graeme J. Hankey, MD, clinical professor of neurology at the University of Western Australia School of Medicine and Pharmacology in Perth, and head of the stroke unit at Royal Perth Hospital, in an accompanying editorial.
Although the reduction in secondary strokes was less than that reported in previous trials with similar systolic blood pressure lowering, several factors might explain the difference, according to Dr. Hankey.
First, he noted that reducing systolic blood pressure could be less effective in preventing secondary strokes after lacunar ischemic stroke than for all types of ischemic stroke, even though limited data from previous trials indicate that lowering blood pressure has a consistent effect for all subtypes.
The study's estimate of the reduction might also have been confounded by greater use of beta blockers in the lower-target group, he said, noting that beta blockers can increase variability in blood pressure levels at different times, thereby increasing all-stroke risk. He also said that the association between systolic blood pressure and stroke risk might be weaker with systolic blood pressures below 130 mm Hg than with higher levels.
“When the SPS3 results are viewed in the context of all evidence for lowering of blood pressure in individuals with previous stroke, the 19 percent rate reduction for all recurrent strokes seems likely to be real rather than a chance observation.”
Scott E. Kasner, MD, professor of neurology at the University of Pennsylvania in Philadelphia, is current chair of the American Heart/Stroke Association Council's Scientific Statements Oversight Committee.
“I think the results should change the guidelines,” he told Neurology Today. “We have never really had specific blood pressure targets based on trial evidence. While imperfect, SPS3 gives us a basis for recommending a target blood pressure benchmark of less than 130 mm Hg in patients with lacunar stroke.”
LINK UP FOR MORE INFORMATION:
•. The SPS3 Study Group. Blood-pressure targets in patients with recent lacunar stroke: the SPS3 randomised trial. The Lancet
2013; 382(9891): 507–515. E-pub 2013 Aug 10.
•. Benavente OR, White CL, Pearce L, et al. The Secondary Prevention of Small Subcortical Strokes (SPS3) study. Int J Stroke
•. Furie KL, Kasner SE, Adams RJ, et al. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke
2011; 42: 227–276.
•. Rashid P, Leonardi-Bee J, Bath P. Blood pressure reduction and secondary prevention of stroke and other vascular events: a systematic review. Stroke
•. Chapman N, Huxley R, Anderson C, et al.. for the Writing Committee for the PROGRESS Collaborative Group. Effects of a perindopril-based blood-lowering regimen on the risk of recurrent stroke according to stroke subtype and medical history: the PROGRESS Trial. Stroke