Combining aspirin and clopidogrel (known commercially as Plavix) was thought to hold promise in preventing recurring lacunar strokes – the death of brain cells caused by a narrowing of small blood vessels – by reducing the formation of clots in arteries supplying the brain.
Dr. Oscar Benavente, a UBC professor of neurology and research director of the Stroke and Cerebrovascular Health Program at Vancouver Coastal Health, sought to determine if a combination of clopidogrel and aspirin –another anti-clotting agent that is used to prevent strokes — would lower the recurrence of lacunar strokes more than aspirin alone. The study involved 3,020 patients from 82 sites in North America, Latin America, and Spain who were followed for several years.
The results, published August 30 in the New England Journal of Medicine, found that the two-drug combination (known as “dual antiplatelet therapy”) did not significantly reduce the risk of recurrent stroke, and significantly increased the risk of bleeding and death, compared to people who were taking aspirin alone or aspirin combined with a placebo.
“Previous randomized trials assessing the effect of clopidogrel alongside aspirin did not show an overall increase in mortality, so our results are a bit surprising,” said Dr. Benavente, who is also a member of the Brain Research Centre at UBC and the VCH Research Institute. “The results of our research support the current guidelines for secondary stroke prevention: the use of either aspirin or clopidogrel, or the approved combination therapy of aspirin and dipyridamole [known commercially as Persantine].”
BACKGROUND | Lacunar strokes
Lacunar strokes: Also known as small subcortical strokes, they account for 25 percent of ischemic strokes – the death of brain tissue caused by a blockage of small penetrating arteries. They usually strike a person repeatedly, tend to occur at a younger age than other strokes, and are particularly frequent in Hispanics. They usually cause mild disability but are the leading cause of cognitive impairment and dementia.
Study safety: The trial of aspirin and clopidogrel was ended prematurely because of the possible harm and lack of efficacy. It was monitored by an independent data and safety monitoring committee selected by the U.S. National Institute of Neurological Disorders, which funded the study.
Ongoing research: Dr. Benavente is leading a $66-million international study funded by the U.S. National Institutes for Health seeking to reduce recurrence of lacunar strokes and to minimize the consequences. Additional results are expected later this year, which will help determine the optimal combination of blood pressure control and anti-clotting therapy. More information on the Secondary Prevention of Small Subcortical Strokes project (SPS3) is available at www.sps3.org.
Brain Research Centre: Comprising more than 225 investigators with multidisciplinary expertise in neuroscience research ranging from the test tube, to the bedside, to industrial spin-offs. The Centre is a partnership of the UBC Faculty of Medicine and VCHRI. www.brain.ubc.ca
UBC Faculty of Medicine: Providing innovative programs in the health and life sciences, and teaching students at the undergraduate, graduate and postgraduate levels. Its faculty members received $295 million in research funds, 54 percent of UBC’s total research revenues, in 2010-11. For more information, visit www.med.ubc.ca.
Vancouver Coastal Health & Vancouver Coastal Health Research Institute: Providing a full range of health care services, ranging from hospital treatment to community-based residential, home health, mental health and public health services, to residents of Vancouver, North Vancouver, West Vancouver, Richmond, and in the coastal mountain communities. VCH Research Institute is the research body of Vancouver Coastal Health. In academic partnership with the University of British Columbia, VCHRI brings innovation and discovery to patient care. For more information, visit www.vch.ca or www.vchri.ca.