SAN FRANCISCO — Long-term use of adenosine diphosphate receptor blockade therapy may be beneficial to patients with non-ST-segment elevation myocardial infarction who have had prior MI, stroke, or peripheral artery disease, Dr. Marc Sabatine said at a meeting sponsored by the California chapter of the American College of Cardiology.
In the few years since the ADP receptor blocker clopidogrel entered the medical armamentarium, studies have shown that acute therapy significantly reduces the risk of death, MI, or stroke in patients with non-ST-elevation acute coronary syndrome or ST-segment elevation MI (STEMI), and that the benefits appear within 24 hours. Other data show that this treatment is not useful for primary prevention of coronary syndromes and that there is variability in patient responses to clopidogrel.
A secondary analysis of the large Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial, which established clopidogrel's efficacy for non-ST-elevation acute coronary syndrome in 2001, found that a greater reduction in cardiovascular death, MI, or stroke seen initially in patients randomized to clopidogrel instead of placebo continued to be significant up to nearly 1 year (Circulation 2003;107:966–72).
“This suggests that the benefit continues to accrue over time, and that treatment out to at least a year makes sense,” said Dr. Sabatine of Brigham and Women's Hospital, Boston. He is on advisory boards for and has received research funds and honoraria from the companies that market clopidogrel, Bristol-Myers Squibb and Sanofi-Aventis.
In the large Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) study, patients who had a history of atherothrombosis or risk factors for it and were on daily aspirin therapy were randomized to dual-platelet therapy with the addition of clopidogrel or placebo. Follow-up to an average of 2.5 years showed no difference in the risk for cardiovascular death, MI, or stroke between groups, however (Am. Heart J. 2004;148:263–8).
That's because the results with clopidogrel affected two subgroups in opposite ways. The drug significantly reduced risk in patients with a history of atherothrombosis but increased overall risk in patients with no more than risk factors for atherothrombosis such as diabetes or hypertension (N. Engl. J. Med. 2006;354:1706–17). A 1%–2% increase in moderate to severe bleeding with long-term clopidogrel use was not offset by reductions in death, MI, or stroke in the latter subgroup.
Subgroup analyses are not definitive, but this “does start to fit with our prior notion that dual-antiplatelet therapy is most efficacious in those with an acute thrombus, either a complete occlusion as in STEMI or subtotal occlusion as in non-ST-elevation acute coronary syndromes,” he said at the meeting, also sponsored by the University of California, San Francisco. “If you just have risk factors but never manifested atherothrombosis, there's no benefit.”
There are no data yet on long-term use of clopidogrel for STEMI. The pivotal trials lasted only weeks, he noted.
'This suggests that [clopidogrel's] benefit continues to accrue over time, and that treatment out to at least a year makes sense.' DR. SABATINE