In a study of nearly 46,000 patients with suspected acute myocardial infarctions, there was a 9% drop in the combined rate of death, stroke, or reinfarction among patients randomized to received 75 mg of Plavix plus 162 mg of Aspirin daily, compared with those who received Aspirin alone.
So reported Zhengming Chen, M.D., of the Clinical Trial Unit at the University of Oxford, on behalf of the COMMIT (Clopidogrel and Metoprolol in Myocardial Infarction Trial) investigators.
The combined Plavix-aspirin therapy was also associated with a 7% relative reduction in all cause mortality, the investigators noted in a study published in the Nov. 5 issue of The Lancet.
“If early clopidogrel therapy was given in hospital to just one million of the 10 million patients who have a Heart Attack every year then it would, on present evidence, prevent about 5,000 deaths and 5,000 non-fatal reinfarctions and strokes,” Dr. Chen and colleagues wrote. “Moreover, continued treatment with clopidogrel after hospital discharge could lead to further net gains, although the benefits and hazards of more long-term therapy are still under investigation.”
In a second part of the study, also published in Lancet, the COMMIT researchers looked at the effect of giving patients with acute MI early 15mg of intravenous metoprolol then 200mg of oral metoprolol daily. They found that while the treatment could cut the relative risk of repeat Heart Attack and of ventricular fibrillation by about 15% to 20%, it increased the risk of cardiogenic shock by 30%.
The combination of the platelet inhibitor Plavix with Aspirin has been shown in other trials to reduce the risk of ischemic events, compared with Aspirin alone, in patients undergoing percutaneous coronary procedures, as well as those with non ST-segment elevation acute coronary syndromes.
In addition, results of the CLARITY trial, published earlier this year in the New England Journal of Medicine, showed that Plavix plus aspirin helped retain the patency of blocked coronary arteries following clot-busting fibrinolytic therapy, and there was evidence to suggest that the combination could reduce clinical events, the investigators noted.
To see whether the combo could have similar benefits for patients with ST-segment elevation MI (STEMI), the investigators enrolled 45,852 patients from 1,250 specialty and general hospitals throughout China.
Patients with ST elevation, or left-bundle branch block, or ST Depression within 24 hours of onset of symptoms of suspected acute MI were randomly assigned to 162 mg of aspirin plus 75 mg of Plavix daily, or aspirin plus placebo. Each patient was treated until discharge or for up to four weeks.
The primary outcomes were a composite endpoint of death, reinfarction and stroke; and all-cause mortality within the treatment period. Analysis was by intention to treat.
Among patients assigned to Plavix, there were 2,121 cases (9.2%) of death, reinfarction or stroke, compared with 2,310 (10.1%) among patients who received aspirin alone. This translated into a 9% relative reduction in risk for patients taking Plavix (95% CI 3-14%, P=0.002).
This difference is equivalent to nine fewer events per 1,000 patients treated for about two weeks.
In addition, there were 1,726 deaths from all causes in patients on the Plavix-aspirin combo, compared with 1,845 for patients on aspirin and placebo. This translated into a 7% relative reduction in risk of death (95% CI 1-13%, P=0.03).
“These effects on death, reinfarction, and stroke seemed consistent across a wide range of patients and independent of other treatments being used,” the investigators noted.
There were no significant differences between the groups in episodes of fatal bleeds, bleeds requiring transfusion, or cerebral bleeding, including 22,794 patients who underwent fibrinolytic therapy before randomization, or in patients older than 70 years.
In the second part of the COMMIT study, the investigators examined, in the same cohort whether adding beta-blocker therapy in the emergency department to other interventions such as anti-platelet agents and fibrinolytic therapy could be beneficial for patients with acute MI.
Patients were assigned to receive either to intravenous beta-blockers followed by oral metoprolol or placebo. The primary outcomes of interest were composite of death, reinfarction, or cardiac arrest, and all-cause mortality during the treatment period.
They found that neither of the primary outcomes was significantly reduced by allocation to the beta-blocker metoprolol. When events were considered separately, however, they found that the beta-blocker reduced the relative risk of reinfarction and ventricular fibrillation by about 18%, but also increased the risk of cardiogenic shock by 30%, especially within the first few days following admission.
“It might generally be prudent to consider starting beta-blocker therapy in hospital only when the hemodynamic condition after MI has stabilized,” the investigators wrote.
“The Oxford Clinical Trial Service Unit is to be commended for once again providing definitive practice-changing data for clinicians,” wrote Marc S. Sabatine, M.D., of the cardiovascular division at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, in an accompanying editorial. Dr. Sabatine was lead author of the CLARITY trial.
“Their findings show the value in STEMI of routinely administering clopidogrel as part of the initial pharmacological reperfusion regimen and starting beta-blockers once it is hemodynamically prudent to do,” he concluded.”
Source: The Lancet
Revision date: June 14, 2011
Last revised: by Jorge P. Ribeiro, MD