Advances & Insights: Heart Health
September 15, 2006
What the news means for you
David J. Moliterno, MD
Use of aspirin-Plavix combo not beneficial for everyone
With the results of the CHARISMA study, the benefits and uses of the combination of aspirin and Plavix has been more clearly defined. The study showed that it’s best to keep the initiation of the combination of aspirin and Plavix in the hospital or in an ischemic heart-disease setting.
“It’s best to keep the initiation of the combination of aspirin and Plavix in the hospital or in an ischemic heart-disease setting."
Combo proven useful for specific purposes
Initially, the aspirin-Plavix combination was used for protecting patients who were receiving a coronary artery stent and later for those receiving a drug-eluting stent when those became common. The combination was also shown to be helpful in patients with acute ischemic heart disease-unstable angina or a recent myocardial infarction.
This drug combination was most commonly prescribed in a hospital setting. Patients received it while hospitalized after a heart attack or for acute coronary syndrome or when having a coronary artery procedure performed. Eventually, some physicians considered using it as a preventive therapy by initiating it in an outpatient setting among patients who did not have established ischemic heart disease.
The CHARISMA study was undertaken to see if this combination in fact should be extended for primary prevention, as opposed to limiting it to patients with established and active arterial disease. This was a way to take a step back and see if would be helpful upfront to prevent ischemic events in patients who might develop heart disease in the future. However, it was not found to be beneficial for patients who did not yet have established heart disease or ischemic symptoms.
“If you have diagnosed [cardiac] disease, past cardiac episodes or other serious risk factors, you should be sitting down with your doctor to discuss your options, including medications.”
Drugs for prevention of heart disease
Many articles and advertisements promote the benefits of aspirin in preventing heart disease. If aspirin has been shown to be an effective drug for prevention, people might ask why this effectiveness doesn’t this extend to Plavix and aspirin together? The answer is, aspirin and Plavix are good for prevention, but only in selected patients. Neither of them is beneficial for the general population.
As far as aspirin is concerned, physicians and patients need to focus on it as a preventive therapy for patients at higher risk of heart disease or ischemic events, such as smokers above the age of 55. And the combination of aspirin and Plavix needs to be limited to patients at higher risk or who have had specific ischemic heart disease events.
Talk to your doctor first
What if you are currently taking aspirin and Plavix together? Patients should consult with their physician before stopping any medication. While as doctors we want our patients integrally involved in all aspects of their care, patients should always consult their doctor before starting or stopping a medication based on news reports of a study. There are many patients who benefit from this therapy and should not discontinue it because of a misunderstanding of some particular study’s results.
In the same regard, if you are considering taking aspirin as a preventive measure for heart disease, talk to your doctor. Aspirin does have side effects and may not be indicated for some, especially over the long term.
The bottom line is, you and your doctor should have a discussion about whether you have risk factors for cardiac disease, how serious those risk factors are, and whether there are preventive steps you should take to reduce your risk. Much can be done to reduce one’s risk for heart disease that does not involve medication. But if you have diagnosed disease, past cardiac episodes or other serious risk factors, you should be sitting down with your doctor to discuss your options, including medications.
Dr. Moliterno is chief of cardiovascular medicine at the UK Gill Heart Institute, as well as the Jefferson M. Gill professor of cardiology and vice-chairman of internal medicine at the University of Kentucky. Prior to joining UK, Dr. Moliterno was an attending cardiologist at the Cleveland Clinic Foundation.
Aspirin-blood thinner combo effective only for certain heart patients
A recent study of the effectiveness and safety of a common anticlotting drug plus aspirin as compared with aspirin alone in patients at high risk for a cardiovascular event has found many do not benefit from the combination.
“There was no significant benefit associated with clopidogrel plus aspirin in reducing the incidence of heart attack, stroke or death in patients with stable cardiovascular disease or those with multiple cardiovascular risk factors.”
Atherothrombosis is a complex disease in which cholesterol deposits, inflammation and thrombus or clot formation play a major role. The disease can lead to coronary thrombosis, the main cause of unstable angina, heart attack and sudden cardiac death. According to the authors of the research summarized below, atherothrombotic disorders of the coronary, cerebrovascular and peripheral arteries are collectively the leading cause of death and disability in the world. “Their prevalence is increasing;” wrote the authors, “they are significantly undertreated, and better means of prevention are needed.”
Researchers had been interested in looking at the antiplatelet agent clopidogrel (Plavix®) because it is more potent at reducing obstructive clotting than aspirin. Previous studies had already shown the combination of clopidogrel and aspirin to be better than aspirin alone in the treatment of patients with acute coronary syndromes and for use after coronary stenting.
About the trial
This latest study published April 20, 2006, in The New England Journal of Medicine, is named CHARISMA (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance). CHARISMA was designed to evaluate the safety and effectiveness of dual antiplatelet therapy-as opposed to aspirin alone-for prevention of cardiac events in high risk patients.
Investigators enrolled 15,603 patients in 32 countries with multiple atherothrombotic risk factors or documented coronary disease, cerebrovascular disease or symptomatic peripheral arterial disease between October 1, 2002, and November 14, 2003. The median age of enrolled patients was 64 years. Of those enrolled, 29.8 percent were women. More than three-fourths of the participants had established cardiovascular disease; most of the remainder had multiple atherothrombotic risk factors.
Eligible participants were randomly assigned to either receive clopidogrel (75 mg per day) plus low-dose aspirin (75 to 162 mg per day)or a placebo plus low-dose aspirin for a median time of 28 months. The researchers’ stated goal was to “test the hypothesis that long-term treatment with a combination of clopidogrel plus aspirin may provide greater protection against cardiovascular events than aspirin alone in a broad population of patients at high risk.”
In addition to the study therapy, all participants also received standard therapy for their conditions, such as statins or beta-blockers. Follow up evaluations were performed at one month, three months, six months and every six months thereafter to the end of the trial.
Steven Steinhubl, MD, director of clinical cardiovascular research at the University of Kentucky, was a member of the study’s international steering committee.
Dual therapy shown to be no more effective
Results from the study indicated that 6.8 percent of the patients who received clopidogrel plus aspirin and 7.3 percent who received the placebo plus aspirin experienced heart attack, stroke or death from cardiovascular causes. Once all of the data was analyzed, the researchers determined there was no significant benefit associated with clopidogrel plus aspirin as compared with placebo plus aspirin in reducing the incidence of heart attack, stroke or death from cardiovascular causes in patients with stable cardiovascular disease or those with multiple cardiovascular risk factors.
When hospitalization for an ischemic symptom such as unstable angina or a transient ischemic attack (TIA) was considered along with the above adverse events, researchers found one of these endpoint events occurred in 16.7 percent of those receiving clopidogrel and 17.9 percent of those receiving placebo. In this case, dual therapy provided a “moderate, though significant, benefit" according to the study’s authors.
In answer to their questions regarding the dual therapy’s safety, the rate of severe abdominal bleeding was 1.7 percent in those receiving clopidogrel and 1.3 percent in those receiving the placebo. Overall, the study’s authors noted the risk of moderate-to-severe bleeding was increased.
Although it was noted the dual therapy might benefit patients with established vascular disease, the researchers cautioned this finding would require additional study.
UK HealthCare cardiac services:
Gill Heart Institute
Gill Heart care services
For more information, or to make an appointment with a UK HealthCare physician, please call UK Health Connection at 1-800-333-8874.