In new research published in the Jan. 29 issue of The Lancet, sibrafiban, a new drug that inhibits blood platelet clumping, showed no benefit over aspirin for treatment of patients who had just had a heart attack.
The study investigated whether sibrafiban would prevent more cardiovascular events than aspirin when given within seven days of and sustained for 90 days after an acute coronary syndrome event, defined as acute chest pain (angina) or heart attack (acute myocardial infarction). Dr. Kristin Newby from Duke University Medical Center in Durham, N.C., led the international study, called a SYMPHONY trial.
Over 9,000 patients were randomly assigned to take either 80 milligrams of aspirin (one baby aspirin) twice daily, low-dose sibrafiban or high-dose sibrafiban. The patients were assessed for recurrence of cardiovascular events after 90 days.
The results of the study showed no significant difference in the rates of heart attack or cardiac-related death between the groups assigned aspirin, low-dose sibrafiban and high-dose sibrafiban. Major bleeding was more common with high-dose sibrafiban than with aspirin or low-dose sibrafiban.
The investigators concluded that sibrafiban showed no additional benefit over aspirin for prevention of further major events after an acute coronary syndrome and was associated with more dose-related bleeding. Patients with bleeding disorders, severe asthma or aspirin allergy are not eligible to take aspirin for heart disease treatment or prevention without careful evaluation of these risks by medical caregivers.
In order to reduce the severity of acute myocardial infarction, or AMI, patients with angina are often advised to take an aspirin, while simultaneously getting immediate medical care. Other agents that also work against AMI by interfering with platelet clumping, or adhesion, are given intravenously in the hospital emergency room. Sibrafiban is a similar agent that can be given orally.
Aspirin lowers the risk of heart attack and death in patients with acute coronary syndromes, such as unstable angina. One way aspirin works is by interfering with platelet adhesion, which is part of the process that leads to the formation of clots in coronary blood vessels. The result of a coronary arterial clot, or thrombosis, is often a heart attack, or even death.
Use of stronger inhibitors of platelet adhesion, substances called glycoprotein 2b/3a receptor antagonists, also reduces the rate of complications immediately after a heart attack. Sibrafiban is one such agent. However, there is no long-term benefit. Since aspirin is an anti-inflammatory agent, and inflammation of the coronary arteries is now thought to be a factor in the process of thrombosis and AMI, this mechanism may also play a role in aspirin’s effectiveness.
In an editorial accompanying the study, Dr. Christopher Heeschen of Stanford University and Dr. Christian Hamm of Germany’s Kerckhoff Heart Center discuss possible explanations for sibrafiban’s lack of additional benefit. They suggest that some of aspirin’s effect may be through its other properties (for example, its anti-inflammatory effects). Also, the safe and effective levels of drugs such as sibrafiban are not yet known. Another possibility is that the patients studied were not at particularly high risk of having another coronary event, so any sibrafiban or aspirin effect would be very small.
But it seems the last word should belong to the study authors, who state: “? given the substantial benefits of aspirin alone and its low cost and lower bleeding risk, none of the completed studies provide evidence that would justify use of an oral glycoprotein 2b/3a inhibitor.”
Aspirin use in suspected or documented AMI has increased significantly over the past decade, which is part of the reason why the in-hospital death rate from AMI has decreased as well. Other reasons for the lower death rate also include the more widespread use of other prescription drugs such as beta-blockers, ACE-inhibitors and intravenous thrombolysis (“clot-busting” drugs), as well as wider use of catheterization and revascularization procedures.
Preventing the development of coronary artery disease has also been a major public-health gain. This has been the result of better control of risk factors such as high blood pressure, high cholesterol levels and especially lowered rates of adult smoking.