Antiplatelet Therapies and Acute Coronary Syndrome

Orlando—Patients with acute coronary syndromes have several options when it comes to antiplatelet therapies, including aspirin, clopidogrel, prasugrel, and glycoprotein IIb/IIIa inhibitors such as abciximab, eptifibatide, and tirofiban. The regimens they should use, however, vary depending on the severity of their condition and other factors.

Michael Miller, MD, professor of medicine at the University of Maryland, spoke about the complexities involved in treating these patients at the Spring Managed Care Forum in a session titled Managing Acute Coronary Syndrome: New Developments in Antiplatelet Therapy.

According to Dr. Miller, there were 1.57 million hospital admissions due to acute coronary syndromes in 2007, the most recent data available. Of these admissions, 1.24 million were due to unstable angina/non-ST elevation myocardial infarction (non-STEMI) and 0.33 million were due to STEMI.

Dr. Miller discussed guidelines from the American College of Cardiology and American Heart Association on how to manage patients with unstable angina/non-STEMI. The American College of Emergency Physicians, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons helped develop these guidelines, as well. He also mentioned an algorithm used to evaluate and manage patients with acute coronary syndrome.

The guidelines suggest patients with unstable angina/non-STEMI, who are selected to have an invasive strategy, should take aspirin plus oral clopidogrel or an intravenous glycoprotein IIb/IIIa inhibitor before undergoing a diagnostic angiography. Dr. Miller said the preferred glycoprotein IIb/IIIa inhibitor is eptifibatide or tirofiban, but patients who do not have a long delay before angiography and percutaneous coronary intervention (PCI) should use abciximab.

Dr. Miller then spoke about several trials involving antiplatelet therapies. A study of 12,562 patients with unstable angina/non-STEMI found that those who took clopidogrel had a reduction in cardiovascular death, myocardial infarction (MI), and rates of recurrent ischemia and revascularization compared with the placebo group. However, there were more instances of major (non-life threatening) bleeding in the clopidogrel group.

Another study of 10,948 patients with unstable angina/non-STEMI found that there was a decreased incidence of death and MI at 4 days, 7 days, and 30 days for those who took eptifibatide compared with those who took placebo. There was also increased major bleeding in the eptifibatide group, although there was no difference in risk of stroke.

In addition, a trial of 2022 patients with unstable angina/non-STEMI found that those taking abciximab plus aspirin and clopidogrel had a decrease in death, MI, and urgent target vessel revascularization (TVR) after 30 days compared with the placebo group. There was no difference in major or minor bleeding between the groups.

The guidelines indicate that patients with unstable angina/non-STEMI who are treated with a noninvasive strategy should take clopidogrel plus aspirin and anticoagulant therapy. The regimen should continue for at least 1 month and up to 1 year, according to Dr. Miller. He mentioned a trial found that patients taking 600 mg of clopidogrel 4 to 8 hours before undergoing PCI had reductions in death, MI, and urgent TVR after 30 days compared with a group that took 300 mg of clopidogrel. However, if patients in this group have recurrent symptoms/ischemia, heart failure, or serious arrhythmias, they should undergo a diagnostic angiography.

Meanwhile, Dr. Miller said the guidelines suggest that patients who plan on having a PCI should begin with a loading dose of thienopyridine. The regimens should be 300 mg to 600 mg of clopidogrel as early as possible before or after the PCI or 60 mg of prasugrel immediately or no longer than 1 hour after the PCI. Dr. Miller added that after the initial dose, patients undergoing a PCI should take 75 mg of clopidogrel daily or 10 mg of prasugrel daily for ≥12 months, although the regimen could be discontinued if there is an increased risk of morbidity because of bleeding.

Dr. Miller mentioned a randomized study that examined 13,608 patients who were scheduled to undergo a PCI. They were assigned to take a 60-mg loading dose of prasugrel plus 10 mg of prasugrel daily or a 300-mg loading dose of clopidogrel plus 75 mg of clopidogrel daily for 6 to 15 months. There was a significant difference in the primary end point of cardiovascular death, nonfatal MI, and nonfatal stroke, which occurred in 9.9% of patients in the prasugrel group and 12.1% in the clopidogrel group (hazard ratio [HR], 0.81; P<.001).

Patients in the prasugrel group also had a significant reduction in MI, urgent TVR, stent thrombosis, and ischemic events, but they had a significant increased risk of major and fatal bleeding. There was no significant difference in overall mortality between the groups, according to Dr. Miller.

Dr. Miller said that clopidogrel comes with a boxed warning from the FDA for patients who are poor metabolizers of the drug, alerting them to consider changing their clopidogrel dosage strategy or switching to another antiplatelet medication. The guidelines suggest poor metabolizers of the drug should consider increasing their clopidogrel regimen to a 600-mg loading dose followed by 150 mg daily, although Dr. Miller said there is no appropriate dosing regimen established.

Prasugrel comes with a package insert stating that the drug should not be used in patients likely to undergo urgent coronary artery bypass graft surgery. Dr. Miller said patients should discontinue prasugrel at least 7 days before undergoing any surgery. He added that patients with active pathological bleeding or a history of stroke or transient ischemic attack (TIA) should not use prasugrel, citing a study that found patients with a previous stroke or TIA had an unfavorable benefit from taking prasugrel compared with those taking clopidogrel (HR, 1.54; P=.04).

Dr. Miller also outlined the recommendations for long-term use of antiplatelet therapies. He said that patients with unstable angina/non-STEMI who were not treated with stenting should take 75 mg to 162 mg of aspirin per day indefinitely and also 75 mg of clopidogrel per day for at least 1 month and up to 1 year.

To emphasize the benefits of antiplatelet therapies, Dr. Miller cited a meta-analysis of 195 randomized trials that included >143,000 patients. The authors found there was a 22% reduction in the odds of vascular death, MI, or stroke in patients who took antiplatelet therapies for a variety of clinical problems, including unstable angina/non-STEMI. Dr. Miller added there was a similar decrease in the odds of vascular events for patients who took between 75 mg and 1500 mg of aspirin on a daily basis.