Cath Lab Digest

Anaheim—To decrease the risk of patients with acute coronary syndrome (ACS) experiencing future coronary episodes, researchers are looking at the effectiveness of dual antiplatelet therapy. There are also emerging strategies such as triple antiplatelet therapy and additional antiplatelet agents in the pipeline that may help ACS patients.

At the ASHP meeting, speakers discussed recent clinical trials and oral antiplatelet therapies during a symposium titled Optimizing Oral Antiplatelet Therapy in Acute Coronary Syndrome.

Toby Trujillo, PharmD, BCPS, associate professor of clinical pharmacy at the University of Colorado Denver School of Pharmacy, Aurora, classified ACS into 2 categories: ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI). The NSTEMI group also included unstable angina.

According to guidelines from the American Heart Association and the American College of Cardiology, several therapies are used to treat NSTEMI ACS, among them beta-blockers, nitrates, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, aldosterone antagonists, statins, anticoagulants, and antiplatelet therapy. Patients with STEMI use the same treatments, and they may also undergo reperfusion therapy.

Dr. Trujillo discussed the CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) trial, which included 12,562 patients with NSTEMI ACS who took clopidogrel plus acetylsalicylic acid (ASA) (n=6259) or placebo plus ASA (n=6303). Clopidogrel is an oral antiplatelet agent intended to prevent strokes and heart attacks.

The clopidogrel group had significantly fewer instances of myocardial infarction, stroke, or cardiovascular death compared with the placebo group (P=.00009; relative risk reduction, 20%). Patients taking clopidogrel plus ASA were significantly more likely to experience major bleeding (3.7% vs 2.7%; P=.001) and minor bleeding (5.1% vs 2.4%; P<.001) compared with the placebo group.

Dr. Trujillo also discussed the CURRENT-OASIS 7 (Clopidogrel Optimal Loading Dose Usage to Reduce Recurrent Events/Optimal Antiplatelet Strategy for Interventions) study of 25,087 patients who either had STEMI or NSTEMI ACS. Patients were assigned to take 300 or 600 mg of clopidogrel as well as 75 to 100 mg or 300 to 325 mg of ASA per day. The authors found that 522 of the 12,520 patients taking the double dose of clopidogrel died from cardiovascular causes, experienced myocardial infarction, or had a stroke compared with 557 of the 12,566 patients taking the single dose (P=.30). In addition, 530 of the 12,507 patients taking the higher dose of ASA died from cardiovascular causes, experienced myocardial infarction, or had a stroke compared with 549 of the 12,579 patients taking the lower dose (P=.61), Dr. Trujillo said.

Dr. Trujillo said there are many advantages of utilizing dual antiplatelet therapy to treat patients with ACS. However, some studies have indicated the limits of dual antiplatelet therapy, such as combining clopidogrel and ASA. Potential problems include increased bleeding, delayed onset or offset, variable response, irreversible mechanisms of action, and residual clinical events.

Next, Julie Oestreich, PharmD, PhD, assistant professor in the University of Nebraska Medical Center’s College of Pharmacy, Omaha, discussed challenges associated with oral antiplatelet therapy. She mentioned that patients vary in their response to taking clopidogrel as well as their on-treatment platelet reactivity.

In a trial of 192 patients undergoing elective percutaneous coronary intervention (PCI) and having a stent while taking clopidogrel, 20% experienced major adverse cardiac events after 6 months. Dr. Oestreich said additional studies found that platelet function tests indicate clopidogrel variability correlates with clinical outcomes in patients undergoing PCI with a good negative predictive value but a poor positive predictive value.

Dr.