Coagulation Counseling

Dr. Garrett is manager, Outpatient Clinical Pharmacy Programs, at Mission Hospitals in Asheville, North Carolina.

Prasugrel Approved by FDA Amidst Controversy

The FDA recently approved prasugrel (Effient), a novel antiplatelet agent. Approval was based on evidence of greater protection against cardiovascular events when compared with clopidogrel; however, the drug has an increased risk of bleeding compared with clopidogrel.

The study on which the approval was based (TRITON-TIMI 38) compared prasugrel plus aspirin against clopidogrel plus aspirin. A statistically significant reduction in cardiovascular events was demonstrated in the prasugrel arm of the study. Major bleeding events were significantly more common with prasugrel, resulting in a “black box” warning for bleeding. The drug is contraindicated in patients with a history of transient ischemic attack or stroke and should not be used in patients over 75 years of age or weighing less than 60 kg.

The approval decision for prasugrel was controversial. Sanjay Kaul, MD, an expert in the field of vascular physiology and critic of prasugrel in the past, was asked not to participate in the FDA advisory panel in February, raising red flags for some cardiologists. FDA staff contended that Dr. Kaul’s exclusion was due to possible intellectual bias. FDA regulations allow for exclusion of committee members who appear to have a wellformed opinion prior to the hearings.

Clinical Recommendations Published for LMWH Use in Morbid Obesity and Renal Failure A recent article published in Annals of Pharmacotherapy offers practical recommendations for the use of lowmolecular- weight heparins (LMWHs) as prophylaxis and treatment of venous thromboembolism and acute coronary syndromes in patients with impaired renal function or obesity. These recommendations were formulated using data from multiple MEDLINE searches for relevant studies.

The authors suggest that, in the majority of patients, standardized prophylaxis or treatment doses of LMWHs can be used without the need for monitoring and adjusting regimens. For patients with severe renal impairment, doses of some LMWHs should be adjusted or unfractionated heparin should be used instead. Differences are present in the degree of accumulation of various LMWHs in patients with moderate-tosevere renal impairment, so the degree of dose adjustment may differ among the various LMWHs.

Increasing the prophylactic doses of LMWH may be appropriate in morbidly obese patients. The use of total body weight is appropriate for therapeutic doses of LMWH in obese patients. Laboratory monitoring of the anticoagulation effect of LMWHs is generally not necessary, but should be considered in patients with morbid obesity (weight >190 kg), those with severe renal impairment, and those with moderate renal impairment with prolonged (>10 days) LMWH use.

Use of Aspiring for Primary Prevention Should Be Carefully Considered

A recent meta-analysis of the safety and efficacy of long-term aspirin for primary prevention of serious vascular events concluded that the benefit of event reduction should be weighed against the potential risk of a major hemorrhagic event.

The meta-analysis, which consisted of 6 primary and 16 secondary prevention trials, evaluated the use of long-term aspirin and risk of serious vascular events, compared with no aspirin. Primary prevention with aspirin resulted in a proportional risk reduction of 12%. A significant difference in risk for primary prevention of major coronary events was observed between men and women until after multiple comparisons, sex was no longer a significant risk factor; age >70 years was the most important predictor of risk.

Aspirin significantly reduced the incidence of ischemic stroke but significantly increased the rate of hemorrhagic stroke in both groups; fatal hemorrhagic strokes outnumbered fatal ischemic strokes 82 to 52. Aspirin for primary prevention also increased the risk of major bleeding (other than intracerebral hemorrhage) by 54%. Major bleeds were also significantly increased in secondary prevention patients; however, these data were collected in only 5 of the trials.

Patients at risk of a cardiovascular event but without a history of an event should discuss the use of aspirin with their prescriber.