Coagulation Counseling

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

Clopidogrel plus Aspirin Decreases Stroke Risk

A large new study found that taking aspirin with clopidogrel decreased the risk of stroke by 28% in patients with atrial fibrillation (AF) who were not able to take anticoagulants like warfarin. The reasons patients were not considered suitable for vitamin K—antagonist therapy included the presence of a specific risk factor for bleeding (23%); a physician assessment that the patient was inappropriate (50%); and in 26%, the only reason given was a patient preference not to receive a vitamin K antagonist.

A total of 7554 patients were included in the study. All had AF, increased risk of stroke, and were unable to take warfarin. Patients were randomly assigned to take aspirin alone or aspirin plus 75 mg of clopidogrel. The combination group had an 11% reduction in deaths and cardiovascular events, including strokes and heart attacks, compared with aspirin alone. Median follow-up was 3.6 years.

The rate of major bleeding in the combination group was significantly increased, however, from 1.3% to 2.0% per year. Increased fatal bleeding that did not reach statistical significance and significant increases in intracranial and extracranial bleeding were also reported.

The investigators concluded that the clopidogrel/aspirin combination may provide a reasonable alternative for patients at high risk of stroke who cannot or choose not to take warfarin.

Do HMG-CoA Reductase Inhibitors Reduce Clot Risk?

A recently published study suggests that rosuvastatin may reduce the risk of venous thromboembolism (VTE). The research studied the effects of rosuvastatin on VTE risk in individuals who had a low level of low-density lipoprotein (LDL) cholesterol and a high level of C-reactive protein (CRP). Individuals who have high levels of CRP are thought to be at greater risk of heart attacks and strokes.

The trial involved 17,802 men and women who had never had a heart attack or stroke and had low LDL cholesterol and high CRP levels. Half of the participants were randomly assigned to receive 20 mg of rosuvastatin daily and half were given a placebo.

Over a period of 5 years, 34 of the 8901 individuals who took rosuvastatin developed blood clots, compared with 60 of the 8901 on the placebo. Although the results suggest that rosuvastatin could reduce the risk of blood clots in the veins of apparently healthy people, three quarters of the subjects were overweight or obese and nearly half had metabolic syndrome. These conditions are known to increase the risk of VTE. In addition, the absolute number of events is minute in the context of the entire population of nearly 18,000 participants. More long-term research is needed before individuals are given statins to reduce their risk of VTE.

Warfarin and the Frail, Elderly Patient: What to Do?

Australian researchers recently published a study of 220 inpatients with atrial fibrillation (AF) aged >70. The objective of the study was to investigate the impact of frailty on the use of antithrombotics and on clinical outcomes.

Frailty was assessed using a validated tool that incorporates cognitive impairment, comorbidities, and functional status. A total of 140 patients (64%) were identified as frail in the study. Frail patients were less likely to receive warfarin than the nonfrail on hospital admission and discharge. During hospitalization, the proportion of frail participants prescribed warfarin decreased by 10.7% and that of nonfrail increased by 6.3%. Over the 6-month follow-up, 43 major or severe hemorrhages (20.8%), 20 cardioembolic strokes (9.7%), and 40 deaths (19.2%) were reported. Compared with the nonfrail, frail participants were significantly more likely to experience embolic stroke, had a small nonsignificant increase in risk of major hemorrhage, and had greater mortality.

The results of this study reinforce the clinical dilemma that is often seen in practice. Elderly patients in general are less likely to receive warfarin due to increased risk of adverse events. Yet, it appears that frail older inpatients with AF are even less likely to receive warfarin than the nonfrail and appear more vulnerable to adverse clinical outcomes, with or without antithrombotic therapy. Frailty may be a better predictor of risk than age in the elderly population.