Hemostasis and Thrombosis Issues

MARCH 14, 2012
Charles H. Brown, MSPharm, RPh, CACP

Statin therapy reported to have antithrombotic activity

Although statin therapy is primarily prescribed to lower cholesterol levels, some added benefits include its anti-inflammatory and antithrombotic activities. People with elevated cholesterol levels are at higher risk of atherosclerotic plaque forming in their arteries. Under certain conditions, plaque inside blood vessels may rupture, activating the formation of a blood clot. Circulating blood clots may either partially or completely occlude critical blood supply to the heart or brain. Without adequate blood supply, heart and brain tissue quickly die.

A recent clinical study reported that statin (simvastatin) therapy reduces the activation of a certain blood-clotting process (tissue factor) that is independent of its lipid-lowering activity. 1 Researchers indicate that statins only target the “bad” and inducible tissue factor, not the “good” one used in normal clotting, and therefore should not be associated with the increased bleeding risk that is a typical side effect of anticoagulant drugs currently on the market.

Increased Heart Risk Found in Patients Taking Dabigatran

Pooled data from 7 previous studies involving 30,514 patients compared dabigatran with warfarin, enoxaparin, or a placebo. 2 Rates of heart attack or angina were increased 33% in those taking dabigatran. Overall, however, the risk remained very small; only 237 of 20,000, or 1.19% of dabigatran users experienced heart-related events, compared with 0.79% of people taking another drug or placebo compared with 0.79% of people taking another drug or placebo.

The exact mechanism(s) involved are not known at this time. Although this increased risk was reported, the FDA concluded that it was not statistically significant. Researchers indicate that physicians may wish to exercise caution when prescribing dabigatran until more research can be done to clarify the potential heart attack risk, especially with patients with known active ischemic heart disease.

Bleeding ADRS Higher with Dabigatran than Warfarin

Concerns about bleeding with dabigatran continue with a new report that adverse drug reactions (ADRs) involving hemorrhage reported to the FDA were higher for dabigatran than for warfarin in the first quarter of 2011. 3 A large portion of the bleeding events with dabigatran involved intracranial hemorrhage in elderly patients (median age 80 years).

The latest data show 505 reports of hemorrhage with dabigatran in the first quarter of 2011, which the QuarterWatch says is “more than any other monitored drug, including warfarin, which ranked second, with 176 cases of hemorrhage.” Although more study is needed, it may be that a “one size fits all” dose of 150 mg twice daily may not be suitable for some patients, especially elderly patients and patients with a very low creatinine clearance.

Aspirin Therapy as Effective as Warfarin in Heart Failure

Heart failure patients have an increased risk of death and stroke caused by thromboembolic events, and are often prescribed warfarin or aspirin. The Warfarin vs Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial, a randomized, double-blind trial, compared 2305 patients taking warfarin (target international normalized ratio 2-3.5) or aspirin 325 mg daily.

Patients from 176 sites in 11 countries were enrolled and followed. There was a total of 4045 patient-years in the warfarin group and 4033 in the aspirin group. Patients’ average age was 61 years; 80% were male. Mean follow-up was 3.5 years, with a range of 1 to 6 years. Researchers concluded that there was no overall difference in the combined primary outcomes of death, ischemic stroke, or intracranial hemorrhage between treatment groups. PT

Mr. Brown is professor emeritus of clinical pharmacy and a clinical pharmacist at Purdue University College of Pharmacy, Nursing, and Health Sciences, Department of Pharmacy Practice, West Lafayette, Indiana. This column’s information is based on current studies and references, but it may be changed without notice with newer studies or with different patient populations.


1. Owens A, Passam F, Antoniak S, et al. Monocyte tissue factor-dependent activation of coagulation in hypercholesterolemic mice and monkeys is inhibited by simvastatin. J Clin Invest. 2012;122(2):558-568.

2. Uchino K, Hernandez AV. Dabigatran association with higher risk of acute coronary events. Arch Intern Med. Published online January 9, 2012. doi:10.1001/archinternmed.2011.1666.

3. Institute of Sage Medication Practices. ISMP Medication Safety Alert, January 12, 2012.

4. Homma S, Thompson JLP. Results of the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial. International Stroke Conference 2012; February 3, 2012. New Orleans, LA. Abstract LB 12-4372.

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