Anticoagulant therapies

Anna D. GarrettThree studies bring you up-to-date on the optimal length of dual antiplatelet therapy; the role (or lack thereof) for platelet transfusion for serious GI bleeding in patients taking antiplatelet medication; and the efficacy of factor Xa reversal agent.

Optimal Duration of Dual Antiplatelet Therapy?

A recent review of 11 randomized controlled trials including 33,051 patients (most of whom had received drug-eluting stents [DES]) sought to clarify questions about the optimal duration of dual antiplatelet therapy (DAPT) after implantation of DES or myocardial infarction (MI). The review included 33,051 patients (most of whom had received DES) and compared use of DAPT for 18 to 48 months vs use for 6 to 12 months.

Longer-term DAPT was associated with no difference in incidence of all-cause death but was associated with increased major hemorrhage, decreased MI, and decreased stent thrombosis. Post hoc analyses provided weak evidence of increased mortality with prolonged DAPT. Use of DAPT >1 year after MI reduced the composite risk of cardiovascular death, MI, or stroke but increased major bleeding.

The investigators concluded that prolonged DAPT after implantation of newer-generation DES entails a tradeoff between reductions in stent thrombosis and MI and increases in major hemorrhage. In patients whose coronary thrombotic risk was defined by a prior MI rather than by DES implantation, the primary analysis provides moderately strong evidence of reduced cardiovascular events at the expense of increased bleeding.

Bittl JA, Baber U, Bradley SM, et al. Duration of dual antiplatelet therapy: a systematic review for the 2016 AHA/ACC guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease. J Am Coll Cardiol. 2016;68:1116-1139.

Platelet Transfusion for GI Bleeding?

Antiplatelet drugs, such as aspirin and thienopyridines, increase the risk for gastrointestinal bleeding (GIB). Because these drugs act for the entire life of the platelet, it is reasonable to assume that platelet transfusion might be helpful in cases of severe bleeding.

To investigate this approach, investigators retrospectively compared outcomes between recipients and non-recipients of platelet transfusion among patients who were taking antiplatelet drugs and admitted for GIB. They identified 204 patients who received platelet transfusions, who were matched by age, sex, and GIB location to 204 patients not receiving transfusion

Transfusion recipients had more cardiovascular events and deaths and a longer length of stay. In multivariable analysis controlling for additional risk factors, only mortality risk was significantly elevated with platelet transfusion. Rebleeding risk was not significantly different between groups.

These findings suggest that platelet transfusions provide no benefit in patients with GIB taking antiplatelet drugs.

Source: Zakko L, Rustagi T, Douglas M, et al. No benefit from platelet transfusion for gastrointestinal bleeding in patients taking antiplatelet agents. Clin Gastroenterol Hepatol. 2016; Jul 25; http://www.ncbi.nlm.nih.gov/pubmed/27464591

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Factor Xa Reversal Agent Shows Rapid Effectiveness

Updated results of the ANNEXA-4 trial showed that andexanet alfa, a factor Xa inhibitor antidote, worked quickly and was well tolerated in reversing acute anticoagulant-related bleeding in 67 study subjects.

The patients required emergency reversal of acute bleeding after receiving the direct factor Xa inhibitors apixaban, rivaroxaban, or edoxaban, or an indirect inhibitor (enoxaparin) within the preceding 18 hours. The primary bleeding sites were gastrointestinal (49%) and intracranial (42%).

The drug was administered in an immediate bolus over 15 to 30 minutes, then by infusion for 2 hours. Dosing was based on which factor Xa inhibitor the patient was taking and when it was received.

Researchers observed an 89% decrease in anti–factor Xa activity within a half hour in patients on rivaroxaban (n=26) and a 93% reduction for patients on apixaban (n=20).

They rated clinical hemostatic efficacy as good to excellent in 79% of patients at 12 hours overall. Thrombotic events occurred within 3 days of andexanet in four patients (6%) and by 30 days in 12 (18%). Eighteen patients (27%) restarted anticoagulation by 30 days. Ten deaths (15%) occurred within 30 days, six of them attributed to cardiovascular causes.

Connolly SJ, Milling TJ, Eikelboom JW, et al. Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. New England J Med, Published online August 30, 2016.

http://www.nejm.org/doi/full/10.1056/NEJMoa1607887#t=article

Anna D. Garrett is a clinical pharmacist and president of Dr. Anna Garrett (www.drannagarrett.com). Her mission is to help women in midlife maximize their mojo! Contact her at info@drannagarrett.com.