New CAD/ACS antiplatelet agents a mixed bag

Emerging agents for the treatment of CAD and ACS include the reversible P2Y12 antagonists ticagrelor (approved July 2011) and cangrelor. Development of elinogrel, another drug in this class, was stopped in January 2012. A new class of oral protease-activated receptor-1 (PAR-1) inhibitors, including vorapaxar and atopaxar, is also under study.

The P2Y12 antagonists have demonstrated an enhanced ability to prevent adverse cardiac outcomes, but there have been new adverse effects, including dyspnea for all the P2Y12 antagonists and ventricular pauses for ticagrelor. Cangrelor, which will be available as an intravenous formulation, may provide additional benefits in patients who undergo coronary artery bypass graft surgery. Clinical trials with the PAR-1 inhibitors have also shown trends toward reductions in cardiac events, but internal bleeding rates have been high with vorapaxar.

Source: Packard KA, Campbell JA, Knezevich JT, Davis EM. Emerging antiplatelet therapy for coronary artery disease and acute coronary syndrome. Pharmacotherapy. 2012;32:244-273.

Emotional state contributes to VTE risk

Depression has been well documented as a contributor to poor outcomes in a variety of chronic disease states such as diabetes mellitus and cardiovascular disease; however, the relationship between emotional states and risk of venous thromboembolism (VTE) has not been explored. A recent population-based prospective study investigated the associations between self-reported emotional states and risk of incident VTE.

Through self-administered questionnaires, patients reported the frequency of depressed, lonely, and happy/optimistic feelings, and answered questions about major comorbidities and lifestyle habits. The study included 25,964 subjects 25 to 96 years of age. Median follow-up was 12.4 years. There were 440 incident VTE events during the study period. Subjects who often felt depressed had a 1.6-fold higher risk of VTE compared to those who did not report depression.

The pathologic explanation for this is not clear, but other studies have shown that depressed patients have higher levels of fibrinogen, haptoglobin, and complement components in plasma. An assumption could be made that depressed patients have poor health/lifestyle behaviors that could contribute to risk, but the authors adjusted for preexisting comorbidities and health behaviors, and the results were still consistent. Further study is needed to define this mechanism.

Source: Enga KF, Braekkan SK, Hansen-Krone IJ, Hansen J-B. Emotional states and future risk of venous thromboembolism: The Tromsø study. Thromb Haemost. 2012;107:485-493.