Ticagrelor tops prasugrel in pharmacodynamic study

September 15, 2012

Ticagrelor is shown to be better at platelet inhibition. Warfarin seen as beneficial to patients with PAH. Dabigatran's problems aren't over.

Forty-four patients with acute coronary syndrome who had high on-treatment platelet reactivity (HTPR) while taking clopidogrel 24 hours after percutaneous coronary intervention were randomized to either 90 mg of ticagrelor twice daily or prasugrel 10 mg once daily for 15 days. This was followed by a crossover directly to the alternative treatment for another 15 days.

At the end of the 2 treatment periods, the primary end point of platelet reactivity was lower for ticagrelor, at 32.9 platelet reactivity units (PRU), compared with prasugrel, at 101.3 PRU (P<.001). HTPR rate, the secondary end point, was 0% for ticagrelor versus 2.4% for prasugrel (P=.05). No patient had a major bleeding event in either treatment group. Patients in the ticagrelor group experienced more mild side effects such as allergic reactions, dyspepsia, and new-onset/worsening dyspnea.

Source: Alexopoulos D, Galati A, Xanthopoulou I, et al. Ticagrelor versus prasugrel in acute coronary syndrome patients with high on-clopidogrel platelet reactivity following percutaneous coronary intervention: A pharmacodynamic study. J Am Coll Cardiol. 2012;60:193–199.

Warfarin beneficial for patients with PAH

Anticoagulation is often used in patients with pulmonary arterial hypertension (PAH), although its role in treatment has not been fully clarified. Current evidence appears to suggest that abnormalities of blood coagulation factors as well as abnormalities of antithrombotic factors and the fibrinolytic system contribute to a prothrombotic state in patients who have idiopathic PAH (IPAH).

In 2006, a qualitative systematic review of the literature was published to evaluate the effectiveness of anticoagulation therapy with warfarin on survival in patients with IPAH. The review identified seven observational studies that had evaluated a total of 488 patients with IPAH. Five of these studies supported the effectiveness of warfarin with respect to survival in IPAH, whereas two observational studies did not support warfarin use.

The authors discussed weaknesses in these studies such as sample sizes and possible misidentification of patients with true IPAH. They indicated that a randomized, controlled trial is needed to definitively determine the survival benefit of warfarin in IPAH; however, current literature seems to support its use with a goal of an international normalized ratio (INR) of 1.5 to 2.5. Based on retrospective clinical data and an understanding of the disease biology, anticoagulation is generally recommended as an adjunct to other treatment in patients with IPAH.

Source: Johnson SR, Mehta S, Granton JT. Anticoagulation in pulmonary arterial hypertension: A qualitative systematic review. Eur Respir J. 2006;28:999–1004.

Real-world use of dabigatran highlights adverse events

Problems with dabigatran are again surfacing, as demonstrated by the preliminary results of a new real-world study.

Investigators identified 113 patients from anticoagulation clinic records who had been switched from warfarin to dabigatran. Any clinical events that necessitated medication withdrawal from the first 6 months on dabigatran were compared with a 6-month previous warfarin treatment period. Most patients were given dabigatran 150 mg twice daily, with the exception of two patients who received dabigatran 75 mg twice daily. The mean treatment time for dabigatran was 3.9 months. During the warfarin treatment period, time in therapeutic range was 70%.

Results showed that during the warfarin treatment period, there was one event necessitating drug discontinuation - the patient was hospitalized because of a high INR. This compared with 13 events in the dabigatran treatment period. These included one treatment-related death (gastrointestinal bleed), and a variety of other embolic and hemorrhagic complications.

These adverse reactions were more common in older patients and in women. The mean age of patients experiencing complications on dabigatran was 73.4 years, compared with 66.5 years for the whole population. Whereas women accounted for 29% of the overall population, they represented 71% of patients with complications.

Source: Wurster MW, Howard M, Price C, et al. Dabigatran use in the real world: Preliminary results of a prospective trial comparing outcomes with dabigatran and warfarin therapy. Proceedings of the Thrombosis and Hemostasis Summit of North America: Research abstracts. Am J Hematol. 2012;87:S175.

Anna D. Garrett is a clinical pharmacist and president of Find Your Best Thinking, a health and wellness coaching company. Contact her at anna@findyourbestthinking.com