Age- and Weight-Adapted Dose of Prasugrel Versus Standard Dose of Ticagrelor in Patients With Acute Coronary Syndromes

Subgroup analysis (n=3997) found that in elderly or low-weight patients with ACS, a reduced dose of prasugrel compared with the standard dose of ticagrelor is associated with maintained anti-ischaemic efficacy while protecting these patients against the excess risk for bleeding.

SPS commentary:

The efficacy end point of study, a composite of death, MI, or stroke at 12 months, occurred in 12.7% of patients on prasugrel and 14.6% on ticagrelor (HR 0.82 [95% CI, 0.60 to 1.14]). The safety end point was bleeding at 12 months; Bleeding Academic Research Consortium type 3 to 5 bleeding occurred in 8.1% of and 10.6% (HR, 0.72;0.46 to 1.12), respectively.


An editorial notes that in the original publication, among 2012 patients with ACS treated with ticagrelor, the primary end point occurred significantly more often than among 2006 patients receiving prasugrel (321 events; HR, 1.36; 95% CI, 1.09 to 1.70; p= 0.006). The incidence of major bleeding—defined as Bleeding Academic Research types 3, 4, and 5—was 5.4% and 4.8%, respectively (175 events; HR, 1.12; 0.83 to 1.51; p= 0.46). It discusses limitations of this current study; namely subgroup analyses are usually underpowered, and if no subgroup effect is demonstrated, caution is usually needed in interpreting whether a subgroup effect has been excluded. It notes that adherence to study medication was suboptimal, decreasing the power to identify a treatment effect; however, suboptimal adherence in a trial comparing 2 active drugs may introduce bias if the reasons for poor adherence differ across groups and result in an imbalance of prognosis across the treatment groups among the adherent patients. Also for for randomisation, the investigators used sealed opaque envelopes, which previous research has shown to be vulnerable to deciphering of assignments by clinicians and others. It concludes that despite these limitations, these data provide important evidence supporting the modified dosing algorithm for prasugrel in elderly or underweight patients, though it is important to point out that the risks for both efficacy and safety end points were at least double in the elderly or low-weight group than in the neither elderly nor low-weight group, suggesting that these patients face a much higher risk for adverse events, independent of the treatment strategy used.


Annals of Internal Medicine

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