Bleeding events and maintenance dose of prasugrel: BLESS pilot study

Nazario Carrabba, Guido Parodi, Rossella Marcucci, Renato Valenti, Anna Maria Gori, Angela Migliorini, Vincenzo Comito, Benedetta Bellandi, Rosanna Abbate, Gian Franco Gensini, David Antoniucci, Nazario Carrabba, Guido Parodi, Rossella Marcucci, Renato Valenti, Anna Maria Gori, Angela Migliorini, Vincenzo Comito, Benedetta Bellandi, Rosanna Abbate, Gian Franco Gensini, David Antoniucci

Abstract

Objective: To evaluate changes in residual platelet reactivity (RPR) over time, and bleeding and ischaemic events rate using 5 vs 10 mg maintenance dose (MD) regimens of prasugrel 1 month after acute coronary syndrome (ACS).

Background: The optimal level of RPR with prasugrel may change over time after an ACS.

Methods: After 60 mg loading dose of prasugrel (T0) followed by 10 mg/day for 1 month, patients were randomised to receive prasugrel 10 mg/day (n=95, group A) or 5 mg/day MD (n=98, group B) up to 1 year. RPR was assessed at T0, 37 (T1) and 180 days (T2). The primary end point was Bleeding Academic Research Consortium (BARC) bleeding events ≥2 between 1 and 12 months, and the secondary composite end point was cardiac death, myocardial infarction, stroke and definite/probable stent thrombosis.

Results: From T0 to T1, RPR significantly increased in both groups A and B and the increase was higher for group B (δ ADP 10 µmol: 13.8%±14.7% vs 23.5%±19.2%, p=0.001). At T2 a lower rate of high RPR patients were found in group A (2.6% vs13.3%; p=0.014). The BARC type ≥2 bleeding occurred in 12.6% of group A versus 4.1% of group B (OR 0.29, 95% CI 0.09 to 0.94) and secondary end point in 2.1% vs 1.0% (p=0.542), respectively, without stent thrombosis.

Conclusions: RPR increases shifting from 60 mg loading dose to 10 mg/day prasugrel MD with a further increase of RPR reducing prasugrel MD to 5 mg 1 month after ACS. Clinical value of these pharmacodynamic findings should be proved in larger clinical trials.

Trial registration number: NCT01790854.

Keywords: PERCUTANEOUS CORONARY INTERVENTION; PHARMACOLOGY.

Conflict of interest statement

GP reported receiving consulting fee from: AstraZeneca, Eli Lilly, The Medicines Company and Bayer. RM reported receiving honoraria for lectures from Daiichi Sankyo/Eli Lilly and Merck Sharp & Dohme. RA reported receiving consulting fees from Eli Lilly; lecture fees from Instrumentation Laboratory and Sigma Tau; and research grant funding from Bayer, BoehringerIngelheim and Pfizer. GFG reported receiving consulting fees from Bayer, BoehringerIngelheim and Eli Lilly; lecture fees from AstraZeneca, GlaxoSmithKline, Instrumentation Laboratory, Menarini and Sigma Tau; and research grant funding from Novo Nordisk, Merck Sharp & Dohme, Pfizer, Pierrel, Sanofi-Aventis and Servier. DA reported receiving consulting fees from Daiichi Sankyo/Eli Lilly and The Medicines Company and serving on the advisory boards of Cordis and CID.

Figures

Figure 1
Figure 1
BLESS trial flow chart. ACS, acute coronary syndrome; BLESS, Bleeding Events and Maintenance Dose of Prasugrel; PCI, percutaneous coronary intervention.
Figure 2
Figure 2
Time course and magnitude of changes of RPR within group B prasugrel 10/5 mg/day (─○─) and group A prasugrel 10/10 mg/day (─□─) and between groups. RPR, residual platelet reactivity.
Figure 3
Figure 3
BARC type ≥2 bleeding-free survival according to the treatment with 5 mg/day prasugrel MD group B (─), or 10 mg/day prasugrel MD group A (─). Event rates were compared by log-rank test. BARC, Bleeding Academic Research Consortium; MD, maintenance dose.

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Source: PubMed

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