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Off-label use of prasugrel in stable coronary artery disease is associated with greater degree of platelet inhibition compared with use after acute coronary syndrome

2013; Elsevier BV; Volume: 168; Issue: 3 Linguagem: Inglês

10.1016/j.ijcard.2013.04.052

1874-1754

Thomas Cuisset, Guillaume Cayla, Jacques Quilici, Mathieu Pankert, Pierre Deharo, Guillaume Bonnet, Charlotte Grosdidier, Shirley Beguin, Pierre‐Emmanuel Morange, Jean‐Louis Bonnet, Marie‐Christine Alessi,

Acute Myocardial Infarction Research

Dual antiplatelet therapy with aspirin and clopidogrel has been considered as the gold standard therapy for patients undergoing percutaneous coronary interventions (PCI) and/or after acute coronary syndrome (ACS) [ 1 Bertrand M.E. Rupprecht H.J. Urban P. Gershlick A.H. Investigators F.T. Double-blind study of the safety of clopidogrel with and without a loading dose in combination with aspirin compared with ticlopidine in combination with aspirin after coronary stenting: the clopidogrel aspirin stent international cooperative study (CLASSICS). Circulation. 2000; 102: 624-629 Crossref PubMed Scopus (1030) Google Scholar , 2 Yusuf S. Zhao F. Mehta S.R. Chrolavicius S. Tognoni G. Fox K.K. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001; 345: 494-502 Crossref PubMed Scopus (6004) Google Scholar ]. Recently, new P2Y12 blockers demonstrated their clinical benefit in large randomized controlled trials including ACS patients [ 3 Wiviott S.D. Braunwald E. McCabe C.H. et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007; 357: 2001-2015 Crossref PubMed Scopus (5470) Google Scholar , 4 Wallentin L. Becker R.C. Budaj A. et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009; 36: 1045-1057 Crossref Scopus (5417) Google Scholar ] with a dramatic reduction of stent thrombosis. In spite of lack of any clinical evidence, prasugrel has been also used in ‘real life’ in patients at high risk of stent thrombosis after elective percutaneous coronary intervention (PCI) for stable coronary artery disease (SCAD). Therefore, the purpose of the present study was to compare biological response to prasugrel 10 mg between patients treated for ACS or SCAD. Consecutive patients undergoing PCI and treated with prasugrel were included in the present study. Prasugrel response was assessed by PRI VASP calculated from the median fluorescence intensity (MFI) of samples incubated with PGE1 or PGE1 and ADP according to the formula: PRI VASP = [(MFI(PGE1) − MFI(PGE1+ADP) / MFIPGE1] × 100. High on treatment platelet reactivity (HTPR) was defined as PRI VASP > 50% and very low on-treatment platelet reactivity (VLTPR) as PRI VASP ≤ 10% as previously proposed [ [5] Bonello L. Camoin-Jau L. Arques S. et al. Adjusted clopidogrel loading doses according to vasodilator-stimulated phosphoprotein phosphorylation index decrease rate of major adverse cardiovascular events in patients with clopidogrel resistance: a multicenter randomized prospective study. J Am Coll Cardiol. 2008; 51: 1404-1411 Crossref PubMed Scopus (531) Google Scholar ]. The ethics committee of our institution approved the study protocol, and patients gave written informed consent for participation. The primary endpoints of the present study were defined as prasugrel response among patients treated for stable CAD or CAS with mean PRI VASP, incidence of HTPR and incidence of VLTPR. The clinical endpoints were the occurrence of bleeding events according to the Academic Bleeding Consensus Definitions with type 1, 2, 3 or 5 (type 4 was not expected while no patient had planned coronary artery bypass grafting). Statistical analyses were performed using PASW Statistics version 17.0. Continuous variables were reported as means and standard deviation or as medians and range (according to their distribution), and categorical variables were reported as count and percentages. Odds ratios (OR) were estimated with a 95% confidence interval. For all tests, statistical significance was defined as p < 0.05. 415 consecutive patients undergoing coronary stenting and treated with prasugrel 10 mg at discharge were analyzed, including 388 ACS patients and 27 patients with SCAD. Characteristics of SCAD patients treated with prasugrel are summarized in Table 1, with mean age of 62 ± 10 years, high incidence of diabetes (56%, n = 15) and complex CAD and/or PCI (85% drug eluting stent, 63% multivessel disease, mean stent length of 28 ± 14 mm). Baseline characteristics between ACS and SCAD patients were not significantly different. Prasugrel response was assessed 30 days after discharge by PRI VASP. Patients treated for SCAD had significantly lower PRI VASP values than ACS patients: 22 ± 12% vs. 28 ± 13%, p = 0.03 (Fig. 1). Incidence of HTPR (PRI VASP > 50%) and VLTPR (PRI VASP ≤ 10%), associated respectively with ischemic and bleeding risk in prasugrel patients was also recorded. No SCAD patients had HTPR, while 6% (n = 22/388) of ACS patients had HTPR (p = 0.30). Moreover, patients treated for SCAD had significantly higher incidence of VLTPR: 22% (n = 6/27) vs. 8% (n = 31/388), OR [95% CI]: 3.3 [1.2–8.8]; p = 0.02 (Fig. 1). We observed a trend, although nonsignificant, toward higher incidence of bleeding complications in patients treated for SCAD: 22% (6/27) vs. 15% (58/388), p = 0.20.