Concomitant administration of clopidogrel with statins or calcium-channel
blockers: insights from the TRITON-TIMI 38 (trial to assess improvement in
therapeutic outcomes by optimizing platelet inhibition with
prasugrel-thrombolysis in myocardial infarction 38).
Author(s): Ojeifo O(1), Wiviott SD(2), Antman EM(2), Murphy SA(2), Udell JA(3), Bates ER(4),
Mega JL(2), Sabatine MS(2), O'Donoghue ML(5).
Affiliation(s): Author information:
(1)Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
(2)TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston,
Massachusetts.
(3)Division of Cardiology, Women's College Hospital, University of Toronto, Toronto,
Ontario, Canada.
(4)Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
(5)TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston,
Massachusetts. Electronic address: modonoghue@partners.org.
Publication date & source: 2013, JACC Cardiovasc Interv. , 6(12):1275-81
OBJECTIVES: This study sought to evaluate the clinical relevance of potential
clopidogrel drug-drug interactions.
BACKGROUND: Some studies have demonstrated that statins and calcium-channel
blockers (CCBs) may attenuate the pharmacodynamic effects of clopidogrel.
METHODS: The TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes
by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial
Infarction 38) enrolled 13,608 patients with an acute coronary syndrome (ACS) and
planned percutaneous coronary intervention (PCI), and randomized them to
clopidogrel or prasugrel. Use of a statin or CCB was left to the discretion of
the treating physician. A multivariable Cox model with propensity score was
employed to evaluate the association between statin or CCB use and clinical
outcomes.
RESULTS: Of the 6,795 subjects assigned to clopidogrel, 4,794 (70.6%) were on a
CYP3A4-metabolized statin, and 966 (14.2%) were on a CCB at randomization. The
risk of cardiovascular (CV) death, myocardial infarction (MI), or stroke was
similar regardless of baseline use of statins (adjusted hazard ratio [HR]: 1.02,
95% confidence interval [CI]: 0.85 to 1.22) or CCBs (adjusted HR: 1.16; 95% CI:
0.94 to 1.43) in clopidogrel-treated patients. Further, the combined use of a CCB
and atorvastatin 80 mg daily (adjusted HR: 0.82; 95% CI: 0.37 to 1.84), or a CCB,
statin, and proton pump inhibitor (adjusted HR: 1.04; 95% CI: 0.70 to 1.54) were
not associated with an increased risk of CV death, MI, or stroke. The use of
statins or CCBs did not modify the relative efficacy of prasugrel versus
clopidogrel for the primary endpoint (p for interaction = 0.43, 0.55,
respectively).
CONCLUSIONS: In patients with ACS undergoing PCI, the use of statins or CCBs was
not associated with an increased risk of CV events in clopidogrel-treated
patients. Consistent results were observed when the drugs were administered
alone, together, or in combination with proton pump inhibitors.
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