Calcium-channel blockers do not alter the clinical efficacy of clopidogrel after myocardial infarction: a nationwide cohort study.
OBJECTIVE
The purpose of this study was to determine the risk of adverse cardiovascular events associated with concomitant use of clopidogrel and calcium-channel blockers (CCBs) in patients with myocardial infarction (MI).


BACKGROUND
CCBs inhibit a variety of cytochrome P-450 enzymes, some of which contribute to clopidogrel metabolic activation. This interaction may diminish the efficacy of clopidogrel.


METHODS
All patients surviving 30 days after a first-time MI in the period 2000 to 2006 in Denmark were identified by individual-level linkage of nationwide administrative registers. The cohort was divided into patients treated with and without clopidogrel and followed for 1 year after discharge. The risk of a composite of cardiovascular death, MI, or stroke and the risk of the individual components of the composite end point and all-cause death associated with CCBs were analyzed with multivariable Cox proportional hazard models and in univariate propensity score-matched models.


RESULTS
A total of 56,800 patients were included, of whom 24,923 were treated with clopidogrel and 13,380 with CCBs. In the Cox analyses, the risk of the composite end point associated with CCBs was increased in both patients treated and not treated with clopidogrel, with a hazard ratio of 1.15 (95% confidence interval [CI]: 1.07 to 1.24) and 1.05 (95% CI: 1.01 to 1.11), respectively. The increased risk was independent of clopidogrel use; the hazard rate ratio was 1.08 (95% CI: 0.99 to 1.18). Analyses of all additional adverse end points and propensity score-matched models provided similar results.


CONCLUSIONS
The clinical efficacy of clopidogrel in patients with a recent MI is not modified by concomitant CCB treatment. This potential drug interaction is unlikely to have clinical significance.
Department of Cardiology, Copenhagen University Hospital Gentofte, Hellerup, Denmark. jo@heart.dk
Jonas B
JB
Olesen
Gunnar H
GH
Gislason
Mette G
MG
Charlot
Emil L
EL
Fosbøl
Charlotte
C
Andersson
Peter
P
Weeke
Ole
O
Ahlehoff
Christian
C
Selmer
Christian
C
Torp-Pedersen
Peter R
PR
Hansen
D000368:Aged; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D002423:Cause of Death; D000077144:Clopidogrel; D015331:Cohort Studies; D016001:Confidence Intervals; D003718:Denmark; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D016016:Proportional Hazards Models; D012042:Registries; D012189:Retrospective Studies; D016019:Survival Analysis; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
D002121:Calcium Channel Blockers; D000077144:Clopidogrel; D013988:Ticlopidine