Calcium-channel blockers decrease clopidogrel-mediated platelet inhibition.
BACKGROUND
The extent of clopidogrel-mediated platelet inhibition varies considerably from one person to the next. Numerous studies have shown that low responders have significantly more adverse events after coronary stenting than patients who respond well to antithrombotic treatment with clopidogrel. Dihydropyridine calcium-channel blockers (CCBs) inhibit the cytochrome P450 3A4 enzyme, which metabolises clopidogrel to its active form.


OBJECTIVE
To investigate the influence of CCBs on clopidogrel-mediated platelet inhibition.


METHODS
Adenosine-5-diphosphate (ADP)-inducible platelet reactivity was assessed by light transmission aggregometry (LTA) and the VerifyNow P2Y12 assay in 162 patients after percutaneous intervention with stent implantation. Results in the fourth quartiles of both assays were considered as high on-treatment residual ADP-inducible platelet reactivity.


RESULTS
Patients with concomitant CCB therapy showed a significantly higher on-treatment platelet reactivity than patients without CCB medication (p=0.001 for both assays). Further, high on-treatment residual ADP-inducible platelet reactivity was significantly more common among patients currently taking CCBs (p=0.001 for LTA and p=0.004 for the VerifyNow P2Y12 assay). A multivariate regression analysis confirmed CCB therapy as an independent predictor of reduced clopidogrel-mediated platelet inhibition (p=0.006 for LTA and p=0.004 for the VerifyNow P2Y12 assay).


CONCLUSIONS
CCBs decrease clopidogrel-mediated platelet inhibition in patients undergoing angioplasty and stenting for cardiovascular disease.
Gremmel
Thomas
T
Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. thomas.gremmel@meduniwien.ac.at
Steiner
Sabine
S
Seidinger
Daniela
D
Koppensteiner
Renate
R
Panzer
Simon
S
Kopp
Christoph W
CW
D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D000077144:Clopidogrel; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011446:Prospective Studies; D015607:Stents; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D002121:Calcium Channel Blockers; D004338:Drug Combinations; D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine