Impact of Calcium Channel Blockers on Aspirin Reactivity in Patients With Coronary Artery Disease

Abstract Purpose: Calcium channel blockers (CCBs) do not reduce the risk of initial or recurrent myocardial infarction (MI) in patients diagnosed with stable coronary artery disease (CAD). The aim of this current study was to evaluate the association between CCBs and aspirin resistance in patients with CAD. Methods: Patients with stable CAD who were regularly taking aspirin (75-100 mg qd) for at least one month prior to enrollment in the study were included. The VerifyNow system was used for platelet function testing with high on-aspirin platelet reactivity (HAPR) defined as aspirin reaction units (ARU) >550. We compared patients treated with CCBs versus control group. Results: 503 patients with CAD were included in this study, 88 were treated with CCBs; Mean age (67.9±9.7 in the CCB group vs 66.5±11.4 in the control group, p=0.288), gender (77.3 male vs. 82.9%, p=0.214) and rates of diabetes mellitus (34.7 vs. 36.9%, p=.121) were similar. Rates of hypertension were higher in the CCB group (83.9 vs. 63.5%, p<0.01), but rates of past MI were lower (47.1 vs. 59.7%, p=0.039). The mean ARU was 465.4P70.0 for patients treated with CCBs versus 445.2u60.0 in controls (p=0.006). Similarly, 15.9% of CCB patients demonstrated HAPR compared to 7.0% (p=0.006). In a multivariate analysis, the administration of CCBs was independently associated with HAPR (OR- 1.72, 95% CI 1.04 – 8.91, p=0.047). Conclusions: Usage of CCBs is positively correlated with aspirin resistance. These findings may suggest an adverse pharmacologic effect of CCBs among patients with stable CAD treated with aspirin.

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Abstract 1716: Calcium Channel Blockers Reduce the Antiplatelet Effect of Clopidogrel

Circulation ◽

10.1161/circ.118.suppl_18.s_375-a ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Jolanta Siller-Matula ◽

Irene Lang ◽

Guenter Christ ◽

Bernd Jilma

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Platelet Aggregation ◽

Calcium Channel ◽

Calcium Channel Blocker ◽

Calcium Channel Blockers ◽

Channel Blocker ◽

Platelet Reactivity ◽

Channel Blockers ◽

Artery Disease

Due to the known CYP3A4 inhibition by calcium channel blockers, we hypothesized that there might be a pharmacodynamic interaction between clopidogrel and dihydropyridines in patients with coronary artery disease (CAD). Clopidogrel is activated by CYP3A4 which also metabolizes calcium channel blockers of the dihydropyridine class. Methods: Responsiveness to clopidogrel was assessed by the vasodilator stimulated phosphoprotein (VASP) phosphorylation assay and aggregometry in 200 patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). The platelet reactivity index (PRI in the VASP assay, normal range 69–100%) was higher in patients on both clopidogrel and calcium channel blockers (61%) as compared to patients on clopidogrel without calcium channel blockers (48%). The absolute difference was 13% (95%CI: 6 –20%; p = 0.001) and the relative difference approached 21%. A high post-treatment platelet reactivity (PRI > 69%) was seen in 40% of patients with concomitant calcium channel blocker treatment compared to 20% without (X2-test: p = 0.008). Intake of calcium channel blocker remained an independent predictor of high platelet reactivity after adjustment for cardiovascular risk factors. This corresponded to an increased platelet aggregation of similar magnitude (p < 0.05). In vitro incubation with calcium channel blockers (nimodipine, verapamil, amlodipine and diltiazem) did not alter the PRI or the ADP-induced platelet aggregation of patients on clopidogrel, indicating that the interaction occurs in vivo, conceivably at the level of the CYP3A4 cytochrome. Co-administration of calcium channel blockers is associated with a decreased platelet inhibition by clopidogrel.

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