Calcium-Channel Blockers Attenuate the Antiplatelet Effect of Clopidogrel
Thomas Gremmel1, Markus Durstberger1, Beate Eichelberger2
1Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
Insights
Dihydropyridine calcium-channel blockers (CCBs) reduce clopidogrel
Area of Science:
- Cardiology
- Pharmacology
- Hematology
Background:
- Dihydropyridine calcium-channel blockers (CCBs) are known to inhibit cytochrome 3A4.
- This inhibition may interfere with the conversion of clopidogrel to its active metabolite.
- The direct impact of CCBs on clopidogrel's antiplatelet effect, measured by platelet activation assays, remains understudied.
Purpose of the Study:
- To investigate the effect of CCBs on adenosine diphosphate (ADP)-induced platelet activation in patients treated with clopidogrel.
- To assess platelet activation using flow cytometry, specifically measuring P-selectin expression and activated glycoprotein (GP) IIb/IIIa.
- To determine if CCB use influences the antiplatelet efficacy of clopidogrel.
Main Methods:
- Flow cytometry was used to measure platelet surface P-selectin and activated GP IIb/IIIa.
- Measurements were taken in response to ADP stimulation in 302 patients on dual antiplatelet therapy (aspirin and clopidogrel) post-angioplasty with stent implantation.
- Patients were categorized based on concomitant CCB use (92 patients, 30.5%) versus no CCB use.
Main Results:
- Patients on CCBs exhibited significantly higher P-selectin and activated GP IIb/IIIa expression in response to ADP compared to those without CCBs (P ≤ 0.03).
- The fold increase in these markers upon ADP stimulation was also significantly more pronounced in patients taking CCBs (P ≤ 0.03).
- These associations remained significant after multivariate regression analysis, indicating an independent effect of CCBs on clopidogrel response.
Conclusions:
- Concomitant use of dihydropyridine CCBs attenuates the antiplatelet effect of clopidogrel.
- This attenuation is evident in reduced ADP-induced platelet activation, as measured by P-selectin and activated GP IIb/IIIa.
- The findings suggest a potential clinical implication for managing antiplatelet therapy in patients using both clopidogrel and CCBs.
Aims:
Dihydropyridine calcium-channel blockers (CCBs) inhibit cytochrome 3A4 and could therefore interfere with the conversion of clopidogrel to its active form. The impact of CCBs on the antiplatelet effect of clopidogrel has not been studied with assays directly capturing platelet activation to adenosine diphosphate (ADP), so far. We therefore sought to investigate platelet activation in response to ADP by flow cytometry in clopidogrel-treated patients without and with CCBs.
Methods:
Platelet surface P-selectin expression and activated glycoprotein (GP) IIb/IIIa in response to ADP were determined by flow cytometry in 302 patients on dual antiplatelet therapy with aspirin and clopidogrel after successful angioplasty with stent implantation.
Results:
Ninety-two patients (30.5%) received CCBs. Patients with concomitant CCB therapy showed significantly higher platelet surface expressions of P-selectin and activated GPIIb/IIIa in response to ADP than patients without CCBs (both P ≤ 0.03). Moreover, the fold increase of P-selectin and activated GPIIb/IIIa in response to ADP was significantly more pronounced in patients taking CCBs (both P ≤ 0.03). The associations of ADP-inducible activated GPIIb/IIIa and fold increase of activated GPIIb/IIIa after the addition of ADP with CCB therapy remained significant after adjustment for differences in patient characteristics and factors that were previously associated with clopidogrel response by multivariate regression analyses (both P < 0.05). High levels of ADP-inducible P-selectin and activated GPIIb/IIIa were seen significantly more frequent in patients with CCBs than in patients without CCB therapy (both P ≤ 0.01).
Conclusion:
Dihydropyridine CCBs attenuate the effect of clopidogrel on ADP-inducible platelet activation in patients undergoing angioplasty and stenting for cardiovascular disease.
More Related Videos
09:13Turbidimetry on Human Washed Platelets: The Effect of the Pannexin1-inhibitor Brilliant Blue FCF on Collagen-induced Aggregation
Published on: April 6, 2017
07:13Author Spotlight: Developing Parmodulins to Target Protease-Activated Receptors for Inflammation Control
Published on: May 24, 2024
Related Concept Videos
01:25Antianginal Drugs: Calcium Channel Blockers and Ranolazine
CCBs, a diverse class that includes dihydropyridines (nifedipine) and diphenylalkylamines (verapamil and diltiazem), exert their effect by blocking calcium channels in cardiac and smooth muscle cells. This...
01:18Antihypertensive Drugs: Action of Calcium Channel Blockers
01:20Antiarrhythmic Drugs: Class IV Agents as Calcium Channel Blockers
Verapamil, a calcium channel blocker, inhibits calcium movement across myocardial cell membranes and vascular smooth muscle. This results in the dilation of coronary and...
01:20Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
01:17Antiepileptic Drugs: Calcium Channel Blockers
Calcium channel blockers exert their antiepileptic effects by targeting T-type calcium channels, which are integral to transmitting nerve signals in the central nervous system. These channels allow the passage of calcium ions, which are vital for neuronal communication. By inhibiting T-type calcium channels, calcium channel blockers effectively reduce the release of neurotransmitters and...
01:22Antiarrhythmic Drugs: Class I Agents as Sodium Channel Blockers
Class 1A Antiarrhythmic Drugs: These drugs work by moderately blocking sodium channels,...