Effects of colchicine on platelet aggregation in patients on dual antiplatelet therapy with aspirin and clopidogrel

Plinio Cirillo, Vittorio Taglialatela, Grazia Pellegrino, Andrea Morello, Stefano Conte, Luigi Di Serafino, Giovanni Cimmino, Plinio Cirillo, Vittorio Taglialatela, Grazia Pellegrino, Andrea Morello, Stefano Conte, Luigi Di Serafino, Giovanni Cimmino

Abstract

Platelets aggregation leading to thrombosis plays a pivotal role in the pathophysiology of acute coronary syndrome (ACS) and of stent thrombosis. Antiplatelet therapy with aspirin plus an ADP-receptor inhibitor (ticagrerol, prasugrel or clopidogrel) is recommended to reduce the risk of other platelet-mediated events. Clopidogrel is recommended in patients with Chronic Coronary Syndromes (CCS) or in ACS patients at high bleeding risk. Unfortunately, up to 30% of patients are non-responders to clopidogrel and show residual high platelet reactivity (HPR). Colchicine (COLC) is a drug with cardiovascular effects. We have demonstrated that COLC might exert protective cardiovascular effects by interfering with cytoskeleton rearrangement, a phenomenon involved in platelet aggregation. Here, we investigate in vitro the effects of colchicine on platelet aggregation of patients on DAPT with clopidogrel. Platelets obtained from 35 CCS patients on therapy with clopidogrel were pre-incubated with COLC 10 µM before being stimulated with ADP (20 µM), or TRAP (25 µM) at 0, 30, 60 and 90 min to measure max aggregation by LTA. Platelets not COLC-preincubated served as controls. Seven patients were pre-selected as clopidogrel non-responders. COLC significantly reduced TRAP-induced platelet aggregation in clopidogrel responders and non-responders. Interestingly, COLC inhibited ADP-induced platelet aggregation in clopidogrel non-responders in which ADP still caused activation despite DAPT. We demonstrate that COLC inhibits platelet aggregation in clopidogrel non-responders with HPR despite DAPT with this ADP receptor-inhibitor. Further in vivo studies should be designed to evaluate the opportunity to prescribe colchicine after ACS/CCS to overcome the clopidogrel limitations in the DAPT therapy.

Keywords: Clopidogrel; Colchicine; DAPT; Platelets.

Conflict of interest statement

All Authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Platelet aggregation in patients’ clopidogrel responders. Panel A, Stimulation with ADP did not cause significant platelet aggregation. Any significant difference was observed after colchicine (COL) preincubation. Panel B, Stimulation with TRAP caused significant platelet aggregation. Preincubation with COL significantly reduced TRAP-induced platelet aggregation. Data are expressed as mean ± SD; *p < 0.05 vs TRAP alone
Fig. 2
Fig. 2
Platelet aggregation in patients’ clopidogrel non-responders. Panel A, Platelets stimulated with ADP showed significant activation. Colchicine (COL) reduced ADP-induced platelet aggregation. Panels B, Stimulation with TRAP caused significant platelet aggregation. Preincubation with COL significantly reduced TRAP-induced platelet aggregation. Data are expressed as mean ± SD; *p < 0.05 vs ADP or TRAP alone

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Source: PubMed

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