Remote Ischaemic Preconditioning Causes Pathway Specific Attenuation of Platelet Glycoprotein IIb-IIIa Activation in Response to Potent In-Vitro Agonist Stimulation in Spite of Dual Antiplatelet Therapy

Abstract

Introduction: Remote ischaemic preconditioning (RIPC) leads to reduced myocardial injury after elective and primary PCI, with the mechanism unclear. Dual antiplatelet therapy (DAPT) is important during PCI and reduces thrombotic events. Our aim was to investigate the effect of RIPC on circulating platelet activation. Methods: Patients referred for cardiac catheterisation were invited to participate prior to their procedure and were randomised to RIPC (3 × 5 min 200 mmHg sphygmomanometer inflations, left arm, separated by 5 min deflations) or sham. Venous blood was collected from the contralateral cubital fossa before and immediately after RIPC/sham. Whole blood was incubated with antibodies against CD62P, CD63 and active GPIIb-IIIa (PAC-1) and stimulated with ADP, TRAP6, thrombin + - collagen before analysis by flow-cytometry. Results: Fifty-five patients (29 RIPC, 26 sham) were recruited, mean age 62.7 years, 87% male. There were no differences between the groups with respect to baseline characteristics and medications. DAPT amongst RIPC and sham groups was similar (72% vs 81%, p = 0.54). Compared to aspirin alone, DAPT was effective at reducing GPIIb-IIIa activation in response to ADP (65.5% vs 41.5%, p = 0.001) with less effect against thrombin + collagen (81.1% vs 75.0%, p = 0.31). RIPC reduced GPIIb-IIIa activation in response to TRAP6 (48.4% vs 44.2%, p = 0.003) and thrombin + collagen (78.9% vs 68.8%, p < 0.001) in-spite of dual antiplatelet therapy. There were no changes with other agonists, other platelet markers or with sham treatment. Conclusions: RIPC causes rapid attenuation of platelet GPIIb-IIIa activation to potent agonists, against which DAPT is relatively ineffective. This effect may contribute to the benefit during PCI.