Evolving pattern of platelet P2Y₁₂inhibition in patients with acute coronary syndromes

Abstract

Dual antiplatelet therapy consisting of clopidogrel in addition to aspirin has previously been the standard of care for patients with acute coronary syndromes (ACS) but international guidelines have been evolving over the last 4 years with the introduction of prasugrel and ticagrelor. In October 2009, prasugrel was approved in the UK by the National Institute of Health and Clinical Excellence (NICE) for use in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), diabetic patients with non-ST-elevation (NSTE) ACS undergoing PCI and patients with stent thrombosis while other ACS patients were to continue receiving clopidogrel. Ticagrelor was approved in October 2011 by NICE for use in patients with moderate-to-high risk NSTE ACS and STEMI undergoing primary PCI and was recommended in preference to clopidogrel in European guidelines. These recommendations were adopted in our region, constituting a population of 1.8 million. We studied the effect of changing patterns of P2Y12 inhibitor usage on levels of platelet inhibition during maintenance therapy. Patients admitted to Northern General Hospital, Sheffield, with NSTE ACS or STEMI managed with primary PCI were enrolled over two periods of time: May 2010 to November 2011 (T1); and October 2012 to February 2013 (T2). Venous blood samples were obtained at 1 month after the onset of ACS. Light transmittance aggregometry (LTA) was performed and maximum aggregation response to ADP 20 μM was determined. A total of 116 patients were enrolled in T1 of whom 82 were receiving clopidogrel and 34 were receiving prasugrel. Twenty-nine patients were enrolled in T2, all of whom were receiving ticagrelor. Mean LTA results according to treatment with clopidogrel, prasugrel and ticagrelor were 57 ± 18%, 41 ± 20%, and 31 ± 12%, respectively. Prasugrel was associated with significantly lower platelet aggregation responses than clopidogrel (p < 0.001) and ticagrelor was associated with significantly lower platelet aggregation responses than both prasugrel (p = 0.015) and clopidogrel (p < 0.001). We conclude that international guidelines and NICE approval have led to increasing levels of P2Y12 inhibition in ACS patients in this UK centre between May 2010 and February 2013. Ticagrelor was associated with significantly greater P2Y12 inhibition than both clopidogrel and prasugrel during maintenance therapy.

Aspirin, clopidogrel and prasugrel monotherapy in patients with type 2 diabetes mellitus: a double-blind randomised controlled trial of the effects on thrombotic markers and microRNA levels

“…Prasugrel provided the strongest effect on ADP-induced platelet aggregation, as did aspirin on AA-induced aggregation. Prasugrel also provided greater and more consistent inhibition of ADP-induced platelet aggregation when compared to clopidogrel, in agreement with previous studies on populations with and without diabetes receiving dual antiplatelet therapy [44,48] and of studies of prasugrel vs. clopidogrel loading doses when given as SAPT [49]. In concert with this was the fact that there was a large reduction in the proportion of patients with HRPR when receiving clopidogrel vs. aspirin, and again when receiving prasugrel vs. either comparator.…”

“…Monotherapy with clopidogrel offers only modest clinical benefits over aspirin in the setting of secondary prevention, but these may be amplified in those with T2DM [11]. Furthermore, the newer P2Y 12 inhibitors ticagrelor and prasugrel are more potent and consistent in effect than clopidogrel [44]. Certainly, when given in combination with aspirin, ticagrelor and prasugrel offer net clinical benefit after ACS [6].…”

Monitoring Antiplatelet Therapy

“…18 Over the last 20 years, however, PFTs have been used in some centers for monitoring antiplatelet therapy, since a suboptimal response to the antiplatelet regimen may be associated with cardiovascular, cerebrovascular, and peripheral arterial events. 19 PFTs have also become important in the assessment of bleeding risk pre-and perioperatively for patients undergoing surgical procedures or posttrauma. 6,20 PFT is also used in the assessment of platelet function in transfusion medicine pre-and posttransfusion.…”

Comparison of P2Y12 inhibitors for mortality and stent thrombosis in patients with acute coronary syndromes: Single center study of 10 793 consecutive ‘real-world’ patients

“…For patients undergoing PCI, the procedure and adjunctive pharmacotherapy was at the discretion of the operator, but adhered to relevant local, national, and international guidelines. Consequently, there was a gradual evolution of treatment during the course of the study from use of clopidogrel as the only P2Y 12 inhibitor in 2009 to introduction of the option of prasugrel in 2010, predominantly for STEMI, followed by the introduction of ticagrelor as first-line therapy in February 2012, according to our previously published protocols that included the prescription of high-intensity statin therapy, angiotensin pathway inhibitors and beta-blockers throughout the study period [16]. Of particular note, dual antiplatelet therapy for 12 months for all ACS patients was the default approach throughout the study period.…”