High on-treatment platelet reactivity with ticagrelor versus prasugrel: a systematic review and meta-analysis.

BACKGROUND: Ticagrelor and prasugrel have shown superiority over clopidogrel. However, it remains unclear if one is superior to another regarding on-treatment platelet reactivity. OBJECTIVES: To compare the impact of ticagrelor and prasugrel on high on-treatment platelet reactivity (HTPR). METHODS: The PubMed and Cochrane databases were searched for eligible studies in December 2014. Studies were eligible if they compared ticagrelor and prasugrel regarding high on-treatment platelet reactivity (HTPR). Pooled estimates were calculated by using a random-effects model with 95% confidence intervals. RESULTS: We included 14 studies and 1822 patients: 805 and 1017 in the ticagrelor and prasugrel groups, respectively. The rate of HTPR was significantly lower in the ticagrelor group: 1.5% vs. 9.8% (RR = 0.27 [0.14-0.50]). The pre-specified analysis focusing on randomized trials (n = 10) showed consistent results (RR = 0.27 [0.12-0.60]). CONCLUSION: Our results suggest that ticagrelor allows a higher platelet reactivity inhibition as compared with prasugrel and leads to a further decrease in the rate of HTPR.

Antithrombotic therapy in diabetic patients with coronary artery disease.

In case of coronary artery disease (CAD), diabetic patients are at higher risk than their non-diabetic counterparts. Antithrombotics are therefore of key importance to decrease the risk of ischemic complications. A careful assessment of the benefit-risk balance is however needed to limit the risk of bleeding. Diabetic CAD patients are characterized by a pro-thrombotic milieu and by an impaired response to both aspirin and P2Y12 receptor inhibitors, especially to clopidogrel. When combined with aspirin, the new P2Y12 receptor inhibitors prasugrel and ticagrelor provide superior efficacy for the diabetic patients with acute coronary syndromes. In stable CAD, antiplatelet monotherapy (aspirin) remains for the time being the reference treatment for diabetic as well as for non-diabetic patients; further studies are however ongoing to test whether the antithrombotic strategy should be reinforced, particularly in case of diabetes mellitus. Finally, although chronic oral anticoagulation is rarely indicated for CAD management in itself, it is often prescribed for the concomitant treatment of atrial fibrillation. The combination of anticoagulation and antiplatelet therapy is associated with a high risk of bleeding and should only be prescribed for limited periods of time when the estimated benefits exceed the risks.

[Therapeutic hypothermia and management of sudden death]. / Hypothermie thérapeutique et prise en charge de la mort subite.

Due to its protective effects on the brain and potentially the myocardium, cooling therapy is clearly part of the standard of care of any sudden death especially in the setting of myocardial infarction. Recent guidelines recommend cooling therapy (32 to 34 °C) for 12 to 24 hours in unconscious patients with spontaneous circulation after resuscitated sudden death. We provide here a review of clinical evidence, cooling techniques and potential adverse effects of cooling therapy.

Relationship between post-treatment platelet reactivity and ischemic and bleeding events at 1-year follow-up in patients receiving prasugrel.

BACKGROUND: Post-treatment platelet reactivity (PR) is associated with ischemic and bleeding events in patients receiving P2Y12 receptor antagonists. OBJECTIVES: We aimed to study the relationship between post-treatment PR after a 60-mg loading dose (LD) of prasugrel and 1-year thrombotic and bleeding events. METHOD: Patients were prospectively included in this multicenter study if they had a successful percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) and received prasugrel. The platelet reactivity index (PRI) was measured using the Vasodilator-Stimulated Phosphoprotein index (VASP) after a prasugrel LD. Endpoints included the rate of thrombotic events and bleeding events at 1 year. RESULTS: Among the 301 patients enrolled, 9 (3%) were lost to follow-up at 1 year. The rates of thrombotic and bleeding events at 1 year were of 7.5% and 6.8%, respectively. Receiver-operating curve (ROC) analysis demonstrated an optimal cut-off value of 53.5% of PRI to predict thrombotic events at 1 year. Using this cut-off value we observed that patients exhibiting high on-treatment platelet reactivity (HTPR) had a higher rate of thrombotic events (22.4% vs. 2.9%; P < 0.001). In parallel the optimal cut-off value of PRI to predict bleeding was 16%. Patients with a PRI ≤ 16% had a higher rate of bleeding events compared with those with a PRI > 16% (15.6% vs. 3.3%; P < 0.001). In multivariate analysis, the PRI predicted both thrombotic and bleeding events (OR: 1.44, 95% confidence interval [CI]: 1.2-1.72; P < 0.001 and OR: 0.75, 95% CI: 0.59-0.96; P = 0.024 [respectively, per 10% increase]). CONCLUSION: Platelet reactivity measurement after a prasugrel LD predicts both ischemic and bleeding events at 1 year follow-up for ACS patients undergoing PCI.

[Decreasing incidence of stent thrombosis]. / La thrombose de stent, de plus en plus rare !

Stent thrombosis (ST) remains a major pitfall of stent implantation in contemporary percutaneous coronary intervention (PCI) leading to high rates of death and non-fatal myocardial infarction. Many predictors of ST have been reported worldwide but the strongest have to be highlighted regarding the catastrophic prognosis of such an event. Because platelet aggregation has a pivotal role in ST pathogenesis, the new antiplatelet regimens combining aspirin and P2Y12 receptor inhibitors have led to a remarkable decrease in the ST incidence, especially in the setting of acute coronary syndrome (ACS). In this article, our purpose is to review the evolution of ST incidence since first stent use in PCI. We will also overview the main predictors of ST focusing on ACS and clopidogrel low response.

A critical appraisal of the safety and efficacy of drug-eluting stents.

Drug-eluting stents (DESs) have largely demonstrated their superiority to bare-metal stents (BMSs) with respect to in-stent restenosis. Since the US Food and Drug Administration (FDA) approved the first DES in 2003, there has been a significant increase in the use of these devices. They are used in 70-80% of all stent procedures worldwide. Nevertheless, safety concerns stemming from reports of increased risk of late stent thrombosis (ST) and myocardial infarction (MI) have tempered the enthusiasm that the advent of these stents originally generated. New generation DESs with novel polymers, antiproliferative drugs, and improved platforms are now approved and available for use. In this review we provide a critical appraisal, based on published clinical data, of the safety and efficacy of various DESs.

Emergence of the concept of platelet reactivity monitoring of response to thienopyridines.

Clinical trials have demonstrated the beneficial impact of clopidogrel in preventing major adverse cardiovascular events (MACE), particularly in patients undergoing percutaneous coronary intervention (PCI). The concept of biological clopidogrel resistance emerged with the finding of persistent platelet activation despite clopidogrel therapy in some patients. Further, a link between biological clopidogrel resistance and thrombotic recurrence after PCI was observed and a threshold of platelet reactivity (PR) for thrombotic events was suggested. Consistently, in recent trials, enhanced PR inhibition translated into a reduction in the rate of MACE after PCI. This review aims to present the emergence of the concept of PR monitoring in patients undergoing PCI following recent advances in this field.