Clopidogrel vs. prasugrel vs. ticagrelor in patients with acute myocardial infarction complicated by cardiogenic shock: a pooled IABP-SHOCK II and CULPRIT-SHOCK trial sub-analysis.

AIMS: The aim of this pooled sub-analysis of the Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) and Culprit Lesion Only PCI versus Multivessel PCI in Cardiogenic Shock (CULPRIT-SHOCK) trial was to compare the clinical outcome of patients with acute myocardial infarction complicated by cardiogenic shock treated either with clopidogrel or the newer, more potent ADP-receptor antagonists prasugrel or ticagrelor. METHODS AND RESULTS: For the current analysis the primary endpoint was 1-year mortality and the secondary safety endpoint was moderate or severe bleedings until hospital discharge with respect to three different ADP-receptor antagonists. 856 patients were eligible for analysis. Of these, 507 patients (59.2%) received clopidogrel, 178 patients (20.8%) prasugrel and 171 patients (20.0%) ticagrelor as acute antiplatelet therapy. The adjusted rate of mortality after 1-year did not differ significantly between prasugrel and clopidogrel (hazard ratio [HR]: 0.81, 95% confidence interval [CI] 0.60-1.09, padj = 0.17) or between ticagrelor and clopidogrel treated patients (HR: 0.86, 95% CI 0.65-1.15, padj = 0.31). In-hospital bleeding events were significantly less frequent in patients treated with ticagrelor vs. clopidogrel (HR: 0.37, 95% CI 0.20 -0.69, padj = 0.002) and not significantly different in patients treated with prasugrel vs. clopidogrel (HR: 0.73, 95% CI 0.43 -1.24, padj = 0.24). CONCLUSION: This pooled sub-analysis is the largest analysis on safety and efficacy of three oral ADP-receptor antagonists and shows that acute therapy with either clopidogrel, prasugrel or ticagrelor is no independent predictor of 1-year mortality. Treatment with ticagrelor seems independently associated with less in-hospital moderate and severe bleeding events compared to clopidogrel. This finding might be due to selection bias and should be interpreted with caution.

Extended dual antiplatelet therapy after acute coronary syndrome in Spain: Results from the EPICOR study.

INTRODUCTION: Real-world, country-specific studies of dual antiplatelet therapy (DAPT) duration among survivors of acute coronary syndrome (ACS) are important for improving long-term prognosis. AIMS: To investigate DAPT duration after hospital discharge for ACS in Spain. RESULTS: Data from patients enrolled in the Spanish cohort of the EPICOR (long-tErm follow-up of antithrombotic management Patterns In acute CORonary syndrome patients) study (NCT01171404) were analyzed for changes to antithrombotic medication up to 2 years postdischarge according to index event diagnosis and patient characteristics. Deaths, coronary events, and bleeding events were analyzed over the same period. Overall, a high proportion of patients remained on DAPT at 2 years (53.1%). Among patients who experienced any on-treatment bleeding event, almost two-thirds remained on DAPT at the end of follow-up. Patients >65 years, diabetic, or those that were medically managed were more likely to continue with DAPT until 2 years following discharge. At 2 years, the incidence of bleeding events requiring hospitalization was low compared with the incidence of coronary events (1.4% vs 6.6%). There was a numerical reduction in coronary events, but no increase in bleeding events, with DAPT continuation compared with single antiplatelet therapy. CONCLUSIONS: More than half of patients in this unselected cohort study remained on DAPT at 2 years following discharge for ACS. Continuation with DAPT was greater among patients with additional cardiovascular risk factors, which suggests that treating physicians in Spain prioritizes ischemic risk reduction over bleeding risk in patients with ACS, according to patient's risk profile.

Proton Pump Inhibitors in Cardiovascular Disease: Drug Interactions with Antiplatelet Drugs.

Aspirin and P2Y12 receptor antagonists are widely used across the spectrum of cardiovascular diseases. Upper gastrointestinal complications, including ulcer and bleeding, are relatively common during antiplatelet treatment and, therefore, concomitant proton pump inhibitor (PPI) treatment is often prescribed.PPIs provide gastroprotection by changing the intragastric milieu, essentially by raising intragastric pH. In recent years, it has been heavily discussed whether PPIs may reduce the cardiovascular protection by aspirin and, even more so, clopidogrel. Pharmacodynamic and pharmacokinetic studies suggested an interaction between PPIs and clopidogrel, and subsequent clinical studies were conducted to evaluate the clinical impact of this interaction. More recently, it was reported that PPIs may also attenuate the antiplatelet effect of aspirin. This may be clinically important, because a fixed combination of aspirin and a PPI (esomeprazole) has recently been approved and because aspirin is the most widely used drug in patients with cardiovascular disease. The antiplatelet effect of the new P2Y12 receptor antagonists, ticagrelor and prasugrel, seems less influenced by PPI co-treatment.Given the large number of patients treated with antithrombotic drugs and PPIs, even a minor reduction of platelet inhibition potentially carries considerable clinical impact. The present book chapter summarizes the evidence regarding the widespread use of platelet inhibitors and PPIs in combination. Moreover, it outlines current evidence supporting or opposing drug interactions between these drugs and discusses clinical implications.

High prevalence of pharmacologically induced platelet dysfunction in the acute setting of brain injury.

BACKGROUND: The management of patients with traumatic brain injury (TBI), primary intracerebral hemorrhage (pICH) and primary subarachnoid hemorrhage (pSAH) remains a highly demanding challenge in critical care medicine. Antithrombotic agents are one of the most relevant risk factors for poor outcome. However, in the acute setting of brain injury, information on preexisting medication might not be available. This group of patients is insufficiently characterized regarding pharmacologically induced platelet impairment. METHODS: We retrospectively analyzed consecutive patients with TBI, pICH and pSAH admitted to our department with unknown preexisting medication. The impact of acetylsalicylic acid and ADP-receptor antagonists on platelet function was tested via the Multiplate analyzer. Patients' characteristics, management and the influence of platelet impairment on outcome were evaluated. RESULTS: Within 25 months 103 patients with TBI (61), pICH (32) or pSAH (10) and unknown antithrombotic medication were admitted to our department. In 54 (52.4 %) of the patients reduced platelet function was detected, mainly caused by acetylsalicylic acid. In the TBI group, 30 patients (49.2 %) were identified, while Multiplate analysis detected platelet dysfunction in 19 (59.4 %) subjects in the pICH group and 5 in the pSAH group (50 %). In multivariable analysis the pathological Multiplate result was not associated with worse outcome; however, in our cohort 47 (87 %) patients received hemostatic therapy following detection of impaired platelet function. CONCLUSION: Our results demonstrate the high frequency of pharmacologically impaired platelet function in patients with unknown preexisting medication. Early assessment of platelet function is an important tool to allow optimized treatment in these patients.

Pharmacogenomics in cardiovascular disease: focus on aspirin and ADP receptor antagonists.

Antiplatelet agents like aspirin and adenosine diphosphate receptor antagonists are effective in reducing recurrent ischemic events. Considerable inter-individual variability in the platelet inhibition obtained with these drugs has initiated a search for explanatory mechanisms and ways to improve treatment. In recent years, numerous genetic polymorphisms have been linked with reduced platelet inhibition and lack of clinical efficacy of antiplatelet drugs, particularly clopidogrel and aspirin. Consequently, attempts to adjust antiplatelet treatment according to genotype have been made, but the clinical benefit has been modest in studies performed so far. The progress in genome science over the last decade and the declining cost of sequencing technologies hold the promise of enabling genetically tailored antiplatelet therapy. However, more evidence is needed to clarify which polymorphisms may serve as targets to improve treatment. The present review outlines the panel of polymorphisms affecting the benefit of aspirin and adenosine diphosphate receptor antagonists, including novel and ongoing studies evaluating whether genotyping may be beneficial in tailoring antiplatelet therapy.