Objectives The aim of this study was to test whether the left ventricular assist device (LVAD) Impella LP2.5 (Abiomed Europe GmbH, Aachen, Germany) provides superior hemodynamic support compared with ...the intra-aortic balloon pump (IABP). Background Cardiogenic shock caused by left ventricular failure is associated with high mortality in patients with acute myocardial infarction (AMI). An LVAD may help to bridge patients to recovery from left ventricular failure. Methods In a prospective, randomized study, 26 patients with cardiogenic shock were studied. The primary end point was the change of the cardiac index (CI) from baseline to 30 min after implantation. Secondary end points included lactic acidosis, hemolysis, and mortality after 30 days. Results In 25 patients the allocated device (n = 13 IABP, n = 12 Impella LP2.5) could be safely placed. One patient died before implantation. The CI after 30 min of support was significantly increased in patients with the Impella LP2.5 compared with patients with IABP (Impella: ΔCI = 0.49 ± 0.46 l/min/m2 ; IABP: ΔCI = 0.11 ± 0.31 l/min/m2 ; p = 0.02). Overall 30-day mortality was 46% in both groups. Conclusions In patients presenting with cardiogenic shock caused by AMI, the use of a percutaneously placed LVAD (Impella LP 2.5) is feasible and safe, and provides superior hemodynamic support compared with standard treatment using an intra-aortic balloon pump. (Efficacy Study of LV Assist Device to Treat Patients With Cardiogenic Shock ISAR-SHOCK; NCT00417378 )
The addition of clopidogrel to aspirin treatment reduces ischemic events in a wide range of patients with cardiovascular disease. However, recurrent ischemic event occurrence during dual antiplatelet ...therapy, including stent thrombosis, remains a major concern. Platelet function measurements during clopidogrel treatment demonstrated a variable and overall modest level of P2Y12 inhibition. High on-treatment platelet reactivity to adenosine diphosphate (ADP) was observed in selected patients. Multiple studies have now demonstrated a clear association between high on-treatment platelet reactivity to ADP measured by multiple methods and adverse clinical event occurrence. However, the routine measurement of platelet reactivity has not been widely implemented and recommended in the guidelines. Reasons for the latter include: 1) a lack of consensus on the optimal method to quantify high on-treatment platelet reactivity and the cutoff value associated with clinical risk; and 2) limited data to support that alteration of therapy based on platelet function measurements actually improves outcomes. This review provides a consensus opinion on the definition of high on-treatment platelet reactivity to ADP based on various methods reported in the literature and proposes how this measurement may be used in the future care of patients.
Dual-antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor is the standard treatment for patients undergoing percutaneous coronary intervention. The availability of different P2Y12 ...receptor inhibitors (clopidogrel, prasugrel, ticagrelor) with varying levels of potency has enabled physicians to contemplate individualized treatment regimens, which may include escalation or de-escalation of P2Y12-inhibiting therapy. Indeed, individualized and alternative DAPT strategies may be chosen according to the clinical setting (stable coronary artery disease vs. acute coronary syndrome), the stage of the disease (early- vs. long-term treatment), and patient risk for ischemic and bleeding complications. A tailored DAPT approach may be potentially guided by platelet function testing (PFT) or genetic testing. Although the routine use of PFT or genetic testing in percutaneous coronary intervention–treated patients is not recommended, recent data have led to an update in guideline recommendations that allow considering selective use of PFT for DAPT de-escalation. However, guidelines do not expand on when to implement the selective use of such assays into decision making for personalized treatment approaches. Therefore, an international expert consensus group of key leaders from North America, Asia, and Europe with expertise in the field of antiplatelet treatment was convened. This document updates 2 prior consensus papers on this topic and summarizes the contemporary updated expert consensus recommendations for the selective use of PFT or genotyping in patients undergoing percutaneous coronary intervention.
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•Different P2Y12 inhibitors have enabled physicians to contemplate individualized treatment regimens.•In selective scenarios, PFT and genotyping may be used as optional tools for guiding treatment.•Further studies on DAPT de-escalation and escalation are needed to refine existing treatment options.
Although platelet reactivity during P2Y12-inhibitors is associated with stent thrombosis (ST) and bleeding, standardized and clinically validated thresholds for accurate risk stratification after ...percutaneous coronary intervention (PCI) are lacking. We sought to determine the prognostic value of low platelet reactivity (LPR), optimal platelet reactivity (OPR), or high platelet reactivity (HPR) by applying uniform cut-off values for standardized devices.
Authors of studies published before January 2015, reporting associations between platelet reactivity, ST, and major bleeding were contacted for a collaborative analysis using consensus-defined, uniform cut-offs for standardized platelet function assays. Based on best available evidence for each device (exploratory studies), LPR-OPR-HPR categories were defined as <95, 95-208, and >208 PRU for VerifyNow, <19, 19-46, and >46 U for the Multiplate analyser and <16, 16-50, and >50% for VASP assay. Seventeen studies including 20 839 patients were used for the analysis; 97% were treated with clopidogrel and 3% with prasugrel. Patients with HPR had significantly higher risk for ST risk ratio (RR) and 95% CI: 2.73 (2.03-3.69), P < 0.00001, yet a slight reduction in bleeding RR: 0.84 (0.71-0.99), P = 0.04 compared with those with OPR. In contrast, patients with LPR had a higher risk for bleeding RR: 1.74 (1.47-2.06), P < 0.00001, without any further benefit in ST RR: 1.06 (0.68-1.65), P = 0.78 in contrast to OPR. Mortality was significantly higher in patients with HPR compared with other categories (P < 0.05). Validation cohorts (n = 14) confirmed all results of exploratory studies (n = 3).
Platelet reactivity assessment during thienopyridine-type P2Y12-inhibitors identifies PCI-treated patients at higher risk for mortality and ST (HPR) or at an elevated risk for bleeding (LPR).
Summary
Plaque erosions and ruptures are the histopathological hallmarks of arterial thrombus formation in the coronary arteries. The clinical condition associated with this process is usually ...referred to as acute coronary syndrome (ACS). Importantly, both blood platelets and the coagulation cascade are key players for initiation, amplification and perpetuation of ACS. There has been great progress in ACS treatment in recent decades, both at the technical level of (percutaneous) revascularisation and at the level of antithrombotic treatment. Numerous trials have led to significant advancements in the development of effective anticoagulant and antiplatelet drugs. The large number of randomised controlled clinical trials (RCTs) and the huge number of patients enrolled in these RCTs, with mega trials including >10,000 patients, is unique in the history of medical research and also reflects the exceptional efforts associated with these huge research activities. The crucial issue, however, with respect to optimising treatment, relates to finding the delicate balance between the reduction of thrombotic events by effective drug treatment and the induction of bleeding that is linked to the use of potent or multiple antithrombotic agents. Interestingly, there is a gap in modern days between current guideline recommendations favouring potent platelet inhibition in ACS and the utilization of the respective drugs in clinical practice. In this review, we will summarise and discuss the past, present and future antithrombotic treatment for ACS patients with a focus on the development of optimised antiplatelet treatment strategies and their utilisation in the real world.
Objectives This study sought to evaluate whether prasugrel may serve as an alternative to clopidogrel in patients with triple therapy. Background Approximately 10% of patients who receive dual ...antiplatelet therapy after percutaneous coronary intervention have an indication for oral anticoagulation and are thus treated with triple therapy. The standard adenosine diphosphate receptor blocker in this setting is clopidogrel. Data regarding prasugrel as part of triple therapy are not available. Methods We analyzed a consecutive series of 377 patients who underwent drug-eluting stent implantation and had an indication for oral anticoagulation between February 2009 and December 2011 and were treated with a 6-month regimen of aspirin and oral anticoagulation with either prasugrel or clopidogrel. The primary endpoint was a composite of Thrombolysis In Myocardial Infarction (TIMI) major and minor bleeding at 6 months. The secondary endpoint was a composite of death, myocardial infarction, ischemic stroke, or definite stent thrombosis. Results Twenty-one patients (5.6%) received prasugrel instead of clopidogrel. These patients had a higher-risk profile at baseline, and the majority had high platelet reactivity to clopidogrel. TIMI major and minor bleeding occurred significantly more often in the prasugrel compared with the clopidogrel group (6 28.6%) vs. 24 6.7%; unadjusted hazard ratio (HR): 4.6, 95% confidence interval CI: 1.9 to 11.4, p < 0.001; adjusted HR: 3.2, 95% CI: 1.1 to 9.1, p = 0.03). There was no significant difference regarding the combined ischemic secondary endpoint (2 9.5% vs. 25 7.0%; unadjusted HR: 1.4, 95% CI: 0.3 to 6.1, p = 0.61). Conclusions These findings suggest that substitution of prasugrel for clopidogrel in patients needing triple therapy increases the risk of bleeding. However, specific randomized trials are needed to define the role of newer adenosine diphosphate receptor antagonists in this setting.
Dual antiplatelet therapy with aspirin and a P2Y12 receptor blocker is a key strategy to reduce platelet reactivity and to prevent thrombotic events in patients treated with percutaneous coronary ...intervention. In an earlier consensus document, we proposed cutoff values for high on-treatment platelet reactivity to adenosine diphosphate (ADP) associated with post–percutaneous coronary intervention ischemic events for various platelet function tests (PFTs). Updated American and European practice guidelines have issued a Class IIb recommendation for PFT to facilitate the choice of P2Y12 receptor inhibitor in selected high-risk patients treated with percutaneous coronary intervention, although routine testing is not recommended (Class III). Accumulated data from large studies underscore the importance of high on-treatment platelet reactivity to ADP as a prognostic risk factor. Recent prospective randomized trials of PFT did not demonstrate clinical benefit, thus questioning whether treatment modification based on the results of current PFT platforms can actually influence outcomes. However, there are major limitations associated with these randomized trials. In addition, recent data suggest that low on-treatment platelet reactivity to ADP is associated with a higher risk of bleeding. Therefore, a therapeutic window concept has been proposed for P2Y12 inhibitor therapy. In this updated consensus document, we review the available evidence addressing the relation of platelet reactivity to thrombotic and bleeding events. In addition, we propose cutoff values for high and low on-treatment platelet reactivity to ADP that might be used in future investigations of personalized antiplatelet therapy.
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