Pranab Das

Bleeding complications in patients with acute coronary syndrome undergoing early invasive management can be reduced with radial access, smaller sheath sizes, and timely sheath removal

Objectives: Our objective was to analyze the impact of arterial access site, sheath size, timing of sheath removal, and use of access site closure devices on high‐risk patients with acute coronary syndromes (ACS). Background: In the SYNERGY trial, 9,978 patients with ACS were randomly assigned to receive enoxaparin or unfractionated heparin. Methods: This analysis includes 9,404 patients for whom sheath access information was obtained for the first PCI procedure or diagnostic catheterization. Comparisons of baseline, angiographic, and procedural characteristics were carried out according to access site and sheath size. Results: Overall, 9,404 (94%) patients underwent angiography at a median of 21 hr (25th and 75th percentiles: 5, 42) and 4,687 (50%) underwent PCI at a median of 23 hr (6,49) of enrollment. The access site was femoral for 94.9% of cases, radial for 4.4%, and brachial for 0.7%. Radial access was associated with fewer transfusions than femoral access (0.9% vs. 4.8%, P = 0.007). For femoral access, the rates of noncoronary artery bypass grafting (CABG)‐related TIMI major bleeding by sheath size was 1.5% for 4 or 5 French (Fr), 1.6% for 6 Fr, 3.3% for 7 Fr, and 3.8% for ≥ 8 Fr (P < 0.0001). After adjustment for baseline characteristics, femoral access site, larger sheath size, and delayed sheath removal were independent predictors of need for transfusion. Conclusions: Smaller sheaths, radial access, and timely sheath removal may mitigate the bleeding risk associated with potent antithrombotic/platelet therapy and early catheterization.

Early coronary revascularization diminishes the risk of ischemic stroke with acute myocardial infarction

Background and Purpose— Ischemic stroke is an uncommon but devastating complication of myocardial infarction (MI). It is possible that delay in the acute revascularization of these patients influences the risk of peri-MI ischemic stroke independent of size of infarction or residual ventricular function. The influence of the timing and type of revascularization on risk of ischemic stroke in the patient with MI has not previously been assessed. Methods— We used the National Registry of Myocardial Infarction 3 and 4 databases to identify 45 997 subjects who received thrombolytic therapy and 47 876 patients who were treated with primary percutaneous transluminal coronary angioplasty for MI. In-hospital ischemic stroke occurred in 248 (0.54%) and 150 (0.31%) patients in the two groups, respectively. Patients were stratified based on time from presentation to initial therapy. Results— A statistically significant linear relationship between time to revascularization therapy and risk of in-hospital ischemic stroke was seen on univariate analysis. A multivariate model incorporating 26 other variables showed thrombolytic therapy within 15 minutes was associated with a lower risk of ischemic stroke (odds ratio, 0.58; 95% CI, 0.36–0.94). Primary angioplasty within 90 minutes of arrival was associated with a nonsignificant trend toward lower stroke risk (odds ratio, 0.68; 95% CI, 0.41–1.12). Interestingly, his benefit of early reperfusion therapy did not appear to be related to improvements in left ventricular function. Conclusion— Risk of in-hospital ischemic stroke with MI is closely tied to the time to revascularization with both thrombolytic and percutaneous transluminal coronary angioplasty therapies. Early revascularization is independently predictive of a lower risk of ischemic stroke, but the mechanism of this does not appear to be related to improved cardiac function. The records of 45 997 subjects who received thrombolytic therapy and 47 876 patients who were treated with primary percutaneous transluminal coronary angioplasty for myocardial infarction were analyzed to determine the relationship between time to revascularization and the occurrence of ischemic stroke. A statistically significant linear relationship between time to revascularization therapy and risk of in-hospital ischemic stroke was seen on univariate analysis. A multivariate model incorporating 26 other variables showed thrombolytic therapy within 15 minutes of presentation was associated with a lower risk of ischemic stroke, and angioplasty within 90 minutes was similarly associated with a nonsignificant trend toward lower stroke risk.

Emerging P2Y12 receptor antagonists: role in coronary artery disease.

The use of oral antiplatelet therapy in reducing vascular events has been extensively studied. Currently available oral antiplatelet agents include aspirin and the thienopyridine P2Y12 receptor antagonists. These classes are combined frequently in the setting of acute coronary syndrome and percutaneous coronary intervention (PCI). Resistance to either or both of these agents is a major concern, as antiplatelet resistance has been linked to an increase in thrombotic events and worse clinical outcomes. As a result, there is a need for newer, more effective antiplatelet agents to address the limitations of currently available therapy. Prasugrel, a third generation thienopyridine, has been approved by both the FDA and European Commission. Two additional P2Y12 agents, ticagrelor and cangrelor are in advanced stages of development. The possible advantages of prasugrel over clopidogrel include a faster onset of action, reduced inter-patient variability and more potent platelet inhibition. Ticagrelor is an oral reversible P2Y12 antagonist with greater platelet inhibition compared with clopidogrel. Cangrelor is being developed as an intravenous P2Y12 antagonist with a very fast onset and offset, which may offer advantages particularly in the setting of coronary intervention. These emerging antiplatelet agents may offer advantages such as faster onset of action, greater potency and reversibility of platelet inhibition. This article summarizes the available clinical data on the upcoming P2Y12 antiplatelet agents in the treatment of coronary artery disease.

Enoxaparin in Clinical Practice and Clinical Trials of Non-ST-Elevation Acute Coronary Syndrome (NSTE-ACS)

Non-ST elevation Acute Coronary Syndrome (NSTE-ACS) is a myocardial ischemic disorder frequently caused by coronary artery plaque rupture and partial or transient vessel occlusion. Platelets and thrombin play pivotal roles in formation and propagation of thrombus at the site of plaque disruption and embolization into the vascular bed. With the outgoing development of antithrombotic, antiplatelet, and mechanical therapies, the management of NSTE-ACS is constantly evolving. Heparins are the cornerstone of antithrombotic therapy in the current management of NSTE-ACS. Unfractionated heparin and fractionated heparins like enoxaparin have been studied in several large clinical trials and found to be effective in reducing death and myocardial infarction rates. For medical management alone or primarily (conservative strategy), enoxaparin has been shown to be superior to unfractionated heparin. With an early invasive strategy providing better clinical outcome compared to a conservative strategy, the paradigm of ACS management has shifted in favor of early (within 48 hours of admission) cardiac catheterization. The effectiveness of enoxaparin compared to unfractionated heparin is now being re-considered in the era of poly-pharmacotherapy and an early invasive strategy for ACS management. We review the role of enoxaparin in the contemporary treatment of NSTE-ACS utilizing recent clinical trial data.

Update on the use of direct oral anticoagulants for the prevention and treatment of thromboembolism

Following publication of our review article 4 years ago, there has been an uptake in the use of nonvitamin K oral antagonists, also known as direct oral anticoagulants. The most recent Xa inhibitors to receive approval are edoxaban, which has been approved for use in both atrial fibrillation and venous thromboembolism prevention and betrixaban, which has been approved in the USA for extended thromboprophylaxis in the medically ill population. Additional analyses of certain types of atrial fibrillation patients have now become available. Ongoing prescriber vigilance is recommended as additional information continues to emerge with this class of medications. The purpose of this paper is to provide an update on the use of the direct oral anticoagulant agents for the prevention and treatment of thromboembolism.