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Dual antiplatelet therapy (DAPT) with aspirin and a platelet P2Y12 receptor inhibitor is the standard antithrombotic treatment after percutaneous coronary interventions (PCI). Several trials have challenged guideline-recommended DAPT after PCI by testing the relative clinical effect of an aspirin-free antiplatelet approach—consisting of P2Y12 inhibitor monotherapy after a short course (mostly 1–3 months) of DAPT—among patients undergoing PCI without a concomitant indication for oral anticoagulation (OAC). Overall, these studies have shown P2Y12 inhibitor monotherapy after short DAPT to be associated with a significant reduction in the risk of bleeding without an increase in thrombotic or ischaemic events compared with continued DAPT. Moreover, the effects of the P2Y12 inhibitor monotherapy without prior DAPT or following a very short course of DAPT after PCI are being investigated in emerging studies, of which one has recently reported unfavourable efficacy results associated with the aspirin-free approach compared with conventional DAPT. Finally, P2Y12 inhibitor alone has been compared with aspirin alone as chronic therapy after DAPT discontinuation, thus challenging the historical role of aspirin as a standard of care for secondary prevention following PCI. A thorough understanding of study designs, populations, treatments, results, and limitations of trials testing P2Y12 inhibitor monotherapy vs. DAPT or vs. aspirin is required to consider adopting this treatment in clinical practice. This review addresses the use of aspirin-free antiplatelet strategies among patients undergoing PCI without a concomitant indication for OAC, providing an overview of clinical evidence, guideline indications, practical implications, ongoing issues, and future perspectives. [ABSTRACT FROM AUTHOR]

Purpose of Review: Acute coronary syndromes (ACS) often occur in individuals with prior coronary artery bypass graft surgery (CABG). Our goal was to describe the prevalence, clinical characteristics, prognosis, and treatment strategies in this group of patients. Recent Findings: Studies demonstrate that both acute and long-term major adverse cardiovascular outcomes are increased in patients with ACS and prior CABG compared to those without CABG. Much of this risk is attributed to the greater comorbid conditions present in patients with prior CABG. Data regarding optimal management of ACS in patients with prior CABG are limited, but most observational studies favor an early invasive approach for treatment. Native vessel percutaneous coronary intervention (PCI), if feasible, is generally preferred to bypass graft PCI. Summary: Patients with ACS and prior CABG represent a high-risk group of individuals, and implementing optimal preventive and treatment strategies are critically important to reduce the risk. [ABSTRACT FROM AUTHOR]

An editorial discusses the potential of drug-coated balloons (DCBs) as a treatment for in-stent restenosis in coronary artery disease. It highlights the AGENT IDE study, the first U.S. trial evaluating DCBs, which showed superiority over conventional balloons in reducing adverse events. It notes that using noncoated balloons as the control may not reflect current practice.

The University of Kentucky College of Medicine and Albert B. Chandler Hospital opened over 50 years ago to serve Kentucky. After initial growth and expansion, both were struggling clinically, academically, and financially in the early 2000s. Difficulties were apparent in cardiovascular (CV) services, which captured only 11% of the regional patients hospitalized for cardiac disease. Over the next 15 years, CV services dynamically transformed to become the leading provider with a large network of regional partners, garnering 42% of market share. This article describes strategic plans and initiatives leading to clinical and academic growth. Future value-based initiatives are also described. [ABSTRACT FROM AUTHOR]

Background: The disruption of dual antiplatelet therapy (DAPT) due to non-compliance or bleeding is known to significantly increase the risk of adverse outcomes after percutaneous coronary intervention (PCI). However, it is currently unknown if there are differences in the predictors and clinical impact of disruption due to non-compliance compared with bleeding. Methods: The patterns of non-adherence to antiplatelet regimens in stented patients (PARIS) registry was an international, multicenter prospective study of PCI patients discharged on DAPT (aspirin + a P2Y12 receptor). We analyzed the incidence, patient characteristics, predictors, and outcomes in patients with DAPT disruption due to non-compliance as compared to DAPT disruption due to bleeding in the PARIS registry. Predictors of non-recommended disruption and bleeding disruption were assessed using logistic regression. Risks associated with disruption on major adverse cardiac events (MACE, a composite of cardiac death, definite or probable stent thrombosis, spontaneous myocardial infarction, and target lesion revascularization) were analyzed using time-updated Cox regression over 2-year follow-up. Results: Out of 5018 patients, the rate of non-compliant DAPT disruption was 1.6% at 30 days (n = 79), 6.5% at 12 months (n = 328), and 9.1% at 2 years from PCI (n = 457). The rate of bleeding DAPT disruption was 0.6% at 30 days (n = 32), 3.1% at 12 months (n = 156), and 4.6% at 2 years (n = 229). Multivariate predictors of non-compliant disruption included female gender, history of smoking, acute coronary syndrome, and US patients which were associated with greater risk; and dyslipidemia and discharge PPI which were associated with lower risk. Multivariate predictors of bleeding disruption included older age, prior MI, and discharge warfarin which were associated with greater risk; and US region and intervention to the LAD which were associated with lower risk. Non-compliant disruption was associated with a significantly greater risk for MACE (HR 1.73, 95% CI 1.17–2.54, p = 0.006) and spontaneous myocardial infarction (HR 2.93, 95% CI 1.85–4.65, p < 0.001). Bleeding disruption was associated with a significantly greater risk for all-cause death (HR 1.93, 95% CI 1.22–3.08, p = 0.005). Conclusion: Approximately 1 in 10 patients disrupts DAPT due to non-compliance and 1 in 20 disrupts DAPT due to bleeding. Disruption due to non-compliance resulted in higher risk for ischemic events and disruption due to bleeding had higher subsequent mortality. These data warrant efforts to focus on patient education in those at high risk of non-compliance. [ABSTRACT FROM AUTHOR]

The article focuses on the results of the TAILOR-PCI randomized study examining a clinical decision strategy that depends on CYP2C19 genotyping to guide antiplatelet drug assignment following percutaneous coronary interventions. Study subjects received clopidogrel without initial genetic testing while another group of subjects received clopidogrel versus ticagrelor or prasugel. It suggests the use of a personalized medicine approach that involved genotyping for therapeutic interventions.

Aims Dual antiplatelet therapy reduces non-fatal ischaemic events after acute coronary syndrome (ACS) but increases bleeding to a similar extent. We sought to determine the prognostic impact of myocardial infarction (MI) vs. bleeding during an extended follow-up period to gain insight into the trade-off between efficacy and safety among patients after ACS. Methods and results In 12 944 patients with non-ST-segment elevation ACS from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial, we investigated the relative impact of MI and bleeding occurring>30 days post-ACS and subsequent all-cause mortality. Bleeding was graded according to Bleeding Academic Research Consortium (BARC) criteria. MI was associated with a five-fold increase in mortality. BARC type 2 and 3, but not type 1, bleeding had a significant impact on mortality. MI was associated with a greater risk of mortality compared with BARC 2 [relative risk (RR) 3.5; 95% confidence interval (CI) 2.08-4.77; P<0.001] and BARC 3a bleeding (RR 2.23; 95% CI 1.36-3.64; P=0.001), and a risk similar to BARC 3b bleeding (RR 1.37; 95% CI 0.81-2.30; P=0.242). Risk of death after MI was significantly lower than after BARC 3c bleeding (RR 0.22; 95% CI 0.13-0.36; P<0.001). MI and bleeding had similar time-associations with mortality, which remained significant for several months, still being higher early after the event. Conclusion In patients treated with antiplatelet therapy after ACS, both MI and bleeding significantly impacted mortality with similar time-dependency. Although BARC 2 and 3a bleeding were less prognostic for death than MI, the risk of mortality was equivalent between BARC 3b bleeding and MI, and was higher following BARC 3c bleeding. [ABSTRACT FROM AUTHOR]

The authors comment on a Japanese study that examined iterations of shorter-duration dual antiplatelet therapy (DAPT) in patients in Japan who received everolimus-eluting stents by discontinuing aspirin instead of the P2Y12 inhibitor as has commonly been the approach. They compare the findings of the study with those of a similar study in Korea that involved patients who received a current-generation drug-eluting stent. They also discuss the possible impact of the results on clinical practice.

Thrombin-induced platelet activation is initiated by PAR1 and PAR4 receptors. Vorapaxar, a PAR1 antagonist, has been assessed in patients with acute coronary syndromes (ACS) and stable atherosclerotic disease in addition to standard-of-care treatment. In clinical trials, vorapaxar has been observed to reduce the frequency of ischaemic events in some subgroups though in others has increased the frequency of bleeding events. Among patients undergoing CABG surgery, which is associated with excess thrombin generation, bleeding was not increased. The aim of these studies was to investigate the effects of selective PAR1 antagonism on thrombin-induced platelet activation in patients receiving vorapaxar or placebo in the TRACER trial and to explore the roles of PAR1 and PAR4 in thrombin-induced platelet activation in healthy volunteers. ACS patients receiving vorapaxar or placebo in the TRACER trial were studied at baseline and 4 hours, 1 and 4 months during drug administration. Thrombin-induced calcium mobilisation in platelet-rich plasma was assessed by flow cytometry. In vitro studies were performed in healthy volunteers using the PAR1 antagonist SCH79797 or PAR4 receptor desensitisation. Vorapaxar treatment significantly inhibited thrombin-induced calcium mobilisation, leaving a residual, delayed response. These findings were consistent with calcium mobilisation mediated via the PAR4 receptor and were reproduced in vitro using SCH79797. PAR4 receptor desensitization, in combination with SCH79797, completely inhibited thrombin-induced calcium mobilisation confirming that the residual calcium mobilisation was mediated via PAR4. In conclusion vorapaxar selectively antagonises the PAR1-mediated component of thrombin-induced platelet activation, leaving the PAR4-mediated response intact, which may explain why vorapaxar is well tolerated in patients undergoing CABG surgery since higher thrombin levels in this setting may override the effects of PAR1 antagonism through PAR4 activation, thus preserving haemostasis. Further assessment may be warranted. [ABSTRACT FROM AUTHOR]

Aims: The association of QRS duration (QRSd) with morbidity and mortality is understudied in patients with atrial fibrillation (AF). We sought to assess any association of prolonged QRS with increased risk of death or hospitalization among patients with AF.Methods and Results: QRS duration was retrieved from the baseline electrocardiograms of patients enroled in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) study and divided into three categories: <90, 90-119, ≥120 ms. Cox models were applied relating the hazards of mortality and hospitalizations to QRSd. Among 3804 patients with AF, 593 died and 2305 were hospitalized. Compared with those with QRS < 90 ms, patients with QRS ≥ 120 ms, had an increased mortality [hazard ratio (HR) 1.61, 95% confidence interval (CI): 1.29-2.03, P < 0.001] and hospitalizations (HR 1.14, 95% CI: 1.07-1.34, P = 0.043) over an average follow-up of 3.5 years. Importantly, for patients with QRS 90-119 ms, mortality and hospitalization were also increased (HR 1.31, P = 0.005 and 1.11, P = 0.026, respectively). In subgroup analysis based on heart failure (HF) status (previously documented or ejection fraction <40%), mortality was increased for QRS ≥ 120 ms patients with (HR 1.87, P < 0.001) and without HF (HR 1.63, P = 0.02). In the QRS 90-119 ms group, mortality was increased (HR 1.38, P = 0.03) for those with HF, but not significantly among those without HF (HR 1.23, P = 0.14).Conclusion: Among patients with AF, QRSd ≥ 120 ms was associated with a substantially increased risk for mortality (all-cause, cardiovascular, and arrhythmic) and hospitalization. Interestingly, an increased mortality was also observed among those with QRS 90-119 ms and concomitant HF. [ABSTRACT FROM AUTHOR]

Aims The association of QRS duration (QRSd) with morbidity and mortality is understudied in patients with atrial fibrillation (AF). We sought to assess any association of prolonged QRS with increased risk of death or hospitalization among patients with AF. Methods and results QRS duration was retrieved from the baseline electrocardiograms of patients enroled in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) study and divided into three categories: <90, 90–119, ≥120 ms. Cox models were applied relating the hazards of mortality and hospitalizations to QRSd. Among 3804 patients with AF, 593 died and 2305 were hospitalized. Compared with those with QRS < 90 ms, patients with QRS ≥ 120 ms, had an increased mortality [hazard ratio (HR) 1.61, 95% confidence interval (CI): 1.29–2.03, P < 0.001] and hospitalizations (HR 1.14, 95% CI: 1.07–1.34, P = 0.043) over an average follow-up of 3.5 years. Importantly, for patients with QRS 90–119 ms, mortality and hospitalization were also increased (HR 1.31, P = 0.005 and 1.11, P = 0.026, respectively). In subgroup analysis based on heart failure (HF) status (previously documented or ejection fraction <40%), mortality was increased for QRS ≥ 120 ms patients with (HR 1.87, P < 0.001) and without HF (HR 1.63, P = 0.02). In the QRS 90–119 ms group, mortality was increased (HR 1.38, P = 0.03) for those with HF, but not significantly among those without HF (HR 1.23, P = 0.14). Conclusion Among patients with AF, QRSd ≥ 120 ms was associated with a substantially increased risk for mortality (all-cause, cardiovascular, and arrhythmic) and hospitalization. Interestingly, an increased mortality was also observed among those with QRS 90–119 ms and concomitant HF. [ABSTRACT FROM PUBLISHER]

Due to their tissue specificity and ease of detection, the cardiac troponins (cTn) have emerged as the most important and most utilized biomarkers for the diagnosis of acute myocardial infarction (AMI). The recent achievement of greater sensitivity by cTn assay systems, however, has resulted in the detection of cTn in a wide array of medical conditions, highlighting myocardial cellular necrosis as a feature in several, seemingly unrelated medical conditions, yet complicating the interpretation of a positive test. Since elevated cTn levels are associated with worse clinical outcomes and, thereby, influence medical decisions, careful consideration should be given to the method by which these biomarkers are measured, the patient population on which the test is being applied, and applicable thresholds based on particular clinical conditions. The objective of this review is to trace the clinical evolution of the cTn biomarker from a test for AMI to a general marker of myocardial cellular necrosis with clinically important prognostic information. [ABSTRACT FROM AUTHOR]

Aims The TRA·CER trial compared vorapaxar, a novel platelet protease-activated receptor (PAR)-1 antagonist, with placebo in 12 944 patients with high-risk non–ST-segment elevation acute coronary syndromes (NSTE ACS). In this analysis, we explored the effect of vorapaxar on myocardial infarction (MI). Methods and results A blinded, independent central endpoint adjudication committee prospectively defined and classified MI according to the universal MI definition, including peak cardiac marker value (creatine kinase-MB [CK-MB] and/or troponin). Because the trial failed to meet its primary endpoint, these analyses are considered exploratory. During a median follow-up of 502 days, 1580 MIs occurred in 1319 patients. The majority (n = 1025, 64.9%) were type 1 (spontaneous) MI, followed by type 4a [percutaneous coronary intervention (PCI)-related] MI (n = 352; 22.3%). Compared with placebo, vorapaxar reduced the hazard of a first MI of any type by 12% [hazard ratio (HR), 0.88; 95% confidence interval (CI), 0.79–0.98; P = 0.021] and the hazard of total number of MIs (first and subsequent) by 14% (HR, 0.86; 95% CI, 0.77–0.97; P = 0.014), an effect that was sustained over time. Vorapaxar reduced type 1 MI by 17% (HR, 0.83; 95% CI, 0.73–0.95; P = 0.007). Type 4a MIs were not significantly reduced by vorapaxar (HR, 0.90; 95% CI, 0.73–1.12; P = 0.35). Vorapaxar effect was consistent across MI sizes defined by peak cardiac marker elevations and across key clinical subgroups; however, in patients not treated with thienopyridine at baseline (HR, 0.65; 95% CI, 0.46–0.92) compared with patients who received thienopyridine (HR, 0.91; 95% CI, 0.81–1.02), there was a trend towards a higher effect (Pint = 0.077). Conclusion The PAR-1 antagonist vorapaxar was associated with a reduction of MI, including total number of infarctions. This reduction was sustained over time and was mostly evident in type 1 MI, the most common type of MI observed. [ABSTRACT FROM PUBLISHER]

Historically, the use of oral anticoagulants in acute coronary syndromes (ACS) has been controversial. Several prospective trials have shown that vitamin K antagonists (VKAs), such as warfarin or dicoumarol, reduce recurrent ischemic events but with a concomitant increased risk of bleeding. Other trial data have shown a neutral or net negative effect. Regardless, these prior observations are not readily transposable to contemporary practice where many ACS patients receive dual antiplatelet therapy and undergo cardiac catheterization and percutaneous coronary intervention. Because recurrent ischemic events continue to occur following index ACS presentation despite evidence-based practice and knowing the limitations of current oral anticoagulation strategies with VKA, the endeavor continues to find a more effective anticoagulant with predictable, dose-proportional pharmacokinetics, and minimal interactions with food and drugs. We review novel, emerging classes of anticoagulants that focus on specific targets in the coagulation cascade with the aim of improving long-term net clinical outcomes. [ABSTRACT FROM AUTHOR]

Coronary plaque rupture is associated with a systemic inflammatory response. The relationship between baseline N-terminal pro B-type natriuretic peptide (NT-proBNP), a prognostic marker in patients with acute coronary syndromes, and systemic inflammatory mediators in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) is not well described. Of 5,745 STEMI patients treated with primary PCI in the APEX-AMI trial, we evaluated the relationship between baseline NT-proBNP levels and baseline levels of inflammatory markers and markers of myonecrosis in a subset of 772 who were enrolled in a biomarker substudy. Spearman correlations ( r) were calculated between baseline NT-proBNP levels and a panel of ten systemic inflammatory biomarkers. Interleukin (IL)-6, a pro-inflammatory cytokine, was significantly positively correlated with NT-proBNP ( r = 0.317, P < 0.001). In a sensitivity analysis excluding all heart failure patients, the correlation between baseline IL-6 and NT-proBNP remained significant ( n = 651, r = 0.296, P < 0.001). A positive association was also observed with high sensitivity C-reactive protein ( r = 0.377, P < 0.001) and there was a weak negative correlation with the anti-inflammatory cytokine IL-10 ( r = −0.109, P = 0.003). No other significant correlations were observed among the other testes inflammatory cytokines and chemokines. In STEMI patients undergoing primary PCI, the pro-inflammatory cytokine IL-6 was modestly correlated with baseline NT-proBNP levels. This relationship remained significant in patients without heart failure. This finding is consistent with pre-clinical and clinical research suggesting that systemic inflammation may influence NT-proBNP expression independently of myocardial stretch. [ABSTRACT FROM AUTHOR]

Dual antiplatelet therapy with aspirin and clopidogrel is a well-established standard of care for patients with acute coronary syndromes. Whether there are other drug strategies or therapies that will achieve fewer ischemic events, and at the same time be associated with fewer bleeding complications, is a question recurrently asked. Finding the appropriate pharmacologic calibration of antiplatelet potency and applying such a pharmacodynamic effect to all patients has only been partially successful. The shadow of this one-size-fits-all dilemma is now being recast with the arrival of newer antiplatelet agents, which are attempting to decouple antithrombotic potency from bleeding liability. Novel antiplatelet agents that act faster and have more consistent pharmacokinetics and higher potency are steadily emerging. Additionally, newer agents that target unique sites, such as the thrombin receptor on platelets, are being studied in large-scale clinical trials. Each of these new agents has the potential to extend net clinical benefits beyond those provided by aspirin and clopidogrel. [ABSTRACT FROM AUTHOR]

(J Interven Cardiol 2010;23:565-568) [ABSTRACT FROM AUTHOR]

Aims: To perform a thorough and updated systematic review of randomized clinical trials comparing tirofiban vs. placebo or vs. abciximab. [ABSTRACT FROM PUBLISHER]

The article presents consensus recommendations from the American College of Cardiology Foundation (ACCF), the American Heart Association (AHA), and the American College of Gastroenterology (ACG) on the combined use of antiplatelets and nonsteroidal anti-inflammatory drug (NSAID) agents. Although oral antiplatelet therapy decreases ischemic risks in some patients, this treatment may increase bleeding complications. Concomitant use of NSAIDs further increases the risk of gastrointestinal (GI) bleeding.

The article focuses on the study on the prognostic significance of patients with Thrombocytopenia treated with heparin therapy. According to the author, association of heparin use with the thrombocytopenia is underrecognized and undertreated. The study was conducted in 2420 patients in 48 hospitals in the United States, of which 48 percent are women. The author concludes that the thrombocytopenia frequently occurs with patients who are treated with prolonged heparin therapy, and that it is associated with a worse but short-term clinical outcome.

Objective: To investigate whether the beneficial and harmful effects of platelet glycoprotein IIb/IIIa receptor blockers in non-ST elevation acute coronary syndromes (NSTE-ACS) depend on age. Methods: A meta-analysis of six trials of platelet glycoprotein IIb/IIIa receptor blockers in patients with NSTE-ACS (PRISM, PRISM-PLUS, PARAGON-A, PURSUIT, PARAGON-B, GUSTO IV-ACS; n = 31 402) was performed. We applied multivariable logistic regression analyses to evaluate the drug effects on death or non-fatal myocardial infarction at 30 days, and on major bleeding, by age subgroups (<60, 60-69, 70-79, ⩾80 years). We quantified the reduction of death or myocardial infarction as the number needed to treat (NNT), and the increase of major bleeding as the number needed to harm (NNH). Results: Subgroups had 11 155 (35%), 9727 (31%), 8468 (27%) and 2049 (7%) patients, respectively. The relative benefit of platelet glycoprotein Ib/IIIa receptor blockers did not differ significantly (p=0.5) between age subgroups (OR (95% CI) for death or myocardial infarction: 0.86 (0.74 to 0.99), 0.90 (0.80 to 1.02), 0.97(0.86 to 1.10), 0.90 (0.73 to 1.16); overall 0.91 (0.86 to 0.99). ORs for major bleeding were 1.9 (1.3 to 2.8), 1.9 (1.4 to 2.7), 1 .6 (1.2 to 2.1) and 2.5 (1.5-4.1). Overall NNT was 105, and overall NNH was 90. The oldest patients had larger absolute increases in major bleeding, but also had the largest absolute reductions of death or myocardial infarction. Patients ⩾80 years had half of the NNT and a third of the NNH of patients <60 years. Conclusions: In patients with NSTE-ACS, the relative reduction of death or non-fatal myocardial infarction with platelet glycoprotein IIb/IIIa receptor blockers was independent of patient age. Larger absolute outcome reductions were seen in older patients, but with a higher risk of major bleeding. Close monitoring of these patients is warranted. [ABSTRACT FROM AUTHOR]

This article focuses on a placebo-controlled phase 3 study of the effectiveness of the drug, pexelizumab, as an adjunct to percutaneous transliminal coronary intervention (PCI) in the treatment of patients with acute ST-elevation myocardial infarction. Patients received either placebo or pexelizumab prior to PCI. The main outcome measures were all-cause mortality up to the 30th day, death up to the 90th day and either death, cardiogenic shock or congestive heart failure through days 30 and 90. This study determined that mortality was low in the subjects studied and the administration of pexelizumab did not affect mortality rate.

Aims Stroke is an uncommon but serious complication after non-ST-segment elevation acute coronary syndrome (NSTE-ACS). We aimed to identify predictors of stroke within 30 days in patients who suffered NSTE-ACS. [ABSTRACT FROM PUBLISHER]

Aims To explore variations in invasive care of the elderly with acute coronary syndromes across international practice. [ABSTRACT FROM PUBLISHER]