Ticagrelor in patients with heart failure after acute coronary syndromes-Insights from the PLATelet inhibition and patient Outcomes (PLATO) trial.

BACKGROUND: Heart failure (HF) following acute coronary syndromes (ACS) is associated with worse prognosis; however, the efficacy and safety of ticagrelor in patients with HF and if ticagrelor influences the risk of new-onset HF are unknown. METHODS: We examined the efficacy and safety of ticagrelor compared to clopidogrel in patients with ACS in the randomized PLATelet inhibition and patient Outcomes (PLATO) trial subdivided by strata: (1) previous HF and/or clinical signs of HF on admission or (2) no HF on admission. The primary outcome was the combination of cardiovascular death, myocardial infarction, or stroke evaluated by multivariable Cox regression models. The safety outcome was major bleeding. New-onset HF was defined as an HF event after discharge in patients without previous HF. RESULTS: Data were available in 18,556 patients, whom 2,862 (15.4%) patients had HF, including 1,584 (8.5%) patients with previous HF. Patients randomized to ticagrelor had lower risk of the composite end point regardless of HF status: hazard ratio (HR) 0.87 (95% CI: 0.73-1.03) in patients with HF and HR 0.84 (95% CI: 0.75-0.93) in patients with no HF (P = .76). Corresponding HR for major bleeding were HR 1.08 (95% CI: 0.87-1.34) and HR 1.03 (95% CI: 0.94-1.14) (P = .71). There was no difference in new-onset HF at 12 months between patients randomized to ticagrelor (4.1%, n = 278) or clopidogrel (4.0%, n = 276). CONCLUSIONS: In patients with ACS, ticagrelor is more efficacious in protecting against new ischemic events and mortality than clopidogrel irrespective of the presence of HF. There is no difference between ticagrelor or clopidogrel treatment in new-onset HF post-ACS.

Neuromuscular electrical stimulation improves exercise tolerance in patients with advanced heart failure on continuous intravenous inotropic support use-randomized controlled trial.

OBJECTIVE: To evaluate the impact of a short-term neuromuscular electrical stimulation program on exercise tolerance in hospitalized patients with advanced heart failure who have suffered an acute decompensation and are under continuous intravenous inotropic support. DESIGN: A randomized controlled study. SUBJECTS: Initially, 195 patients hospitalized for decompensated heart failure were recruited, but 70 were randomized. INTERVENTION: Patients were randomized into two groups: control group subject to the usual care ( n = 35); neuromuscular electrical stimulation group ( n = 35) received daily training sessions to both lower extremities for around two weeks. MAIN MEASURES: The baseline 6-minute walk test to determine functional capacity was performed 24 hours after hospital admission, and intravenous inotropic support dose was daily checked in all patients. The outcomes were measured in two weeks or at the discharge if the patients were sent back home earlier than two weeks. RESULTS: After losses of follow-up, a total of 49 patients were included and considered for final analysis (control group, n = 25 and neuromuscular electrical stimulation group, n = 24). The neuromuscular electrical stimulation group presented with a higher 6-minute walk test distance compared to the control group after the study protocol (293 ± 34.78 m vs. 265.8 ± 48.53 m, P < 0.001, respectively). Neuromuscular electrical stimulation group also demonstrated a significantly higher dose reduction of dobutamine compared to control group after the study protocol (2.72 ± 1.72 µg/kg/min vs. 3.86 ± 1.61 µg/kg/min, P = 0.001, respectively). CONCLUSION: A short-term inpatient neuromuscular electrical stimulation rehabilitation protocol improved exercise tolerance and reduced intravenous inotropic support necessity in patients with advanced heart failure suffering a decompensation episode.

Noncardiovascular deaths are more common than cardiovascular deaths in patients with cardiovascular disease or cardiovascular risk factors and impaired glucose tolerance: Insights from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial.

BACKGROUND: Patients with impaired glucose tolerance have an elevated risk of cardiovascular (CV) death; however, the causes and risk factors associated with non-CV deaths are poorly understood. METHODS: The NAVIGATOR trial enrolled 9,306 participants with impaired glucose tolerance and CV disease or at high CV risk, with a median follow-up of 6.4years. Using this population, we identified (1) the proportion of deaths attributed to CV, non-CV, and unknown causes, and (2) the risk factors associated with non-CV death. RESULTS: During the NAVIGATOR trial follow-up, 622 patients died. Investigators reported 244 (39.2%) CV deaths, 313 (50.3%) non-CV deaths, and 65 (10.5%) deaths of unknown cause. Myocardial infarction was the leading cause of investigator-reported death (57/622 [9.2%]). Among non-CV deaths, the most commonly identified cause related to malignancy (177/313 [56.5%]). Using adjudicated causes of death, Cox proportional hazard models identified 3 independent prognostic markers that increased the risk of non-CV death: history of non-melanoma skin cancer (hazard ratio 2.67 [95% CI 1.65-4.33]; P<.0001), white blood cell count (1 unit >5000/mm3; 1.10 [1.02-1.18]; P=.011), and serum potassium levels (per 1mmol/L above any value; 1.67 [1.302.15]; P<.0001). CONCLUSIONS: Despite the high baseline CV risk among patients in the NAVIGATOR trial, the most common cause of death was non-CV. The high burden of non-CV death in this population has potential implications for future CV event-driven trials.

Percutaneous mechanical assistance for the failing heart.

One of the most challenging situations in contemporary medicine is, doubtlessly, the approach and treatment of patients presenting with severe left ventricle failure. Since its first clinical application in patients with cardiogenic shock in 1968, the intraaortic balloon pump (IABP) has been widely accepted by heart failure physicians. Although IABP therapy has been shown to be effective for the support and stabilization of hemodynamically compromised patients, it has failed to promote any improvements in patient outcomes. For this reason, much attention has been invested in the development of external devices that can collaborate with the treatment of this condition. In this context, the percutaneous left ventricle assist device (pLVAD), like TandemHeart (Cardiac Assist, Inc.; Pittsburgh, PA, USA), and, more recently, the Impella 2.5 (Abiomed Europe, Aachen, Germany) has emerged. The purpose of this review is to describe the history of pLVAD, from its beginning, to the other devices currently available, including those created for right ventricle and biventricular support.

Acute Coronary Syndrome After Ondansetron Administration in a Pregnant Woman: Kounis Syndrome?

We report on a pregnant woman with acute coronary syndrome probably caused by an allergic reaction to ondansetron. It also discusses the pathophysiology, main allergic triggers, clinical presentation, and management of Kounis syndrome. (Level of Difficulty: Beginner.).

Nonsteroidal Anti-Inflammatory Drugs and Clinical Outcomes in Patients Undergoing Coronary Artery Bypass Surgery.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in perioperative pain management of patients undergoing coronary artery bypass graft surgery. However, the association of periprocedural use of NSAIDs and clinical outcomes after coronary artery bypass graft is understudied. METHODS: We conducted a retrospective analysis using pooled data from 2 multicenter randomized controlled trials (PREVENT IV [n = 3014] and MEND-CABG II [n = 3023]). Rates of death, death or myocardial infarction, and death, myocardial infarction, or stroke in the 30 days following coronary artery bypass graft surgery were compared in patients using or not using perioperative NSAIDs. Inverse probability of treatment weighting and Cox proportional hazards regression models were used to adjust for confounding. RESULTS: A total of 5887 patients were studied. Median age was 65 years, 78% were male, and 91% were White. NSAIDs were used in 2368 (40.2%) patients. The majority of patients (1822 [30.9%]) received NSAIDs after coronary artery bypass graft surgery; 289 (4.9%) used them prior to and after the surgery; and 257 (4.4) received NSAIDs prior to the surgery only. Adjusted 30-day outcomes were similar in patients receiving and not receiving NSAIDs (death: hazard ratio [HR] 1.18; 95% confidence interval [CI], 0.48-2.92; death or myocardial infarction: HR 0.87; 95% CI, 0.42-1.79; death, myocardial infarction, or stroke: HR 0.87; 95% CI, 0.46-1.65). CONCLUSION: In this pooled data analysis, perioperative NSAID use was common among patients undergoing coronary artery bypass graft surgery and was not associated with an increased short-term risk for major adverse clinical outcomes.

Novel anti-platelet agents: focus on thrombin receptor antagonists.

Platelets are the key in the pathogenesis of atherothrombotic disease such as acute coronary syndromes, stroke, and peripheral arterial disease. Current anti-platelet treatments are mainly based on inhibition of two important pathways of platelet activation: thromboxane A2 (TXA2) mediated (aspirin) and adenosine diphosphate (ADP)-P2Y12 receptor mediated (clopidogrel, prasugrel, and ticagrelor). Despite the dual anti-platelet therapy with aspirin and P2Y12 inhibitors have reduced ischemic events in patients with acute coronary syndromes (ACS), the rate of recurrent ischemic complication after ACS remains high. Combination of multiple anti-platelet agents is also associated with increased risk of bleeding. Thrombin is a potent platelet agonist and the increase of its activity has been reported in patients with ACS. Platelet effects of thrombin are mediated by protease-activated receptors (PAR), and PAR-1 is the most important receptor in human platelets. Two PAR-1 antagonists, vorapaxar and atopaxar, have undergone clinical investigation. In this review, we will describe the pharmacology of PAR-1 antagonists and will review and discuss results of randomized clinical trials with PAR-1 antagonists.

The safety and efficacy of apixaban : where do we stand in 2013?

INTRODUCTION: Traditional oral anticoagulants, such as warfarin, are effective but require frequent laboratory monitoring for dose adjustment and have several known interactions with food and other drugs. Oral direct factor Xa inhibitors are an emerging class of anticoagulants that do not require routine laboratory monitoring. We reviewed the pharmacokinetics and pharmacology as well as the clinical safety and efficacy of apixaban , an oral direct factor Xa inhibitor. AREAS COVERED: Data from Phase II and III clinical trials and secondary analysis involving apixaban were included. Studies using apixaban for stroke prevention in patients with atrial fibrillation, for the prevention and treatment of venous thromboembolism, and for secondary prevention of ischemic events in patients with acute coronary syndromes are discussed. EXPERT OPINION: Apixaban is a safe, effective, and attractive alternative to warfarin for stroke prevention in patients with nonvalvular atrial fibrillation. It is also a good option for the prevention of venous thromboembolic events after major orthopedic surgery and for the extended treatment of deep vein thrombosis and pulmonary embolism. Apixaban at a dose of 5 mg twice daily did not have a favorable risk/benefit profile for secondary prevention in high-risk patients with acute coronary syndromes.