ticagrelor and Heart-Failure

Ticagrelor is a new oral antagonist of the platelet P2Y₁₂ receptor that offers several potential advantages compared to clopidogrel including faster and more effective inhibition of platelet aggregation. Ticagrelor has been compared to clopidogrel in the PLATelet inhibition and patient Outcomes (PLATO) trial in a broad population of patients with acute coronary syndrome showing a reduction of the 12-month risk of death from vascular causes, myocardial infarction and stroke without increasing the overall risk of major bleeding. In a subanalysis of the PLATO trial focusing on patients with ST-elevation myocardial infarction, ticagrelor results were consistent with those of the overall trial. Additionally, possible pleiotropic effects of ticagrelor, including an appealing interaction with adenosine, might constitute a specific advantage in this particular subset of patients.

Topics: Adenosine; Animals; Arrhythmias, Cardiac; Evidence-Based Medicine; Heart Failure; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor

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.. 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.. 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).. 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.

Topics: Acute Coronary Syndrome; Aged; Clopidogrel; Female; Heart Failure; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Proportional Hazards Models; Stroke; Ticagrelor

Major adverse cardiac event (MACE) and bleeding risks following percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS) are not well defined in individuals with heart failure (HF). We followed 1,145 individuals in the Pharmacogenomic Resource to improve Medication Effectiveness Genotype Guided Antiplatelet Therapy cohort for MACE and bleeding events following PCI for ACS. We constructed Cox proportional hazards models to compare MACE and bleeding in those with versus without HF, adjusting for sociodemographics, comorbidities, and medications. We also determined predictors of MACE and bleeding events in both groups. 370 (32%) individuals did and 775 (68%) did not have HF prior to PCI. Mean age was 61.7 ± 12.2 years, 31% were female, and 24% were African American. After a median follow-up of 0.78 years, individuals with HF had higher rates of MACE compared to those without HF (48 vs. 24 events per 100 person years) which remained significant after multivariable adjustment (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.00 to 1.72). Similarly, bleeding was higher in those with versus without HF (22 vs. 11 events per 100 person years), although this was no longer statistically significant after multivariable adjustment (HR 1.29, 95% CI 0.86 to 1.93). Diabetes and peripheral vascular disease were predictors of MACE, and end-stage renal disease was a predictor of bleeding among participants with HF. MACE risk is higher in individuals with versus without HF following PCI for ACS. However, the risk of bleeding, especially among those with end-stage renal disease , must be considered when determining post-PCI anticoagulant strategies.

Topics: Acute Coronary Syndrome; Aged; Angina, Unstable; Aspirin; Case-Control Studies; Clopidogrel; Diabetes Mellitus; Dual Anti-Platelet Therapy; Female; Heart Failure; Hemorrhage; Hospitalization; Humans; Ischemic Attack, Transient; Ischemic Stroke; Kidney Failure, Chronic; Male; Middle Aged; Mortality; Multivariate Analysis; Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Percutaneous Coronary Intervention; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Proportional Hazards Models; Risk Factors; ST Elevation Myocardial Infarction; Stroke Volume; Ticagrelor; Treatment Outcome

Background Peripheral artery disease (PAD) and heart failure (HF) are each independently associated with poor outcomes. Risk factors associated with new-onset HF in patients with primary PAD are unknown. Furthermore, how the presence of HF is associated with outcomes in patients with PAD is unknown. Methods and Results This analysis examined risk relationships of HF on outcomes in patients with symptomatic PAD randomized to ticagrelor or clopidogrel as part of the EUCLID (Examining Use of Ticagrelor in Peripheral Arterial Disease) trial. Patients were stratified based on presence of HF at enrollment. Cox models were used to determine the association of HF with outcomes. A separate Cox model was used to identify risk factors associated with development of HF during follow-up. Patients with PAD and HF had over twice the rate of concomitant coronary artery disease as those without HF. Patients with PAD and HF had significantly increased risk of major adverse cardiovascular events (hazard ratio [HR], 1.31; 95% CI, 1.13-1.51) and all-cause mortality (HR, 1.39; 95% CI, 1.19-1.63). In patients with PAD, the presence of HF was associated with significantly less bleeding (HR, 0.65; 95% CI, 0.45-0.96). Characteristics associated with HF development included age ≥66 (HR, 1.29; 95% CI, 1.18-1.40 per 5 years), diabetes mellitus (HR, 1.85; 95% CI, 1.41-2.43), and weight (bidirectionally associated, ≥76 kg, HR, 0.77; 95% CI, 0.64-0.93; <76 kg, HR, 1.12; 95% CI, 1.07-1.16). Conclusions Patients with PAD and HF have a high rate of coronary artery disease with a high risk for major adverse cardiovascular events and death. These data support the possible need for aggressive treatment of (recurrent) atherosclerotic disease in PAD, especially patients with HF.

Topics: Age Factors; Aged; Clopidogrel; Comorbidity; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome

Topics: Adenosine; Adult; Aged; Anticoagulants; Aspirin; Drug Therapy, Combination; Heart Failure; Heart-Assist Devices; Heparin; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Prosthesis Design; Thrombosis; Ticagrelor; Treatment Outcome; Ventricular Function, Left

In the cardiovascular area, the rate of occurrence of relevant clinical events decreased over the last decades due to the large adoption of evidence-based treatments. This implies that large numbers of patients are needed to provide reliable answers to research open questions. Therefore, the conduction of multinational large-scale studies became necessary. In this setting, it is not infrequent to find relevant differences in the trial results across countries. The interpretation of these differences should be extremely cautious to avoid the well known mistakes related to subgroup analyses. To believe in differences, it is necessary to adopt appropriate methodologies in the analysis of data but, even more important, to find a biological plausibility that can explain the observed difference. A further confirmation from other studies can also help in the interpretation. In the literature there are some examples of such differences that, in some cases, produced erroneous interpretations of the results of a trial, and also induced regulatory authorities to take decisions based on these differences.

Topics: Acute Coronary Syndrome; Adenosine; Americas; Benzazepines; Cardiovascular Agents; Cardiovascular Diseases; Clinical Trials as Topic; Clopidogrel; Ethnicity; Europe; Female; Georgia (Republic); Heart Failure; Humans; Internationality; Male; Metoprolol; Multicenter Studies as Topic; Platelet Aggregation Inhibitors; Russia; Sample Size; Spironolactone; Ticagrelor; Ticlopidine; Tolvaptan