Pharmacogenetic determinants of the response of patients to clopidogrel contribute to variability in the biologic antiplatelet activity of the drug. The effect of these determinants on clinical ...outcomes after an acute myocardial infarction is unknown.
We consecutively enrolled 2208 patients presenting with an acute myocardial infarction in a nationwide French registry and receiving clopidogrel therapy. We then assessed the relation of allelic variants of genes modulating clopidogrel absorption (ABCB1), metabolic activation (CYP3A5 and CYP2C19), and biologic activity (P2RY12 and ITGB3) to the risk of death from any cause, nonfatal stroke, or myocardial infarction during 1 year of follow-up.
Death occurred in 225 patients, and nonfatal myocardial infarction or stroke in 94 patients, during the follow-up period. None of the selected single-nucleotide polymorphisms (SNPs) in CYP3A5, P2RY12, or ITGB3 were associated with a risk of an adverse outcome. Patients with two variant alleles of ABCB1 (TT at nucleotide 3435) had a higher rate of cardiovascular events at 1 year than those with the ABCB1 wild-type genotype (CC at nucleotide 3435) (15.5% vs. 10.7%; adjusted hazard ratio, 1.72; 95% confidence interval CI, 1.20 to 2.47). Patients carrying any two CYP2C19 loss-of-function alleles (*2, *3, *4, or *5), had a higher event rate than patients with none (21.5% vs. 13.3%; adjusted hazard ratio, 1.98; 95% CI, 1.10 to 3.58). Among the 1535 patients who underwent percutaneous coronary intervention during hospitalization, the rate of cardiovascular events among patients with two CYP2C19 loss-of-function alleles was 3.58 times the rate among those with none (95% CI, 1.71 to 7.51).
Among patients with an acute myocardial infarction who were receiving clopidogrel, those carrying CYP2C19 loss-of-function alleles had a higher rate of subsequent cardiovascular events than those who were not. This effect was particularly marked among the patients undergoing percutaneous coronary intervention. (ClinicalTrials.gov number, NCT00673036.)
Abstract Background Out of hospital cardiac arrest (OHCA) mortality rates remain very high with poor neurological outcome in survivors. Extracorporeal cardiopulmonary resuscitation (ECPR) is one of ...the treatments of refractory OHCA. This study used data from the mobile intensive care unit (MOICU) as part of the emergency medical system of Paris, and included all consecutive patients treated with ECPR (including pre-hospital ECPR) from 2011 to 2015 for the treatment of refractory OHCA, comparing two historical ECPR management strategies. Methods We consecutively included refractory OHCA patients. In Period 1, ECPR was indicated in selected patients after 30 min of advanced life support; in- or pre-hospital implementation depended on estimated transportation time and ECPR team availability. In Period 2, patient care relied on early ECPR initiation after 20 min of resuscitation, stringent patient selection, epinephrine dose limitation and deployment of ECPR team with initial response team. Primary outcome was survival with good neurological function Cerebral Performance Category score (CPC score) 1 and 2 at ICU discharge or day 28. Findings A total of 156 patients were included. (114 in Period 1 and 42 in Period 2). Baseline characteristics were similar. Mean low-flow duration was shorter by 20 min (p < 0.001) in Period 2. Survival was significantly higher in Period 2: 29% vs 8% (P < 0.001), as confirmed by the multivariate analysis and propensity score. When combining stringent patient selection with an aggressive strategy, the survival rate increased to 38%. Pre-hospital ECPR implementation in itself was not an independent predictor of improved survival, but it was part of the strategy in Period 2. Interpretation Our data suggest that ECPR in specific settings in the management of refractory OHCA is feasible and can lead to a significant increase in neurological intact survivors. These data, however, need to be confirmed by a large RCT.
Abstract Background For acute myocardial infarction (AMI) without heart failure (HF), it is unclear if β-blockers are associated with reduced mortality. Objectives The goal of this study was to ...determine the association between β-blocker use and mortality in patients with AMI without HF or left ventricular systolic dysfunction (LVSD). Methods This cohort study used national English and Welsh registry data from the Myocardial Ischaemia National Audit Project. A total of 179,810 survivors of hospitalization with AMI without HF or LVSD, between January 1, 2007, and June 30, 2013 (final follow-up: December 31, 2013), were assessed. Survival-time inverse probability weighting propensity scores and instrumental variable analyses were used to investigate the association between the use of β-blockers and 1-year mortality. Results Of 91,895 patients with ST-segment elevation myocardial infarction and 87,915 patients with non–ST-segment elevation myocardial infarction, 88,542 (96.4%) and 81,933 (93.2%) received β-blockers, respectively. For the entire cohort, with >163,772 person-years of observation, there were 9,373 deaths (5.2%). Unadjusted 1-year mortality was lower for patients who received β-blockers compared with those who did not (4.9% vs. 11.2%; p < 0.001). However, after weighting and adjustment, there was no significant difference in mortality between those with and without β-blocker use (average treatment effect ATE coefficient: 0.07; 95% confidence interval CI: −0.60 to 0.75; p = 0.827). Findings were similar for ST-segment elevation myocardial infarction (ATE coefficient: 0.30; 95% CI: −0.98 to 1.58; p = 0.637) and non–ST-segment elevation myocardial infarction (ATE coefficient: −0.07; 95% CI: −0.68 to 0.54; p = 0.819). Conclusions Among survivors of hospitalization with AMI who did not have HF or LVSD as recorded in the hospital, the use of β-blockers was not associated with a lower risk of death at any time point up to 1 year. (β-Blocker Use and Mortality in Hospital Survivors of Acute Myocardial Infarction Without Heart Failure; NCT02786654 )
Acute myocardial infarction is a common condition responsible for heart failure and sudden death. Here, we show that following acute myocardial infarction in mice, CD8
T lymphocytes are recruited and ...activated in the ischemic heart tissue and release Granzyme B, leading to cardiomyocyte apoptosis, adverse ventricular remodeling and deterioration of myocardial function. Depletion of CD8
T lymphocytes decreases apoptosis within the ischemic myocardium, hampers inflammatory response, limits myocardial injury and improves heart function. These effects are recapitulated in mice with Granzyme B-deficient CD8
T cells. The protective effect of CD8 depletion on heart function is confirmed by using a model of ischemia/reperfusion in pigs. Finally, we reveal that elevated circulating levels of GRANZYME B in patients with acute myocardial infarction predict increased risk of death at 1-year follow-up. Our work unravels a deleterious role of CD8
T lymphocytes following acute ischemia, and suggests potential therapeutic strategies targeting pathogenic CD8
T lymphocytes in the setting of acute myocardial infarction.
There is a shortage of information on regional variations in ST-segment elevation myocardial infarction (STEMI) management and prognosis at a global level. We aimed to compare patient profiles, ...in-hospital management and post-discharge mortality across several world regions.
In total, 11,559 patients with STEMI were enrolled in two prospective studies of acute coronary syndrome survivors: EPICOR (4943 patients from 555 hospitals in 20 countries in Europe and Latin America recruited between September 2010 and March 2011) and EPICOR Asia (6616 patients from 218 hospitals in eight Asian countries recruited between June 2011 and May 2012). Comparisons were performed by eight pre-defined regions: Northern Europe (NE), Southern Europe (SE), Eastern Europe (EE), Latin America (LA), China (CN), India (IN), Southeast Asia (SA), and South Korea/Hong Kong/Singapore (KS).
Reperfusion therapy rates ranged between 53.9% (IN) and 81.2% (SE), primary percutaneous coronary intervention (PCI) between 24.8% (IN) and 65.6% (NE) and fibrinolysis between 8.1% (CN) and 34.2% (SA). Median time to primary PCI (h) ranged from 3.9 (NE) to 20.9 (IN) and to fibrinolysis from 2.4 (SE) to 6.3 (IN). Two-year mortality ranged between 2.5% in NE and 7.4% in LA. Regional variations in mortality persisted after adjustment for reperfusion therapy and known prognostic factors.
Among patients with STEMI, there is a wide regional variation in clinical profiles, hospital care and mortality. Substantial room for improvement remains at a global level for increasing reperfusion rates, reducing delays and post-discharge mortality in patients with STEMI.
Aim
To address the paucity of data on the characteristics, outcome and temporal trends in mortality of cardiogenic shock (CS) patients admitted to intensive care units (ICUs) we examined key ...features, variations in mortality from CS, and predictors of death in ICU patients over the past 15 years.
Methods and results
From the 1997–2012 database of the Collège des Utilisateurs de Bases de données en Réanimation (CUB‐Réa) that prospectively collects data from ICUs in the greater Paris area, we determined temporal trends in the incidence of CS, patient outcomes Crude and Simplified Acute Physiology Score (SAPS)‐II Standardized Mortality and predictors of in‐ICU mortality. Of the 316 905 ICU admissions, 19 416 (6.1%) exhibited CS, with incidence increasing from 4.1% to 7.7% (P < 0.001). Over time, the age of admitted patients decreased by 2.7 years 95% confidence interval (CI), −2.0 to −3.4 and SAPS‐II increased by 5.8% (95% CI 4.8–6.8) from 58.7 ± 25.3 to 64.5 ± 23.3 (P < 0.001). Crude in‐ICU mortality declined from 50% to 45% (−5.6%; 95% CI −7.7 to −3.5) as SAPS‐II Standardized ICU mortality rates decreased from 56.5% to 44.2% (P < 0.001). A more recent time‐period was an independent correlate of decreased mortality in multivariate analyses. The decrease in mortality rate was more marked in patients with decompensated heart failure, cardiac arrest, or acute myocardial infarction.
Conclusions
Patients with CS represent a greater proportion of patients admitted to ICUs over the past 15 years, having become younger but more critically ill. Although their mortality has decreased, suggesting improved overall patient management, it remains particularly high, warranting further research specifically focused on this population.
Although angina is common in patients with stable coronary artery disease, limited data are available on its prevalence, natural evolution, and outcomes in the era of effective cardiovascular drugs ...and widespread use of coronary revascularization.
Using data from 32 691 patients with stable coronary artery disease from the prospective observational CLARIFY registry (Prospective Observational Longitudinal Registry of Patients with Stable Coronary Artery Disease), anginal status was mapped each year in patients without new coronary revascularization or new myocardial infarction. The use of medical interventions in the year preceding angina resolution was explored. The effect of 1-year changes in angina status on 5-year outcomes was analyzed using multivariable analysis.
Among 7212 (22.1%) patients who reported angina at baseline, angina disappeared (without coronary revascularization) in 39.6% at 1 year, with further annual decreases. In patients without angina at baseline, 2.0% to 4.8% developed angina each year. During 5-year follow-up, angina was controlled in 7773 patients, in whom resolution of angina was obtained with increased use of antianginal treatment in 11.1%, with coronary revascularization in 4.5%, and without any changes in medication or revascularization in 84.4%. Compared to patients without angina at baseline and 1 year, persistence of angina and occurrence of angina at 1 year with conservative management were each independently associated with higher rates of cardiovascular death or myocardial infarction (adjusted hazard ratio, 1.32 95% CI, 1.12-1.55 for persistence of angina; adjusted hazard ratio, 1.37 95% CI, 1.11-1.70 for occurrence of angina) at 5 years. Patients whose angina had resolved at 1 year with conservative management were not at higher risk of cardiovascular death or myocardial infarction than those who never experienced angina (adjusted hazard ratio, 0.97 95% CI, 0.82-1.15).
Angina affects almost one-quarter of patients with stable coronary artery disease but resolves without events or coronary revascularization in most patients. Resolution of angina within 1 year with conservative management predicted outcomes similar to lack of angina, whereas persistence or occurrence was associated with worse outcomes. Because most patients with angina are likely to experience resolution of symptoms, and because there is no demonstrated outcome benefit to routine revascularization, this study emphasizes the value of conservative management of stable coronary artery disease. Registration: URL: https://www.isrctn.com; Unique identifier: ISRCTN43070564.
Abstract
Aims
Over the last decades, the profile of chronic coronary syndrome has changed substantially. We aimed to determine characteristics and management of patients with chronic coronary ...syndrome in the contemporary era, as well as outcomes and their determinants.
Methods and results
Data from 32 703 patients (45 countries) with chronic coronary syndrome enrolled in the prospective observational CLARIFY registry (November 2009 to June 2010) with a 5-year follow-up, were analysed. The primary outcome cardiovascular death or non-fatal myocardial infarction (MI) 5-year rate was 8.0% 95% confidence interval (CI) 7.7–8.3 overall male 8.1% (7.8–8.5); female 7.6% (7.0–8.3). A cox proportional hazards model showed that the main independent predictors of the primary outcome were prior hospitalization for heart failure, current smoking, atrial fibrillation, living in Central/South America, prior MI, prior stroke, diabetes, current angina, and peripheral artery disease. There was an interaction between angina and prior MI (P = 0.0016); among patients with prior MI, angina was associated with a higher primary event rate 11.8% (95% CI 10.9–12.9) vs. 8.2% (95% CI 7.8–8.7) in patients with no angina, P < 0.001, whereas among patients without prior MI, event rates were similar for patients with 6.3% (95% CI 5.4–7.3) or without angina 6.4% (95% CI 5.9–7.0), P > 0.99. Prescription rates of evidence-based secondary prevention therapies were high.
Conclusion
This description of the spectrum of chronic coronary syndrome patients shows that, despite high rates of prescription of evidence-based therapies, patients with both angina and prior MI are an easily identifiable high-risk group who may deserve intensive treatment.
Clinical registry
ISRCTN43070564
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