Delayed Care and Mortality Among Women and Men with Myocardial Infarction

Background-Women with ST-segment-elevation myocardial infarction (STEMI) have higher mortality rates than men. We investigated whether sex-related differences in timely access to care among STEMI patients may be a factor associated with excess risk of early mortality in women. Methods and Results-We identified 6022 STEMI patients who had information on time of symptom onset to time of hospital presentation at 41 hospitals participating in the ISACS-TC (International Survey of Acute Coronary Syndromes in Transitional Countries) registry (NCT01218776) from October 2010 through April 2016. Patients were stratified into time-delay cohorts. We estimated the 30-day risk of all-cause mortality in each cohort. Despite similar delays in seeking care, the overall time from symptom onset to hospital presentation was longer for women than men (median: 270 minutes [range: 130-776] versus 240 minutes [range: 120-600]). After adjustment for baseline variables, female sex was independently associated with greater risk of 30-day mortality (odds ratio: 1.58; 95% confidence interval, 1.27-1.97). Sex differences in mortality following STEMI were no longer observed for patients having delays from symptom onset to hospital presentation of (odds ratio: 0.77; 95% confidence interval, 0.29-2.02). Conclusions-Sex difference in mortality following STEMI persists and appears to be driven by prehospital delays in hospital presentation. Women appear to be more vulnerable to prolonged untreated ischemia

Patients with coronary artery disease and diabetes need improved management: a report from the EUROASPIRE IV survey: a registry from the EuroObservational Research Programme of the European Society of Cardiology

Background: In order to influence every day clinical practice professional organisations issue management guidelines. Cross-sectional surveys are used to evaluate the implementation of such guidelines. The present survey investigated screening for glucose perturbations in people with coronary artery disease and compared patients with known and newly detected type 2 diabetes with those without diabetes in terms of their life-style and pharmacological risk factor management in relation to contemporary European guidelines. Methods: A total of 6187 patients (18–80 years) with coronary artery disease and known glycaemic status based on a self reported history of diabetes (previously known diabetes) or the results of an oral glucose tolerance test and HbA1c (no diabetes or newly diagnosed diabetes) were investigated in EUROASPIRE IV including patients in 24 European countries 2012–2013. The patients were interviewed and investigated in order to enable a comparison between their actual risk factor control with that recommended in current European management guidelines and the outcome in previously conducted surveys. Results: A total of 2846 (46%) patients had no diabetes, 1158 (19%) newly diagnosed diabetes and 2183 (35 %) previously known diabetes. The combined use of all four cardioprotective drugs in these groups was 53, 55 and 60%, respectively. A blood pressure target of 9.0% (>75 mmol/mol). Of the patients with diabetes 69% reported on low physical activity. The proportion of patients participating in cardiac rehabilitation programmes was low (≈40%) and only 27% of those with diabetes had attended diabetes schools. Compared with data from previous surveys the use of cardioprotective drugs had increased and more patients were achieving the risk factor treatment targets. Conclusions: Despite advances in patient management there is further potential to improve both the detection and management of patients with diabetes and coronary artery disease

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Benefit of early invasive therapy for diabetic patients with NSTE ACS. A landmark study from the ISACS-TC registry

Background: Diabetic (DM) patients are at increased risk of cardiovascular events after an acute coronary syndrome, yet it remains unknown whether they derive enhanced benefit from an invasive strategy. Objective: We investigated the relation between coronary revascularization by percutaneus coronary intervention (PCI) and in-hospital survival of DM patients admitted to hospitals with a diagnosis of Unstable angina/ Non-ST-elevation myocardial infarction (UA/NSTEMI). Methods: This was a prospective cohort study using data from the International Survey of Acute Coronary Syndromes in Transitional Countries (ISACSTC, NCT01218776) registry on patients admitted to the coronary care units of 58 Eastern European hospitals from January 2010 to February 2015. A total of 4,996 first-day survivors who were admitted with a diagnosis of UA/NSTEMI were included. To avoid survival bias, a landmark time was set to 24 hours after hospital admission. Patients who died before the landmark time were excluded. Patients, who had undergone coronary artery bypass grafting, were also excluded leaving a final study population of 4,965 patients. Results: The study populations consisted of 4,965 NSTE-ACS patients. There were 1,381 patients (27.8%) with DM. Patients with DM were older and prevalently women, and had higher rates of hypercholesterolemia, hypertension, prior cardiovascular events and chronic kidney disease. They had more severe clinical presentation and higher rates of atypical chest pain. Patients with DM underwent less (p<0.001) PCI (58.9% versus 65.9%) and had significantly higher (p<0.001) in-hospital mortality (6.2% versus 3.7%) than their non- DM counterpart. Multivariate regression analyses showed DM as a predictor of in-hospital mortality in patients who did not undergo PCI (odds ratio [OR] 2.21, 95% confidence interval [CI] 1.18–4.13, p=0.013), but not in those who underwent revascularization (OR: 1.79, 95% CI: 0.60–5.32, p=0.29). Conclusions: There is an independent association between DM and in hospital mortality in UA/NSTEMI patients who were not offered coronary revascularization. An invasive strategy has significant effect in reducing the likelihood of cardiovascular death in diabetic patients

Acute coronary syndromes without typical chest pain: the role of comorbidities

Background: Not all patients exhibit the classic symptoms of chest pain. Patients who present with acute coronary syndrome (ACS) without typical chest pain have a very high in-hospital mortality. Purpose: To investigate the impact of atypical symptoms on management and outcomes of ACS patients. Methods: Between 2010 and 2016, 11458 ACS patients were admitted at 57 hospitals included in the network of the ISACS-TC registry (ClinicalTrials.gov, NCT01218776). Of these patients 8.7% did not have typical chest pain at the initial evaluation. Results: More women (10.5%) than men (7.8%) exhibit ACS without typical presentation. ACS patients with atypical presentation were older (67.8\ub112.2 vs 62.9\ub112.1, p<0.001). Patients with comorbidities were not equally distributed: 38.7% were with typical presentation and 55.2% without typical presentation, (p<0.001). The probability of having ACS without typical presentation was greater as the number of comorbidities increased (OR: 1.64 for one comorbid; OR: 2.52 for two comorbidities; and OR: 4.57 for three or more comorbidities). Stepwise logistic analysis showed that the absence of ST elevation (OR 2.98), Killip class 652 (OR 2.12, history of stroke (OR 1.78), peripheral artery disease (OR 1.68), chronic kidney disease (OR 1. 56), diabetes mellitus (OR 1.36), age (OR 1.02 per year) were all independent predictors of ACS without typical presentation. Conversely smoking habit (OR 0.75) and hypercholesterolemia (OR 0.72) had protective effect (p<0.01). In-hospital mortality rate was much higher in patients without typical presentation than in patients with the typical presentation (15.5% versus 6.3%, p<0.001). The presence of atypical presentation increased the risk of death either in non ST segment elevation acute coronary syndrome (NSTE-ACS) (OR 2.57, 95% CI 1.91\u20133.47) or ST segment elevation myocardial infarction (STEMI) patients (OR 3.48, 95% CI 2.70\u20134.49). The presence of comorbidities was also independently associated with an increased risk of death, both in NSTE ACS (OR 2.24, 95% CI 1.70\u20132.93) and in STEMI (OR 2.22, 95% CI 1.56\u20132.63) patients. Conclusions: Patients with ACS who present without typical chest pain are at increased risk of dying. Atypical presentation is frequently found in patients with comorbidities. The unfavorable outcomes of ACS without chest pain may be partly attributable to concomitant diseases

Atypical presentation and comorbidities mutually influence management of ACS patients

Background: Limited data are available on the association between comorbidities and acute myocardial ischemia with atypical presentation. Purpose: The aim of this study was to investigate the impact of comorbidities on the management and outcomes of ACS patients with atypical presentation (i.e. ACS without chest pain). Methods: Between 2010 and 2016, 11458 ACS patients were admitted at 57 hospitals included in the network of the ISACS-TC registry (ClinicalTrials.gov, NCT01218776). There were 1394 (12.2%) patients with unstable angina, 2855 (24.9%) with NSTEMI, and 7203 (62.9%) with STEMI. Results: 995 (8.7%) ACS patients have atypical presentation at the initial evaluation, and the 40.2% of the overall study population have comorbidities (diabetes mellitus, heart failure, CKD, COPD, stroke, PAD, GERD or active cancer). Patients with comorbidities were not equally distributed: 38.7% were with typical presentation and 55.2% without typical presentation, (p<0.001). In-hospital mortality rate was much higher in patients with atypical presentation than in patients with the typical one (15.5% vs 6.3%, p<0.001). As well, mortality rate was lower for ACS patients with no-comorbidities than for ACS patients with comorbidities (5.1% versus 10.1%, p<0.001). Stratifying the population by the presence/absence of comorbiditis and the presence/absence typical presentation, we found a decreasing trend in use of evidence base treatment (aspirin, beta-blocker, statin and reperfusion) and invasive procedure. Compare to patients with typical presentation and no-comorbidities (OR: 1, referent), patients with typical presentation and comorbidities (OR: 0.70), as well as those with atypical presentation and no-comorbidities (OR: 0.23), and those with atypical presentation and comorbidities (OR: 0.18) had a significant (p<0.001) lower probability to undergo in-hospital cardiac catheterization. On the opposite, there was an increasing trend (p<0.001) over subgroups in the risk of death (OR:1 referent, typical ACS presentation and no-comorbid; OR:2.00 typical ACS presentation and comordidities; OR: 2.52 atypical ACS presentation and no-comorbid; OR: 4.83 atypical ACS presentation and comordidities). Conclusions: The presence of comorbidities and atypical ACS presentation dramatically influence the process of care. Patients with atypical presentation and comorbidities are those who receive the lowest treatment and those who have the highest risk of in-hospital death