Long-term excess mortality associated with diabetes following acute myocardial infarction: a population-based cohort study

The long-term excess risk of death associated with diabetes following acute myocardial infarction is unknown. We determined the excess risk of death associated with diabetes among patients with ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) after adjustment for comorbidity, risk factors and cardiovascular treatments.Nationwide population-based cohort (STEMI n=281 259 and NSTEMI n=422 661) using data from the UK acute myocardial infarction registry, MINAP, between 1 January 2003 and 30 June 2013. Age, sex, calendar year and country-specific mortality rates for the populace of England and Wales (n=56.9 million) were matched to cases of STEMI and NSTEMI. Flexible parametric survival models were used to calculate excess mortality rate ratios (EMRR) after multivariable adjustment. This study is registered at ClinicalTrials.gov (NCT02591576).Over 1.94 million person-years follow-up including 120 568 (17.1%) patients with diabetes, there were 187 875 (26.7%) deaths. Overall, unadjusted (all cause) mortality was higher among patients with than without diabetes (35.8% vs 25.3%). After adjustment for age, sex and year of acute myocardial infarction, diabetes was associated with a 72% and 67% excess risk of death following STEMI (EMRR 1.72, 95% CI 1.66 to 1.79) and NSTEMI (1.67, 1.63 to 1.71). Diabetes remained significantly associated with substantial excess mortality despite cumulative adjustment for comorbidity (EMRR 1.52, 95% CI 1.46 to 1.58 vs 1.45, 1.42 to 1.49), risk factors (1.50, 1.44 to 1.57 vs 1.33, 1.30 to 1.36) and cardiovascular treatments (1.56, 1.49 to 1.63 vs 1.39, 1.36 to 1.43).At index acute myocardial infarction, diabetes was common and associated with significant long-term excess mortality, over and above the effects of comorbidities, risk factors and cardiovascular treatments

Excess mortality and guideline-indicated care following non-ST-elevation myocardial infarction

BACKGROUND: Adherence to guideline-indicated care for the treatment of non-ST-elevation myocardial infarction (NSTEMI) is associated with improved outcomes. We investigated the extent and consequences of non-adherence to guideline-indicated care across a national health system. METHODS: A cohort study (ClinicalTrials.gov identifier: NCT02436187) was conducted using data from the Myocardial Ischaemia National Audit Project (n = 389,057 NSTEMI, n = 247 hospitals, England and Wales, 2003-2013). Accelerated failure time models were used to quantify the impact of non-adherence on survival according to dates of guideline publication. RESULTS: Over a period of 1,079,044 person-years (median 2.2 years of follow-up), 113,586 (29.2%) NSTEMI patients died. Of those eligible to receive care, 337,881 (86.9%) did not receive one or more guideline-indicated intervention; the most frequently missed were dietary advice (n = 254,869, 68.1%), smoking cessation advice (n = 245,357, 87.9%), P2Y12 inhibitors (n = 192,906, 66.3%) and coronary angiography (n = 161,853, 43.4%). Missed interventions with the strongest impact on reduced survival were coronary angiography (time ratio: 0.18, 95% confidence interval (CI): 0.17-0.18), cardiac rehabilitation (time ratio: 0.49, 95% CI: 0.48-0.50), smoking cessation advice (time ratio: 0.53, 95% CI: 0.51-0.57) and statins (time ratio: 0.56, 95% CI: 0.55-0.58). If all eligible patients in the study had received optimal care at the time of guideline publication, then 32,765 (28.9%) deaths (95% CI: 30,531-33,509) may have been prevented. CONCLUSION: The majority of patients hospitalised with NSTEMI missed at least one guideline-indicated intervention for which they were eligible. This was significantly associated with excess mortality. Greater attention to the provision of guideline-indicated care for the management of NSTEMI will reduce premature cardiovascular deaths

A nationwide causal mediation analysis of survival following ST-elevation myocardial infarction

Objective: International studies report a decline in mortality following ST-elevation myocardial infarction (STEMI). The extent to which the observed improvements in STEMI survival are explained by temporal changes in patient characteristics and utilisation of treatments is unknown. Methods: Cohort study using national registry data from the Myocardial Ischaemia National Audit Project between first January 2004 and 30th June 2013. 232 353 survivors of hospitalisation with STEMI as recorded in 247 hospitals in England and Wales. Flexible parametric survival modelling and causal mediation analysis were used to estimate the relative contribution of temporal changes in treatments and patient characteristics on improved STEMI survival. Results: Over the study period, unadjusted survival at 6 months and 1 year improved by 0.9% and 1.0% on average per year (HR: 0.991, 95% CI: 0.988 to 0.994 and HR: 0.990, 95% CI: 0.987 to 0.993, respectively). The uptake of primary percutaneous coronary intervention (PCI) (HR: 1.025, 95% CI: 1.021 to 1.028) and increased prescription of P2Y12 inhibitors (HR: 1.035, 95% CI: 1.031 to 1.039) were significantly associated with improvements in 1-year survival. Primary PCI explained 16.8% (95% CI: 10.8% to 31.6%) and 13.2% (9.2% to 21.9%) of the temporal survival improvements at 6 months and 1 year, respectively, whereas P2Y12 inhibitor prescription explained 5.3% (3.6% to 8.8%) of the temporal improvements at 6 months but not at 1 year. Conclusions: For STEMI in England and Wales, improvements in survival between 2004 and 2013 were significantly explained by the uptake of primary PCI and increased use of P2Y12 inhibitors at 6 months and primary PCI only at 1 year. Trial registration number: NCT0374969

Geographic variation in the treatment of non-ST-segment myocardial infarction in the English National Health Service: a cohort study

Objectives: To investigate geographic variation in guideline-indicated treatments for NSTEMI in the English National Health Service (NHS). Design: Cohort study using registry data from the Myocardial Ischaemia National Audit Project. Setting: All Clinical Commissioning Groups (CCGs) (n=211) in the English NHS. Participants: 357,228 patients with NSTEMI between 1st January, 2003 and 30th June, 2013. Main outcome measure: Proportion of eligible NSTEMI who received all eligible guideline-indicated treatments (optimal care) according to the date of guideline publication. Results: The proportion of NSTEMI who received optimal care was low (48,257/357,228; 13.5%) and varied between CCGs (median 12.8%, interquartile range 0.7 to 18.1%). The greatest geographic variation was for aldosterone antagonists (16.7%, 0.0 to 40.0%) and least for use of an electrocardiogram (96.7%, 92.5 to 98.7%). The highest rates of care were for acute aspirin (median 92.8%, interquartile range 88.6 to 97.1%), and aspirin (90.1%, 85.1 to 93.3%) and statins (86.4%, 82.3 to 91.2%) at hospital discharge. The lowest rates were for smoking cessation advice (median 11.6%, interquartile range 8.7 to 16.6%), dietary advice (32.4%, 23.9 to 41.7%) and the prescription of P2Y12 inhibitors (39.7%, 32.4 to 46.9%). After adjustment for case mix, nearly all (99.6%) of the variation was due to between hospitals differences (median 64.7%, interquartile range 57.4% to 70.0%; between hospital variance: 1.92, 95% confidence interval 1.51 to 2.44; interclass correlation 0.996, 0.976 to 0.999). Conclusions: Across the English NHS, the optimal use of guideline-indicated treatments for NSTEMI was low. Variation in the use of specific treatments for NSTEMI was mostly explained by between-hospital differences in care. Performance-based commissioning may increase the use of NSTEMI treatments and, therefore, reduce premature cardiovascular deaths

Determinants of excess mortality following unprotected left main stem percutaneous coronary intervention.

For percutaneous coronary intervention (PCI) to the unprotected left main stem (UPLMS), there are limited long-term outcome data. We evaluated 5-year survival for UPLMS PCI cases taking into account background population mortality.A population-based registry of 10 682 cases of chronic stable angina (CSA), non-ST-segment elevation acute coronary syndrome (NSTEACS), ST-segment elevation myocardial infarction with (STEMI+CS) and without cardiogenic shock (STEMI-CS) who received UPLMS PCI from 2005 to 2014 were matched by age, sex, year of procedure and country to death data for the UK populace of 56.6 million people. Relative survival and excess mortality were estimated.Over 26 105 person-years follow-up, crude 5-year relative survival was 93.8% for CSA, 73.1% for NSTEACS, 77.5% for STEMI-CS and 28.5% for STEMI+CS. The strongest predictor of excess mortality among CSA was renal failure (EMRR 6.73, 95% CI 4.06 to 11.15), and for NSTEACS and STEMI-CS was preprocedural ventilation (6.25, 5.05 to 7.75 and 6.92, 4.25 to 11.26, respectively). For STEMI+CS, the strongest predictor of excess mortality was preprocedural thrombolysis in myocardial infarction (TIMI) 0 flow (2.78, 1.87 to 4.13), whereas multivessel PCI was associated with improved survival (0.74, 0.61 to 0.90).Long-term survival following UPLMS PCI for CSA was high, approached that of the background populace and was significantly predicted by co-morbidity. For NSTEACS and STEMI-CS, the requirement for preprocedural ventilation was the strongest determinant of excess mortality. By contrast, among STEMI+CS, in whom survival was poor, the strongest determinant was preprocedural TIMI flow. Future cardiovascular cohort studies of long-term mortality should consider the impact of non-cardiovascular deaths

Association of Clinical Factors and Therapeutic Strategies With Improvements in Survival Following Non-ST-Elevation Myocardial Infarction, 2003-2013.

Importance: International studies report a decline in mortality following non–ST-elevation myocardial infarction (NSTEMI). Whether this is due to lower baseline risk or increased utilization of guideline-indicated treatments is unknown. Objective: To determine whether changes in characteristics of patients with NSTEMI are associated with improvements in outcomes. Design, Setting, and Participants: Data on patients with NSTEMI in 247 hospitals in England and Wales were obtained from the Myocardial Ischaemia National Audit Project between January 1, 2003, and June 30, 2013 (final follow-up, December 31, 2013). Exposures: Baseline demographics, clinical risk (GRACE risk score), and pharmacological and invasive coronary treatments. Main Outcomes and Measures: Adjusted all-cause 180-day postdischarge mortality time trends estimated using flexible parametric survival modeling. Results: Among 389 057 patients with NSTEMI (median age, 72.7 years [IQR, 61.7-81.2 years]; 63.1% men), there were 113 586 deaths (29.2%). From 2003-2004 to 2012-2013, proportions with intermediate to high GRACE risk decreased (87.2% vs 82.0%); proportions with lowest risk increased (4.2% vs 7.6%; P= .01 for trend). The prevalence of diabetes, hypertension, cerebrovascular disease, chronic obstructive pulmonary disease, chronic renal failure, previous invasive coronary strategy, and current or ex-smoking status increased (all P < .001). Unadjusted all-cause mortality rates at 180 days decreased from 10.8% to 7.6% (unadjusted hazard ratio [HR], 0.968 [95% CI, 0.966-0.971]; difference in absolute mortality rate per 100 patients [AMR/100], −1.81 [95% CI, −1.95 to −1.67]). These findings were not substantially changed when adjusted additively by baseline GRACE risk score (HR, 0.975 [95% CI, 0.972-0.977]; AMR/100, −0.18 [95% CI, −0.21 to −0.16]), sex and socioeconomic status (HR, 0.975 [95% CI, 0.973-0.978]; difference in AMR/100, −0.24 [95% CI, −0.27 to −0.21]), comorbidities (HR, 0.973 [95% CI, 0.970-0.976]; difference in AMR/100, −0.44 [95% CI, −0.49 to −0.39]), and pharmacological therapies (HR, 0.972 [95% CI, 0.964-0.980]; difference in AMR/100, −0.53 [95% CI, −0.70 to −0.36]). However, the direction of association was reversed after further adjustment for use of an invasive coronary strategy (HR, 1.02 [95% CI, 1.01-1.03]; difference in AMR/100, 0.59 [95% CI, 0.33-0.86]), which was associated with a relative decrease in mortality of 46.1% (95% CI, 38.9%-52.0%). Conclusions and Relevance: Among patients hospitalized with NSTEMI in England and Wales, improvements in all-cause mortality were observed between 2003 and 2013. This was significantly associated with use of an invasive coronary strategy and not entirely related to a decline in baseline clinical risk or increased use of pharmacological therapies

Effect of oral β-blocker treatment on mortality in contemporary post-myocardial infarction patients: a systematic review and meta-analysis

Aims: Guidelines concerning β-blocker treatment following acute myocardial infarction (AMI) are based on studies undertaken before the implementation of reperfusion and secondary prevention therapies. We aimed to estimate the effect of oral β-blockers on mortality in contemporary post-AMI patients with low prevalence of heart failure and/or reduced left ventricular ejection fraction. Methods and results: A random effects model was used to synthetize results of 16 observational studies published between 1 January 2000 and 30 October 2017. Publication bias was evaluated, and heterogeneity between studies examined by subgroup and random effects meta-regression analyses considering patient-related and study-level variables. The pooled estimate showed that β-blocker treatment [among 164 408 (86.8%) patients, with median follow-up time of 2.7 years] was associated with a 26% reduction in all-cause mortality [rate ratio (RR) 0.74, 95% confidence interval (CI) 0.64-0.85] with moderate heterogeneity (I2 = 67.4%). The patient-level variable mean age of the cohort explained 31.5% of between study heterogeneity. There was presence of publication bias, or small study effect, and when controlling for bias by the trim and fill simulation method, the effect disappeared (adjusted RR 0.90, 95% CI 0.77-1.04). Also, small study effect was demonstrated by a cumulative meta-analysis starting with the largest study showing no effect, with increasing effect as the smaller studies were accumulated. Conclusion: Evidence from this study suggests that there is no association between β-blockers and all-cause mortality. A possible beneficial effect in AMI survivors needs to be tested by large randomized clinical trials

Development and Validation of a Novel Risk Score for In-Hospital Major Bleeding in Acute Myocardial Infarction:-The SWEDEHEART Score

Background: Bleeding risk stratification in acute coronary syndrome is of highest clinical interest but current risk scores have limitations. We sought to develop and validate a new in‐hospital bleeding risk score for patients with acute myocardial infarction. Methods and Results: From the nationwide SWEDEHEART (Swedish Web‐System for Enhancement and Development of Evidence‐Based Care in Heart Disease Evaluated According to Recommended Therapies) register, 97,597 patients with acute myocardial infarction enrolled from 2009 until 2014 were selected. A full model with 23 predictor variables and 8 interaction terms was fitted using logistic regression. The full model was approximated by a model with 5 predictors and 1 interaction term. Calibration, discrimination, and clinical utility was evaluated and compared with the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) and CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines) scores. Internal and temporal validity was assessed. In‐hospital major bleeding, defined as fatal, intracranial, or requiring surgery or blood transfusion, occurred in 1356 patients (1.4%). The 5 predictors in the approximate model that constituted the SWEDEHEART score were hemoglobin, age, sex, creatinine, and C‐reactive protein. The ACTION and CRUSADE scores were poorly calibrated in the derivation cohort and therefore were recalibrated. The SWEDEHEART score showed higher discriminative ability than both recalibrated scores, overall (C‐index 0.80 versus 0.73/0.72) and in all predefined subgroups. Decision curve analysis demonstrated consistently positive and higher net benefit for the SWEDEHEART score compared with both recalibrated scores across all clinically relevant decision thresholds. The original ACTION and CRUSADE scores showed negative net benefit. Conclusions: The 5‐item SWEDEHEART score discriminates in‐hospital major bleeding in patients with acute myocardial infarction and has superior model performance compared with the recalibrated ACTION and CRUSADE scores

International comparison of acute myocardial infarction care and outcomes using quality indicators

Objective: To compare temporal changes in European Society of Cardiology (ESC) acute myocardial infarction (AMI) quality indicator (QI) attainment in the UK and Israel. Methods: Data cross-walking using information from the Myocardial Ischaemia National Audit Project and the Acute Coronary Syndrome in Israel Survey for matching 2-month periods in 2006, 2010 and 2013 was used to compare country-specific attainment of 14 ESC AMI QIs. Results: Patients in the UK (n=17 068) compared with Israel (n=5647) were older, more likely to be women, and had less diabetes, dyslipidaemia and heart failure. Baseline ischaemic risk was lower in Israel than the UK (Global Registry of Acute Coronary Events (GRACE) risk, 110.5 vs 121.0). Overall, rates of coronary angiography (87.6% vs 64.8%) and percutaneous coronary intervention (70.3% vs 41.0%) were higher in Israel compared with the UK. Composite QI performance increased more in the UK (1.0%-86.0%) than Israel (70.2%-78.0%). Mortality rates at 30 days declined in each country, with lower rates in Israel in 2013 (4.2% vs 7.6%). Composite QI adherence adjusted for GRACE risk score was inversely associated with 30-day mortality (OR 0.95; CI 0.95 to 0.97, p<0.001). Conclusions: nternational comparisons of guideline recommended AMI care and outcomes can be quantified using the ESC AMI QIs. International implementation of the ESC AMI QIs may reveal country-specific opportunities for improved healthcare delivery

Sex differences in health-related quality of life trajectories following myocardial infarction: national longitudinal cohort study

Objectives To investigate sex-based differences in baseline values and longitudinal trajectories of health-related quality of life (HRQoL) in a large cohort of myocardial infarction (MI) survivors after adjusting for other important factors. Design Longitudinal cohort study. Setting Population-based longitudinal study the Evaluation of the Methods and Management of Acute Coronary Events study linked with national cardiovascular registry. Data were collected from 77 hospitals in England between 1 November 2011 and 24 June 2015. Participants 9551 patients with MI. Patients were eligible for the study if they were ≥18 years of age. Primary and secondary outcome measures HRQoL was measured by EuroQol five-dimension, visual analogue scale (EQ-5D, EQ VAS) survey at baseline, 1, 6 and 12 months after discharge. Multi-level linear and logistic regression models coupled with inverse probability weighted propensity scoring were used to evaluate sex differences in HRQoL following MI. Results Of the 9551 patients with MI and complete data on sex, 25.1% (2,397) were women. At baseline, women reported lower HRQoL (EQ VAS (mean (SD) 59.8 (20.4) vs 64.5 (20.9)) (median (IQR) 60.00 (50.00–75.00) vs 70.00 (50.00–80.00))) (EQ-5D (mean (SD) 0.66 (0.31) vs 0.74 (0.28)) (median (IQR) 0.73 (0.52–0.85) vs 0.81 (0.62–1.00))) and were more likely to report problems in each HRQoL domain compared with men. In the covariate balanced and adjusted multi-level model sex differences in HRQoL persisted during follow-up, with lower EQ VAS and EQ-5D scores in women compared with men (adjusted EQ VAS model sex coefficient: −4.41, 95% CI −5.16 to −3.66 and adjusted EQ-5D model sex coefficient: −0.07, 95% CI −0.08 to −0.06). Conclusions Women have lower HRQoL compared with men at baseline and during 12 months follow-up after MI. Tailored interventions for women following an MI could improve their quality of life. Trial registration number ClinicalTrials.gov (NCT04598048, NCT01808027, NCT0181910