Chris P Gale

β-Blockers and Mortality After Acute Myocardial Infarction in Patients Without Heart Failure or Ventricular Dysfunction

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)

Cardiovascular sequelae in long-term survivors of young peoples’ cancer: a linked cohort study

Background:We aimed to define the incidence and risk of cardiovascular late effects (LEs) identified from inpatient hospital episode statistics (HES) among long-term survivors of cancer in young people by age at diagnosis (0–14 and 15–29 years).Methods:Records from the Yorkshire Specialist Register of Cancer in Children and Young People (1991–2006) were linked to inpatient HES data (1996–2011) to assess rates of cardiovascular LEs. Rates were compared with the general population in Yorkshire using age–sex-matched HES records for the entire region.Results:Of 3247 survivors of cancer, 3.6% had at least one cardiovascular LE. Overall, cardiovascular hospitalisations for the childhood cohort were threefold higher compared with the general population, but did not differ for young adults. For young adults, increased rates were limited to pericardial disease, cardiomyopathy and heart failure, pulmonary heart disease, hypertension and conduction disorders.Conclusions:Survivors of childhood and young adult cancer remain at increased risk of cardiovascular LEs compared with the general population.

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.

Patient and hospital determinants of primary percutaneous coronary intervention in England, 2003–2013

Objective Primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI) is insufficiently implemented in many countries. We investigated patient and hospital characteristics associated with PPCI utilisation. Methods Whole country registry data (MINAP, Myocardial Ischaemia National Audit Project) comprising PPCI-capable National Health Service trusts in England (84 hospital trusts; 92 350 hospitalisations; 90 489 patients), 2003–2013. Multilevel Poisson regression modelled the relationship between incidence rate ratios (IRR) of PPCI and patient and trust-level factors. Results Overall, standardised rates of PPCI increased from 0.01% to 86.3% (2003–2013). While, on average, there was a yearly increase in PPCI utilisation of 30% (adjusted IRR 1.30, 95% CI 1.23 to 1.36), it varied substantially between trusts. PPCI rates were lower for patients with previous myocardial infarction (0.95, 0.93 to 0.98), heart failure (0.86, 0.81 to 0.92), angina (0.96, 0.94 to 0.98), diabetes (0.97, 0.95 to 0.99), chronic renal failure (0.89, 0.85 to 0.90), cerebrovascular disease (0.96, 0.93 to 0.99), age >80 years (0.87, 0.85 to 0.90), and travel distances >30 km (0.95, 0.93 to 0.98). PPCI rates were higher for patients with previous percutaneous coronary intervention (1.09, 1.05 to 1.12) and among trusts with >5 interventional cardiologists (1.30, 1.25 to 1.34), more visiting interventional cardiologists (1–5: 1.31, 1.26 to 1.36; ≥6: 1.42, 1.35 to 1.49), and a 24 h, 7-days-a-week PPCI service (2.69, 2.58 to 2.81). Half of the unexplained variation in PPCI rates was due to between-trust differences. Conclusions Following an 8 year implementation phase, PPCI utilisation rates stabilised at 85%. However, older and sicker patients were less likely to receive PPCI and there remained between-trust variation in PPCI rates not attributable to differences in staffing levels. Compliance with clinical pathways for STEMI is needed to ensure more equitable quality of care.

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

Background 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. Methods 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). Results 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). Conclusions 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.

Sex Differences in Treatments, Relative Survival, and Excess Mortality Following Acute Myocardial Infarction: National Cohort Study Using the SWEDEHEART Registry

Background This study assessed sex differences in treatments, all‐cause mortality, relative survival, and excess mortality following acute myocardial infarction. Methods and Results A population‐based cohort of all hospitals providing acute myocardial infarction care in Sweden (SWEDEHEART [Swedish Web System for Enhancement and Development of Evidence‐Based Care in Heart Disease Evaluated According to Recommended Therapies]) from 2003 to 2013 was included in the analysis. Excess mortality rate ratios (EMRRs), adjusted for clinical characteristics and guideline‐indicated treatments after matching by age, sex, and year to background mortality data, were estimated. Although there were no sex differences in all‐cause mortality adjusted for age, year of hospitalization, and comorbidities for ST‐segment–elevation myocardial infarction (STEMI) and non‐STEMI at 1 year (mortality rate ratio: 1.01 [95% confidence interval (CI), 0.96–1.05] and 0.97 [95% CI, 0.95–0.99], respectively) and 5 years (mortality rate ratio: 1.03 [95% CI, 0.99–1.07] and 0.97 [95% CI, 0.95–0.99], respectively), excess mortality was higher among women compared with men for STEMI and non‐STEMI at 1 year (EMRR: 1.89 [95% CI, 1.66–2.16] and 1.20 [95% CI, 1.16–1.24], respectively) and 5 years (EMRR: 1.60 [95% CI, 1.48–1.72] and 1.26 [95% CI, 1.21–1.32], respectively). After further adjustment for the use of guideline‐indicated treatments, excess mortality among women with non‐STEMI was not significant at 1 year (EMRR: 1.01 [95% CI, 0.97–1.04]) and slightly higher at 5 years (EMRR: 1.07 [95% CI, 1.02–1.12]). For STEMI, adjustment for treatments attenuated the excess mortality for women at 1 year (EMRR: 1.43 [95% CI, 1.26–1.62]) and 5 years (EMRR: 1.31 [95% CI, 1.19–1.43]). Conclusions Women with acute myocardial infarction did not have statistically different all‐cause mortality, but had higher excess mortality compared with men that was attenuated after adjustment for the use of guideline‐indicated treatments. This suggests that improved adherence to guideline recommendations for the treatment of acute myocardial infarction may reduce premature cardiovascular death among women. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02952417.

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.

Impact of initial hospital diagnosis on mortality for acute myocardial infarction: A national cohort study

Aims: Early and accurate diagnosis of acute myocardial infarction is central to successful treatment and improved outcomes. We aimed to investigate the impact of the initial hospital diagnosis on mortality for patients with acute myocardial infarction. Methods and results: Cohort study using data from the Myocardial Ischaemia National Audit Project of patients discharged with a final diagnosis of ST-elevation myocardial infarction (STEMI, n=221,635) and non-STEMI (NSTEMI, n=342,777) between 1 April 2004 and 31 March 2013 in all acute hospitals (n = 243) in England and Wales. Overall, 168,534 (29.9%) patients had an initial diagnosis which was not the same as their final diagnosis. After multivariable adjustment, for STEMI a change from an initial diagnosis of NSTEMI (time ratio 0.97, 95% confidence interval 0.92–1.01) and chest pain of uncertain cause (0.98, 0.89–1.07) was not associated with a significant reduction in time to death, whereas for other initial diagnoses the time to death was significantly reduced by 21% (0.78, 0.74–0.83). For NSTEMI, after multivariable adjustment, a change from an initial diagnosis of STEMI was associated with a reduction in time to death of 10% (time ratio 0.90, 95% confidence interval 0.83–0.97), but not for chest pain of uncertain cause (0.99, 0.96–1.02). Patients with NSTEMI who had other initial diagnoses had a significant 14% reduction in their time to death (time ratio 0.86, 95% confidence interval 0.84–0.88). STEMI and NSTEMI with other initial diagnoses had low rates of pre-hospital electrocardiograph (24.3% and 21.5%), aspirin on hospitalisation (61.6% and 48.5%), care by a cardiologist (60.0% and 51.5%), invasive coronary procedures (38.8 % and 29.2%), cardiac rehabilitation (68.9% and 62.6%) and guideline indicated medications at time of discharge from hospital. Had the 3.3% of patients with STEMI and 17.9% of NSTEMI who were admitted with other initial diagnoses received an initial diagnosis of STEMI and NSTEMI, then 33 and 218 deaths per year might have been prevented, respectively. Conclusion: Nearly one in three patients with acute myocardial infarction had other diagnoses at first medical contact, who less frequently received guideline indicated care and had significantly higher mortality rates. There is substantial potential, greater for NSTEMI than STEMI, to improve outcomes through earlier and more accurate diagnosis of acute myocardial infarction.

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

Objective 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. Methods 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. Results 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). Conclusions 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.

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 non-ST-elevation myocardial infarction (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 1 January 2003 and 30 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%, IQR 0.7–18.1%). The greatest geographic variation was for aldosterone antagonists (16.7%, 0.0–40.0%) and least for use of an ECG (96.7%, 92.5–98.7%). The highest rates of care were for acute aspirin (median 92.8%, IQR 88.6–97.1%), and aspirin (90.1%, 85.1–93.3%) and statins (86.4%, 82.3–91.2%) at hospital discharge. The lowest rates were for smoking cessation advice (median 11.6%, IQR 8.7–16.6%), dietary advice (32.4%, 23.9–41.7%) and the prescription of P2Y12 inhibitors (39.7%, 32.4–46.9%). After adjustment for case mix, nearly all (99.6%) of the variation was due to between-hospital differences (median 64.7%, IQR 57.4–70.0%; between-hospital variance: 1.92, 95% CI 1.51 to 2.44; interclass correlation 0.996, 95% CI 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. Trial registration number NCT02436187.