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.

Acute coronary syndrome management in older adults: guidelines, temporal changes and challenges.

Advancing age is a risk factor for the development of coronary artery disease and is an important indicator of outcome after acute coronary syndrome. As the number of older adults increases, the burden of cardiovascular disease is set to grow particularly as older adults remain disadvantaged in the delivery of acute cardiac care. This article reviews the temporal changes in the provision of guideline recommended therapies for the management of acute coronary syndrome, discusses reasons for age-dependent inequalities in care and the challenges facing clinicians.

Relative survival and excess mortality following primary percutaneous coronary intervention for ST-elevation myocardial infarction.

BACKGROUND:: High survival rates are commonly reported following primary percutaneous coronary intervention for ST-elevation myocardial infarction, with most contemporary studies reporting overall survival. AIMS:: The aim of this study was to describe survival following primary percutaneous coronary intervention for ST-elevation myocardial infarction corrected for non-cardiovascular deaths by reporting relative survival and investigate clinically significant factors associated with poor long-term outcomes. METHODS AND RESULTS:: Using the prospective UK Percutaneous Coronary Intervention registry, primary percutaneous coronary intervention cases ( n=88,188; 2005-2013) were matched to mortality data for the UK populace. Crude five-year relative survival was 87.1% for the patients undergoing primary percutaneous coronary intervention and 94.7% for patients <55 years. Increasing age was associated with excess mortality up to four years following primary percutaneous coronary intervention (56-65 years: excess mortality rate ratio 1.61, 95% confidence interval 1.46-1.79; 66-75 years: 2.49, 2.26-2.75; >75 years: 4.69, 4.27-5.16). After four years, there was no excess mortality for ages 56-65 years (excess mortality rate ratio 1.27, 0.95-1.70), but persisting excess mortality for older groups (66-75 years: excess mortality rate ratio 1.72, 1.30-2.27; >75 years: 1.66, 1.15-2.41). Excess mortality was associated with cardiogenic shock (excess mortality rate ratio 6.10, 5.72-6.50), renal failure (2.52, 2.27-2.81), left main stem stenosis (1.67, 1.54-1.81), diabetes (1.58, 1.47-1.69), previous myocardial infarction (1.52, 1.40-1.65) and female sex (1.33, 1.26-1.41); whereas stent deployment (0.46, 0.42-0.50) especially drug eluting stents (0.27, 0.45-0.55), radial access (0.70, 0.63-0.71) and previous percutaneous coronary intervention (0.67, 0.60-0.75) were protective. CONCLUSIONS:: Following primary percutaneous coronary intervention for ST-elevation myocardial infarction, long-term cardiovascular survival is excellent. Failure to account for non-cardiovascular death may result in an underestimation of the efficacy of primary percutaneous coronary intervention.

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.

In an era of rapid STEMI reperfusion with Primary Percutaneous Coronary Intervention is there a role for adjunct therapeutic hypothermia? A structured literature review.

Mild hypothermia has been shown to improve neurological outcome and reduce mortality following out of hospital cardiac arrest. In animal models the application of hypothermia with induced coronary occlusion has demonstrated a reduction in infarct size. Consequently, hypothermia has been proposed as a treatment, in addition to Primary Percutaneous Coronary Intervention (PPCI) for ST segment elevation myocardial infarction (STEMI). However, there is incomplete understanding of the mechanism and magnitude of the protective effect of hypothermia on the myocardium, and limited outcome data. We undertook a structured literature review of therapeutic hypothermia as adjuvant to PPCI for acute STEMI. We examined the feasibility, safety, impact on infarct size and the resultant effect on major adverse cardiac events and mortality. There were 13 studies between 1946 and 2016. With the exception of one study, therapeutic hypothermia for STEMI was reported to be feasible and safe, and its only demonstrable benefit was a modest reduction in post-infarct heart failure events. Evidence to date, however, is from small clinical trials and in an era of low early mortality following PPCI for STEMI, demonstrating a mortality benefit will be challenging. Post-myocardial infarction left ventricular dysfunction is a more frequent, alternative clinical outcome and therefore any intervention that mitigates this warrants further investigation.

Ambulatory heart rate range predicts mode-specific mortality and hospitalisation in chronic heart failure.

OBJECTIVE: We aimed to define the prognostic value of the heart rate range during a 24 h period in patients with chronic heart failure (CHF). METHODS: Prospective observational cohort study of 791 patients with CHF associated with left ventricular systolic dysfunction. Mode-specific mortality and hospitalisation were linked with ambulatory heart rate range (AHRR; calculated as maximum minus minimum heart rate using 24 h Holter monitor data, including paced and non-sinus complexes) in univariate and multivariate analyses. Findings were then corroborated in a validation cohort of 408 patients with CHF with preserved or reduced left ventricular ejection fraction. RESULTS: After a mean 4.1 years of follow-up, increasing AHRR was associated with reduced risk of all-cause, sudden, non-cardiovascular and progressive heart failure death in univariate analyses. After accounting for characteristics that differed between groups above and below median AHRR using multivariate analysis, AHRR remained strongly associated with all-cause mortality (HR 0.991/bpm increase in AHRR (95% CI 0.999 to 0.982); p=0.046). AHRR was not associated with the risk of any non-elective hospitalisation, but was associated with heart-failure-related hospitalisation. AHRR was modestly associated with the SD of normal-to-normal beats (R(2)=0.2; p<0.001) and with peak exercise-test heart rate (R(2)=0.33; p<0.001). Analysis of the validation cohort revealed AHRR to be associated with all-cause and mode-specific death as described in the derivation cohort. CONCLUSIONS: AHRR is a novel and readily available prognosticator in patients with CHF, which may reflect autonomic tone and exercise capacity.

Risk stratification for ST segment elevation myocardial infarction in the era of primary percutaneous coronary intervention.

Acute coronary syndromes presenting with ST elevation are usually treated with emergency reperfusion/revascularisation therapy. In contrast current evidence and national guidelines recommend risk stratification for non ST segment elevation myocardial infarction (NSTEMI) with the decision on revascularisation dependent on perceived clinical risk. Risk stratification for STEMI has no recommendation. Statistical risk scoring techniques in NSTEMI have been demonstrated to improve outcomes however their uptake has been poor perhaps due to questions over their discrimination and concern for application to individuals who may not have been adequately represented in clinical trials. STEMI is perceived to carry sufficient risk to warrant emergency coronary intervention [by primary percutaneous coronary intervention (PPCI)] even if this results in a delay to reperfusion with immediate thrombolysis. Immediate thrombolysis may be as effective in patients presenting early, or at low risk, but physicians are poor at assessing clinical and procedural risks and currently are not required to consider this. Inadequate data on risk stratification in STEMI inhibits the option of immediate fibrinolysis, which may be cost-effective. Currently the mode of reperfusion for STEMI defaults to emergency angiography and percutaneous coronary intervention ignoring alternative strategies. This review article examines the current risk scores and evidence base for risk stratification for STEMI patients. The requirements for an ideal STEMI risk score are discussed.

Evaluation of the NICE mini-GRACE risk scores for acute myocardial infarction using the Myocardial Ischaemia National Audit Project (MINAP) 2003-2009: National Institute for Cardiovascular Outcomes Research (NICOR).

OBJECTIVE: To evaluate the performance of the National Institute for Health and Clinical Excellence (NICE) mini-Global Registry of Acute Coronary Events (GRACE) (MG) and adjusted mini-GRACE (AMG) risk scores. DESIGN: Retrospective observational study. SETTING: 215 acute hospitals in England and Wales. PATIENTS: 137 084 patients discharged from hospital with a diagnosis of acute myocardial infarction (AMI) between 2003 and 2009, as recorded in the Myocardial Ischaemia National Audit Project (MINAP). MAIN OUTCOME MEASURES: Model performance indices of calibration accuracy, discriminative and explanatory performance, including net reclassification index (NRI) and integrated discrimination improvement. RESULTS: Of 495 263 index patients hospitalised with AMI, there were 53 196 ST elevation myocardial infarction and 83 888 non-ST elevation myocardial infarction (NSTEMI) (27.7%) cases with complete data for all AMG variables. For AMI, AMG calibration was better than MG calibration (Hosmer-Lemeshow goodness of fit test: p=0.33 vs p<0.05). MG and AMG predictive accuracy and discriminative ability were good (Brier score: 0.10 vs 0.09; C statistic: 0.82 and 0.84, respectively). The NRI of AMG over MG was 8.1% (p<0.05). Model performance was reduced in patients with NSTEMI, chronic heart failure, chronic renal failure and in patients aged ≥85 years. CONCLUSIONS: The AMG and MG risk scores, utilised by NICE, demonstrated good performance across a range of indices using MINAP data, but performed less well in higher risk subgroups. Although indices were better for AMG, its application may be constrained by missing predictors.

Diabetes mellitus is associated with adverse prognosis in chronic heart failure of ischaemic and non-ischaemic aetiology.

BACKGROUND: It is unclear whether diabetes mellitus (DM) is an adverse prognostic factor in chronic heart failure (CHF) of ischaemic and non-ischaemic aetiology managed with contemporary evidence-based care. METHODS: In total, 1091 outpatients with CHF with reduced ejection fraction were prospectively observed for a mean of 960 days. Total and cardiovascular mortality was quantified after accounting for potential confounders. RESULTS: In total, 25.7% of patients had DM; this group was more likely to have CHF of ischaemic aetiology and was more symptomatic. Patients with DM received comparable medical- and device-based therapies, except for greater doses of loop diuretic. DM was associated with approximately doubled crude and adjusted risk of total and cardiovascular mortality. The association of diabetes with these outcomes in patients with ischaemic and non-ischaemic cardiomyopathies was of similar magnitude. CONCLUSIONS: In spite of advances in the management of CHF, DM remains a major adverse prognostic feature, irrespective of ischaemic/non-ischaemic aetiology.

An assessment of composite measures of hospital performance and associated mortality for patients with acute myocardial infarction. Analysis of individual hospital performance and outcome for the National Institute for Cardiovascular Outcomes Research (NICOR).

AIM: To investigate whether a hospital-specific opportunity-based composite score (OBCS) was associated with mortality in 136,392 patients with acute myocardial infarction (AMI) using data from the Myocardial Ischaemia National Audit Project (MINAP) 2008-2009. METHODS AND RESULTS: For 199 hospitals a multidimensional hospital OBCS was calculated on the number of times that aspirin, thienopyridine, angiotensin-converting enzyme inhibitor (ACEi), statin, ß-blocker, and referral for cardiac rehabilitation was given to individual patients, divided by the overall number of opportunities that hospitals had to give that care. OBCS and its six components were compared using funnel plots. Associations between OBCS performance and 30-day and 6-month all-cause mortality were quantified using mixed-effects regression analysis. Median hospital OBCS was 95.3% (range 75.8-100%). By OBCS, 24.1% of hospitals were below funnel plot 99.8% CI, compared to aspirin (11.1%), thienopyridine (15.1%), ß-blockers (14.7%), ACEi (19.1%), statins (12.1%), and cardiac rehabilitation (17.6%) on discharge. Mortality (95% CI) decreased with increasing hospital OBCS quartile at 30 days [Q1, 2.25% (2.07-2.43%) vs. Q4, 1.40% (1.25-1.56%)] and 6 months [Q1, 7.93% (7.61-8.25%) vs. Q4, 5.53% (5.22-5.83%)]. Hospital OBCS quartile was inversely associated with adjusted 30-day and 6-month mortality [OR (95% CI), 0.87 (0.80-0.94) and 0.92 (0.88-0.96), respectively] and persisted after adjustment for coronary artery catheterization [0.89 (0.82-0.96) and 0.95 (0.91-0.98), respectively]. CONCLUSIONS: Multidimensional hospital OBCS in AMI survivors are high, discriminate hospital performance more readily than single performance indicators, and significantly inversely predict early and longer-term mortality.

Is cardiac rehabilitation still relevant in the new millennium?

Cardiac rehabilitation is an evidence-based intervention which has evolved over time and incorporates physical, psycho-social and educational components with the aim of improving the patients' functioning following a cardiac event. The evidence base for cardiac rehabilitation following acute myocardial infarction has been growing over the past half a century. Individual randomized control trials were small and, therefore, mortality outcomes usually failed to reach significance; however, meta-analyses have proven consistently that participation in cardiac rehabilitation following a myocardial infarction is associated with a significant improvement in mortality. In the era of revascularization and improved drug therapies, observational studies still provide evidence that independent of other treatments, cardiac rehabilitation is a life-saving measure. Although early studies often only studied young males, more contemporary data include patients from all sectors of society and have found that groups such as women, the elderly and those with heart failure appear to have greater mortality benefits compared with the traditional young male cohort. Uptake remains a problem and one challenge for the future is ensuring improved uptake on to good-quality rehabilitation programmes and demonstrating these positive effects.

Changing characteristics and mode of death associated with chronic heart failure caused by left ventricular systolic dysfunction: a study across therapeutic eras.

BACKGROUND: Therapies for patients with chronic heart failure caused by left ventricular systolic dysfunction have advanced substantially over recent decades. The cumulative effect of these therapies on mortality, mode of death, symptoms, and clinical characteristics has yet to be defined. METHODS AND RESULTS: This study was a comparison of 2 prospective cohort studies of outpatients with chronic heart failure caused by left ventricular systolic dysfunction performed between 1993 and 1995 (historic cohort: n=281) and 2006 and 2009 (contemporary cohort: n=357). In the historic cohort, 83% were prescribed angiotensin-converting enzyme inhibitors and 8.5% were prescribed ß-adrenoceptor antagonists, compared with 89% and 80%, respectively, in the contemporary cohort. Mortality rates over the first year of follow-up declined from 12.5% to 7.8% between eras (P=0.04), and sudden death contributed less to contemporary mortality (33.6% versus 12.7%; P<0.001). New York Heart Association class declined between eras (P<0.001). QTc dispersion across the chest leads declined from 85 ms (SD, 2) to 34 ms (SD, 1) and left ventricular end-diastolic dimensions declined from 65 mm (SD, 0.6) to 59 mm (SD, 0.5) (both P<0.001). CONCLUSIONS: Survival has significantly improved in patients with chronic heart failure caused by left ventricular systolic dysfunction over the past 15 years; furthermore, sudden death makes a much smaller contribution to mortality, and noncardiac mortality is a correspondingly greater contribution. This has been accompanied by an improvement in symptoms and some markers of adverse electric and structural left ventricular remodeling.