Design and setting: Multicentre study of drug therapy for patients with MI in 16 major metropolitan teaching hospitals in Australia over a 1-month period at each hospital in the period November 2004 – March 2005.
Results: 116 of the 479 patients admitted for MI (24.2%) had heart failure at some point during their hospitalisation. Patients with heart failure were older (68 v 63 years; P < 0.05), more likely to be women (34% v 24%; P < 0.05) and a higher proportion had diabetes (26% v 21%). There was significantly reduced prescribing of β-blockers, clopidogrel and statins for patients with heart failure compared with those without heart failure. Mineralocorticoid receptor antagonist use was low (< 10%) in the former group.
Conclusions: We found reduced prescribing of some prognostically relevant medications for patients with heart failure. For β-blockers, this may be explained by the greater clinical instability in patients with heart failure. Given the absolute benefit of drug therapy in patients with heart failure after MI, our findings suggest suboptimal prescribing in Australian teaching hospital practice.
Heart failure is a common and potentially lethal complication of myocardial infarction (MI), conferring a four- to fivefold increase in mortality.1 Taking angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers2 and β-blockers3 reduces morbidity and mortality in these patients. Furthermore, aldosterone receptor blockade, specifically with the selective agent eplerenone, has recently been shown to provide additional benefit.4 However, to what extent these and other beneficial cardiovascular drugs are prescribed for patients with MI and heart failure in Australian hospitals is not known.
The aim of our study was to ascertain prescribing of cardiovascular pharmacological agents after MI in those with and without heart failure to determine whether evidence-based prescribing occurs in Australian teaching hospitals. The study was performed in the period November 2004 – March 2005.
Twenty Australian teaching and major metropolitan hospitals were recruited for the study. Sixteen hospitals provided data in a timely fashion to permit meaningful analysis. The hospitals were located in all mainland states except South Australia, and comprised those with the highest number of documented separations of patients after MI in each state (data from the Australian Institute of Health and Welfare).5
At each site, the coronary care unit coordinator obtained patient data on discharge after hospitalisation for MI. Data were collected on teleform, then faxed and, finally, transferred electronically to a Structured Query Language (SQL) database (Microsoft SQL Server 2000, Microsoft Corp, Redmond, Wash, USA) for statistical analysis. Data quality was verified by double data entry and manual checking of more than 95% of fields.
The data collected on the form included the location of the MI, the type of MI (with or without ST-segment elevation) and any percutaneous coronary interventions performed during the patient’s index hospitalisation.
Heart failure status was recorded before hospitalisation, on admission, during hospitalisation and at discharge. Cardiovascular drug therapies (the main focus of our analysis) were recorded before hospitalisation, during admission and at discharge. Prehospitalisation data were obtained from the patient’s hospital admission and subsequent in-hospital notes. Additional data obtained were presence of risk factors for MI and results of assessment of ventricular function (if available).
Myocardial infarction was defined according to each hospital’s individual diagnostic criteria, and included MI with and without ST-segment elevation.
Heart failure was defined according to the heart failure guidelines of the National Heart Foundation and the Cardiac Society of Australia and New Zealand,6 but ultimately left to the discretion of individual investigators at each site.
Risk factors were defined by the individual hospitals.
Differences in prescribing were determined by χ2 analysis, with a two-tailed P value < 0.05 considered to be statistically significant. Age was compared between those with and without heart failure by Student’s unpaired t test. Predictors of heart failure were determined by logistic regression analysis, entering all relevant parameters into a backwards stepwise model. Predictors of drug prescribing in heart failure patients were determined by multivariate logistic regression analysis, entering the main univariate parameters of difference between patients with and without heart failure into the multivariate model.
The age, sex and pre-existing risk factors of the 479 patients in our cohort are summarised in Box 1.
Characteristics of the study patients with and without heart failure during hospitalisation or at discharge after MI are summarised in Box 2. In the group with heart failure (24.2% of all patients with MI), there was a higher proportion of women and patients with prior heart failure. The association between diabetes and heart failure was of borderline statistical significance.
Significantly fewer percutaneous coronary intervention procedures were performed in patients with heart failure; in particular, significantly fewer angiography and angioplasty procedures were performed during the index hospitalisation (Box 2).
The proportion of patients taking the various cardiovascular medications on arrival at hospital (prior to admission) are shown in Box 3, and the proportion of patients with and without heart failure prescribed these medications on discharge are shown in Box 4. Fewer patients in the cohort with heart failure were prescribed an ACE inhibitor or an angiotensin receptor blocker, but these differences did not reach statistical significance. Univariate analysis showed that significantly fewer patients with heart failure, compared with those without heart failure, received β-blockers. Interestingly, fewer patients with heart failure were prescribed aspirin, clopidogrel or statin therapy. However, there was greater use of warfarin, diuretics and spironolactone in patients with heart failure. Spironolactone use, even in patients with established heart failure, was low at 7.8%.
Uncorrected differences in prescribing at discharge according to heart failure status are summarised in Box 5. To assess use of accepted heart failure medication after MI (ACE inhibitor/angiotensin receptor blocker, β-blockers and aldosterone receptor blockade), drug utilisation was adjusted for baseline covariates of age, sex and the presence of diabetes mellitus (these differed significantly [or almost significantly] at baseline between patients with and without heart failure). This showed that differences in prescribing between patients with and without heart failure remained non-significant for ACE inhibitors/angiotensin receptor blockers (P = 0.136), became non-significant for β-blockers (P = 0.106), and remained significant for spironolactone (P = 0.015).
Only prior heart failure was a univariate predictor of heart failure after MI. Hyperlipidaemia, diabetes, hypertension, prior stroke, current smoking and prior acute coronary syndrome/angina did not predict heart failure after MI. Backwards, stepwise multiple logistic regression analysis showed that prior heart failure remained a significant independent predictor (P = 0.001) of heart failure after MI.
We found substantial differences in prescribing of standard medications to patients after MI according to their heart failure status. Compared with patients without heart failure, there was significantly less prescribing of β-blockers, clopidogrel and statins in patients with heart failure after MI. In addition, fewer patients with heart failure after MI were prescribed ACE inhibitors/angiotensin receptor blockers, although these differences did not reach statistical significance in our cohort. In contrast, spironolactone, warfarin and diuretics were prescribed significantly more frequently for those with heart failure (compared with those without heart failure) after MI.
These data are of clinical significance, given the greatly elevated risk of major cardiovascular events and mortality in patients with heart failure complicating an MI.1,7,8 These risks have been well documented in datasets such as the Global Registry of Acute Coronary Events (GRACE);1 mortality at 6 months was found to be three- to fourfold higher than that in patients without heart failure during their index hospitalisation after MI.
The heart failure rate in our patients (24.2% of patients having heart failure at some point during their hospitalisation for MI) agrees with data from other studies, such as GRACE, where the rate was 19.9%,1 and the Second National Registry of Myocardial Infarction (NRMI-2), where the rate was 19.1%.7
The underuse of effective therapies for patients with heart failure specifically applies to prescribing of ACE inhibitors/angiotensin receptor blockers and β-blockers. Perhaps concerns about hypotension and clinical instability in the period immediately after MI may have limited prescribing of these agents.9
The use of aldosterone-receptor blockade after MI was of interest, given the release of the results of the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS)4 2 years before we conducted our study: the selective aldosterone-receptor blocker, eplerenone, conferred a 15% reduction in all-cause mortality. Eplerenone was not available in Australia during our study period. However, the older non-selective aldosterone-receptor blocker, spironolactone,10 could be used “off label” for these patients to block mineralocorticoid receptors. There was a significant increase in spironolactone use in patients with heart failure compared with those without heart failure after MI. However, fewer than 10% of eligible patients were prescribed this drug after MI.
These data also raise the issue of multiple drug prescribing (polypharmacy). In managing patients with heart failure, there is a clear need for polypharmacy and the net benefit of multiple agents, particularly in older patients, has to be weighed against the risks and the possibility of adverse events and drug interactions.11 Recent analyses have confirmed that older patients and those with comorbid risk factors do indeed derive substantial benefit from proven heart failure therapies12,13 and their use should therefore be encouraged.
In summary, our analysis has shown that patients with heart failure receive fewer life-saving drug therapies compared with those who do not have heart failure. Given the greater absolute risk of future cardiovascular events, these deficiencies in prescribing may lead to substantial increases in events in these patients. Our findings suggest that, in general, prescribing for patients with heart failure after MI is suboptimal in Australian teaching hospitals.
1 Age, sex and risk factors of study patients admitted to hospital with myocardial infarction (n = 479)
2 Age, sex and risk factors of study patients by heart failure status, during hospitalisation or at discharge, after myocardial infarction
4 Cardiovascular medications on discharge according to heart failure status (proportion of patients). A: no heart failure (n = 363); B: heart failure (n = 116)
5 Difference in prescribing of medications at discharge according to heart failure status
Received 1 December 2005, accepted 21 June 2006
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