Derek Chew Department of Cardiovascular Medicine, Flinders University, Adelaide, Australia; , Harvey D White Green Lane Cardiovascular Service, Auckland City Hospital, New Zealand

Originally printed in:
» US Cardiovascular Disease 2007 - Issue I - July 2007

Early non-compliance with evidence-based therapy is also associated with substantial excess in mortality and morbidity. Within a US registry of 1,521 patients with myocardial infarction, discontinuation of beta-blockers, statins, or aspirin occurred in 34% of patients by 30 days. In multivariable modeling, therapy discontinuation of these agents was associated with a hazard ratio of 3.81 (95% CI 1.88–7.72).13 Observations from the same registry showed that among patients undergoing PCI with drug-eluting stents, cessation of clopidogrel by 30 days was associated with a nine-fold increase in late mortality (7.5% versus 0.7%; p<0.0001). These potential gains in survival associated with improved ‘quality of care’ substantially exceed the potential benefits expected from refinements in drug and device therapy for the treatment of myocardial infarction.

Within these inclusive observational registries, a clearer representation of the heterogeneity of the clinical risk of patients presenting with myocardial infarction is evident. Evidence from the Global Registry of Acute Coronary Events (GRACE) study not only demonstrated that the subset of patients enrolled within clinical trials experience a lower risk of mortality compared with eligible but not enrolled patients, but also that those not considered eligible experience an approximately 2-fold excess risk of mortality after adjusting for baseline clinical and treatment differences.14 These findings highlight the fact that there are important under-represented groups within our evidence base. These groups include patients over the age of 75 years, patients with reduced renal function, and racial minorities.15,16 Importantly, not only are these patients associated with increased risk, but several analyses now document that the increased risk is associated with a decrease in the use of proven evidence-based therapies.17,18 Hence, a more complete understanding of the determinants of the ‘high risk/less therapy’ paradox is urgently required.

These observations highlight the need for more objective and effective care systems for the timely and more complete provision of clinical care in the management of patients presenting with myocardial infarction. In contrast to innovations and refinements of pharmacological agents, extending the already robust evidence base of current care to underserved groups and improving compliance with these therapies is more likely to provide substantial gains in survival given the high early and late event rates seen among these patients.

Several initiatives in this regard have been conducted. These include the Guideline Applied in Practice (GAP) and Get with the Guidelines programs.19,20 These programs seek to embed tools designed to increase the application of guidelines within clinical practice, as well as foster local champions for the process. Such programs have been shown to be associated with improvements in the prescription of evidence-based medicines and reductions in mortality. For example, in the GAP program, a standardized discharge tool was associated with a substantial reduction in one-year mortality (OR 0.53; 95% CI 0.36–0.76; p=0.0006).21 While these efforts are encouraging, more widespread application and evidence of efficacy is required. Furthermore, the determinants of poor compliance and evidence application are incompletely characterized, although evidence in this regard continues to emerge.22–24 Clearly, these factors are multifactorial and influenced by patient, physician, and healthcare system characteristics.25–28 Consequently, the capacity to limit missed opportunities in order to maximize the survival gains promised by the current evidence base depends on specific local solutions. Likewise, the resources required to adequately address these issues remains unclear and the cost-effectiveness of such initiatives requires further exploration. The potential improvements in outcome associated with improved systems of care may be large. This highlights the importance of assessing the effectiveness of such programs with the same rigor as that utilized in clinical trials of innovative therapies in order to permit accurate quantification of the incremental costs and benefits. Formal costeffectiveness evaluation would be of value in order to focus healthcare resource allocation.

Coupled with the need for improved health promotion strategies aimed at encouraging earlier presentation to hospital, specific local programs facilitating implementation and ongoing compliance with life-saving evidence-based therapies offer a substantial capacity to reduce mortality. While current innovations in devices and therapies promise to improve the ease and safety of clinical care, programs that focus on the ‘last mile’ of delivering the evidence to individual patients present a substantial opportunity for mitigating the mortality associated with myocardial infarction.