BMJ  2005;330:E351-E352 (14 May), doi:10.1136/bmj.330.7500.E351

BMJ USA: Editorial

Editorial

Benefits of early invasive treatment for acute coronary syndromes: lost in translation?

In this issue (p 166) the GRACE investigators report a prospective cohort study comparing the outcomes of patients with acute coronary syndromes (ACS)—unstable angina or myocardial infarction with or without ST-segment elevation—admitted initially to hospitals with and without cardiac catheterization facilities. Their findings challenge us to think more deeply about how we interpret the results of recent clinical trials and translate them into practice.

Quantitative reviews^1,2 of nearly two dozen clinical trials have compared primary percutaneous coronary intervention (PCI) to thrombolytic therapy for ST-elevation myocardial infarction (MI) and established that patients randomized to primary PCI had fewer deaths, subsequent nonfatal MIs, and hemorrhagic strokes, both in short-term (4-6 week) and long-term (6-18 month) follow-up. Early PCI is increasingly being favored for non-ST-elevation MI and unstable angina as well.³ Several studies have shown that the benefit of primary PCI can be realized even when the patient is admitted to a hospital without the capability of PCI and must be transferred to a center that provides it.^4,5

Yet in their multinational cohort of unselected patients admitted for ACS, the GRACE investigators found that patients admitted to hospitals with catheterization facilities had worse outcomes: no short-term survival benefit, worse long-term survival, and more bleeding and stroke complications in the short term. The benefits of primary PCI seem to be unrealized in practice, for all its proven efficacy. To understand how that could be, let us consider the translation of research into practice and the differences between efficacy, treatment effectiveness, and implementation effectiveness.⁶

These findings remind us that in order to get our patients the benefits shown in clinical trials, we must do what was done in the trials.

Treatment effectiveness is less than efficacy because patients who could benefit may not receive the treatment, either because they refuse it or are not offered it, and because patients who are less likely to benefit may be given (or may demand) the treatment. The high PCI rates in hospitals with their own catheterization suites suggests the latter. Primary PCI is a selectively useful treatment⁷ that in practice is probably being used to some extent nonselectively. Absent exceptionally strong external constraints, it is virtually inevitable that such "indication creep"⁸ will occur. If the hospital has the facilities to do it, PCI will be performed for patients who fall outside the carefully designed inclusion and exclusion criteria of the clinical efficacy trials.

Implementation effectiveness is less than efficacy because the treatment is performed in the real world by practitioners other than the highly skilled and practiced teams that participated in the research studies, and in systems that are not set up to achieve the interhospital transport times or door-to-balloon times of those in the studies. US national registry data⁹ show that primary PCI is superior to thrombolysis for MI only in high-volume PCI centers; that superiority disappears in hospitals performing relatively few PCIs. It is also not clear in how many settings interhospital transfer times can be kept down to those of trials like DANAMI-2,⁴ or whether study hospitals could achieve those times under ordinary non-research conditions. Even with careful patient selection, ordinary community practice may not be able to accomplish the delivery of the patient to a highly skilled PCI team within a time interval that would offer any advantage for invasive therapy.

Considered in light of the issues of treatment effectiveness and implementation effectiveness, the GRACE investigators' findings are unsurprising. Patients unlike those in trials who are treated in settings and systems unlike those in trials will get less benefit than those in trials—but not less harm, as evidenced by the excess of strokes and hemorrhagic complications among the GRACE patients admitted to hospitals with catheterization suites. The discrepancy between efficacy and effectiveness will be greater the more selectively useful the treatment.

For practitioners, these findings remind us that in order to get our patients the benefits shown in clinical trials, we must do what was done in the trials. That means honestly assessing our own skills and the abilities of the systems in which we practice. It also means exercising the self-discipline to avoid indication creep. It is hard not to use the cath lab when it is just down the hall; nonetheless, we must be selective about using selectively beneficial interventions if we are to help our patients more than harm them.

For medical research, these findings highlight the need for prospective cohort studies in unselected community populations: "postmarketing surveillance" of treatment strategies to measure the efficacy-effectiveness gap. They also suggest that translational research must pay more attention to the fidelity of translation and to means of limiting indication creep. Perhaps it is time also to start considering whether translation of selectively beneficial treatments should be explicitly limited until effectiveness in the "real world" has been demonstrated.

Department of Family Medicine University of Michigan Medical School Ann Arbor, Michigan greenla{at}umich.edu

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Paper p 166

Competing interests: None declared.

References

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3. Bach RG, Cannon CP, Weintraub WS, DiBattiste PM, Demopoulos LA, Anderson HV, et al. The effect of routine, early invasive management on outcome for elderly patients with non-ST-segment elevation acute coronary syndromes. Ann Intern Med 2004;141: 186-95.[Abstract/Free Full Text]
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• Yan, A. T., Yan, R. T., Tan, M., Fung, A., Cohen, E. A., Fitchett, D. H., Langer, A., Goodman, S. G., for the Canadian Acute Coronary Syndromes 1 and 2, (2007). Management Patterns in Relation to Risk Stratification Among Patients With Non-ST Elevation Acute Coronary Syndromes. Arch Intern Med 167: 1009-1016 [Abstract] [Full text]  

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