American Heart Journal
Volume 155, Issue 1 , Pages 6-8, January 2008

Establishing the effectiveness of coronary intervention for acute myocardial infarction

Christiana Care Health System, Newark, DE

Received 11 October 2007; accepted 12 October 2007.

Article Outline

 

An invasive strategy has been shown to decrease coronary events in the setting of acute coronary syndromes. This has been demonstrated in clinical trials in the setting of both ST elevation and non-ST elevation myocardial infarction (MI).1., 2. Balloon angioplasty was shown to reduce mortality compared to thrombolysis in the PAMI trial, and this result has been confirmed in a meta-analysis of 23 trials.1., 3. The results have also been updated to show that there is no increased mortality with coronary stenting compared to balloon angioplasty and that stenting offers a simpler, more reliable procedure with fewer repeat procedures than balloon angioplasty.4 The results with stenting are now being expanded from bare metal stents to drug-eluting stents, with promising results and still fewer additional procedures.5 In ST elevation MI, the key performance criteria is to perform the intervention as early as possible because the sooner an occluded artery is opened and blood flow is restored, the less myocardium is lost and the lower the mortality.6 In non-ST elevation MI, the need for coronary intervention and the timeliness of the intervention are less clear. This is because non-ST elevation MI will be caused by rupture on a vulnerable plaque and ensuing thrombosis, but without a total occlusion, or at least without a persistent total occlusion. Thus in non-ST elevation MI, there may not be ongoing ischemia and myocardial cell death. Here clinical trial results show the benefit of an invasive approach with coronary angiography within a day or two and percutaneous coronary intervention (PCI) as appropriate.2., 7. Clinical trial data show that in this setting an invasive strategy will reduce the incidence of additional myocardial infarction, with some showing a decrease in mortality. A meta-analysis in non-ST elevation has also shown the benefit of an invasive approach.8 Furthermore, in both ST elevation MI and non-ST elevation MI, studies have shown the cost-effectiveness of an invasive approach.9., 10.

Thus, efficacy of mechanical, invasive therapeutic approaches to the treatment of acute myocardial infarction has been established and incorporated into guidelines.11., 12. If efficacy were taken to mean the effectiveness was proven, then outcome did not have to be measured, and efforts could be devoted largely to performance—that is how well can an invasive approach be administered. This is the core of efforts by both the American Heart Association and the American College of Cardiology to improve the care of patients with acute myocardial infarction. However, proven efficacy in clinical trials does not necessarily mean that an invasive approach will prove effective when applied widely in the community. Providing timely, high-quality invasive service on a wide scale may prove a difficult challenge. It is not clear that society would be using resources appropriately by trying to provide PCI to all patients with acute myocardial infarction. In the United States, the decision has largely been made to try to provide an invasive approach at least as widely as possible. Interestingly, in Canada, the same decision has not clearly been made.

If efficacy is proven, or at least agreed to, but effectiveness is uncertain, then this is an appropriate area of investigation. This is the subject of the study by Pilote and et al.13 Pilote et al13 have attempted to assess the effectiveness of an invasive compared to a noninvasive strategy on a grand scale using administrative databases in the Canadian provinces Ontario, Quebec, and British Columbia. At the simplest level, it would seem that databases that included survival of patients treated noninvasively and invasively could be used, and then just choose the therapeutic strategy offering the best outcome. The problem is that there is confounding or selection bias as to who are treated invasively and who are treated noninvasively. If the patients who underwent noninvasive treatment are sicker, then this could explain worse outcomes. The best method of avoiding selection bias is the randomized trial, and actually, that is the only thing that randomization accomplishes. However, a whole society randomized trial to establish effectiveness does not make sense and, at an individual level, may be viewed as unethical, given the clinical trial data. This problem of confounding has been addressed in multiple studies using multivariate analysis or by creating a propensity score for one form of therapy and then using the propensity score in the multivariate analysis or to create matched groups.14 The problem with all multivariate methods, of which propensity score analysis is a variant, is that there may be residual confounding that was not measured.

Pilote et al take15 a somewhat different approach by creating an instrumental variable, which is a measure that separates the therapeutic groups, accounts for confounding, and does not affect outcome. The best instrumental variable, of course, is randomization, which is not generally available in large-scale effectiveness studies. The instrumental variable used by Pilote et al13 was distance to the nearest hospital with on-site availability of cardiac catheterization. The main independent variable that was investigated was whether the patient received diagnostic cardiac catheterization within 90 days. The main outcome variable was 1-year mortality. Using this design and administrative databases in Ontario, Quebec, and British Columbia, outcome was investigated in 141 718 patients with an acute myocardial infarction. In Ontario, 27% underwent cardiac catheterization within 90 days compared with 39% in British Columbia and Quebec. Unadjusted results found that mortality was 7% with an invasive approach versus 29% with a noninvasive approach. Using statistical methodology that accounted for age, sex, and comorbidity differences as well as the instrumental variable of distance to the catheterization laboratory, an invasive approach was associated with an absolute 11% reduction in mortality at 1 year.

The study of Pilote et al13 reveals many of the problems associated with trying to establish effectiveness, especially to widely applied therapy. There is a lack of adequate clinical databases, which are generally regarded as more reliable than administrative databases.16., 17. Administrative databases generally do not have a lot of clinical detail. Thus, in this study, it is not possible to separate ST elevation from non-ST elevation MI. In this study, it is also not possible to separate primary PCI for ST elevation MI from diagnostic catheterization some weeks later, although the reasons for which are obscure in this study. It is also not clear that the instrumental variable of distance from the catheterization laboratory reasonably separates invasive versus noninvasive approaches independently of confounding. Even with additional adjustment there may be residual confounding. Thus, we can view the study of Pilote et al13 as interesting, thought provoking, and an excellent effort given the limitations of the data available to them. However, it is not clear that this effort establishes effectiveness of an invasive approach in the community.

Thus, in Canada and to a greater extent in the United States, we have developed facilities for an invasive approach to myocardial infarction based on clinical trial efficacy. Studies of performance are available.6 However, credible studies on outcome are generally lacking. It is important to recognize that implementation of evidence-based guidelines in a community setting may not lead to the same level of effectiveness as might be expected based on the results from clinical trials, even if the population involved in the trials is general enough to be valid in the new setting. The overall impact of a guideline or intervention on clinical outcomes in a community will depend upon a variety of issues unrelated to clinical efficacy and may be specific to the community. These factors include the degree to which institutions and providers adopt the guidelines and provide the infrastructure and technical support needed to apply those, their ability to reach the target patient population, and the willingness of that population to follow or adhere to the recommendations. The focus of the Pilote paper is distance to a facility where interventional therapy is available. This is one of many important factors, and a more global analysis of the acceptance of and fidelity to guidelines is also critical to understanding effectiveness across different communities or regions. It should be pointed out that there is a literature and science on how to conduct implementation studies.18 Implementation of care and establishing effectiveness and cost-effectiveness of therapy for chronic disease in the community will become increasingly critical as efforts are made to broadly apply efficacious but expensive therapies on a societal basis in a time of increasing resource constraint.

Back to Article Outline

References 

  1. Grines CL, Browne KF, Marco J, et al. A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction. The Primary Angioplasty in Myocardial Infarction Study Group. N Engl J Med. 1993;328:673–679
  2. Cannon CP, Weintraub WS, Demopoulos LA, et al. Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban. N Engl J Med. 2001;344:1879–1887
  3. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet. 2003;361:13–20
  4. Grines CL, Cox DA, Stone GW, et al. Coronary angioplasty with or without stent implantation for acute myocardial infarction. Stent Primary Angioplasty in Myocardial Infarction Study Group. N Engl J Med. 1999;341:1949–1956
  5. Spaulding C, Henry P, Teiger E, et al. Sirolimus-eluting versus uncoated stents in acute myocardial infarction. N Engl J Med. 2006;355:1093–1104
  6. Bradley EH, Herrin J, Wang Y, et al. Strategies for reducing the door-to-balloon time in acute myocardial infarction. N Engl J Med. 2006;355:2308–2320
  7. Bertrand ME, Simoons ML, Fox KA, et al. Management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2002;23:1809–1840
  8. Mehta SR, Cannon CP, Fox KA, et al. Routine vs selective invasive strategies in patients with acute coronary syndromes: a collaborative meta-analysis of randomized trials. JAMA. 2005;293:2908–2917
  9. Cohen DJ, Taira DA, Berezin R, et al. Cost-effectiveness of coronary stenting in acute myocardial infarction: results from the stent primary angioplasty in myocardial infarction (stent-PAMI) trial. Circulation. 2001;104:3039–3045
  10. Mahoney EM, Jurkovitz CT, Chu H, et al. Cost and cost-effectiveness of an early invasive vs conservative strategy for the treatment of unstable angina and non–ST-segment elevation myocardial infarction. JAMA. 2002;288:1851–1858
  11. Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction; A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the management of patients with acute myocardial infarction). J Am Coll Cardiol. 2004;44:E1–E211
  12. Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 Guidelines for the management of patients with unstable angina/non–ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 2002 Guidelines for the management of patients with unstable angina/non–ST-elevation myocardial infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. J Am Coll Cardiol. 2007;50:e1–e157
  13. Pilote L, Beck CA, Eisenberg MJ, et al. Comparing invasive and non-invasive management strategies for acute myocardial infarction using administrative databases. Am Heart J 2008;155:42-8.
  14. D'Agostino RB. Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med. 1998;17:2265–2281
  15. Angrist J, Imbens G, Rubin D. Identification of causal effects using instrumental variables. J Am Stat Assn. 1996;91:444–455
  16. Hannan EL, Racz MJ, Jollis JG, et al. Using Medicare claims data to assess provider quality for CABG surgery: does it work well enough?. Health Serv Res. 1997;31:659–678
  17. Weintraub WS, Deaton C, Shaw L, et al. Can cardiovascular clinical characteristics be identified and outcome models be developed from an in-patient claims database?. Am J Cardiol. 1999;84:166–169
  18. Glasgow RE, Lichtenstein E, Marcus AC. Why don't we see more translation of health promotion research to practice? Rethinking the efficacy-to-effectiveness transition. Am J Public Health. 2003;93:1261–1267

PII: S0002-8703(07)00832-0

doi:10.1016/j.ahj.2007.10.018

American Heart Journal
Volume 155, Issue 1 , Pages 6-8, January 2008

Article Tools