Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Mounting Evidence for Lack of PCI Benefit in Stable Ischemic Heart Disease:What More Will It Take to Turn the Tide of Treatment?: Comment on Initial Coronary Stent Implantation With Medical Therapy vs Medical Therapy Alone for Stable Coronary Artery Disease

Mounting Evidence for Lack of PCI Benefit in Stable Ischemic Heart Disease:What More Will It Take... When treating patients with symptomatic coronary artery disease (CAD), clinicians frequently consider whether the initial management approach should be optimal medical therapy (OMT) alone or OMT in addition to coronary revascularization—generally percutaneous coronary intervention (PCI) in the vast majority of patients for whom revascularization would be considered. Over the past several years, several trials such as the Clinical Outcomes Utilizing Revascularization and Aggressive drug Evaluation (COURAGE) Trial,1 Bypass Angioplasty Revascularization 2 Diabetes Trial (BARI-2D),2 and Japan Stable Angina Pectoris (JSAP) study3 have challenged the conventional wisdom that the triad of angina, objective evidence of myocardial ischemia, and the presence of 1 or more flow-limiting coronary stenoses necessitating revascularization are the sine qua non of optimal CAD management. In the aggregate, these studies have failed to show any incremental clinical benefit for PCI above and beyond OMT for the reduction of death or nonfatal myocardial infarction (MI), findings quite in contrast to those achieved with PCI in acute MI or high-risk patients with acute coronary syndrome (ACS). In addition, there have been many meta-analyses of PCI vs OMT in patients with nonacute CAD that have purported to show evidence of a mortality reduction for myocardial revascularization compared with OMT, despite initial criticisms in the aftermath of the COURAGE Trial1 that it told us nothing new, that PCI was already well known to not reduce death or MI in patients with stable CAD.4 Schömig and coworkers5 in 2008 published a meta-analysis in which they demonstrated a 20% mortality reduction in patients with stable coronary artery disease for PCI compared with OMT, yet this meta-analysis was extremely flawed in that it included trials of patients with acute MI and post-MI patients, which largely contributed to the mortality reduction attributed to PCI. In 2009, Jeremias et al6 published a meta-analysis of 28 studies of nonacute CAD published from 1977 to 2007 that included 17 studies of PCI, 6 studies of coronary artery bypass graft (CABG) surgery, and 5 studies in which either PCI or CABG were compared with OMT; the study found a benefit on mortality but not on nonfatal MI for revascularization.6 The inclusion of both acute and post-MI trials comingled with stable angina and stable ischemic heart disease (SIHD) trials and revascularization (either PCI or CABG) was likewise a significant methodologic flaw because the purported mortality benefit was largely a function of the salutary effect of revascularization in acute and status post-MI patients, which completely distorts the conclusion that such patients with nonacute CAD derive a mortality benefit of revascularization. These shortcomings of meta-analyses by Schömig et al5 and Jeremias et al6 were addressed in a subsequent “corrected” meta-analysis in which Wijeysundera and coworkers7 demonstrated quite convincingly that when the acute and post-MI trials as well as the trials that compared CABG to OMT were excluded from the meta-analyses that evaluated PCI vs OMT in patients with unstable angina, there indeed was no evidence for any mortality benefit with PCI. In this issue of the Archives, we have yet another meta-analysis8 in which 8 prospective randomized controlled trials (RCTs) involving 7229 patients compared initial coronary stent implantation with OMT to determine the effect of treatment assignment on death, nonfatal MI, unplanned revascularization, and persistent angina as the outcomes of interest during a mean weighted follow-up of 4.3 years. The respective event rates in stent implantation and medical therapy for death were 8.9% and 9.1%, (odds ratio [OR], 0.98; 95% CI, 0.84-1.16); for nonfatal MI, 8.9% and 8.1%, (OR, 1.12; 95% CI, 0.93-1.34); for unplanned revascularization, 21.4% and 30.7% (OR, 0.78; 95% CI, 0.57-1.06); and for persistent angina, 29% and 34% (OR, 0.80; 95% CI, 0.60-1.05).8 In other words, when PCI with stenting was compared with aggressive, multifaceted, contemporary secondary prevention and lifestyle intervention (the very definition of OMT), no incremental benefit for PCI was observed for hard outcomes or for persistent angina. This meta-analysis restricted the pooled studies to those in which stents were used in more than 50% of randomized patients and in which more contemporary COURAGE-like optimal medical therapy was used as the comparator. Thus, studies that included patients treated with percutaneous transluminal coronary angioplasty or more minimalistic medical therapy were omitted. What is the practicing clinician to take away from the present study8 in the context of other published meta-analyses?5-7 First, the totality of evidence does not support any demonstrable clinical benefit for PCI in patients with stable CAD in terms of reducing death, nonfatal MI, hospitalization for ACS, need for unplanned revascularization, and a durable, sustained effect on angina relief. While a great deal of attention has been focused more recently on the need to develop and implement appropriate use criteria for PCI, especially in patients with SIHD and chronic angina, the inescapable fact is that it is increasingly harder to justify use of PCI solely for angina relief in such patients—especially as an initial approach to management, and if medical therapy has not been first instituted (or if efforts to optimize pharmacologic treatment in those treated initially medically are not undertaken). Second, given the notable lack of benefit on improving hard clinical outcomes, the continued practice of a PCI-first strategy compared with an OMT-first strategy in patients with stable CAD may lead to the performance of many unnecessary PCI procedures. In fact, Diamond and Kaul9 have postulated that if even one-third of elective PCI procedures in patients with SIHD (300 000 to 500 000 PCIs annually) could be averted or deferred as a consequence of OMT, the cost saving associated with this approach could net $6 billion to $8 billion annually that could be redirected to more productive preventive cardiology initiatives. Third, despite the enormous commitment by the US government and funding agencies to support comparative effectiveness research as the best approach to defining the most effective and cost-effective approaches to patient management, this policy-level imperative has not translated into changes in clinical practice, and trials such as COURAGE,1 BARI-2D,2 and others studies are seemingly ignored.10 While physicians outwardly worship at the altar of evidence-based medicine, in reality, we more often tend to practice selective evidence-based medicine by adopting and embracing those trials and studies with results that reinforce our existing clinical practice preferences or biases, while we ignore or disdain the results of studies with results that are unpopular, conflict with our existing clinical practice beliefs, or collide with the conventional wisdom. Certainly, one explanation for the current management of SIHD is the existing fee-for-service model of physician and hospital reimbursement, which clearly encourages a model that is procedurally driven and one that provides differentially enhanced financial rewards to perform more, not less, revascularization. Finally, given the spiraling health care costs that we have witnessed in the United States over the past decade, and the financial burden this places on our existing health care system, businesses, and health care consumers, we certainly have abundant scientific evidence to support a more selective, measured, and balanced approach to the initial management of SIHD1-8 and one that promotes and embraces optimal medical therapy for the majority of patients as a proven alternative to revascularization. With such an evidence base derived from multiple RCTs and meta-analyses, what more will it take to turn the tide of treatment for patients with SIHD and chronic angina from a PCI-first to an OMT-first approach? While prospective studies are ongoing, comparing therapeutic approaches in patients with more extensive anatomic CAD and functional severity with moderate-severe ischemic burden, we should be more willing to accept and embrace existing, available medical evidence that can guide patient management in a manner that encourages balance, transparency, equipoise, and full disclosure of all available treatment options. Back to top Article Information Correspondence: Dr Boden, Department of Medicine (111), Samuel Stratton VA Medical Center, 113 Holland Ave, Room A700, Albany, NY 12208 (william.boden@va.gov). Financial Disclosure: None reported. This article was corrected for incorrect event rates for unplanned revascularization on February 27th, 2012. References 1. Boden WE, O’Rourke RA, Teo KK, et al; COURAGE Trial Research Group. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med. 2007;356(15):1503-151617387127PubMedGoogle ScholarCrossref 2. Frye RL, August P, Brooks MM, et al; BARI 2D Study Group. A randomized trial of therapies for type 2 diabetes and coronary artery disease. N Engl J Med. 2009;360(24):2503-251519502645PubMedGoogle ScholarCrossref 3. Nishigaki K, Yamazaki T, Kitabatake A, et al; Japanese Stable Angina Pectoris Study Investigators. Percutaneous coronary intervention plus medical therapy reduces the incidence of acute coronary syndrome more effectively than initial medical therapy only among patients with low-risk coronary artery disease a randomized, comparative, multicenter study. JACC Cardiovasc Interv. 2008;1(5):469-47919463347PubMedGoogle ScholarCrossref 4. Kereiakes DJ, Teirstein PS, Sarembock IJ, et al. The truth and consequences of the COURAGE trial. J Am Coll Cardiol. 2007;50(16):1598-160317936161PubMedGoogle ScholarCrossref 5. Schömig A, Mehilli J, de Waha A, Seyfarth M, Pache J, Kastrati A. A meta-analysis of 17 randomized trials of a percutaneous coronary intervention-based strategy in patients with stable coronary artery disease. J Am Coll Cardiol. 2008;52(11):894-90418772058PubMedGoogle ScholarCrossref 6. Jeremias A, Kaul S, Rosengart TK, Gruberg L, Brown DL. The impact of revascularization on mortality in patients with nonacute coronary artery disease. Am J Med. 2009;122(2):152-16119185092PubMedGoogle ScholarCrossref 7. Wijeysundera HC, Ko DT. Does percutaneous coronary intervention reduce mortality in patients with stable chronic angina: are we talking about apples and oranges? Circ Cardiovasc Qual Outcomes. 2009;2(2):123-12620031824PubMedGoogle ScholarCrossref 8. Stergiopoulos K, Brown DL. Initial coronary stent implantation with medical therapy vs medical therapy alone for stable coronary artery disease: meta-analysis of randomized controlled trials. Arch Intern Med. 2012;172(2):ira110003312-319Google Scholar 9. Diamond GA, Kaul S. Evidence-based financial incentives for healthcare reform: putting it together. Circ Cardiovasc Qual Outcomes. 2009;2(2):134-14020031826PubMedGoogle ScholarCrossref 10. Borden WB, Redberg RF, Mushlin AI, Dai D, Kaltenbach LA, Spertus JA. Patterns and intensity of medical therapy in patients undergoing percutaneous coronary intervention. JAMA. 2011;305(18):1882-188921558519PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

Mounting Evidence for Lack of PCI Benefit in Stable Ischemic Heart Disease:What More Will It Take to Turn the Tide of Treatment?: Comment on Initial Coronary Stent Implantation With Medical Therapy vs Medical Therapy Alone for Stable Coronary Artery Disease

Archives of Internal Medicine , Volume 172 (4) – Feb 27, 2012

Loading next page...
 
/lp/american-medical-association/mounting-evidence-for-lack-of-pci-benefit-in-stable-ischemic-heart-ifwwtSKwZk
Publisher
American Medical Association
Copyright
Copyright © 2012 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinternmed.2011.2321
Publisher site
See Article on Publisher Site

Abstract

When treating patients with symptomatic coronary artery disease (CAD), clinicians frequently consider whether the initial management approach should be optimal medical therapy (OMT) alone or OMT in addition to coronary revascularization—generally percutaneous coronary intervention (PCI) in the vast majority of patients for whom revascularization would be considered. Over the past several years, several trials such as the Clinical Outcomes Utilizing Revascularization and Aggressive drug Evaluation (COURAGE) Trial,1 Bypass Angioplasty Revascularization 2 Diabetes Trial (BARI-2D),2 and Japan Stable Angina Pectoris (JSAP) study3 have challenged the conventional wisdom that the triad of angina, objective evidence of myocardial ischemia, and the presence of 1 or more flow-limiting coronary stenoses necessitating revascularization are the sine qua non of optimal CAD management. In the aggregate, these studies have failed to show any incremental clinical benefit for PCI above and beyond OMT for the reduction of death or nonfatal myocardial infarction (MI), findings quite in contrast to those achieved with PCI in acute MI or high-risk patients with acute coronary syndrome (ACS). In addition, there have been many meta-analyses of PCI vs OMT in patients with nonacute CAD that have purported to show evidence of a mortality reduction for myocardial revascularization compared with OMT, despite initial criticisms in the aftermath of the COURAGE Trial1 that it told us nothing new, that PCI was already well known to not reduce death or MI in patients with stable CAD.4 Schömig and coworkers5 in 2008 published a meta-analysis in which they demonstrated a 20% mortality reduction in patients with stable coronary artery disease for PCI compared with OMT, yet this meta-analysis was extremely flawed in that it included trials of patients with acute MI and post-MI patients, which largely contributed to the mortality reduction attributed to PCI. In 2009, Jeremias et al6 published a meta-analysis of 28 studies of nonacute CAD published from 1977 to 2007 that included 17 studies of PCI, 6 studies of coronary artery bypass graft (CABG) surgery, and 5 studies in which either PCI or CABG were compared with OMT; the study found a benefit on mortality but not on nonfatal MI for revascularization.6 The inclusion of both acute and post-MI trials comingled with stable angina and stable ischemic heart disease (SIHD) trials and revascularization (either PCI or CABG) was likewise a significant methodologic flaw because the purported mortality benefit was largely a function of the salutary effect of revascularization in acute and status post-MI patients, which completely distorts the conclusion that such patients with nonacute CAD derive a mortality benefit of revascularization. These shortcomings of meta-analyses by Schömig et al5 and Jeremias et al6 were addressed in a subsequent “corrected” meta-analysis in which Wijeysundera and coworkers7 demonstrated quite convincingly that when the acute and post-MI trials as well as the trials that compared CABG to OMT were excluded from the meta-analyses that evaluated PCI vs OMT in patients with unstable angina, there indeed was no evidence for any mortality benefit with PCI. In this issue of the Archives, we have yet another meta-analysis8 in which 8 prospective randomized controlled trials (RCTs) involving 7229 patients compared initial coronary stent implantation with OMT to determine the effect of treatment assignment on death, nonfatal MI, unplanned revascularization, and persistent angina as the outcomes of interest during a mean weighted follow-up of 4.3 years. The respective event rates in stent implantation and medical therapy for death were 8.9% and 9.1%, (odds ratio [OR], 0.98; 95% CI, 0.84-1.16); for nonfatal MI, 8.9% and 8.1%, (OR, 1.12; 95% CI, 0.93-1.34); for unplanned revascularization, 21.4% and 30.7% (OR, 0.78; 95% CI, 0.57-1.06); and for persistent angina, 29% and 34% (OR, 0.80; 95% CI, 0.60-1.05).8 In other words, when PCI with stenting was compared with aggressive, multifaceted, contemporary secondary prevention and lifestyle intervention (the very definition of OMT), no incremental benefit for PCI was observed for hard outcomes or for persistent angina. This meta-analysis restricted the pooled studies to those in which stents were used in more than 50% of randomized patients and in which more contemporary COURAGE-like optimal medical therapy was used as the comparator. Thus, studies that included patients treated with percutaneous transluminal coronary angioplasty or more minimalistic medical therapy were omitted. What is the practicing clinician to take away from the present study8 in the context of other published meta-analyses?5-7 First, the totality of evidence does not support any demonstrable clinical benefit for PCI in patients with stable CAD in terms of reducing death, nonfatal MI, hospitalization for ACS, need for unplanned revascularization, and a durable, sustained effect on angina relief. While a great deal of attention has been focused more recently on the need to develop and implement appropriate use criteria for PCI, especially in patients with SIHD and chronic angina, the inescapable fact is that it is increasingly harder to justify use of PCI solely for angina relief in such patients—especially as an initial approach to management, and if medical therapy has not been first instituted (or if efforts to optimize pharmacologic treatment in those treated initially medically are not undertaken). Second, given the notable lack of benefit on improving hard clinical outcomes, the continued practice of a PCI-first strategy compared with an OMT-first strategy in patients with stable CAD may lead to the performance of many unnecessary PCI procedures. In fact, Diamond and Kaul9 have postulated that if even one-third of elective PCI procedures in patients with SIHD (300 000 to 500 000 PCIs annually) could be averted or deferred as a consequence of OMT, the cost saving associated with this approach could net $6 billion to $8 billion annually that could be redirected to more productive preventive cardiology initiatives. Third, despite the enormous commitment by the US government and funding agencies to support comparative effectiveness research as the best approach to defining the most effective and cost-effective approaches to patient management, this policy-level imperative has not translated into changes in clinical practice, and trials such as COURAGE,1 BARI-2D,2 and others studies are seemingly ignored.10 While physicians outwardly worship at the altar of evidence-based medicine, in reality, we more often tend to practice selective evidence-based medicine by adopting and embracing those trials and studies with results that reinforce our existing clinical practice preferences or biases, while we ignore or disdain the results of studies with results that are unpopular, conflict with our existing clinical practice beliefs, or collide with the conventional wisdom. Certainly, one explanation for the current management of SIHD is the existing fee-for-service model of physician and hospital reimbursement, which clearly encourages a model that is procedurally driven and one that provides differentially enhanced financial rewards to perform more, not less, revascularization. Finally, given the spiraling health care costs that we have witnessed in the United States over the past decade, and the financial burden this places on our existing health care system, businesses, and health care consumers, we certainly have abundant scientific evidence to support a more selective, measured, and balanced approach to the initial management of SIHD1-8 and one that promotes and embraces optimal medical therapy for the majority of patients as a proven alternative to revascularization. With such an evidence base derived from multiple RCTs and meta-analyses, what more will it take to turn the tide of treatment for patients with SIHD and chronic angina from a PCI-first to an OMT-first approach? While prospective studies are ongoing, comparing therapeutic approaches in patients with more extensive anatomic CAD and functional severity with moderate-severe ischemic burden, we should be more willing to accept and embrace existing, available medical evidence that can guide patient management in a manner that encourages balance, transparency, equipoise, and full disclosure of all available treatment options. Back to top Article Information Correspondence: Dr Boden, Department of Medicine (111), Samuel Stratton VA Medical Center, 113 Holland Ave, Room A700, Albany, NY 12208 (william.boden@va.gov). Financial Disclosure: None reported. This article was corrected for incorrect event rates for unplanned revascularization on February 27th, 2012. References 1. Boden WE, O’Rourke RA, Teo KK, et al; COURAGE Trial Research Group. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med. 2007;356(15):1503-151617387127PubMedGoogle ScholarCrossref 2. Frye RL, August P, Brooks MM, et al; BARI 2D Study Group. A randomized trial of therapies for type 2 diabetes and coronary artery disease. N Engl J Med. 2009;360(24):2503-251519502645PubMedGoogle ScholarCrossref 3. Nishigaki K, Yamazaki T, Kitabatake A, et al; Japanese Stable Angina Pectoris Study Investigators. Percutaneous coronary intervention plus medical therapy reduces the incidence of acute coronary syndrome more effectively than initial medical therapy only among patients with low-risk coronary artery disease a randomized, comparative, multicenter study. JACC Cardiovasc Interv. 2008;1(5):469-47919463347PubMedGoogle ScholarCrossref 4. Kereiakes DJ, Teirstein PS, Sarembock IJ, et al. The truth and consequences of the COURAGE trial. J Am Coll Cardiol. 2007;50(16):1598-160317936161PubMedGoogle ScholarCrossref 5. Schömig A, Mehilli J, de Waha A, Seyfarth M, Pache J, Kastrati A. A meta-analysis of 17 randomized trials of a percutaneous coronary intervention-based strategy in patients with stable coronary artery disease. J Am Coll Cardiol. 2008;52(11):894-90418772058PubMedGoogle ScholarCrossref 6. Jeremias A, Kaul S, Rosengart TK, Gruberg L, Brown DL. The impact of revascularization on mortality in patients with nonacute coronary artery disease. Am J Med. 2009;122(2):152-16119185092PubMedGoogle ScholarCrossref 7. Wijeysundera HC, Ko DT. Does percutaneous coronary intervention reduce mortality in patients with stable chronic angina: are we talking about apples and oranges? Circ Cardiovasc Qual Outcomes. 2009;2(2):123-12620031824PubMedGoogle ScholarCrossref 8. Stergiopoulos K, Brown DL. Initial coronary stent implantation with medical therapy vs medical therapy alone for stable coronary artery disease: meta-analysis of randomized controlled trials. Arch Intern Med. 2012;172(2):ira110003312-319Google Scholar 9. Diamond GA, Kaul S. Evidence-based financial incentives for healthcare reform: putting it together. Circ Cardiovasc Qual Outcomes. 2009;2(2):134-14020031826PubMedGoogle ScholarCrossref 10. Borden WB, Redberg RF, Mushlin AI, Dai D, Kaltenbach LA, Spertus JA. Patterns and intensity of medical therapy in patients undergoing percutaneous coronary intervention. JAMA. 2011;305(18):1882-188921558519PubMedGoogle ScholarCrossref

Journal

Archives of Internal MedicineAmerican Medical Association

Published: Feb 27, 2012

Keywords: percutaneous coronary intervention,myocardial ischemia,coronary arteriosclerosis,coronary artery stents

References