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Anesth Analg 2008; 106:759-763
© 2008 International Anesthesia Research Society
doi: 10.1213/ane.0b013e3181685054
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CARDIOVASCULAR ANESTHESIOLOGY

PRO: Preoperative Coronary Revascularization in High-Risk Patients Undergoing Vascular Surgery

Giora Landesberg, MD, DSc, MBA*, and Morris Mosseri, MD**

From the Departments of *Anesthesiology, Critical Care Medicine and {dagger}Cardiology Hebrew University–Hadassah Medical Center, Jerusalem, Israel.

Address Correspondence and reprint requests to Giora Landesberg, MD, DSc, MBA, Department of Anesthesiology, Critical Care Medicine, Hebrew University–Hadassah Medical Center, Jerusalem, Israel. Address e-mail to gio{at}cc.huji.ac.il.

Dr. Kertai has done an excellent job in the core review1 in distilling the essence from the complex and multifaceted literature on preoperative coronary revascularization. However, under the surface, a titanic debate takes place on some major issues: Does any randomized controlled trial (RCT) always provide better evidence than any observational study? Can two recent RCTs completely overturn the data accumulated by a number of previous observational studies? Was the methodology used to generate the data adequately convincing? First some basic facts that must be acknowledged in the discussion:

  1. Vascular surgery patients have high prevalence of significant coronary artery disease (CAD) of which 18% have severe triple vessel disease (TVD) and 4% left main disease (LMD),2 who are the target of any possible coronary revascularization.
  2. Patients with peripheral vascular disease have a 6–15-fold higher long-term mortality from CAD than patients without peripheral vascular disease.3
  3. Patients with TVD or LMD have worse long-term survival than those with only single or double-vessel CAD. This is not only true for patients with unstable but also for patients with stable CAD4 and more so for patients with coexisting reduced left ventricular function.
  4. Coronary revascularization by coronary artery bypass graft (CABG) improves long-term survival and event-free survival in patients with multi-vessel (TVD and/or LMD) CAD, especially if left ventricular function is impaired.5,6,7,8 This has never been proven though for percutaneous coronary intervention (PCI) with or without stenting, although several studies have reported comparable long-term results for PCI and CABG. Recently the COURAGE study found no survival benefit with PCI over optimal medical therapy;9 however, this RCT has been criticized regarding patient selection bias (less than 10% of the patients evaluated were included), PCI methodology and incomplete revascularization in most patients (59%), weakening its conclusions.10,11
  5. Large areas of moderate-to-severe ischemia on noninvasive radionuclide imaging of the heart predict long-term outcome even better than the number of diseased vessels on coronary angiography.12 Similar or even better results have been obtained for dobutamine stress echocardiography.13
  6. Although no RCT was designed to compare survival with revascularization versus medical therapy in patients with ischemia on myocardial perfusion scans, a large scale observational study (10,627 consecutive patients)14 demonstrated a better survival with revascularization over medical therapy when moderate-to-severe ischemia (>20%) was present on myocardial perfusion scan, especially in high-risk patients (elderly, women, diabetics) (Fig. 1).


Figure 19
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  		Figure 1. Log Hazard ratio for revascularization (Revasc) versus medical therapy (Medical Rx) as a function of % myocardium ischemic Based on final Cox proportional hazards model. (Adopted with permission from Circulation 2003;107;2900–7).

 

LIMITATIONS OF RCTS

There is an abundance of literature discussing the pros and cons of RCTs versus observational studies.15,16,17 All agree that RCT is the best study design for investigating primary treatment effects in large phase III pharmaceutical trials in compliant populations. However, observational studies are not only more feasible but may actually give more accurate results than RCTs when a clinical dilemma is seeking an answer where there is no one clear-cut solution but rather it strongly depends on various complex patients’ features and on overall clinical judgment. Although the impact of allocation biases, spurious observations, and missing covariates cannot be ignored, patients in observational studies better represent those seen in real clinical practice. A RCT provides optimal results when the clinicians providing a new drug or treatment are blinded (preferably, double-blinded) and impartial to its effect. A RCT loses its effectiveness when the physicians enrolling patients are biased as to the potential benefits or harms of the investigated treatment, simply because of their often justifiable reluctance to randomize patients who they believed may either benefit or be harmed by the treatment (or its prevention). Typical to such RCTs is that too few screened patients, those who are not likely to be affected by the randomization, are finally randomized. This obviously raises a fundamental issue of selection bias, and seriously calls into question the validity and generalizeability of such RCTs. Also, typically, these RCTs are likely to find lack of treatment effect on patient outcomes, since most patients who could have benefited or been harmed by the treatment were excluded. Two RCTs opposing preoperative coronary revascularization in candidates for vascular surgery have been recently published.18,19 However, these RCTs suffer from many of the above-mentioned limitations.

LIMITATIONS OF THE CARP TRIAL17

The CARP trial aimed to challenge the long debated concept that preoperative coronary revascularization in high-risk vascular surgery patients improves long-term outcome. While this is a worthy and justifiable goal, it must be judged also by the means used to achieve it.

  1. The trial screened 5859 vascular surgery patients from 18 Veterans Adminstration hospitals in the United States, each center using different methods for screening patients (Eagle's criteria/Revised Cardiac Risk Index, with or without noninvasive testing). There was no unified method for screening patients’ preoperative risk, neither were the American Heart Association/American College of Cardiology guidelines systematically implemented which recommend noninvasive testing before coronary angiography in patients with moderate clinical predictors.
  2. Vascular surgery patients typically have low functional capacity and asymptomatic CAD, which is difficult to evaluate with noninvasive testing. Preoperative nuclear stress testing was performed in only 62% of randomized CARP patients, and only 44% of randomized patients had moderate-large ischemia on nuclear imaging.
  3. As a result, only 32% of randomized patients had TVD or 2.9% of all 5859 screened patients. This proportion is in marked contrast to the expected 18% of patients with TVD according to the data obtained from Hertzer et al.'s study using systematic coronary angiography in 1000 vascular surgery patients. Thus, the majority of patients with TVD in the CARP trial – those most likely to benefit from revascularization – were either not identified by the screening process or excluded because of the clinicians’ judgment that they should not be randomized. The other 68% of randomized patients with single or double-vessel disease were unlikely to have a survival benefit from coronary revascularization.
  4. Although the CARP study did not find differences in postoperative myocardial infarction (MI) with or without preoperative revascularization, it did find (in one of its sub-studies)20 that the more complete the preoperative coronary revascularization, particularly with CABG, the less were postoperative MIs. However, the same authors previously reported that postoperative MI after elective vascular surgery is associated with worse long-term survival.21 Thus, based on CARP's own data, complete preoperative revascularization in the right patients prevented postoperative MI, and therefore improved long-term survival.

LIMITATIONS OF THE DECREASE-V TRIAL18

In theory, the DECREASE-V trial could have filled the gap that the CARP study created by aiming to randomize the very high-risk patients with significant inducible ischemia on noninvasive preoperative testing who are most likely to benefit from coronary revascularization. However, several issues in the methodology and results make this study unrealistic and cast serious doubt on its generalizeability:

  1. "Of 430 high-risk patients, 101 (23%) showed extensive ischemia and were randomly assigned to revascularization (n = 49) or no revascularization." Apparently, all 49 patients with extensive ischemia on preoperative testing eventually underwent coronary revascularization. However, this is not compatible with real life as we know it. Up to 1/3 of vascular surgery patients with severe ischemia on noninvasive testing may not be suitable for revascularization, based on their coronary anatomy. Problems such as poor runoff, multiple small vessel CAD mainly in diabetics, chronic total obstructions not suitable for PCI in patients who are too sick for CABG, etc. may render them unsuitable for revascularization. The DECREASE-V trial "forced" all 49 patients with severe ischemia on noninvasive testing to undergo coronary revascularization, with no exclusions. The only clinical judgment applied was if it would be by PCI or CABG. This may explain the extremely high morbidity in the revascularization arm (two patients had ruptured aortic aneurysm before the vascular surgery) and the lack of postoperative benefit.
  2. Patients in the revascularization arm had extremely high 30-day mortality after vascular surgery, twice as high as the control arm (22% vs. 11%). This is in contrast to multiple studies which report reduced mortality and MI after vascular surgery in patients who had prior successful coronary revascularization, particularly with CABG.22,23 No explanation was given to the markedly high postoperative mortality despite successful and complete revascularization (in 86% of patients). Perhaps the "catastrophic" incidence of postoperative complications was because double antiplatelet therapy was not discontinued in patients who had surgery shortly after PCI,24 but this is not reported.
  3. Postoperative MI rate was also extremely high in both groups (35% and 31%) and all were Q-wave infarctions.25 This is in contrast to multiple studies in vascular surgery patients, which showed that postoperative Q-wave MI is rare whereas close to 100% are non-Q-wave infarctions. In a study that monitored hundreds of vascular surgery patients with continuous on-line 12-lead electrocardiogram perioperatively, none of the patients had Q-wave MI.26
  4. The same group that published the DECREASE-V trial has reported that prophylactic perioperative beta-blockage does not prevent postoperative cardiac events in patients with extensive myocardial ischemia on preoperative testing, similar to those randomized in the DECREASE-V trial.27

POSTOPERATIVE MI: UNSTABLE PLAQUE OR UNSTABLE PATIENT?

One of the main arguments of those opposed to preoperative coronary revascularization is that revascularization to arteries with stable coronary lesions is futile because it does not prevent postoperative MI allegedly caused by plaque rupture of relatively non-occluding (<70% stenosis) but unstable coronary plaques. We will not elaborate much on this issue here. However, after years that we have been preaching for the concept that prolonged, stress-induced ST-depression-type ischemia is a distinct and common mechanism for MI, particularly in the postoperative period,28 it has recently been accepted by the widest community of cardiologists. A new "Universal classification of MI" has been presented in the European Society of Cardiologists congress (2007) as a consensus document by the European Society of Cardiologists, American College of Cardiologists, American Heart Association and World Heart Federation (in press). This new universal classification includes 5 types of MI: Type I is spontaneous MI related to an acute coronary event (plaque rupture, fissuring or erosion); Type II is MI secondary to prolonged oxygen supply-demand imbalance (anemia, hypotension etc.); Types III to IV are sudden cardiac death, post-PCI and post CABG, respectively. The purpose of coronary revascularization in major vascular surgery patients with typically long-standing and stable CAD is to prevent type-II MI, both perioperatively and in the long-term. Although beta-blockers may help prevent some of these perioperative events, they are not yet a substitute for coronary revascularization in patients with severe CAD.

PREOPERATIVE CORONARY REVASCULARIZATION AS A CLINICAL DILEMMA

RCTs treat scientific questions as if they have only one possible answer – yes or no – given that all confounding factors are controlled. However, in reality, complex clinical issues may have more than one answer and a careful clinical judgment must be made for each individual patient with his/her special complex combination of predictors and demographic features. When the clinical judgment itself is evaluated, rather than the quality of a specific medication or therapy, there is probably no better alternative but to refer to observational cohort studies. Such is the case when coronary revascularization is considered in patients with complex preoperative clinical features, different results on preoperative cardiac stress testing and multiple possible combinations of coronary anatomy findings. Our recent findings29 show that intermediate-risk vascular surgery patients, those with 2–3 risk predictors of the Long-Term Survival Score (LTSS), were most likely to benefit from preoperative coronary revascularization. In contrast, low-risk patients, those with low LTSS 0–1 had good long-term survival that was not significantly affected by the revascularization. Similarly, high-risk patients (LTSS ≥4) had poor early and long-tern survival after vascular surgery that was also not significantly affected by coronary revascularization, even if severe ischemia on noninvasive testing was found and treated. This result could only be obtained by a cohort study that included all consecutive patients undergoing vascular surgery, without the unavoidable exclusions curtailing RCTs.

Footnotes

Accepted for publication December 3, 2007.

REFERENCES

  1. Kertai MD. Preoperasurgery: a core review Anesth Analg (in press) tive revascularization in high-risk patients undergoing vascular
  2. Hertzer NR, Bever EG, Young JR O'Hara PJ, Ruschhaupt WF 3rd, Graor RA, Dewolfe VG, Maljovec LC. Coronary artery disease in peripheral vascular patients: A classification of 1000 coronary angiograms and results of surgical management. Ann Surg 1984;199:223–33[Web of Science][Medline]
  3. Criqui MH, Langer RD, Fronek A Feigelson HS, Klauber MR, McCann TJ, Browner D. Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med 1992;326:381–6[Abstract]
  4. Bigi R, Cortigiani L, Colombo P, Desideri A, Bax JJ, Parodi O. Prognostic and clinical correlates of angiographically diffuse non-obstructive coronary lesions. Heart. 2003;89:1009–13[Abstract/Free Full Text]
  5. Kwok YS, Kim C and Heidenreich PA, Medical therapy or coronary artery bypass graft surgery for chronic stable angina: an update using decision analysis. Am J Med 2001;111:89 –95
  6. Caracciolo EA, Davis KB, Sopko G, Kaiser GC, Corley SD, Schaff H, Taylor HA, Chaitman BR. Comparison of surgical and medical group survival in patients with left main equivalent coronary artery disease. Long-term CASS experience. Circulation 1995;91:2335–44[Abstract/Free Full Text]
  7. O'Connor CM, Velazquez EJ, Gardner LH, Smith PK, Newman MF, Landolfo KP, Lee KL, Califf RM, Jones RH. Comparison of coronary artery bypass grafting versus medical therapy on long-term outcome in patients with ischemic cardiomyopathy (a 25-year experience from the Duke Cardiovascular Disease Databank). Am J Cardiol 2002;90:101–7[Web of Science][Medline]
  8. Yusuf S, Zucker D, Peduzzi P, Fisher LD, Takaro T, Kennedy JW, Davis K, Killip T, Passamani E, Norris R. Effect of coronary artery bypass graft surgery on survival: overview of 10-year results from randomised trials by the Coronary Artery Bypass Graft Surgery Trialists Collaboration. Lancet 1994;344:563–570[Web of Science][Medline]
  9. Boden WE, O'Rourke RA, Teo KK, Hartigan PM, Maron DJ, Kostuk WJ, Knudtson M, Dada M, Casperson P, Harris CL, Chaitman BR, Shaw L, Gosselin G, Nawaz S, Title LM, Gau G, Blaustein AS, Booth DC, Bates ER, Spertus JA, Berman DS, Mancini GB, Weintraub WS; COURAGE Trial Research Group. Optimal Medical Therapy with or without PCI for Stable Coronary Disease. N Engl J Med 2007;356:1–14[Free Full Text]
  10. Shah AP, Shavelle DM, French WJ. PCI for stable coronary disease. N Engl J Med 2007 Jul 26;357(4):415–6
  11. Stone GW. PCI in Stable CAD: COURAGE and Beyond - An Interventionalist's Perspective. www.tctmd.com
  12. Hachamovitch R, Berman DS, Shaw LJ, Kiat H, Cohen I, Cabico JA, Friedman J, Diamond GA. Incremental prognostic value of myocardial perfusion SPECT for the prediction of cardiac death: differential stratification for risk of cardiac death and MI. Circulation 1998;97:535–543[Abstract/Free Full Text]
  13. Hoque A, Maaieh M, Longaker RA, Stoddard MF. Exercise echocardiography and thallium-201 single-photon emission computed tomography stress test for 5- and 10-year prognosis of mortality and specific cardiac events. J Am Soc Echocardiogr 2002;15:1326–34[Web of Science][Medline]
  14. Hachamovitch R, Hayes SW, Friedman JD, Cohen I, Berman DS. Comparison of the short-term survival benefit associated with revascularization compared with medical therapy in patients with no prior coronary artery disease undergoing stress myocardial perfusion single photon emission computed tomography. Circulation 2003;107:2900–7[Abstract/Free Full Text]
  15. Grossman J, Mackenzie FJ. Perspectives in Biology and Medicine 2005;48:516–34
  16. Concato J, Shah N, Horwitz RI. Randomized controlled trials, observational studies and the hierarchy of research design. NEJM 2000;342:1887–92[Abstract/Free Full Text]
  17. Fielding LJ, Grace R, Hittinger R. Limitations of randomised controlled trials. BMJ 1995;310:1410[Free Full Text]
  18. McFalls EO, Ward HB, Moritz TE, Goldman S, Krupski WC, Littooy F, Pierpont G, Santilli S, Rapp J, Hattler B, Shunk K, Jaenicke C, Thottapurathu L, Ellis N, Reda DJ, Henderson WG. Coronary-artery revascularization before elective major vascular surgery. N Engl J Med 2004;351:2795–804[Abstract/Free Full Text]
  19. Poldermans D, Schouten O, Vidakovic R, Bax JJ, Thomson IR, Hoeks SE, Feringa HH, Dunkelgrun M, de Jaegere P, Maat A, van Sambeek MR, Kertai MD, Boersma E; DECREASE Study Group. A clinical randomized trial to evaluate the safety of a noninvasive approach in high-risk patients undergoing major vascular surgery. J Am Coll Cardiol 2007;49:1763–9[Abstract/Free Full Text]
  20. Ward HB, Kelly RF, Thottapurathu L, Moritz TE, Larsen GC, Pierpont G, Santilli S, Goldman S, Krupski WC, Littooy F, Reda DJ, McFalls EO. Coronary artery bypass grafting is superior to percutaneous coronary intervention in prevention of perioperative myocardial infarctions during subsequent vascular surgery. Ann Thorac Surg 2006;82:795–801[Abstract/Free Full Text]
  21. McFalls EO, Ward HB, Santilli S, Scheftel M, Chesler E, Doliszny KM. The influence of perioperative myocardial infarction on long-term prognosis following elective vascular surgery. Chest 1998;113:681–6[Web of Science][Medline]
  22. Eagle KA, Rihal CS, Mickel MC, Holmes DR, Foster ED, Gersh BJ. Cardiac risk of noncardiac surgery: influence of coronary disease and type of surgery in 3368 operations. CASS Investigators and University of Michigan Heart Care Program. Coronary Artery Surgery Study. Circulation 1997;96:1882–7[Abstract/Free Full Text]
  23. Rihal CS. The role of myocardial revascularization preceding noncardiac surgery. Prog Cardiovasc Dis 1998;40:383–404[Web of Science][Medline]
  24. Kaluza GL, Joseph J, Lee JR, Raizner ME, Raizner AE. Catastrophic outcomes of noncardiac surgery soon after coronary stenting. J Am Coll Cardiol 2000;35:1288–94[Abstract/Free Full Text]
  25. Landesberg G. Monitoring for myocardial ischemia. Best Pract Res Clin Anaesthesiol 2005;19:77–95[Medline]
  26. Landesberg G, Shatz V, Akopnik I, Wolf YG, Mayer M, Berlatzky Y, Weissman C, Mosseri M. Association of cardiac troponin, CK-MB, and postoperative myocardial ischemia with long-term survival after major vascular surgery. J Am Coll Cardiol 2003;42:1547–54[Abstract/Free Full Text]
  27. Boersma E, Poldermans D, Bax JJ, Steyerberg EW, Thomson IR, Banga JD, van De Ven LL, van Urk H, Roelandt JR; DECREASE Study Group (Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiogrpahy). Predictors of cardiac events after major vascular surgery: Role of clinical characteristics, dobutamine echocardiography, and beta-blocker therapy. JAMA 2001;285:1865–73[Abstract/Free Full Text]
  28. Landesberg G. The pathophysiology of perioperative myocardial infarction: facts and perspectives. J Cardiothorac Vasc Anesth 2003;17:90–100[Web of Science][Medline]
  29. Landesberg G, Berlatzky Y, Bocher M, Alcalai R, Anner H, Ganon-Rozental T, Luria MH, Akopnik I, Weissman C, Mosseri M. A clinical survival score predicts the likelihood to benefit from preoperative thallium scanning and coronary revascularization before major vascular surgery. Eur Heart J 2006;28: 533–9[Web of Science][Medline]




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press