Coronary-artery revascularization before elective major vascular surgery

McFalls EO, Ward HB, Mortiz TE, et al. N Engl J Med 2004; 351(27):2795-804.

Reviewer: KW Tim Park, MD
Santa Clara Valley Medical Center
San Jose, CA

Background: Patients presenting for major vascular surgery (MVS) have a high prevalence of coronary artery disease (CAD) and their perioperative cardiovascular morbidity and mortality are high.1 This has led to a number of guidelines on stratifying the patients for risks, including the oft-quoted guideline by the American College of Cardiology and the American Heart Association.2 Yet, there is no clear consensus on the role of coronary revascularization (CR) before MVS. On the one hand, in a retrospective review of the Coronary Artery Surgery Study (CASS) registry,3 patients with both CAD and peripheral vascular disease (PVD) had improved long-term survival, if treated surgically for CAD, compared to medical treatment. Of note, this study did not examine postoperative outcome after vascular surgery, but rather long-term outcome in the presence of PVD. In two reports from the Cleveland Clinic,4,5 cardiac catheterization was performed in 1000 patients under consideration for elective MVS. Of these, 246 patients for infrarenal aortic aneurysms and 381 for infrainguinal vascular surgery were analyzed. Mortality from coronary artery bypass surgery (CABG) in those with surgically correctable CAD was 5.1% (7/138). But survivors of CABG had reduced operative mortality in subsequent MVS. On the other hand, PVD is a significant risk factor for major cardiovascular, pulmonary, and infectious morbidity after CABG6 and this may alter the timing of subsequent MVS. In the current study, the authors conducted a prospective, multi-center, randomized study of the effect of CR prior to MVS on the long-term mortality of the patients.

Methods: Patients scheduled for elective MVS were randomized to either preoperative coronary revascularization or medical therapy. Patients who needed an urgent MVS, had prior CR without evidence of recurrent ischemia, or had a severe coexisting illness were excluded. Coronary angiography was recommended by a cardiology consultant, based on clinical risk factors and the result on a non-invasive stress imaging study. If a patient had ≥ 70% stenosis in one or more coronary arteries that was amenable to CR, the patient was considered eligible for the study and randomized to CR or medical therapy. However, those with a left main stenosis ≥ 50%, left ventricular ejection fraction < 20%, severe aortic stenosis, or CAD non amenable to revascularization were also excluded. Which CR to use (i.e., CABG vs. PCI (percutaneous coronary intervention)) was left to the local investigators. After randomization, CR was expected to be performed within three weeks. After CABG, the MVS was expected to occur within three months. After PCI, the MVS was to be delayed for at least two weeks. The primary endpoint was long-term mortality. Secondary end points included myocardial infarction (MI), stroke, limb loss, and dialysis. MI was diagnosed by elevated cardiac enzymes and associated EKG changes.

Results: Five hundred and ten patients were enrolled with 258 randomized to CR and 252 to no CR. About 1/3 of the surgical indications were abdominal aortic aneurysms and the rest were arterial occlusive disease of the legs. 49 % had 2+ risk factors according to the Revised Cardiac Risk Index of Lee et al.7 Of 316 who had a nuclear imaging study, 226 had moderate or large reversible perfusion defects. Of 258 patients randomized to CR, 240 had CABG (99 patients) or PCI (141 patients). Of the remaining 18, nine refused CR and eight required urgent MVS. Procedural mortality associated with CR was 2.0% (2/99) for CABG and 1.4% (2/141) for PCI. Six additional people died before having MVS. Of the 258, 225 underwent the planned MVS a median of 48 days after CABG and 41 days after PCI. Of 252 patients randomized to no CR, nine became unstable and required urgent CR; one died and seven of these subsequently had MVS. Two hundred, thirty-seven of the 252 patients had the planned MVS. Perioperative usage rate for beta-blockers was about 85%, that for aspirin was over 70% and that for statins was about 54%; the usage rates were not significantly different between the groups. Perioperative 30-day mortality was 3.1% in the CR group and 3.4% in the no CR group (P = NS). Perioperative MI was 11.6% in the CR group and 14.3% in the other group (P = NS). There was no difference in any of the major morbidities examined. After a median of 2.7 years of follow-up, mortality was 22% in the CR group and 23% in the other (P = 0.92). When the data were analyzed according to treatment received rather than treatment assigned, mortality at 2.7 years was 22% for those who underwent CR and 23% for those who did not (P = 0.86). CR did not impart a survival benefit in any of the high-risk subgroups.

Discussion and Comments: The study demonstrates that at least when used in the way this study was designed, CR prior to MVS confers no benefit either for perioperative survival or MI or for long-term (2+ years) survival. The study suggests that CR, whether CABG or PCI, should be reserved for patients with unstable cardiac symptoms or advanced CAD, for whom there may be a survival benefit and that the indications for CABG should be the same prior to MVS as in the nonoperative setting.2,8

As suggested in the accompanying editorial, the results of this study should be interpreted in light of its design, exclusion criteria, and ancillary therapies.9 Since the days of the CASS, remarkable advances have been made in medical therapy and in perioperative care by the anesthesiologists and vascular surgeons. In particular, perioperative use of beta-blockers has been repeatedly shown to decrease perioperative cardiac morbidity and mortality.10,11 In the DECREASE trial by Poldermans et al.11, patients who had positive preoperative stress echocardiography were randomized to perioperative bisoprolol or placebo. The study was halted because of a huge difference in perioperative mortality and MI between the groups. In addition, statins may have pleiotrophic and antiinflammatory effects in addition to lowering cholesterol and may lower perioperative cardiovascular morbidity and mortality12. Whether modulators of the renin-angiotensin-aldosterone system (angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone receptor antagonists), antiplatelet agents, Na+-H+ exchange inhibitors, and various other classes of medications under development may have similar cardioprotective effects in the perioperative period remains to be investigated. The patients in the current study were medically well-treated with about 85% receiving beta-blockers and > 50% getting statins. Medical optimization may have neutralized any potential benefit of prior CR.

Another notable point of the study design is the interval from CR to MVS. While the authors are not specific about the duration of the interim period, the MVS took place a median of 48 days after CABG and 41 days after PCI in the CR group. Following PCI, there may be a significant risk of in-stent thrombosis in patients presenting for major noncardiac surgery within six weeks of a bare metal stent.13,14 The risk period may be somewhat longer for a drug-eluting stent, since in-stent endothelialization is delayed by the drug that prevents neointimal proliferation. In a retrospective study, it was shown that the benefit of prior coronary angioplasty in terms of reduction of perioperative adverse cardiac events is not realized until after 90 days.15 Furthermore, patients undergoing MVS within 30 days of CABG have an increased risk of mortality.16 Therefore, it is possible that a significant, but undefined portion of the CR group in this study underwent MVS during a high-risk period following CABG or PCI and before the benefits of PCI were realizable. The question that remains is whether there might have been a difference in mortality and MI, if the patients in the CR group waited at least six weeks before undergoing MVS. As a practical matter, "elective" vascular surgeries cannot usually be postponed for months. The risk of rupture of an abdominal aortic aneurysm may increase, the chances of limb salvage may be decreased, and/or the septic risk from extremity ischemia and/or infection may be increased. If the benefit of CR cannot be realized unless the time interval between CR and MVS has to be for at least four to six weeks, then CR may not always be a practical alternative, even if such a benefit is to be demonstrated in a future study.

References:

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