The evaluation of cardiac risk before noncardiac
surgical procedures and interventions aimed toward reducing that risk have become an integral
part of the contemporary practice of medicine. In
the nonoperative setting, it is generally accepted
that the pathophysiology of acute myocardial infarction is usually due to the disruption of a vulnerable coronary-artery plaque followed by coronaryartery thrombosis. Histopathological analyses of
coronary arteries in patients who had a fatal myocardial infarction soon after noncardiac surgery have
confirmed this pathophysiology, with evidence of
an unstable plaque present in more than half of patients.
1
An association between fatal perioperative myocardial infarction and advanced left main coronary
artery disease, severe three-vessel disease, or both is
also common. Perioperative activation of neurohumoral pathways, an increase in catecholamine levels, a reduction in endogenous levels of tissue plasminogen activator, an increase in shear stress in
association with platelet activation, and possibly
coronary spasm have been postulated to be mechanisms leading to plaque disruption and subsequent
coronary-artery occlusion. However, some patients
appear to have a myocardial infarction without
ST-segment elevation, perhaps caused primarily by
periods of prolonged ischemia as a result of perioperative stresses that occur in the presence of severe fixed coronary-artery obstruction.
Previous studies have shown that patients at increased risk for perioperative events can be identified on the basis of simple clinical markers (e.g.,
angina pectoris, previous myocardial infarction, diabetes mellitus, previous heart failure, renal insufficiency, poor functional capacity, or high-risk surgery) available at the time of the initial evaluation.
2,3
The addition of noninvasive and invasive testing
further improves the accuracy of risk stratification.
4
Applying the lessons learned from risk stratification to the care of patients, in an attempt to reduce risk, has been a challenge, particularly in light
of the large numbers of patients who currently undergo noncardiac surgery and the variable risks.
There is today overwhelming agreement that
aggressive medical management to provide myocardial protection in the perioperative state is a
central element in reducing the risk of adverse clinical events. In a landmark clinical trial, patients undergoing noncardiac surgery who had or were at
risk for coronary artery disease were randomly assigned to receive atenolol intravenously before and
immediately after surgery and orally thereafter for
the duration of hospitalization or to receive placebo.
5
A significant reduction in the incidence of perioperative ischemia was observed among the patients who received atenolol. This reduction was
associated with a lower mortality in the atenolol
group six months after hospital discharge (0 percent, vs. 8 percent in the placebo group; P<0.001),
after one year of follow-up (3 percent vs. 14 percent,
P=0.005), and after two years of follow-up (10 percent vs. 21 percent, P=0.02). The lower mortality
was predominantly due to a reduction in deaths
from cardiac causes during the first six to eight
months after noncardiac surgery.
Poldermans et al., in the Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress
Echocardiography (DECREASE) trial, investigated
the use of the beta-blocker bisoprolol in high-risk
patients referred for vascular surgery.
6
In that study,
the group treated with bisoprolol had a significant
reduction in the incidence of death from cardiac
causes as compared with patients receiving standard care (3.4 percent vs. 17 percent, P=0.02) and
a significant reduction in the incidence of nonfata
myocardial infarction (0 percent vs. 17 percent,
P<0.001).
The benefits of beta-blockers in these two studies
are consistent with the proposed cascade of events
that occur when sympathetic activation is triggered
by perioperative stresses. Interrupting this cascade,
even for a short period of time, might have longterm benefits.
More recently, a large body of data have been reported that support the pleiotropic and antiinflammatory effects of statins, which promote the stabilization of potentially vulnerable coronary plaques
and a reduction in adverse coronary events. In particular, the prehospital or preprocedure use of statins has been found to be associated with reductions
in the incidence of in-hospital death in patients
with acute coronary syndromes, of periprocedural
myocardial infarction after percutaneous coronary
intervention, and of perioperative mortality in patients undergoing major noncardiac vascular surgery.
7
Although no large, randomized clinical trials
have been completed to confirm the efficacy of statins in these settings, the strong association shown
in large observational studies supports the inclusion of statins in the perioperative management of
patients with known or strongly suspected coronary artery disease who are undergoing noncardiac
surgery.
The role of preoperative coronary revascularization in patients being evaluated before noncardiac
surgery has been controversial for several decades.
The limited size and number of observational studies and the absence of randomized clinical trials
have resulted in uncertainty concerning the benefits
and risks of preoperative coronary revascularization for the purpose of improving perioperative
and longer-term coronary outcomes.
In this issue of the Journal, McFalls et al. report
the results of the Coronary Artery Revascularization Prophylaxis trial.
8
Patients with clinically significant, stable coronary artery disease who were
scheduled for elective vascular operations at 18
Veterans Affairs medical centers were randomly assigned to undergo coronary revascularization (percutaneous coronary intervention or coronary-artery
bypass grafting, 258 patients) or medical therapy
alone (252 patients). Medical therapy was optimized in both groups, with 84 percent of patients
in the revascularization group and 86 percent of
those who did not undergo revascularization receiving beta-blockers, 54 percent in both groups
receiving statins, and 70 percent and 76 percent,
respectively, receiving aspirin. Patients with a stenosis of the left main coronary artery of at least 50 percent, a left ventricular ejection fraction of less than
20 percent, and severe aortic stenosis were excluded from randomization. The majority of patients
enrolled had single-vessel or two-vessel disease. After vascular surgery, there were no differences between the two groups in the incidence of myocardial infarction or in-hospital mortality. At a median
follow-up of 2.7 years, the mortality was 22 percent
in the revascularization group and 23 percent in
the no-revascularization group.
Although the randomized study by McFalls et al.
was underpowered to detect differences in event
rates in high-risk subgroups, the study design and
the clinical question answered put the study at the
very top of the list of clinically relevant studies in
this field. The results should be interpreted in light
of its design, the exclusion criteria, and the ancillary therapies. If one carefully screens candidates
for vascular surgery and excludes patients with
symptoms of unstable coronary disease, left main
coronary artery disease, aortic stenosis, or severe left
ventricular dysfunction, and if one provides excellent perioperative medical treatment to those remaining, then coronary revascularization does not
appear to provide an additional benefit in reducing
the incidence of perioperative death or myocardial
infarction. The results mirror those of other randomized clinical trials in the nonoperative setting
that have shown that elective coronary revascularization in “low risk” patients who have stable coronary artery disease does not provide a survival benefit and does not reduce the risk of late myocardial
infarction as compared with excellent medical and
preventive therapies.
However, the issue of whom to screen and how to
screen preoperative patients beyond a history taking, physical examination, and preoperative electrocardiography is far from settled. The data reported
by McFalls et al. are about therapy for patients with
stable, well-defined coronary disease, not screening. There is clearly a tendency to view effective
beta-blockade as sufficient to preclude noninvasive screening in most patients being considered
for noncardiac surgery, especially in those with
known stable coronary disease who are facing lower-risk operations. The DECREASE trial showed a
nearly 85 percent reduction in the combined incidence of nonfatal myocardial infarction and death
from cardiac causes after elective vascular surgery,
owing to effective preoperative, intraoperative, an
postoperative beta-blockade. However, there was a
small group of patients with multiple clinical markers of risk and widespread ischemia on preoperative
stress echocardiography who were not adequately
protected by beta-blockers.
9
Cost-effective identification of this minority of
patients, who have extremely high preoperative risk,
is the subject of the American College of Cardiology–
American Heart Association guidelines for perioperative cardiovascular evaluation for noncardiac surgery.
2,10
The trial by McFalls and colleagues adds to
our foundation of knowledge, answering a critical
question about therapy. Now we need a series of additional randomized studies to settle remaining
questions about screening and about the value of
medical therapies beyond beta-blockade with statins, angiotensin-converting–enzyme inhibitors, antiplatelet agents, and other myocardial protective or
vascular stabilizing drugs that are in development
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