Management of cardiac risk for noncardiac surgery

INTRODUCTION — Cardiovascular complications, such as myocardial infarction (MI), heart failure, or death attributable to coronary heart disease, pose some of the most significant risks to patients undergoing major noncardiac surgery. This topic will discuss potential interventions to reduce this risk in patients at relatively high baseline risk. The following issues of relevance to patients undergoing noncardiac surgery are discussed separately:

●The estimation of baseline risk (see "Evaluation of cardiac risk prior to noncardiac surgery")

●The approach to perioperative MI (see "Perioperative myocardial infarction or injury after noncardiac surgery")

●The perioperative evaluation and management of heart failure (see "Perioperative management of heart failure in patients undergoing noncardiac surgery")

●Noncardiac surgery in patients with valvular heart disease (see "Noncardiac surgery in adults with aortic stenosis" and "Noncardiac surgery in patients with mitral or aortic regurgitation")

INITIAL RISK ASSESSMENT — The risk of perioperative cardiac complications should be assessed in all patients. Risk assessment is discussed in detail separately. (See "Evaluation of cardiac risk prior to noncardiac surgery".)

FOR URGENT OR EMERGENCY SURGERY — For patients who require urgent or emergency surgery and who have known or suspected coronary artery disease, heart failure, or severe valvular heart disease, we suggest urgent consultation with a cardiologist. In most cases, additional cardiovascular testing will not be performed, but suggestions about monitoring and medication management may be made.

Rarely, a patient may have an acute coronary syndrome or decompensated heart failure and a need for urgent or emergency surgery. In these difficult clinical situations, careful consideration of the benefits and risks of differing strategies is necessary. There is no single approach that can be applied in this situation. For these patients, we feel strongly that consultation with a cardiologist should be obtained.

FOR RECENT ACUTE CORONARY SYNDROME INCLUDING MYOCARDIAL INFARCTION — For patients with an acute coronary syndrome (ACS), proposed elective noncardiac surgery is generally delayed to manage the ACS (including urgent revascularization and dual antiplatelet therapy) and, in patients with myocardial infarction (MI) who do not undergo coronary revascularization, to reduce the risk of perioperative MI and mortality, which is highest early after MI, as discussed separately (see "Evaluation of cardiac risk prior to noncardiac surgery", section on 'Management based on risk'). For patients with acute MI who have not undergone revascularization, elective noncardiac surgery is generally delayed for at least 60 days [1]. For patients undergoing coronary revascularization, the timing of elective noncardiac surgery is determined in large part by consideration of the risk of the premature discontinuation of dual antiplatelet therapy (in order for the surgery to occur) and the consequences of delaying surgery (eg, poor quality of life or concern about the progression of a cancer). These issues are discussed separately. (See "Noncardiac surgery after percutaneous coronary intervention", section on 'Our approach' and "Overview of the acute management of non-ST-elevation acute coronary syndromes" and "Overview of the nonacute management of unstable angina and non-ST-elevation myocardial infarction" and "Overview of the acute management of ST-elevation myocardial infarction" and "Overview of the nonacute management of ST-elevation myocardial infarction".)

REVASCULARIZATION BEFORE SURGERY — With the exception of patients with an acute coronary syndrome, we do not recommend myocardial revascularization before noncardiac surgery to improve perioperative outcomes of noncardiac surgery [1]. However, some patients, such as those with significant left main coronary artery disease, will need revascularization with coronary artery bypass graft surgery or percutaneous coronary intervention to improve long-term survival or, on occasion, to improve the quality of their life. The timing of revascularization relative to the planned noncardiac surgery should be determined by the relative benefits and risks consequent to choosing one procedure to be performed before the other. The decision on timing should be discussed with the patient.

The potential downside of performing coronary artery revascularization before noncardiac surgery depends on the form of revascularization. Many patients undergoing coronary artery bypass graft surgery (CABG) need or want to recover from this procedure for two to three months before undergoing elective noncardiac surgery. Some surgeries can be performed as early as four weeks after CABG as long as the sternum has healed such that it can tolerate any stress associated with the noncardiac surgery and recovery.

For patients undergoing coronary artery stenting, elective noncardiac surgery will need to be deferred until after the minimal recommended duration of dual antiplatelet therapy for each type of stent in order to minimize adverse cardiovascular events. This issue is discussed in detail elsewhere. (See "Noncardiac surgery after percutaneous coronary intervention", section on 'Our approach'.).

If delaying noncardiac surgery is an option for patients who need coronary artery revascularization to prolong long-term survival, we believe it is reasonable to proceed with diagnostic angiography in patients with high-risk features on noninvasive testing (eg, reversible large anterior wall defect, multiple reversible defects, ischemia occurring at a low heart rate, extensive stress-induced wall motion abnormalities, and transient ischemic dilatation). However, the available evidence is not robust and suggests that patients with stable coronary artery disease do not benefit from prophylactic revascularization before noncardiac surgery [2-5].

The Coronary Artery Revascularization Prophylaxis trial was a randomized comparison of planned preoperative revascularization (with either percutaneous coronary intervention [PCI] or CABG) and no plan for preoperative coronary revascularization in patients with stable coronary disease undergoing major vascular surgery [5,6]. Both groups received usual medical therapy with approximately 80 percent of both groups receiving beta blockers and aspirin and over 50 percent receiving statins and angiotensin converting enzyme inhibitors. Of 5859 patients scheduled for vascular operations, 1190 were considered to be at increased cardiac risk (based upon clinical factors and/or stress testing) and had no other exclusions to participation (urgent vascular surgery or severe coexisting illness). These patients underwent coronary angiography; an additional 680 patients were excluded because of left main coronary disease, severe left ventricular dysfunction (left ventricular ejection fraction [LVEF] ≤20 percent), severe aortic stenosis, or coronary anatomy not suitable for revascularization. The remaining 510 patients (of the 1190 patients) were randomly assigned to planned preoperative revascularization or no plan for preoperative coronary revascularization. One-third of the study subjects had three-vessel coronary disease. Of those assigned to revascularization, 38 percent underwent CABG, 55 percent underwent PCI, and 7 percent received no revascularization. Of note, 5.8 percent of the patients in the revascularization group had a myocardial infarction (MI) and 1.7 percent died before their elective vascular surgery. The following outcomes were observed:

●MI within the first 30 days after noncardiac surgery in patients assigned to revascularization or no revascularization was 8.4 percent in both groups. However, 5.8 percent of the patients in the coronary revascularization group experienced an MI after their coronary revascularization but before their noncardiac surgery.

●There were no differences between the revascularization and medical arms in LVEF at three months (54 versus 55 percent).

●At a median of 2.7 years, the primary end point (all-cause mortality) was not significantly different in the revascularization and no revascularization groups (22 versus 23 percent, relative risk 0.98, 95% CI 0.70-1.37).

Observational studies have found comparable [7] or improved outcomes with revascularization before noncardiac surgery [8-11].

The discussion of the approach to patients in whom a decision is made for PCI before noncardiac surgery is found elsewhere. (See "Noncardiac surgery after percutaneous coronary intervention", section on 'Our approach'.)

BETA BLOCKERS — Based on the best available evidence, we do not recommend prophylactic beta blocker therapy to improve perioperative outcomes of noncardiac surgery. While there is evidence to start therapy to lower the risk of perioperative myocardial infarction (MI), we do not start beta blockers preoperatively because they increase the risk of death and stroke. (See 'Patients without indications for long-term therapy' below.)

We continue beta blockers in patients taking them for indications such as hypertension, rate control for atrial fibrillation, control of angina, heart failure, or prior MI. (See 'Patients taking beta blockers' below.)

For patients scheduled for noncardiac surgery who should have been started on beta blocker for an appropriate indication (eg, heart failure, angina, hypertension, after MI), we try to avoid starting a beta blocker preoperatively, particularly if the time between initiation and surgery is less than two to four weeks.

Patients without indications for long-term therapy — We do not start preoperative beta blocker to improve perioperative outcomes. Initial small randomized trials of beta blockers before noncardiac surgery suggested that beta blockers reduce perioperative ischemia, long-term mortality, and cardiovascular complications in patients with underlying arterial disease [12-15].

The largest trial to evaluate the efficacy and safety of prophylactic beta blockers, POISE, randomly assigned 8351 patients with or at risk of atherosclerotic disease (most with a revised cardiac risk index [RCRI] of 1 or 2) (table 1) undergoing noncardiac surgery (42 percent vascular surgery) to either metoprolol (100 mg controlled release [CR] metoprolol succinate) or placebo started two to four hours before surgery and repeated 0 to 6 hours after surgery depending on the patients hemodynamics [16]. This was followed the day after surgery by 200 mg of metoprolol or placebo daily for 30 days. Study drug administration was given if the heart rate was ≥50 beats per minute and the systolic blood pressure was ≥100 mmHg. If patients did not fulfill these criteria but later did, their dose of metoprolol CR decreased to 100 mg daily.

The following findings were noted at 30 days:

●The primary end point of cardiovascular death, nonfatal MI, or nonfatal cardiac arrest occurred significantly less often in the metoprolol group (5.8 versus 6.9 percent, hazard ratio [HR] 0.84, 95% CI 0.70-0.99). This benefit was driven entirely by a reduction in MI (4.2 versus 5.7 percent).

●Total mortality and stroke were significantly increased in the metoprolol group (3.1 versus 2.3 percent and 1 versus 0.5 percent, respectively).

Clinically important hypotension occurred significantly more often in the metoprolol group (15 versus 9.7 percent). A post-hoc analysis suggested that hypotension accounted for at least one-third of the deaths and 15 percent of the strokes. The higher frequency of hypotension in the metoprolol group raises the possibility that either the schedule (two to four hours before surgery) or dose (100 mg of long acting metoprolol) of beta blocker was not optimal. The POISE trial emphasizes the importance of avoiding hypotension if beta blockers are used. It is not known whether a lower dose or earlier initiation (eg, 30 days before surgery) would reduce the frequency of hypotension and major events (eg, death and stroke) while maintaining adequate effects to produce benefit (a lower risk of MI).

In an attempt to put the finding of an increased stroke risk into perspective, the POISE investigators performed a meta-analysis of six trials (including POISE, DIPOM, and MaVS, which measured nonfatal stroke as an end point). The use of perioperative beta blockade was associated with a significantly increased risk of nonfatal stroke (HR 2.19, 95% CI 1.26-3.78). While POISE accounted for almost 80 percent of the patients in the meta-analysis, the relative risk of nonfatal stroke in the five trials before POISE was also higher but was not statistically significant (HR 2.98, 95% CI 0.74-12.0). Multiple other meta-analyses have confirmed an increase in mortality and stroke in studies where beta blocker therapy was initiated within 24 hours of surgery [16-21]. For example, a 2014 meta-analysis identified 16 randomized trials and one cohort study (including 12,043 patients) in which a beta blocker was started within 24 hours of surgery. Excluding the DECREASE trials, which have been discredited [17,22-25], there was a 30 percent increase in the 30-day risk of all-cause mortality (risk ratio [RR] 1.30, 95% CI 1.03-1.63) [20,26]. Although beta blockers lowered the risk of non-fatal MI (RR 0.72, 95% CI 0.59-0.86), they increased the risk of non-fatal stroke (RR 1.86, 95% CI 1.09-3.66).

Most of the patients enrolled in POISE, as discussed above, had an RCRI of 1 or 2 (table 1). Some experts have suggested that beta blocker therapy might be of value in patients with an RCRI ≥3. Evidence suggesting that beta blockers are of benefit in these higher-risk patients comes from three observational studies [27-29]. However, information about dosing and timing of initiation of therapy are limited in these observational studies. While these three observational studies of higher-risk patients suggest potential benefit from beta blockers, we are concerned about the potential for bias in patient selection and residual confounding. In a large propensity score-matched study, the use of cardioprotective beta blockers for >30 days before surgery was associated with reduced mortality risk, whereas short-term use of beta blockers was not associated with differences in mortality in patients with diabetes mellitus [30]. The POISE a priori subgroup analysis, based on the RCRI score, did not support a subgroup effect for efficacy in patients with a higher RCRI score. Moreover, there are no reliable randomized controlled trial data demonstrating that beta blocker therapy is safe in the perioperative period in patients with a high RCRI score.

Thus, until better evidence is available, we suggest not starting beta blockers in patients without long-term indications for such therapy simply because they are at high risk as calculated by an RCRI score of three or more (table 1).

Patients with indications for long-term therapy — Occasionally, preoperative evaluation of patients scheduled for noncardiac surgery identifies individuals who should have been receiving long-term beta blocker therapy for indications such as chronic heart failure with reduced ejection fraction (HFrEF), prior MI, or stable angina pectoris. (See "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk", section on 'Beta blockers'.)

Patients who are started on beta blocker therapy more than two to four weeks before surgery should be followed using normal standards of care for beta blocker initiation. (See "Beta blockers in the management of chronic coronary syndrome", section on 'Therapeutic goals'.)

For patients who are identified as needing long-term beta blocker therapy within two to four weeks of surgery, we are uncertain of the optimal approach. We balance the potential benefits of initiation before surgery with the possible increase in risk of all-cause death or stroke (see 'Patients without indications for long-term therapy' above). Care is individualized. For many of these patients, we wait until after surgery to start beta blockade, as the potential benefit (eg, survival in patients with HFrEF) is uncertain or small over a short period of time, whereas the risk of perioperative stroke or death is increased. (See "Perioperative management of heart failure in patients undergoing noncardiac surgery", section on 'Medication management'.)

If a decision is made to start beta blocker within 30 days of noncardiac surgery, the impact of the drug (ie, blood pressure, heart rate, symptoms) should be monitored closely with follow-up visits, and titration should be done cautiously. If the indication for the initiation of beta blocker is either hypertension or slowing of the ventricular rate in atrial fibrillation, it may be prudent to not aim for optimal blood pressure control or rate control, respectively, preoperatively.

Patients taking beta blockers — We suggest continuing beta blocker therapy in most patients taking them long term [28]. While we are concerned about the potential for an increase in adverse events attributable to the presence of beta blocker effect in the perioperative period (see 'Patients without indications for long-term therapy' above), there is no evidence that discontinuing them is beneficial. In a large retrospective study, perioperative withdrawal of beta blockers was associated with increased risk for mortality within 48 hours after noncardiac surgery, decreased risk for need of vasopressor during the early postoperative period, and a shorter stay in the postanesthesia care unit [31].

In addition, we do not recommend switching to another, as the evidence that one agent is significantly better than another has significant limitations. (See 'Choice of agent' below.)

Evidence for an increase in adverse events such as stroke and all-cause mortality comes from the POISE trial, smaller trials (see 'Patients without indications for long-term therapy' above), and from observational studies. In a 2015 study of 14,644 hypertensive patients who received beta blockers and 40,676 who received other antihypertensive therapy, the primary end point of major adverse cardiovascular events (cardiovascular death, nonfatal ischemic stroke, nonfatal MI) at 30 days occurred in 1.3 percent of the former and 0.8 percent of the latter (adjusted odds ratio 1.29, 95% CI 1.01-1.65) [32]. A similar increase in mortality was seen.

Regarding perioperative dosing, lowering the dose may decrease the risk of perioperative hypotension. In POISE, 9.7 percent of the patients in the placebo group developed clinically significant hypotension. Therefore, a titrated beta blocker dose that appears effective preoperatively is unlikely to inform what dose of a beta blocker is safe after surgery when clinically significant hypotension is common. Physicians who continue beta blocker therapy in the perioperative setting may want to give consideration to lowering the dose during the first 48 hours after surgery.

Choice of agent — As there is no strong evidence that outcomes are better with one beta blocker compared with others, we do not switch beta blockers in advance of surgery. All studies that have reported a cardiovascular benefit of perioperative beta blockers have used agents that are moderately (atenolol or metoprolol) or highly (bisoprolol) beta-1 cardioselective [33]. As there is a paucity of high-quality evidence to suggest that one beta-1 cardioselective agent has a better efficacy to safety ratio, we do not have a preference [34-37]. There is, however, evidence from observational studies suggesting that metoprolol, which is the least selective of the three beta blockers in the perioperative randomized controlled trials, was associated with a higher incidence of stroke and cardiovascular morbidity [28,34-37].

For patients who cannot take beta blockers orally in the perioperative period, intravenous atenolol or metoprolol can be used [12,16].

Baseline heart rate and blood pressure — Given the risks of hypotension and stroke in the perioperative period found in the large POISE trial discussed above (see 'Patients without indications for long-term therapy' above), we believe that close attention should be paid to the preoperative heart rate and blood pressure. The optimal preoperative heart rate and blood pressure for any patient receiving long-term beta blocker therapy is not known. We suggest that the resting heart rate be between 60 and 70 beats per minute. Some of our experts hold the dose on the morning of surgery if the systolic blood pressure is <115 mmHg and half the dose if it is between 116 and 130 mmHg. With regard to heart rate, excessive bradycardia should be avoided. Bradycardia severe enough to require atropine has been reported in over 20 percent of patients receiving perioperative beta blockers [12,14]. Similarly, resting tachycardia may indicate inadequate beta blocker effect and should be also avoided. Patients with heart rates higher than 60 to 70 beats/min are at increased risk of death or MI [38-40]. We believe that a resting heart rate between 60 and 70 beats per minute is reasonable [16,41]. Some of our experts evaluate preoperative heart rate with an outpatient Holter monitor to evaluate beta blocker effect during different daily situations. Others evaluate the heart rate response to stress in some patients to be certain that they can achieve a stress-induced minimum of 100 beats per minute.

In POISE and other studies, the use of beta blockers has been associated with perioperative hypotension, which may occur in up to 15 percent of these patients [16]. (See 'Patients without indications for long-term therapy' above.) However, as POISE did not enroll patients on long-term beta blockers, observations about blood pressure in POISE may not be directly applicable to patients on long-term therapy. The mechanism by which beta blockers are associated with an increase in the rate of stroke and death in the studies cited above is not known but may be related to the increased rate of hypotension seen in these patients. Additionally, the reduction in cerebral blood flow may be more pronounced in patients taking less selective beta blockers, particularly in the setting of anemia (see below).

Until an adequately powered trial is undertaken to directly inform this issue, physicians will have to individualize the perioperative management of each patient who is chronically on a beta blocker. Reduction of the dose of beta blocker should be considered in the patient with systolic blood pressure <115 mmHg. This recommendation is based on expert opinion rather than evidence.

Recommendations of others — Our recommendations for the perioperative use of beta blockers are broadly similar to those made in the 2014 American College of Cardiology/American Heart Association and European Society of Cardiology/European Society of Anesthesiology guidelines on noncardiac surgery [1,42,43] and the 2017 Canadian Cardiovascular Society guidelines on perioperative cardiac risk assessment and management.

However, the former of these two guidelines makes the following recommendations with which we differ:

●In patients with known ischemic heart disease or myocardial ischemia, it may be reasonable to begin perioperative beta blockers.

●In patients with multiple clinical risk factors (eg, diabetes mellitus, heart failure, coronary artery disease, renal insufficiency, cerebrovascular accident), and particularly in those scheduled for high-risk surgery, it may be reasonable to begin beta blockers before surgery.

●The European Society of Cardiology/European Society of Anesthesiology guidelines do suggest a preference for atenolol or bisoprolol if starting a beta blocker before surgery.

OTHER MEDICAL THERAPIES

Antiplatelet therapy — Many patients who undergo noncardiac surgery are treated with long-term antiplatelet therapy (most often aspirin) for the primary or secondary prevention of cardiovascular disease events. For most of these patients taking aspirin monotherapy, we recommend that they hold such therapy five to seven days before surgery and that aspirin not be started before noncardiac surgery in those not taking aspirin. Patients with an indication for long-term aspirin usage who have their aspirin held before surgery should have their aspirin re-started when the perioperative risk of major bleeding has passed. However, we continue aspirin in patients with prior PCI and those undergoing carotid endarterectomy, unless the risk of major bleeding is thought to be high and outweighs the benefit of preventing a myocardial infarction (MI). The results are strongly influenced by the results of the POISE-2 trial (and one post-hoc substudy from that trial) discussed below. (See "Aspirin for the secondary prevention of atherosclerotic cardiovascular disease".)

Our approach to the use of dual antiplatelet after percutaneous coronary intervention is discussed separately. (See "Noncardiac surgery after percutaneous coronary intervention", section on 'Our approach'.)

The recommendation to avoid aspirin use perioperatively is based principally on the results of the large POISE-2 trial. POISE-2 was a two-by-two factorial design trial that allowed for separate comparisons of aspirin to placebo and clonidine to placebo in 10,010 patients with or at risk of atherosclerotic disease who were undergoing noncardiac surgery [44]. (See 'Clonidine' below.) Patients scheduled to undergo carotid endarterectomy, retinal surgery, or intracranial surgery were excluded. Patients were enrolled in one of two aspirin strata: the Initiation Stratum (n = 5628) enrolled patients who were not taking aspirin chronically and the Continuation Stratum (n = 4382) enrolled patients who were taking aspirin chronically. Patients started aspirin/placebo (200 mg) just before surgery and continued it daily (100 mg) for 30 days in the Initiation Stratum and for seven days in the Continuation Stratum (after which patients resumed their regular aspirin). The primary outcome of death or nonfatal MI at 30 days was similar in both groups (7 versus 7.1 percent, respectively; hazard ratio [HR] 0.99, 95% CI 0.86-1.15). This finding was similar between those who were taking long-term aspirin and those who were not. As expected, major bleeding was more common in the aspirin group (4.6 versus 3.8 percent; HR 1.23, 95% CI 1.01-1.49).

In contrast to the overall group, a small subgroup (n = 470) analysis found that perioperative aspirin may be more likely to benefit patients with prior percutaneous coronary intervention (PCI) [45]. POISE-2 excluded patients who were within one year of drug-eluting stent or six weeks within bare metal stent placement, as these patients required dual antiplatelet therapy. In the POISE-2 substudy of 470 patients who had a prior PCI before noncardiac surgery, aspirin reduced the risk for the primary outcome (absolute risk reduction, 5.5% [95% CI 0.4-10.5]; hazard ratio [HR], 0.50, CI 0.26-0.95; P for interaction = 0.036) and for MI (absolute risk reduction, 5.9% [CI 1.0-10.8]; HR 0.44, CI 0.22-0.87; P for interaction = 0.021). The effect on the composite of major and life-threatening bleeding in patients with prior PCI was uncertain (absolute risk increase 1.3 percent [CI -2.6 to 5.2]). While we are cautious about interpreting the findings in this post-hoc analysis of a small subgroup, we believe the results are plausible. Moreover, the results persisted at one-year follow-up [46].

POISE-2 included approximately 600 patients undergoing vascular surgery. Our approach to antiplatelet therapy in patients scheduled to undergo coronary artery bypass graft, carotid, or peripheral vascular surgery is presented in separate topic reviews. (See "Carotid endarterectomy", section on 'Antiplatelet therapy' and "Coronary artery bypass surgery: Perioperative medical management", section on 'Aspirin' and "Management of chronic limb-threatening ischemia".)

Prior to POISE-2, the potential harm or benefit from perioperative aspirin was not well studied and there was evidence from small trials and observational studies both against and in favor of its use [44,47-50]. In the Pulmonary Embolism Prevention trial, which randomly assigned 13,356 patients undergoing hip fracture surgery to aspirin or placebo, the secondary end point of non-fatal MI or fatal ischemic heart disease occurred more often in the aspirin group (1.6 versus 1.2 percent; HR 1.33, 95% CI 1.00-1.78) [48].

Clonidine — We do not recommend clonidine, an alpha-2 agonist, to improve perioperative outcomes. Clonidine, similar to beta blockers (see 'Beta blockers' above), has the potential to reduce any adverse impact of the high catecholamine state associated with surgery. Despite some evidence from small randomized trials to support its use [51,52], the large POISE-2 trial found no benefit [53]. In POISE-2 (see 'Antiplatelet therapy' above), clonidine did not reduce the rate of death or MI at 30 days (HR with clonidine 1.08, 95% CI 0.93-1.26). Clonidine did, however, increase the risk of clinically important hypotension and nonfatal cardiac arrest. A Cochrane systematic review of clonidine in noncardiac surgery also found no benefit in reducing death, MI, or stroke but evidence of increased bradycardia and hypotension [54]. However, it should be continued in patients already taking it to prevent rebound hypertension from abrupt withdrawal.

Statins — Patients with coronary artery disease or a coronary equivalent (diabetes mellitus, symptomatic carotid artery disease, peripheral artery disease, abdominal aortic aneurysm, chronic kidney disease, or multiple risk factors that confer a 10-year risk of coronary heart disease greater than 20 percent) should receive therapy with a statin. (See "Management of low density lipoprotein cholesterol (LDL-C) in the secondary prevention of cardiovascular disease".)

Among these patients undergoing surgery, we recommend continuing statin therapy in patients already being treated. Despite weak evidence (presented below), we start statin therapy as early as possible (including up to hours before the surgery) before elective surgery in previously untreated patients [38]. Although few patients underwent urgent or emergency surgery in the relevant studies, we recommend starting statin therapy, if possible, in such patients [55,56].

The rationale to start statin therapy before surgery in patients with indications results from our belief that there are very few risks to doing so and the few studies in patients with vascular disease have suggested benefit [57-59]. Further support for benefit from statin therapy comes from an observational study in which cessation of statin therapy was associated with significant cardiovascular harm [60]. The postulated mechanism for a benefit from statins is related to their pleiotropic effects, primarily reducing inflammation and stabilizing plaques. (See "Mechanisms of benefit of lipid-lowering drugs in patients with coronary heart disease".)

The LOAD trial was an exploratory (feasibility) study of 648 statin-naïve patients who were scheduled for noncardiac surgery and were at relatively high risk for a major vascular complication [61]. Patients were randomly assigned to a loading dose of atorvastatin or placebo within 18 hours before surgery. A 40 mg atorvastatin dose (or placebo) was given for seven days after surgery. There was no significant difference in the composite primary outcome of all-cause mortality, nonfatal myocardial injury, and stroke at 30 days (hazard ratio 0.87, 95% CI 0.60-1.26). However, for patients already on a statin, reloading with atorvastatin or rosuvastatin before emergency surgery resulted in a lower rate of cardiovascular end points at 30 days [62,63].

Although two large observational studies suggest that early perioperative statin use, compared with no statin use, is associated in a significant reduction in all-cause mortality, selection bias in these studies and residual confounding in the analyses cannot be excluded. A prospective, cohort study of 15,478 patients from the VISION trial (see "Perioperative myocardial infarction or injury after noncardiac surgery", section on 'Epidemiology') who were ≥45 years and having noncardiac surgery used a multivariable logistic model and propensity score analysis to evaluate outcomes with perioperative statin use [64]. In the matched population of 2845 patients (18.4 percent) treated with a statin and 4492 (29.0 percent) controls, preoperative statin use was associated with a lower risk of the primary outcome, a composite of all-cause mortality, myocardial injury after noncardiac surgery (MINS), or stroke at 30 days (relative risk [RR], 0.83; 95% CI 0.73–0.95). Statins were also associated with a significantly lower risk of the individual components of all-cause mortality, cardiovascular mortality, and MINS, but there were no statistically significant differences in the risk of MI or stroke. In a retrospective cohort analysis of over 180,000 United States veterans (mostly men) undergoing noncardiac surgery, 30-day all-cause mortality was lower in recently statin-treated patients (approximately 48,000 propensity score matched pairs; relative risk 0.82, 95% CI 0.75-0.89) [65].

A meta-analysis of four randomized controlled trials (n = 675) and 20 observational cohort or case-control studies (n = 22,861), published before the two large observational studies and the LOAD trial presented above, found that perioperative statin therapy was associated with a significantly lower risk of all-cause mortality (odds ratio [OR] 0.54; 95% CI 0.38-0.78), MI (OR 0.62; 95% CI 0.45-0.87), stroke (OR 0.51; 95% CI 0.39-0.67), and the composite of MI, stroke, and death (OR 0.45; 95% CI 0.29-0.70) [66]. There was no significant difference in cardiovascular mortality or incidence of kidney injury. Another meta-analysis of 12 trials involving 4707 patients found that perioperative statins reduced the incidence of postoperative MI, composite of death/MI/stroke, and new cases of atrial fibrillation in patients undergoing noncardiac surgery [67].

ACE inhibitor or ARB — For most patients undergoing noncardiac surgery who are receiving a long-term angiotensin converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB), we omit these during the 24 hours before surgery.

Patients for whom it is reasonable to continue such therapy include those with ongoing hypertension or active/recent heart failure. Some of our contributors continue these medications for these particular patients, while others do not.

The rationale for omitting ACE inhibitor or ARB, which are commonly used in patients with hypertension, prior MI, or heart failure, has been a concern about perioperative hypotension. This phenomenon has been documented in a small randomized trial and most [68,69] but not all observational studies [70]. Thus, if these agents are continued, blood pressure should be carefully monitored to avoid hypotension. (See "Perioperative medication management", section on 'ACE inhibitors and angiotensin II receptor blockers'.)

This issue was addressed in a prospective cohort analysis of patients in the VISION study [71]. (See "Perioperative myocardial infarction or injury after noncardiac surgery", section on 'Epidemiology'.) Compared with 3557 patients who continued their ACE inhibitors/ARBs, the 1245 (26 percent) who did not take them in the 24 hours before surgery had a lower risk of the primary composite outcome of all-cause death, stroke, or myocardial injury (12 versus 12.9 percent; adjusted relative risk [ARR], 0.82, 95% CI 0.70-0.96) and intraoperative hypotension (ARR 0.80, 95% CI 0.72-0.93). However, a meta-analysis did not demonstrate an association between perioperative administration of ACE inhibitors/ARBs and mortality or MACE but did confirm that perioperative continuation is associated with an increased incidence of intraoperative hypotension [68].

If ACE inhibitors/ARBs are withheld before surgery, it is important to restart them as soon as possible postoperatively, assuming hemodynamic stability. Studies from the Veterans Affairs Healthcare System showed that non-resumption of ARBs within two days or ACE inhibitors within 14 days after surgery was associated with higher 30-day mortality rates [72,73].

Nitrate therapy — We do not recommend the use of prophylactic use of nitrates. A 2016 Cochrane review did not find a significant difference in the primary study outcome of all-cause mortality at 30 days for any preparation of nitrate; however, only three trials that included a total of 149 patients reported this outcome [74]. Furthermore, the decrease in preload induced by nitroglycerin may outweigh its benefits.

MONITORING — The intraoperative care, including monitoring and choice of anesthetic agent, of patients at risk for a cardiac complication at the time of noncardiac surgery, is discussed separately. (See "Anesthesia for noncardiac surgery in patients with ischemic heart disease".)

RECOMMENDATIONS OF OTHERS — Recommendations made in this topic are generally consistent with those made in the 2014 American College of Cardiology/American Heart Association (ACC/AHA) and European Society of Cardiology/European Society of Anesthesiology guidelines on noncardiac surgery [1,42,43] and the 2017 Canadian Cardiovascular Society guidelines on perioperative cardiac risk assessment and management:

●The ACC/AHA guidelines make weak recommendations for the use of beta blockers in patients with three or more revised cardiac risk index risk factors (eg, diabetes, renal insufficiency, prior cerebrovascular accident), whereas we recommend against doing so.

●The European Society of Cardiology/European Society of Anesthesia states that prophylactic myocardial revascularization before high-risk surgery may be considered.

The ACC/AHA has published a guideline-focused update on the duration of dual antiplatelet therapy in patients with coronary artery disease [75].

The 2017 Canadian Cardiovascular Society Guidelines on perioperative cardiac risk assessment and management for patients who undergo noncardiac surgery [43] include the following treatment recommendation:

●Initiation of beta blocker therapy within 24 hours before noncardiac surgery is not recommended.

●Withholding angiotensin converting enzyme inhibitor/angiotensin II receptor blocker 24 hours before noncardiac surgery was recommended.

●Discussing and facilitating smoking cessation was recommended.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Perioperative cardiovascular evaluation and management".)

SUMMARY AND RECOMMENDATIONS

●For urgent or emergency surgery – For patients who require urgent or emergency surgery and who have known or suspected coronary artery disease, heart failure, or severe valvular heart disease, we suggest urgent consultation with a cardiologist. (See 'For urgent or emergency surgery' above.)

●For acute coronary syndrome including myocardial infarction – For patients with an acute coronary syndrome (ACS), proposed elective noncardiac surgery is generally delayed to manage the ACS and, in patients with myocardial infarction (MI) who do not undergo coronary revascularization, to reduce the risk of perioperative MI and mortality, which is highest early after MI, as discussed separately (see "Evaluation of cardiac risk prior to noncardiac surgery", section on 'Very high-risk patients'). For patients with acute MI who have not undergone revascularization, elective noncardiac surgery is generally delayed for at least 60 days. (See 'For recent acute coronary syndrome including myocardial infarction' above.)

●Coronary angiography and revascularization – Cardiac catheterization and angiography should be performed in patients with high-risk features on noninvasive testing (eg, reversible large anterior wall defect, multiple reversible defects, ischemia occurring at a low heart rate, extensive stress-induced wall motion abnormalities, transient ischemic dilatation). This approach should be reserved for patients whose surgery can be deferred during the time dual antiplatelet therapy is required after coronary artery stenting. (See 'Revascularization before surgery' above.)

•Among patients in whom preoperative coronary angiography is performed, we recommend revascularization only for patients with high-risk features that fulfill revascularization criteria applicable to all patients with coronary disease (Grade 1A). (See "Chronic coronary syndrome: Indications for revascularization" and 'Revascularization before surgery' above.)

•For patients in whom coronary artery revascularization is indicated, the timing will depend on the benefits and risks of performing it before noncardiac surgery. (See 'Revascularization before surgery' above.)

●Beta blocker use

•In patients scheduled for noncardiac surgery, we do not start beta blockers to improve short-term outcomes. (See 'Patients without indications for long-term therapy' above.)

•In patients scheduled for noncardiac surgery who have an indication for long-term beta blocker therapy but who have not yet had such therapy started, we individualize care, taking into account the benefits and risks associated with the preoperative initiation of therapy. (See 'Patients with indications for long-term therapy' above.)

•In patients treated with long-term beta blockers for recommended indications, we suggest continuing beta blockade perioperatively (Grade 2B). (See 'Patients taking beta blockers' above.)

●Antiplatelet therapy

•For patients taking aspirin for primary or secondary prevention of cardiovascular disease, we recommend holding it approximately five to seven days before noncardiovascular surgery (Grade 1B). (See 'Antiplatelet therapy' above.)

Patients with prior percutaneous coronary intervention with coronary stent placement and those undergoing carotid endarterectomy should have their aspirin continued unless the risk of major bleeding is felt to outweigh the benefit of reducing the risk of MI.

•Patients who have an indication for long-term aspirin usage and who have their aspirin held prior to surgery should have their aspirin restarted after surgery when the perioperative risk of major bleeding has passed.

Our approach to antiplatelet therapy in patients scheduled to undergo coronary artery bypass graft, carotid, or peripheral vascular surgery is presented in separate topic reviews. (See "Carotid endarterectomy", section on 'Antiplatelet therapy' and "Coronary artery bypass surgery: Perioperative medical management", section on 'Aspirin' and "Management of chronic limb-threatening ischemia".)

•Our approach to the perioperative management of patients receiving dual antiplatelet therapy is discussed separately. (See "Noncardiac surgery after percutaneous coronary intervention", section on 'Our approach'.)

●Statin use

•Among patients undergoing elective surgery, we recommend continuing statin therapy in patients already being treated, and in previously untreated patients at high cardiovascular risk, initiating statin therapy as soon as possible before surgery (Grade 1A). (See 'Statins' above.)

•For patients on statin therapy who are undergoing urgent or emergency major vascular surgery, we recommend continuing such therapy (Grade 1B). (See 'Statins' above.)

•For patients not on statin therapy who are undergoing urgent or emergency major vascular surgery, we suggest initiating therapy before surgery, if possible (Grade 2C).

●Monitoring – Recommendations for the use of postoperative electrocardiography or troponin measurement to detect myocardial ischemia are discussed separately. (See "Perioperative myocardial infarction or injury after noncardiac surgery", section on 'Diagnosis' and "Perioperative myocardial infarction or injury after noncardiac surgery", section on 'Summary and recommendations'.)

ACKNOWLEDGMENT — The UpToDate editorial staff thank James P Morgan, MD, PhD, and Jonathan B Shammash, MD, who contributed to earlier versions of this topic review.