Twenty-six patients with severe angina resistant to standard medical therapy were studied in one of the first randomized trials comparing acupuncture and sham acupuncture.917 There was no differ- ence between groups in the frequency of angina or use of nitroglycerin, although patients treated with acupuncture achieved a higher pressure rate product on exercise testing. A subsequent study by the same investigators in patients with less severe ischemia failed to show a difference in either exercise variables or subjective measures between acupunc- ture and placebo patients.916 In contrast, a decrease in anginal episodes and an increase in the workload required to induce ischemia were observed with acupuncture in a crossover study of 21 patients with stable angina. The control condition in this trial was a pill placebo, however, so neither subjects nor investigators were blinded.948 In summary, acupuncture has not been studied sufficiently to warrant recommendation as a treatment option for relief of symptoms in patients with SIHD. 5. CAD Revascularization Recommendations and text in this section are the result of extensive collaborative discussions between the PCI and CABG writing committees, as well as key members of the SIHD and UA/NSTEMI writing committees. Certain issues, such as older versus more contemporary studies, primary analyses versus subgroup analyses, and prospective versus post hoc analyses, have been carefully weighed in designating COR and LOE; they are addressed in the appropriate corre- sponding text. The goals of revascularization for patients with CAD are to 1) improve survival and 2) relieve symptoms. Revascularization recommendations in this section are based predominantly on studies of patients with symptomatic SIHD and should be interpreted in this context. As discussed later in this section, recommendations on the type of revascularization are, in general, applicable to patients with UA/NSTEMI. In some cases (eg, unprotected left main CAD), specific recommendations are made for patients with UA/NSTEMI or STEMI. Historically, most studies of revascularization have been based on and reported according to angiographic criteria. Most studies have defined a significant stenosis as $70% diameter narrowing; therefore, for revascularization decisions and recommendations in this section, a significant stenosis has been defined as $70% diameter narrowing ($50% for left main CAD). Physiological criteria, such as an assessment of FFR, have been used in deciding when revascularization is indicated. Thus, for recommendations about revascularization in this section, coronary stenoses with FFR #0.80 can also be considered to be significant. As noted, the revascularization recommendations have been formulated to address issues related to 1) improved survival and/or 2) improved symptoms. When one method of revascularization is preferred over the other for improved survival, this consideration, in general, takes precedence over improved symptoms. When options for revascularization are discussed with the patient, he or she should understand when the procedure is being performed in an attempt to improve symptoms, survival, or both. Although some results from the SYNTAX (Synergy be- tween Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery) study are best characterized as subgroup analyses and hypothesis generating, SYNTAX nonetheless represents the latest and most comprehensive comparison of PCI and CABG.949,950 Therefore, the results of SYNTAX have been considered appropriately when formulating our revascularization recommendations. Although the limitations of using the SYNTAX score for certain revascularization recommendations are recognized, the SYNTAX score is a reasonable surrogate for the extent of CAD and its complex- ity and serves as important information that should be considered when making revascularization decisions. Recom- mendations that refer to SYNTAX scores use them as surrogates for the extent and complexity of CAD. Revascularization recommendations to improve survival and symptoms are provided in the following text and are summarized in Tables 18 and 19. References to studies comparing revascularization with medical therapy are pre- sented when available for each anatomic subgroup. When such studies have been completed only for CABG, RCTs or cohort studies comparing CABG with PCI are presented, but the LOE for PCI is downgraded. See Online Data Supplements 3 and 4 for additional data regarding the survival and symptomatic benefits with CABG or PCI for different anatomic subsets. 5.1. Heart Team Approach to Revascularization Decisions: Recommendations Class I 1. A Heart Team approach to revascularization is recommended in patients with unprotected left main or complex CAD.950 952 (Level of Evidence: C) Fihn et al Stable Ischemic Heart Disease: Full Text e413 Table 18. Revascularization to Improve Survival Compared With Medical Therapy Anatomic Setting COR LOE References UPLM or complex CAD CABG and PCI I Heart Team approach recommended C (950 952) CABG and PCI IIa Calculation of STS and SYNTAX scores B (949, 950, 953 957) UPLM* PCI IIa For SIHD when both of the following are present: Anatomic conditions associated with a low risk of PCI procedural complications and a high likelihood of good long-term outcome (eg, a low SYNTAX score of #22, ostial or trunk left main CAD) Clinical characteristics that predict a significantly increased risk of adverse surgical outcomes (eg, STS-predicted risk of operative IIa For UA/NSTEMI if not a CABG candidate B (949, 968 971, 976 979, 981) IIa For STEMI when distal coronary flow is TIMI flow grade ,3 and PCI can be performed more rapidly and safely than CABG IIb For SIHD when both of the following are present: Anatomic conditions associated with a low to intermediate risk of PCI procedural complications and an intermediate to high likelihood of good long-term outcome (eg, low-intermediate SYNTAX score of ,33, bifurcation left main CAD) Clinical characteristics that predict an increased risk of adverse surgical outcomes (eg, moderate severe COPD, disability from prior stroke, or prior cardiac surgery; STS-predicted operative mortality III: Harm For SIHD in patients (versus performing CABG) with unfavorable anatomy for PCI and who are good candidates for CABG 3-vessel disease with or without proximal LAD artery disease* IIa It is reasonable to choose CABG over PCI in patients with complex 3-vessel CAD (eg, SYNTAX score .22) who are good candidates for CABG 2-vessel disease with proximal LAD artery disease* 2-vessel disease without proximal LAD artery disease* CABG IIa With extensive ischemia B (327, 990 992) IIb Of uncertain benefit without extensive ischemia C (987) 1-vessel proximal LAD artery disease CABG IIa With LIMA for long-term benefit B (412, 987, 993, 994) 1-vessel disease without proximal LAD artery involvement LV dysfunction PCI Insufficient data N/A (Continued) Class IIa 1. Calculation of the STS and SYNTAX scores is reasonable in patients with unprotected left main and complex CAD.949,950,953 957 (Level of Evidence: B) One protocol used in RCTs950 952,958 often involves a multi- disciplinary approach referred to as the Heart Team. Com- posed of an interventional cardiologist and a cardiac surgeon, the Heart Team 1) reviews the patient s medical condition and coronary anatomy, 2) determines that PCI and/or CABG are technically feasible and reasonable, and 3) discusses revascularization options with the patient before a treatment strategy is selected. Support for using a Heart Team approach comes from reports that patients with complex CAD referred specifically for PCI or CABG in concurrent trial registries have lower mortality rates than those randomly assigned to PCI or CABG in controlled trials.951,952 The SIHD, PCI, and CABG guideline writing committees endorse a Heart Team approach in patients with unprotected left main CAD and/or complex CAD in whom the optimal revascularization strategy is not straightforward. A collabor- ative assessment of revascularization options, or the decision to treat with GDMT without revascularization, involving an interventional cardiologist, a cardiac surgeon, and (often) the patient s general cardiologist, followed by discussion with the patient about treatment options, is optimal. Particularly in patients with SIHD and unprotected left main and/or complex CAD for whom a revascularization strategy is not straight- forward, an approach has been endorsed that involves termi- nating the procedure after diagnostic coronary angiography is completed; this allows a thorough discussion and affords both the interventional cardiologist and cardiac surgeon the opportunity to discuss revascularization options with the patient. Because the STS score and the SYNTAX score Table 18. Continued Anatomic Setting COR LOE References Survivors of sudden cardiac death with presumed ischemia- mediated VT PCI I C (1003) No anatomic or physiological criteria for revascularization *In patients with multivessel disease who also have diabetes mellitus, it is reasonable to choose CABG (with LIMA) over PCI30,991,1005 1011 (Class IIa; LOE: B). CABG indicates coronary artery bypass graft; CAD, coronary artery disease; COPD, chronic obstructive pulmonary disease; COR, class of recommendation; EF, ejection fraction; LAD, left anterior descending; LIMA, left internal mammary artery; LOE, level of evidence; LV, left ventricular; N/A, not available; PCI, percutaneous coronary intervention; SIHD, stable ischemic heart disease; STEMI, ST-elevation myocardial infarction; STS, Society of Thoracic Surgeons; SYNTAX, Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery; TIMI, Thrombolysis In Myocardial Infarction; UA/NSTEMI, unstable angina/non ST-elevation myocardial infarction; UPLM, unprotected left main disease; and VT, ventricular tachycardia. Table 19. Revascularization to Improve Symptoms With Significant Anatomic (>50% Left Main or >70% Non Left Main CAD) or Physiological (FFR <0.80) Coronary Artery Stenoses Clinical Setting COR LOE References $1 significant stenoses amenable to revascularization and unacceptable angina despite GDMT $1 significant stenoses and unacceptable angina in whom GDMT cannot be implemented because of medication contraindications, adverse effects, or patient preferences IIa CABG C N/A IIa PCI C N/A Previous CABG with $1 significant stenoses associated with ischemia and unacceptable angina despite GDMT IIa PCI C (1021 1024) IIb CABG C (1025) Complex 3-vessel CAD (eg, SYNTAX score .22) with or without involvement of the proximal LAD artery and a good candidate for CABG IIa CABG preferred over PCI B (980, 987 989) Viable ischemic myocardium that is perfused by coronary arteries that are not amenable to grafting IIb TMR as an adjunct to CABG B (923, 927, 929, 1026, No anatomic or physiological criteria for revascularization III: Harm CABG C N/A III: Harm PCI C N/A CABG indicates coronary artery bypass graft; CAD, coronary artery disease; COR, class of recommendation; FFR, fractional flow reserve; GDMT, guideline-directed medical therapy; LOE, level of evidence; N/A, not available; PCI, percutaneous coronary intervention; SYNTAX, Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery; and TMR, transmyocardial revascularization. Fihn et al Stable Ischemic Heart Disease: Full Text e415 have been shown to predict adverse outcomes in patients undergoing CABG and PCI, respectively, calculation of these scores is often useful in making revascularization 5.2. Revascularization to Improve Survival: Recommendations Left Main CAD Revascularization Class I 1. CABG to improve survival is recommended for patients with significant (>50% diameter stenosis) left main coronary artery stenosis.73,381,412,959 962 (Level of Evidence: B) Class IIa 1. PCI to improve survival is reasonable as an alterna- tive to CABG in selected stable patients with signif- icant (>50% diameter stenosis) unprotected left main CAD with: 1) anatomic conditions associated with a low risk of PCI procedural complications and a high likelihood of good long-term outcome (eg, a low SYNTAX score [<22], ostial or trunk left main CAD); and 2) clinical characteristics that predict a significantly increased risk of adverse surgical out- comes (eg, STS-predicted risk of operative mortality >5%).949,953,955,958,963 979 (Level of Evidence: B) 2. PCI to improve survival is reasonable in patients with UA/NSTEMI when an unprotected left main coronary artery is the culprit lesion and the patient is not a candidate for CABG.949,968 971,976 979,981 (Level of Evidence: B) 3. PCI to improve survival is reasonable in patients with acute STEMI when an unprotected left main coronary artery is the culprit lesion, distal coronary flow is less than TIMI (Thrombolysis In Myocardial Infarction) grade 3, and PCI can be performed more rapidly and safely than CABG.965,982,983 (Level of Evidence: C) Class IIb 1. PCI to improve survival may be reasonable as an alternative to CABG in selected stable patients with significant (>50% diameter stenosis) unprotected left main CAD with: a) anatomic conditions associ- ated with a low to intermediate risk of PCI proce- dural complications and an intermediate to high likelihood of good long-term outcome (eg, low intermediate SYNTAX score of <33, bifurcation left main CAD); and b) clinical characteristics that predict an increased risk of adverse surgical out- comes (eg, moderate severe chronic obstructive pul- monary disease, disability from previous stroke, or previous cardiac surgery; STS-predicted risk of operative mortality >2%).949,953,955,958,963 979,984 (Level of Evidence: B) Class III: Harm 1. PCI to improve survival should not be performed in stable patients with significant (>50% diameter stenosis) unprotected left main CAD who have un- favorable anatomy for PCI and who are good can- didates for CABG.73,381,412,949,953,955,959 964 (Level of Evidence: B) Non Left Main CAD Revascularization Class I 1. CABG to improve survival is beneficial in patients with significant (>70% diameter) stenoses in 3 major coronary arteries (with or without involve- ment of the proximal LAD artery) or in the proximal LAD artery plus 1 other major coronary ar- tery.353,412,959,985 987 (Level of Evidence: B) 2. CABG or PCI to improve survival is beneficial in survivors of sudden cardiac death with presumed ischemia-mediated ventricular tachycardia caused by significant (>70% diameter) stenosis in a major coronary artery. (CABG Level of Evidence: B350,1003,1004; PCI Level of Evidence: C1003) Class IIa 1. CABG to improve survival is reasonable in patients with significant (>70% diameter) stenoses in 2 major coronary arteries with severe or extensive myocardial ischemia (eg, high-risk criteria on stress testing, abnormal intracoronary hemodynamic eval- uation, or >20% perfusion defect by myocardial perfusion stress imaging) or target vessels supplying a large area of viable myocardium.327,990 992 (Level of Evidence: B) 2. CABG to improve survival is reasonable in patients with mild moderate LV systolic dysfunction (EF 35% to 50%) and significant (>70% diameter stenosis) multives- sel CAD or proximal LAD coronary artery stenosis, when viable myocardium is present in the region of intended revascularization.365,412,999 1002 (Level of Evidence: B) 3. CABG with a left internal mammary artery (LIMA) graft to improve survival is reasonable in patients with significant (>70% diameter) stenosis in the proximal LAD artery and evidence of extensive ischemia.412,987,993,994 (Level of Evidence: B) 4. It is reasonable to choose CABG over PCI to im- prove survival in patients with complex 3-vessel CAD (eg, SYNTAX score >22), with or without involvement of the proximal LAD artery who are good candidates for CABG.964,980,987 989 (Level of Evidence: B) 5. CABG is probably recommended in preference to PCI to improve survival in patients with multi- vessel CAD and diabetes mellitus, particularly if a LIMA graft can be anastomosed to the LAD artery.991,1005 1008,1008 1011 (Level of Evidence: B) Class IIb 1. The usefulness of CABG to improve survival is uncertain in patients with significant (70%) diame- ter stenoses in 2 major coronary arteries not involv- ing the proximal LAD artery and without extensive ischemia.987 (Level of Evidence: C) 2. The usefulness of PCI to improve survival is uncer- tain in patients with 2- or 3-vessel CAD (with or without involvement of the proximal LAD artery) or 1-vessel proximal LAD disease.366,959,985,987 (Level of Evidence: B) 3. CABG might be considered with the primary or sole intent of improving survival in patients with SIHD with severe LV systolic dysfunction (EF <35%) whether or not viable myocardium is pres- ent.355,365,410,412,999 1002 (Level of Evidence: B) 4. The usefulness of CABG or PCI to improve survival is uncertain in patients with previous CABG and extensive anterior wall ischemia on noninvasive test- ing.1021 1025,1029 1032 (Level of Evidence: B) Class III: Harm 1. CABG or PCI should not be performed with the primary or sole intent to improve survival in pa- tients with SIHD with 1 or more coronary stenoses that are not anatomically or functionally significant (eg, <70% diameter non left main coronary artery stenosis, FFR >0.80, no or only mild ischemia on noninvasive testing), involve only the left circumflex or right coronary artery, or subtend only a small area of viable myocardium.306,327,412,985,990,995 998 (Level of Evidence: B) 5.3. Revascularization to Improve Symptoms: Recommendations Class I 1. CABG or PCI to improve symptoms is beneficial in patients with 1 or more significant (>70% diameter) coronary artery stenoses amenable to revascularization and unacceptable angina despite GDMT.366,407,1012 1018,1020,1033 (Level of Evidence: A) Class IIa 1. CABG or PCI to improve symptoms is reasonable in patients with 1 or more significant (>70% diameter) coronary artery stenoses and unacceptable angina for whom GDMT cannot be implemented because of medication contraindications, adverse effects, or pa- tient preferences. (Level of Evidence: C) 2. PCI to improve symptoms is reasonable in patients with previous CABG, 1 or more significant (>70% diameter) coronary artery stenoses associ- ated with ischemia, and unacceptable angina despite GDMT.1021,1023,1024 (Level of Evidence: C) 3. It is reasonable to choose CABG over PCI to im- prove symptoms in patients with complex 3-vessel CAD (eg, SYNTAX score >22), with or without involvement of the proximal LAD artery, who are good candidates for CABG.964,980,987 989 (Level of Evidence: B) Class IIb 1. CABG to improve symptoms might be reasonable for patients with previous CABG, 1 or more signif- icant (>70% diameter) coronary artery stenoses not amenable to PCI, and unacceptable angina despite GDMT.1025 (Level of Evidence: C) 2. TMR performed as an adjunct to CABG to improve symptoms may be reasonable in patients with viable ischemic myocardium that is perfused by arteries that are not amenable to grafting.923,927,929,1026,1027 (Level of Evidence: B) Class III: Harm 1. CABG or PCI to improve symptoms should not be performed in patients who do not meet anatomic (>50% diameter left main or >70% non left main stenosis diameter) or physiological (eg, abnormal FFR) criteria for revascularization. (Level of Evidence: C) 5.4. CABG Versus Contemporaneous Medical Therapy In the 1970s and 1980s, 3 RCTs established the survival benefit of CABG compared with contemporaneous (although minimal by current standards) medical therapy without revas- cularization in certain subjects with stable angina: the Veter- ans Affairs Cooperative Study,1035 European Coronary Surgery Study,986 and CASS.1036 Subsequently, a 1994 meta- analysis of 7 studies that randomized a total of 2649 patients to medical therapy or CABG412 showed that CABG offered a survival advantage over medical therapy for patients with left main or 3-vessel CAD. The studies also established that CABG is more effective than medical therapy for relieving anginal symptoms. These studies have been replicated only once during the past decade. In MASS II (Medicine, Angio- plasty, or Surgery Study II), patients with multivessel CAD who were treated with CABG were less likely than those treated with medical therapy to have a subsequent MI, need additional revascularization, or experience cardiac death in the 10 years after randomization.1016 Surgical techniques and medical therapy have improved substantially during the intervening years. As a result, if CABG were to be compared with GDMT in RCTs today, the relative benefits for survival and angina relief observed several decades ago might no longer be observed. Con- versely, the concurrent administration of GDMT may sub- stantially improve long-term outcomes in patients treated with CABG in comparison with those receiving medical therapy alone. In the BARI 2D (Bypass Angioplasty Revas- cularization Investigation 2 Diabetes) trial of patients with diabetes mellitus, no significant difference in risk of mortality in the cohort of patients randomized to GDMT plus CABG or GDMT alone was observed, although the study was not powered for this endpoint, excluded patients with significant left main CAD, and included only a small percentage of patients with proximal LAD artery disease or LVEF ,0.50 (408). The PCI and CABG guideline writing committees endorse the performance of the ISCHEMIA trial, which will provide contemporary data on the optimal management strat- egy (medical therapy or revascularization with CABG or PCI) of patients with SIHD, including multivessel CAD, and moderate to severe ischemia. 5.5. PCI Versus Medical Therapy Although contemporary interventional treatments have low- ered the risk of restenosis compared with earlier techniques, meta-analyses have not shown that the introduction of bare metal stents (BMS) confers a survival advantage over balloon Fihn et al Stable Ischemic Heart Disease: Full Text e417 angioplasty1037 1039 or that the use of DES confers a survival advantage over BMS.138,1040 No study to date has demonstrated that PCI in patients with SIHD improves survival rates.138,366,408,959,985,987,1041 1044 Nei- ther COURAGE366 nor BARI 2D,408 which treated all pa- tients with contemporary optimal medical therapy, demon- strated any survival advantage with PCI, although these trials were not specifically powered for this endpoint. Although 1 large analysis evaluating 17 RCTs of PCI versus medical therapy (including 5 trials of subjects with ACS) found a 20% reduction in death with PCI compared with medical ther- apy,1043 2 other large analyses did not.138,1042 An evaluation of 13 studies reporting the data from 5442 patients with non- acute CAD showed no advantage of PCI over medical therapy for the individual endpoints of all-cause death, cardiac death or MI, or nonfatal MI.1044 Evaluation of 61 trials of PCI conducted over several decades shows that despite improvements in PCI technology and pharmacother- apy, PCI has not been demonstrated to reduce the risk of death or MI in patients without recent ACS.138 The findings from individual studies and systematic re- views of PCI versus medical therapy can be summarized as follows: PCI reduces the incidence of angina.366,407,1016,1020,1033,1045 PCI has not been demonstrated to improve survival in PCI may increase the short-term risk of MI.366,397,1041,1045 PCI does not lower the long-term risk of 5.6. CABG Versus PCI The results of 26 RCTs comparing CABG and PCI have been published: Of these, 9 compared CABG with balloon angio- plasty,30,368,1017,1046 1059 14 compared CABG with BMS im- plantation,1022,1054,1060 1076 and 3 compared CABG with DES 5.6.1. CABG Versus Balloon Angioplasty or BMS A systematic review of the 22 RCTs comparing CABG with balloon angioplasty or BMS implantation concluded the 1. Survival was similar for CABG and PCI (with balloon angioplasty or BMS) at 1 year and 5 years. Survival was similar for CABG and PCI in subjects with 1-vessel CAD (including those with disease of the proximal portion of the LAD artery) or multivessel CAD. 2. Incidence of MI was similar at 5 years after randomization. 3. Procedural stroke occurred more commonly with CABG than with PCI (1.2% versus 0.6%). 4. Relief of angina was accomplished more effectively with CABG than with PCI 1 year after randomization and 5 years after randomization. 5. During the first year after randomization, repeat coro- nary revascularization was performed less often after CABG than after PCI (3.8% versus 26.5%). This was also demonstrated after 5 years of follow-up (9.8% versus 46.1%). This difference was more pronounced with balloon angioplasty than with BMS. A collaborative analysis of data from 10 RCTs comparing CABG with balloon angioplasty (6 trials) or with BMS implantation (4 trials)1080 permitted subgroup analyses of the data from the 7812 patients. No difference was noted with regard to mortality rate 5.9 years after randomization or the composite endpoint of death or MI. Repeat revascularization and angina were noted more frequently in those treated with balloon angioplasty or BMS implantation.1080 The major new observation of this analysis was that CABG was associated with better outcomes in patients with diabetes mellitus and in those .65 years of age. Of interest, the relative outcomes of CABG and PCI were not influenced by other patient charac- teristics, including the number of diseased coronary arteries. The aforementioned meta-analysis and systematic re- view1079,1080 comparing CABG and balloon angioplasty or BMS implantation were limited in several ways: 1. Many trials did not report outcomes for other important patient subsets. For example, the available data are insufficient to determine if race, obesity, renal dysfunc- tion, PAD, or previous coronary revascularization af- fected the comparative outcomes of CABG and PCI. 2. Most of the patients enrolled in these trials were male, and most had 1- or 2-vessel CAD and normal LV systolic function (EF .50%) subjects known to be unlikely to derive a survival benefit and less likely to experience complications after CABG.412 3. The patients enrolled in these trials represented only a small fraction (generally ,5% to 10%) of those who were screened. For example, most screened patients with 1-vessel CAD and many with 3-vessel CAD were not considered for randomization. See Online Data Supplements 5 and 6 for additional data on CABG versus PCI. 5.6.2. CABG Versus DES Although the results of 9 observational studies comparing CABG and DES implantation have been published,964,1081 1088 most of them had short (12 to 24 months) follow-up periods. In a meta-analysis of 24 268 patients with multivessel CAD treated with CABG or DES,1089 the incidences of death and MI were similar for the 2 procedures, but the frequency with which repeat revascularization was performed was roughly 4 times higher after DES implantation. Only 1 large RCT comparing CABG and DES implantation has been published. The SYNTAX trial randomly assigned 1800 patients (of a total of 4337 who were screened) to receive DES or CABG.949,950,980 MACE, a composite of death, stroke, MI, or repeat revascularization during the 3 years after randomiza- tion, occurred in 20.2% of CABG patients and 28.0% of those undergoing DES implantation (P,0.001). The rates of death and stroke were similar; however, MI (3.6% for CABG, 7.1% for DES) and repeat revascularization (10.7% for CABG, 19.7% for DES) were more likely to occur with DES In SYNTAX, the extent of CAD was assessed by using the SYNTAX score, which is based on the location, severity, and extent of coronary stenoses, with a low score indicating less complicated anatomic CAD. In post hoc analyses, a low score was defined as #22; intermediate, 23 to 32; and high, $33. The occurrence of MACE correlated with the SYNTAX score for DES patients but not for those undergoing CABG. At 12-month follow-up, the primary endpoint was similar for CABG and DES in those with a low SYNTAX score. In contrast, MACE occurred more often after DES implantation than after CABG in those with an intermediate or high SYNTAX score.950 At 3 years of follow-up, the mortality rate was greater in subjects with 3-vessel CAD treated with PCI than in those treated with CABG (6.2% versus 2.9%). The differences in MACE between those treated with PCI or CABG increased with an increasing SYNTAX score Although the utility of using a SYNTAX score in everyday clinical practice remains uncertain, it seems reasonable to conclude from SYNTAX and other data that outcomes of patients undergoing PCI or CABG in those with relatively uncomplicated and lesser degrees of CAD are comparable, whereas in those with complex and diffuse CAD, CABG appears to be preferable.949,980 See Online Data Supplements 6 and 7 for additional data comparing CABG with DES. 5.7. Left Main CAD 5.7.1. CABG or PCI Versus Medical Therapy for Left Main CAD CABG confers a survival benefit over medical therapy in patients with left main CAD. Subgroup analyses from RCTs performed 3 decades ago included 91 patients with left main CAD in the Veterans Administration Cooperative Study.961 A meta-analysis of these trials demonstrated a 66% reduction in RR of death with CABG, with the benefit extending to 10 years.412 The CASS Registry381 contained data from 1484 patients with $50% diameter stenosis left main CAD initially treated surgically or nonsurgically. Median survival duration was 13.3 years in the surgical group and 6.6 years in the medical group. The survival benefit of CABG over medical therapy appeared to extend to 53 asymptomatic patients with left main CAD in the CASS Registry.962 Other therapies that subsequently have been shown to be associated with im- proved long-term outcome, such as the use of aspirin, statins, and internal mammary artery grafting, were not widely used in that era. RCTs and subgroup analyses that compare PCI with medical therapy in patients with unprotected left main CAD do not exist. 5.7.2. Studies Comparing PCI Versus CABG for Left Main CAD Of all subjects undergoing coronary angiography, approxi- mately 4% are found to have left main CAD,1090 .80% of whom have significant ($70% diameter) stenoses in other epicardial coronary arteries. Published cohort studies have found that major clinical outcomes are similar with PCI or CABG 1 year after revascularization and that mortality rates are similar at 1, 2, and 5 years of follow-up; however, the risk of needing target-vessel revascularization is significantly higher with stenting than with CABG. In the SYNTAX trial, 45% of screened patients with unprotected left main CAD had complex disease that pre- vented randomization; 89% of these underwent CABG.949,950 In addition, 705 of the 1800 patients who were randomized had revascularization for unprotected left main CAD. The majority of patients with left main CAD and a low SYNTAX score had isolated left main CAD or left main CAD plus 1-vessel CAD; the majority of those with an intermediate score had left main CAD plus 2-vessel CAD; and most of those with a high SYNTAX score had left main CAD plus 3-vessel CAD. At 1 year, rates of all-cause death and MACE were similar for the 2 groups.949 Repeat revascularization rates were higher in the PCI group than the CABG group (11.8% versus 6.5%), but stroke occurred more often in the CABG group (2.7% versus 0.3%). At 3 years of follow-up, the incidence of death in those undergoing left main CAD revascularization with low or intermediate SYNTAX scores (#32) was 3.7% after PCI and 9.1% after CABG (P50.03), whereas in those with a high SYNTAX score ($33), the incidence of death after 3 years was 13.4% after PCI and 7.6% after CABG (P50.10).949 Because the primary endpoint of SYNTAX was not met (ie, noninferiority comparison of CABG and PCI), these subgroup analyses need to be consid- ered in that context. In the LE MANS (Study of Unprotected Left Main Stenting Versus Bypass Surgery) trial,958 105 patients with left main CAD were randomized to receive PCI or CABG. Although a low proportion of patients treated with PCI received DES (35%) and a low proportion of patients treated with CABG received internal mammary grafts (72%), the outcomes at 30 days and 1 year were similar between the groups. In the PRECOMBAT (Premier of Randomized Com- parison of Bypass Surgery versus Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease) trial of 600 patients with left main disease, the composite endpoint of death, MI, or stroke at 2 years occurred in 4.4% of patients treated with PCI and 4.7% of patients treated with CABG, but ischemia-driven target- vessel revascularization was more often required in the patients treated with PCI (9.0% versus 4.2%).984 The results from these 3 RCTs suggest (but do not definitively prove) that major clinical outcomes in selected patients with left main CAD are similar with CABG and PCI at 1- to 2-year follow-up, but repeat revascularization rates are higher after PCI than after CABG. RCTs with extended follow-up of $5 years are required to provide definitive conclusions about the optimal treatment of left main CAD. In a meta-analysis of 8 cohort studies and 2 RCTs,973 death, MI, and stroke occurred with similar frequency in the PCI- and CABG-treated patients at 1, 2, and 3 years of follow-up. Target-vessel revascularization was performed more often in the PCI group at 1 year (OR: 4.36), 2 years (OR: 4.20), and 3 years (OR: 3.30). See Online Data Supplements 8 to 13 for additional data comparing PCI with CABG for left main CAD. 5.7.3. Revascularization Considerations for Left Main CAD Although CABG has been considered the gold standard for unprotected left main CAD revascularization, more recently Fihn et al Stable Ischemic Heart Disease: Full Text e419 PCI has emerged as a possible alternative mode of revascu- larization in carefully selected patients. Lesion location is an important determinant when PCI is considered for unpro- tected left main CAD. Stenting of the left main ostium or trunk is more straightforward than treating distal bifurcation or trifurcation stenoses, which generally requires a greater degree of operator experience and expertise.1091 In addition, PCI of bifurcation disease is associated with higher restenosis rates than when disease is confined to the ostium or trunk.971,1092 Although lesion location influences technical success and long-term outcomes after PCI, location exerts a negligible influence on the success of CABG. In subgroup analyses, patients with left main CAD and a SYNTAX score $33 with more complex or extensive CAD had a higher mortality rate with PCI than with CABG.949 Physicians can estimate operative risk for all CABG candidates by using a standard instrument, such as the risk calculator from the STS database. The above considerations are important factors when choosing among revascularization strategies for unpro- tected left main CAD and have been factored into revascu- larization recommendations. Use of a Heart Team approach has been recommended in cases in which the choice of revascularization is not straightforward. As discussed in Section 5.9.5., the ability of the patient to tolerate and comply with DAPT is also an important consideration in revascular- ization decisions. The 2005 PCI guideline987 recommended routine angio- graphic follow-up 2 to 6 months after stenting for unprotected left main CAD. However, because angiography has limited ability to predict stent thrombosis and the results of SYNTAX suggest good intermediate-term results for PCI in subjects with left main CAD, this recommendation was removed in the 2009 STEMI/PCI focused update.3 Experts have recommended immediate PCI for unprotected left main CAD in the setting of STEMI.983 The impetus for such a strategy is greatest when left main CAD is the site of the culprit lesion, antegrade coronary flow is diminished (eg, TIMI flow grade 0, 1, or 2), the patient is hemodynamically unstable, and it is believed that PCI can be performed more quickly than CABG. When possible, the interventional car- diologist and cardiac surgeon should decide together on the optimal form of revascularization for these subjects, although it is recognized that these patients are usually critically ill and therefore not amenable to a prolonged deliberation or discus- sion of treatment options. 5.8. Proximal LAD Artery Disease A cohort study985 and a meta-analysis412 from the 1990s suggested that CABG confers a survival advantage over contemporaneous medical therapy for patients with disease in the proximal segment of the LAD artery. Cohort studies and RCTs412,1050,1062,1063,1065,1077,1093 1095 as well as collaborative analyses and meta-analyses1080,1096 1098 showed that PCI and CABG result in similar survival rates in these patients. See Online Data Supplements 6 and 14 for additional data on proximal LAD artery disease. 5.9. Clinical Factors That May Influence the Choice of Revascularization 5.9.1. Completeness of Revascularization Most patients undergoing CABG receive complete or nearly complete revascularization, which seems to influence long- term prognosis positively.1099 In contrast, complete revascu- larization is accomplished less often in subjects receiving PCI (eg, in ,70% of patients), and the extent to which the absence of complete initial revascularization influences outcome is less clear. Rates of late survival and survival free of MI appear to be similar in patients with and without complete revascularization after PCI. Nevertheless, the need for subse- quent CABG is usually higher in those whose initial revas- cularization procedure was incomplete (compared with those with complete revascularization) after PCI.1100 1102 5.9.2. LV Systolic Dysfunction Several older studies and a meta-analysis of the data from these studies reported that patients with LV systolic dysfunc- tion (predominantly mild to moderate in severity) had better survival with CABG than with medical therapy alone.365,412,999 1002 For patients with more severe LV systolic dysfunction, however, the evidence that CABG results in better survival compared with medical therapy is lacking. In the STICH trial of subjects with LVEF ,35% with or without viability testing, CABG and GDMT resulted in similar rates of survival (death from any cause, the study s primary outcome) after 5 years of follow-up. For several secondary outcomes at this time point, including 1) death from any cause or hospitalization for heart failure, 2) death from any cause or hospitalization for cardiovascular causes, 3) death from any cause or hospitalization for any cause, or 4) death from any cause or revascularization with PCI or CABG, CABG was superior to GDMT. Although the primary out- come (death from any cause) was similar in the 2 treatment groups after an average of 5 years of follow-up, the data suggest the possibility that outcomes would differ if the follow-up were longer in duration; as a result, the study is being continued to provide follow-up for up to 10 years.355,410 Only very limited data comparing PCI with medical therapy in patients with LV systolic dysfunction are avail- able.1002 In several ways, these data are suboptimal, in that many studies compared CABG with balloon angioplasty, many were retrospective, and many were based on cohort or registry data. Some of the studies demonstrated a similar survival rate in patients having CABG and PCI,988,1080,1103 1105 whereas others showed that those undergoing CABG had better outcomes.964 The data that exist at present on revascularization in patients with CAD and LV systolic dysfunction are more robust for CABG than for PCI, although data from contempo- rary RCTs in this patient population are lacking. Therefore, the choice of revascularization in patients with CAD and LV systolic dysfunction is best based on clinical variables (eg, coronary anatomy, presence of diabetes mellitus, presence of CKD), magnitude of LV systolic dysfunction, patient prefer- ences, clinical judgment, and consultation between the interven- tional cardiologist and the cardiac surgeon. 5.9.3. Previous CABG In patients with recurrent angina after CABG, repeat revas- cularization is most likely to improve survival in subjects at highest risk, such as those with obstruction of the proximal LAD artery and extensive anterior ischemia.1021 1025,1029 1032 Patients with ischemia in other locations and those with a patent LIMA to the LAD artery are unlikely to experience a survival benefit from repeat revascularization.1023 Cohort studies comparing PCI and CABG among post- CABG patients report similar rates of mid- and long-term survival after the 2 procedures.1022,1024,1025,1029,1031,1032,1106 In the patient with previous CABG who is referred for revascu- larization for medically refractory ischemia, factors that may support the choice of repeat CABG include vessels unsuitable for PCI, number of diseased bypass grafts, availability of the internal mammary artery for grafting chronically occluded coronary arteries, and good distal targets for bypass graft placement. Factors favoring PCI over CABG include limited areas of ischemia causing symptoms, suitable PCI targets, a patent graft to the LAD artery, poor CABG targets, and comorbid conditions. 5.9.4. Unstable Angina/Non ST-Elevation Myocardial Infarction The main difference between management of the patient with SIHD and the patient with UA/NSTEMI is that the impetus for revascularization is stronger in the setting of UA/ NSTEMI, because myocardial ischemia occurring as part of an ACS is potentially life threatening, and associated anginal symptoms are more likely to be reduced with a revascular- ization procedure than with GDMT.1107 1109 Thus, the indi- cations for revascularization are strengthened by the acuity of presentation, the extent of ischemia, and the ability to achieve full revascularization. The choice of revascularization method is generally dictated by the same considerations used to decide on PCI or CABG for patients with SIHD. 5.9.5. DAPT Compliance and Stent Thrombosis: Recommendation Class III: Harm 1. PCI with coronary stenting (BMS or DES) should not be performed if the patient is not likely to be able to tolerate and comply with DAPT for the appropri- ate duration of treatment based on the type of stent implanted.1110 1113 (Level of Evidence: B) The risk of stent thrombosis is increased dramatically in patients who prematurely discontinue DAPT, and stent thrombosis is associated with a mortality rate of 20% to 45%.1110 Because the risk of stent thrombosis with BMS is greatest in the first 14 to 30 days, this is the generally recommended minimum duration of DAPT therapy for these individuals. Consensus in clinical practice is to treat DES patients for $12 months with DAPT to avoid late (after 30 days) stent thrombosis.1110,1114 Therefore, the ability of the patient to tolerate and comply with $30 days of DAPT with BMS treatment and $12 months of DAPT with DES treat- ment is an important consideration in deciding whether to use PCI to treat patients with CAD. 5.10. Transmyocardial Revascularization A single randomized multicenter comparison of TMR (with a holmium:YAG laser) plus CABG and CABG alone in pa- tients in whom some myocardial segments were perfused by arteries considered not amenable to grafting1026 showed a significant reduction in perioperative mortality rate (1.5% versus 7.6%, respectively), and the survival benefit of the TMR CABG combination was present after 1 year of follow- up.1026 At the same time, a large retrospective analysis of data from the STS National Cardiac Database, as well as a study of 169 patients from the Washington Hospital Center who underwent combined TMR CABG, showed no difference in adjusted mortality rate compared with CABG alone.1027,1115 In short, a TMR CABG combination does not appear to improve survival compared with CABG alone. In selected patients, however, such a combination may be superior to CABG alone in relieving angina. 5.11. Hybrid Coronary Revascularization: Recommendations Class IIa 1. Hybrid coronary revascularization (defined as the planned combination of LIMA-to-LAD artery graft- ing and PCI of >1 non-LAD coronary arteries) is reasonable in patients with 1 or more of the follow- ing1116 1122 (Level of Evidence: B): a. Limitations to traditional CABG, such as heavily calcified proximal aorta or poor target vessels for CABG (but amenable to PCI); b. Lack of suitable graft conduits; c. Unfavorable LAD artery for PCI (ie, excessive vessel tortuosity or chronic total occlusion). Class IIb 1. Hybrid coronary revascularization (defined as the planned combination of LIMA-to-LAD artery grafting and PCI of >1 non-LAD coronary arter- ies) may be reasonable as an alternative to multi- vessel PCI or CABG in an attempt to improve the overall risk benefit ratio of the procedures. (Level of Evidence: C) Hybrid coronary revascularization, defined as the planned combination of LIMA-to-LAD artery grafting and PCI of $1 non-LAD coronary arteries,1123 is intended to combine the advantages of CABG (ie, durability of the LIMA graft) and PCI.1124 Patients with multivessel CAD (eg, LAD and $1 non-LAD stenoses) and an indication for revascularization are potentially eligible for this approach. Hybrid revascular- ization is ideal in subjects in whom technical or anatomic limitations to CABG or PCI alone may be present and for whom minimizing the invasiveness (and therefore the risk of morbidity and mortality) of surgical intervention is pre- ferred1118 (eg, patients with severe preexisting comorbidities, recent MI, a lack of suitable graft conduits, a heavily calcified ascending aorta, or a non-LAD coronary artery unsuitable for bypass but amenable to PCI, and situations in which PCI of Fihn et al Stable Ischemic Heart Disease: Full Text e421 the LAD artery is not feasible because of excessive tortuosity or chronic total occlusions). Hybrid coronary revascularization may be performed in a hybrid suite in one operative setting or as a staged procedure (ie, PCI and CABG performed in 2 different operative suites, separated by hours to 2 days, but typically during the same hospital stay). Because most hospitals lack a hybrid operating room, staged procedures are usually performed. With the staged procedure, CABG before PCI is preferred, because this approach allows the interventional cardiologist to 1) verify the patency of the LIMA-to-LAD artery graft before attempting PCI of other vessels and 2) minimize the risk of perioperative bleeding that would occur if CABG were performed after PCI (ie, while the patient is receiving DAPT). Because minimally invasive CABG may be associated with lower graft patency rates compared with CABG performed through a midline sternotomy, it seems prudent to angio- graphically image all grafts performed through a minimally invasive approach to confirm graft patency.1118 To date, no RCTs involving hybrid coronary revascular- ization have been published. Over the past 10 years, several small, retrospective series of hybrid revascularization using minimally invasive CABG and PCI have reported low mor- tality rates (0% to 2%) and event-free survival rates of 83% to 92% at 6 to 12 months of follow-up. The few series that have compared the outcomes of hybrid coronary revascular- ization with standard CABG report similar outcomes at 30 5.12. Special Considerations In addition to patients coronary anatomy and LV function and whether they have undergone prior revascularization, clinical features such as the existence of coexisting chronic conditions might influence decision making. However, the paucity of information about special subgroups represents one of the greatest challenges in developing evidence-based guidelines applicable to large populations. As is the case for many chronic conditions, studies specifically geared toward answering clinical questions about the management of SIHD in women, older adults, and individuals with diabetes mellitus or CKD are lacking. Moreover, clinicians are often guided by misconceptions and biases that serve to deprive patients of potentially beneficial therapies. ACCF/AHA guidelines for the management of patients with UA/NSTEMI4,4a address special subgroups by recommending that diagnostic, pharma- cological and revascularization strategies be congruent with those in men, the young, and those without diabetes mellitus. This section echoes those management recommendations. Although this section will briefly review some special con- siderations in diagnosis and therapy in certain groups of patients, the general approach should be to apply the recom- mendations in this guideline consistently among groups. Women generally have a lower incidence of SIHD than men until older age, but their outcomes after MI are worse.1125 Microvascular disease, typically with preserved LV function, is more common among women, particularly those who are younger, whereas obstructive epicardial CAD is less preva- lent. Up to 50% of women with typical or atypical anginal symptoms undergoing cardiac catheterization are found not to have obstructive CAD.1126,1127 Contrary to earlier percep- tions, the prognosis of women with chest pain and nonob- structive disease is not necessarily better.1128,1129 As women age, the prevalence of obstructive CAD increases. Stable angina is the most frequent initial manifestation of SIHD in women, as opposed to AMI and sudden death in men.35,1130 Atypical chest pain and angina-equivalent symp- toms such as dyspnea are more common in women, although women still present with similar patterns, duration, and frequency of symptoms. The lower prevalence of obstructive disease in conjunction with technical challenges makes the interpretation of ischemia on imaging studies somewhat more difficult. Accumulating evidence suggests that vascular reac- tivity related to abnormalities in microvascular and endothe- lial function and possibly plaque erosion or distal microem- bolization contribute to ischemia to a greater extent in women than in men.75 On exercise testing, ST-segment changes are less accurate for the detection of CAD in women than in men,175 although marked ST-segment changes (a visual interpretation $1 mm of horizontal or downsloping ST-segment depression or elevation for $60 to 80 ms after the end of the QRS complex) remain diagnostic for all patients. Challenges with exercise testing in women include their generally lower physical work capacity and the high prevalence of obesity, diabetes mellitus, frailty, and other comorbid conditions. Numerous re- ports14,315,1131,1132 and an expert consensus statement175 have examined the diagnostic accuracy of the exercise ECG and various imaging modalities in large cohorts of women. Overall, most reports document an improvement in diagnostic accuracy with imaging when compared to a standard exercise ECG,175 although that improvement does not necessarily translate into improved clinical outcomes.147 From a meta- analysis, the diagnostic sensitivity and specificity were 72% and 88% for women undergoing dobutamine stress echocar- diography.149 From a small controlled clinical trial, diagnostic specificity was improved considerably when using gated Tc-99m myocardial perfusion SPECT over Tl-201 myocar- dial perfusion SPECT (92% versus 67%) because of im- proved image quality.1133 Overall, sensitivity and specificity of myocardial perfusion SPECT were reported as 88% and 96% for women.86,175,1134 For CMR, one study reported a diagnostic sensitivity and specificity of 92% and 80% with vasodilator stress magnetic resonance myocardial In part related to differing pathophysiology and clinical presentation, substantial differences in provision of clinical care have been observed between men and women with CAD.1135 Despite increasing recognition of the risks of worsening IHD and attendant complications in women, the frequency with which they are prescribed important risk- modifying therapies such as statins, aspirin, and beta blockers after episodes of ACS remains significantly lower than among men.1136,1137 Among patients with documented SIHD, however, the differences between men and women appear to be much smaller with regard to prescription of these Data from COURAGE suggest that the benefits of GDMT alone in comparison with GDMT plus PCI were similar for men and women.366,1138 Moreover, the outcomes of revascu- larization appear to be less favorable among women than men,1139 1142 although very few women were enrolled in COURAGE. In various risk models, the odds of in-hospital death after PCI have ranged from 25% to 80% higher for women than for men,1143 1147 although this trend might have improved in recent years after the higher incidence of diabetes mellitus and hypertension in women is taken into account.1148 The risk of procedural complications also ap- pears to be significantly higher in women.1149 Although fewer data on the experience of women after CABG are available, in the New York State registry, the odds of in-hospital death for women were 2-fold higher than for men.1149,1150 On the basis of these observations, the initial approach to therapy for women with SIHD should be to prescribe a full regimen of GDMT and to reserve consideration of revascularization for patients who do not obtain a satisfactory response or who experience unacceptable adverse effects. On the basis of the higher risk associated with PCI in women, it might be reasonable to adopt a more conservative approach in under- taking this procedure than in men, although the general principle of using revascularization in patients whose symp- toms are refractory to medical therapy and who are not satisfied with their current level of angina persists. 5.12.2. Older Adults In older adults, often defined as .75 years of age, coronary stenoses are likely to be more diffuse and more severe, with a higher prevalence of 3-vessel and left main disease. Several factors complicate the diagnosis and treatment of SIHD in this age group. Common coexisting conditions of the pulmo- nary, gastrointestinal, and musculoskeletal systems can cause chest pain, making diagnosis more difficult, even in patients with documented IHD. Physiological changes in older adults, including alterations in cardiac output through various mech- anisms, muscle loss and deconditioning, neuropathies, lung disease, and degenerative joint disease, make stress testing more difficult. Thus, many elderly patients are incapable of responding to graded increases in workload as required by standard exercise ECG protocols.118,1151 For patients who are unable to exercise, pharmacological stress imaging is indi- cated. Although the majority of investigations have focused on prognosis by markers of ischemia in the elderly, the results generally reveal a similar accuracy of testing when compared with younger individuals presenting with SIHD.1152 1155 Baseline ECG changes, arrhythmias, and LV hypertrophy, which are more common in older adults who have accumu- lated cardiac comorbidities, also limit the value of stress testing.1156,1157 The higher prevalence of SIHD in older adults results in more tests that are falsely negative, and the prognostic value of the Duke treadmill score in older adults might be limited.1158 Data based on RCTs to guide therapy in older adults are relatively sparse because of the common exclusion of older patients from early clinical trials. Several studies have shown less frequent use of evidence-based therapies in older adults, such as early invasive procedures, anticoagulants, beta block- ers, and glycoprotein IIb/IIIa inhibitors.1156,1159,1160 The find- ings are likely related to several factors. Pharmacotherapy is more difficult in older adults because of changes in drug bioavailability and elimination. Drug drug interactions are more common because of polypharmacy. A more conserva- tive approach to coronary angiography is often appropriate given the higher risk of contrast-induced nephropathy in older adults.1161 Moreover, the risks of morbidity and mortality associated with CABG are increased in older adults. Despite the complexities and concerns related to evaluating and treating elderly patients with SIHD, findings from the COURAGE trial indicated that initial medical therapy was not significantly less effective than medical therapy plus PCI in relieving angina (73% in the GDMT group at 60 months, versus 80% in the medical therapy plus PCI group).1162 Although the mortality rate was 50% higher among patients .65 years of age than among younger patients, there were no significant differences between the 2 treatment groups in either patients younger or older than 65 years. Furthermore, although the incidence of MI and stroke was also higher in older patients, there were no significant differences between treatment groups. In the TIME (Trial of Invasive versus Medical Therapy in the Elderly) trial, 301 patients $75 years of age with chronic angina with CCS Class II or higher despite treatment with $2 antianginal drugs were randomized to GDMT or to an invasive strategy of coronary angiography followed by revascularization with PCI or CABG, if feasi- ble.1163 Patients who were assigned to the early revascular- ization group experienced greater improvement in symptoms at 6 months. This difference disappeared by 12 months, at which time both groups had shown a 2-class improvement in their CCS scores and similar results on other quality-of-life measures. It should be noted that 45% of the group assigned to medical therapy ultimately underwent revascularization because of refractory symptoms. Considerable evidence indicates that elderly patients have higher mortality following PCI and CABG than do younger patients, and the risk appears to rise monotonically when .65 years of age.1144 1147,1164 1166 Compared with patients #65 years of age, adjusted odds of short-term mortality after PCI among patients between the ages of 60 and 80 have ranged from 2.2 to 7.6 in various registries, and the odds of death among those $80 years have ranged from 2.7 to .13. Unfortunately, far fewer data are available on the outcomes of elderly patients undergoing CABG, and much of it could be outdated. On the basis of data from 16 120 patients entered into the New York State registry, the odds of in-hospital mortality rose 8% per year of age .60 years (OR: 1.08; 95% CI: 1.06 to 1.09).1150 On the other hand, in an analysis of 505 645 records from the registry maintained by the STS, age was not found to be a predictor of mortality.1167 In older studies, elderly patients were reported to have favorable results after CABG,1168,1169 and long-term survival rates for elderly pa- tients with SIHD treated medically versus surgically were Older adults constitute a growing proportion of patients with SIHD. On the basis of the available data, it is recom- mended that management by GDMT be the initial approach in most patients. Given concerns about higher mortality rate, Fihn et al Stable Ischemic Heart Disease: Full Text e423 particularly in patients .75 or 80 years of age, decisions to recommend revascularization should be undertaken only after careful consideration of patient preferences, functional capac- ity, quality-of-life and end-of-life issues, as well as therapeu- 5.12.3. Diabetes Mellitus Type 1 and type 2 diabetes mellitus are associated with a greater risk of SIHD, and the effects of other risk factors such as hypercholesterolemia are magnified.1170 Cardiovascular mortality rate is 3-fold higher in men with diabetes mellitus and between 2- and 5-fold higher in women with diabetes than in patients without diabetes mellitus.1171,1172 Sudden cardiac death occurs more frequently in patients with diabetes mellitus. Although direct evidence is lacking, asymptomatic ischemia could be more prevalent in patients with diabetes mellitus, possibly because of autonomic neuropathy.1173 The risk of death in a patient with SIHD and diabetes mellitus has been equated to the risk of death in a patient with SIHD and a previous MI.1171,1174 Aggressive management of cardiovascular risk factors, including hypercholesterolemia, hypertension, smoking, low physical activity, and obesity, is essential, along with appropriate glycemic control. Among patients with IHD, the presence of concomitant diabetes mellitus increases the risk of adverse events, irre- spective of whether the patient is treated medically or with revascularization. Two studies have suggested that survival among patients with diabetes mellitus is more favorable after bypass surgery than with medical therapy, although these results are based on subgroup analyses from observational data.991,1175 Of 2 studies comparing PCI and medical therapy in patients with diabetes mellitus, one reported longer sur- vival,1175 but the other did not.991 A subgroup analysis of data from the BARI trial suggested that patients with diabetes mellitus who underwent CABG with 1 arterial conduit had improved survival compared with those who underwent PCI.368 Several retrospective cohort studies have compared outcomes among patients with diabe- tes mellitus undergoing PCI versus CABG. Three observa- tional studies have reported a survival advantage for CABG over PCI, whereas a fourth found no significant difference, and no studies located reported better outcomes after PCI. In the BARI 2D study, 2368 patients with type 2 diabetes mellitus and SIHD were initially selected as candidates for either PCI or CABG on the basis of clinical and angiographic assessment and then were randomly assigned to undergo either prompt revascularization with intensive medical ther- apy or intensive medical therapy alone and to undergo either insulin-sensitization or insulin-provision therapy.408 The study was not designed to compare PCI with CABG. At 5 years, overall survival was similar between the revasculariza- tion and medical-therapy groups (88.3% versus 87.8%), as was the incidence of MACE (77.2% versus 75.9%).409 Pa- tients with the most severe CAD were assigned to the CABG stratum and those with the least severe CAD to the PCI stratum. In the PCI stratum, there was no significant differ- ence in primary endpoints between the revascularization group and the medical-therapy group. In the 763 patients randomized to the CABG stratum, survival was similar but AMI less frequent among those assigned to revascularization plus intensive medical therapy compared with intensive medical therapy (10.0% versus 17.6%; P50.003), and the composite endpoints of all-cause death or MI (21.1% versus 29.2%; P50.010) and cardiac death or MI (P50.03) were also less frequent. Compared with those selected for PCI, patients in the CABG stratum had more 3-vessel disease more proximal LAD stenoses .50% (10% versus 19%), and a significantly higher myocardial jeopardy score.409 One-year follow-up data from the SYNTAX study demon- strated a higher rate of repeat revascularization in patients with diabetes mellitus treated with PCI than in those treated with CABG, driven by a tendency for higher repeat revascu- larization rates in those with higher SYNTAX scores under- A large meta-analysis that included the BARI trial but not BARI 2D failed to identify any significant difference in mortality rate after CABG versus PCI for patients with diabetes mellitus.1079 In a more recent, collaborative analysis that pooled patient-level data from 10 randomized trials (again, not including BARI 2D), Hlatky and colleagues found that of the 1233 patients with diabetes mellitus, 23% of those assigned to CABG died, compared with 29% of those assigned to PCI.1080 By contrast, of the 6561 patients without diabetes mellitus, 13% and 14% died, respectively (P50.014 for interaction). The interaction between diabetes mellitus and treatment remained highly significant after adjustment for multiple patient characteristics and after exclusion of patients enrolled in the BARI 2D trial. Some evidence indicates that the presence of diabetes mellitus adversely affects the outcomes of revascularization. An analysis of the 2009 data on 7812 patients (1233 with diabetes mellitus) in 10 RCTs demonstrated a worse long- term survival rate in patients with diabetes mellitus after balloon angioplasty or BMS implantation than after CABG.1080 Analyses from 3 registries found significantly elevated adjusted ORs for short-term mortality after PCI that ranged from 1.25 to 1.54 in relation to patients without diabetes mellitus.1144,1146,1165 Data from the STS registry indicated that patients with diabetes mellitus on oral therapy had an adjusted OR of 1.15 for death within 30 days (95% CI: 1.09 to 1.21), as well as significantly higher odds of stroke, renal failure, or sternal wound infection than those of patients without diabetes mellitus.1167 For patients on insulin, the adjusted OR for death within 30 days was 1.50 (95% CI: 1.42 to 1.58), and the risks for other complications were also correspondingly higher. In summary, in subjects requiring revascularization for multivessel CAD, current evidence supports diabetes mellitus as an important factor to consider when deciding on a revascularization strategy, particularly when complex or ex- tensive CAD is present (Figure 14). 