Table 1.

Results of randomized trials of revascularization strategies in patients with stable ischemic heart disease as they relate to the older adult populations ≥75 years of age.

Trial (Author, Year)	Study Population (Sample Size)	Randomized Intervention	Average Age (Years)	Primary Endpoint	Secondary Endpoint (s)	Representation of Older Adults ≥75 Years^*
ECSS (ECSSG, 1982)⁵⁹	Men under the age of 65 with mild to moderate angina of at least 30 months with obstruction of 50% or more in at least 2 major coronary arteries (n=767)	CABG vs. Medical Therapy	Mean Age= 49.9 years (Age>53 years = 33%)	Survival at 5 years: CABG = 92.4% vs. Medical Therapy = 83.6% P<0.001	Men >53 years of age showed significant survival benefit compared with young patients	Older Adults ≥75 excluded
CASS (Passamani, 1985)⁶⁰	Patients who were 65 years or younger with clinical and angiographic coronary disease (n=780)	CABG vs. Medical Therapy	Mean Age = 51 years	Survival at 8 Years: CABG = 87% vs. Medical Therapy = 84% P =0.14	Patients with EF<50% did have a survival advantage at 7 years with surgery (survival 84% vs. 70%, p=0.01). Those with triple vessel disease had most survival advantage with revascularization	Older Adults ≥75 excluded
RITA-2 (RITA-2 trial participants 1997)⁶¹	Patients with at least one significant stenosis in a major epicardial artery judged to be acceptable for medical therapy or coronary angioplasty (n=1018)	PTCA vs. Medical Therapy	Median Age = 58 years Included patients ≥70 years old (n=60)	Death/MI at median 2.7 years follow-up: PTCA 6.3% vs. Medical Therapy = 3.0% P =0.02 Difference due to one death and seven non-fatal myocardial infarctions related to randomized procedures	PTCA associated with greater symptomatic improvement, especially in those with more severe angina	Results by age ≥75 years not reported No significant interaction between treatment and age Older adults are underrepresented
VA Cooperative Study (Peduzzi, 1998)⁶²	Male patients with angina pectoris (n=686)	CABG vs. Medical Therapy	51	Survival at 7 years: CABG = 77% Medical Therapy = 70% P =0.043 Survival at 22 years: CABG = 25% Medical Therapy = 20% P =0.24	MI Free Survival at 11 years: CABG = 49% Medical Therapy = 40% P=0.007 MI Free Survival at 22 years: CABG = 18% Medical Therapy = 11% P=0.003	Results by age ≥75 years not reported Older Adults are underrepresented
TIME (TIME Investigators, 2001)⁵	Patients who were 75 years or older with chronic angina with CCSC >2 and at least two antianginal drugs (n=305)	Revascularization (angioplasty) vs. Medical Therapy	Mean Age = 80 years	QoL at 6 Months (SF-36^†): Revascularization = 11.4 Vs Medical Therapy = 3.8 P=0.008	Other Measures of QoL are improved with revascularization at 6 months MACE at 6 months Revascularization = 19% Vs. Medical Therapy = 49% However, no benefit with revascularization at 1 year.	Older Adults were represented Multimorbidity and polypharmacy were reported at baseline but effects on outcomes were not evaluated. Frailty not reported
DEFER (Pijls, 2007)⁶³	Patients referred for elective PCI of a single angiographically significant de novo stenosis (reference diameter>2.5mm); FFR≥0.75 (n=325)	PCI vs. Medical Therapy	Mean Age = 61	Freedom from Cardiac Event at 5 years PCI = 73% vs Medical Therapy (Defer) = 79% P=0.52	Patients with FFR<0.75 had 5 times higher rate of cardiac death or AMI	Results by age ≥75 years not reported Older Adults are underrepresented
SOS (Booth, 2008)⁶⁴	Patients with multivessel CAD (n=988)	PCI vs CABG	Mean Age ~ 61 N=395 >65 years old	Survival at 6 years: PCI = 10.9% vs CABG = 6.8% P=0.022	Death rate in diabetic sub-group: PCI = 17.6% vs CABG = 5.4% However p interaction = 0.15 for treatment effect on mortality between diabetic and non-diabetic patients	Results by age ≥75 years not reported Older Adults are underrepresented
MASS-II (Hueb, 2010)⁶⁵	Patients with multivessel CAD and documented ischemia (n=611)	CABG vs PCI vs Medical Therapy	Mean Age = 60	MACE at 10-years: CABG = 33% vs PCI = 42.4% vs Medical Therapy = 59.1% P<0.001	Survival at 10-years: CABG = 74.9% vs PCI = 75.1% vs Medical Therapy = 69% P=0.089 No difference by age > vs. ≤65	Results by age ≥75 not reported Older Adults are underrepresented
FAME 2 (De Bruyne, 2014)⁶⁶	Patients with stable coronary disease with one-, two-, or three-vessel CAD suitable for PCI (n=888)	PCI vs Medical Therapy	Mean Age = 63.5	MACE at mean follow-up 213–214 days (trial stopped early): PCI = 4.3% vs Medical Therapy = 12.7% P<0.001	Death or MI did not differ between groups, difference in MACE was driven by difference in urgent revascularization	Results by age ≥75 years not reported Older Adults are underrepresented
COURAGE (Sedlis, 2015)⁵⁸	Patients with chronic stable angina or silent ischemia and angiographic CAD >70% stenosis (n=2,287)	PCI vs Medical Therapy	Mean Age (Extended Follow-up) = 64	Death at 11.9 Years: PCI = 41% vs Medical Therapy = 42% P=0.53	Mortality rates were similar between PCI and medical therapy groups, in both the non-VA and VA patient sub-groups. -	Results by age ≥75 years not reported Older Adults are underrepresented Age at 60 years did not modify outcome
STICH (Velazquez, 2016)⁶⁷	Patients with CAD amenable to CABG and ejection fraction <35% (n=1,212)	CABG vs Medical Therapy	Mean Age ~60 Age 18–85 were included 308 patients >67 years old with median age in that group of 72 years.⁶⁸	Death at median follow-up of 9.8 months: CABG = 58.9% vs Medical Therapy = 66.1% P=0.02	Secondary outcomes including death from cardiovascular causes, HF, any cause, and other MACE favored CABG.	Results by age ≥75 years not reported Older Adults are underrepresented
BARI-2D (Ikeno, 2017)⁶⁹	Patients with type 2 diabetes mellitus and evidence of ischemia (n=2,368)	Prompt Revascularization vs Medical Therapy	Mean Age ~ 63 Maximum age = 89.8 years.	Death, MI or Stroke at 5 Years: Low Syntax <22 CABG = 26.1% vs Medical Therapy = 29.9% P=0.41 Moderate to High Syntax >23 CABG = 15.3% vs Medical Therapy =30.3% P =0.02	Death, MI or Stroke at 5 Years: Low Syntax ≤22 PCI = 17.8% vs Medical Therapy = 19.2% P=0.84 Moderate to High Syntax ≥23 PCI = 35.6% vs Medical Therapy =26.5% P =0.12	Results by age ≥75 years not reported but results reported by age ≥70, n=514; also included health status outcomes.⁷⁰ The effect of revascularization versus medical therapy did not differ by age for death (p interaction=0.99), major cardiovascular events, angina, or health status outcomes. Older adults underrepresented
ORBITA (Al-Lamee, 2018)⁶	Patients with ≥70% single vessel stenosis. (n=230)	PCI vs Placebo Procedure	Mean Age = 66	Exercise Time did not improve with PCI compared with Placebo Procedure (Difference in increment between groups = 16.6 seconds, P=0.200)	No improvement in CCSC, Seattle Angina, or EQ-5D-5L Questionnaire with PCI	Results by age ≥75 years not reported Older Adults are underrepresented
FREEDOM (Farkouh, 2019)⁷¹	Patients with diabetes and multivessel CAD with diameter stenosis ≥70% in 2 or more major epicardial vessels involving with 2 separate coronary territories (n=1,900)	CABG vs PCI	Mean Age ~ 63	All-cause mortality at median follow-up 7.5 Years: CABG = 18.3% vs PCI-DES = 24.3% P=0.01	Younger patients (≤63.3 years) derived preferential benefit from CABG compared with older patients (>63.3 years), P for interaction = 0.001	Results by age ≥75 years not reported Older Adults are underrepresented
ISCHEMIA (Maron, 2020)⁷	Patients with stable coronary disease and moderate or severe ischemia (n=5,179)^‡	Invasive vs Conservative Strategy	Mean Age = 64	MACE at median follow-up of 3.2 Years: Hazard Ratio 0.93 (95%CI 0.80 to 1.08) for invasive vs. conservative strategy. Estimated cumulative event rate at 6 months: Invasive Strategy =5.3% vs Conservative Strategy = 3.4% (difference, 1.9 percentage points; 95% CI, 0.8 to 3.0) Estimated cumulative event rate at 5 years: Invasive Strategy =16.4% vs Conservative Strategy = 18.2% (difference, −1.8 percentage points; 95% CI, −4.7 to 1.0)	Modest improvement in angina-related health status with invasive strategy, driven by greater benefit in those with more symptomatic patients and those with moderate to severe ischemia.⁷²	Results by age ≥75 years not yet reported Older Adults are underrepresented
ISCHEMIA-CKD (Bangalore, 2020)⁵⁷	Patients with advanced kidney disease and moderate or severe ischemia (n=777)	Invasive vs Conservative Strategy	Median Age = 63	Death from any cause or MI at 3 Years: Invasive Strategy = 36.4% vs Conservative Strategy = 36.7% P=0.95	Death from any cause, MI, Hospitalization for Angina or Heart Failure, or Resuscitated Cardiac Arrest at 3 Years Invasive Strategy = 38.5% vs Conservative Strategy = 39.7%	Results by age ≥75 years not reported Older Adults are underrepresented

Representation of Older Adults ≥75 years refers refer to both 1) the inclusion of individuals with chronologic age ≥75 years, as well as 2) the underrepresentation of geriatric participants including those with geriatric syndromes and reporting on those conditions

^†

SRF-36 score 0 to 100 with higher scores indicating more favorable status.

^‡

Patients were excluded if they had eGFR<30, a recent acute coronary syndrome, unprotected left main of at least 50%, systolic dysfunction of less than 35, New York Heart Association class III or IV heart failure, and unstable angina.

Abbreviation: CCSC: Canadian Cardiovascular Society Class; QoL = Quality of Life; MACE = major adverse cardiovascular events; PCI = percutaneous coronary intervention; FFR = Fractional Flow Reserve; AMI = Acute Myocardial Infarction; CAD = coronary artery disease; MI = Myocardial Infarction; DES = Drug Eluting Stent; PTCA = Percutaneous transluminal coronary angioplasty.