Maester’s Collection: Stable Coronary Artery Disease


Managing stable ischemic heart disease is challenging in our current age of readily available PCI and improving stent technology.  To paraphrase Shakespeare,


“To cath or not to cath, that is the question”

First, we should define the severity of cardiac symptoms, so that everyone is on the same page. A common method used in guidelines and studies is the Canadian Cardiovascular Society Angina Severity Class.

Class I: Ordinary activity such as walking and climbing stairs does not cause angina.
Class II: Slight/modest limitation of ordinary activity such as brisk walking or walking greater than 2 blocks or climbing more than a flight of stairs.
Class III: Marked limitation of ordinary activity such was walking 1-2 blocks or climbing a set of stairs at normal pace.
Class IV: Any physical activity causes discomfort and symptoms maybe present at rest.



Incidence of coronary artery disease is around 1% annually, but increases to nearly 4% in the elderly.


In women, the prevalence of CAD is 5-7% in 45-64 year olds and 10-12% in 65-84 year olds. The prevalence is surprisingly a bit lower in men age 45-64 years at 4-7% compared to women of the same age group. However, the prevalence rises to 12-14% in 65-84 year old men.


PCI versus OMT for Stable CAD

COURAGE is a North American multi-center RCT. It was composed of 2 parallel groups. The intervention arm was optimal medical therapy (OMT) plus PCI, while the control arm was OMT alone. The study enrolled 2297 patients from 1999 to 2004. Patients were followed for a mean of 4.6 years. Inclusion criteria included Stable CAD, CCS class I, II, III, or stabilized IV, at least one vessel with 70% stenosis, and objective myocardial ischemia. Patients were excluded if they had unstable CCS class IV, marked ischemia during Bruce I – early part of the exercise protocol, LVEF <30%, refractory HF, shock, >50% occlusion of the left main, had revascularization in past 6 months, and if they were deemed unsuitable for PCI. As an aside, I’m uncertain as to what “unsuitable for PCI” means exactly and how much freedom the investigators had to include/exclude based on this criteria, however we must acknowledge it may contribute to bias.

Courage-BaselineDemographicsThe primray endpoint was a composite of death from any cause and nonfatal MI. 


PCI + OMT did not improve the risk of death or MI, but did improve rates of revascularization. Further, rates of angina or “symptoms” were consistently lower in the PCI group. However, medical therapy alone also improved symptoms by 1-year. Interestingly, in sub group analyses women trended towards benefit as it related to the primary outcome, but in the extended follow up this trend was lost.

Critiques/Criticisms: The predominance of white men limits the generalizability of the COURAGE trial. The rate of medical adherence was impressive and likely could not be achieved in a “real clinical setting”. The majority of patients received older bare metal stents because drug-eluting were not approved until the final 6 months of the study.  Furthermore, 14.5% of lesions were treated only with angioplasty without stenting. Lastly, the results were not stratified by ischemic burden, as it would reason that those with greater ischemic burden would preferentially benefit from PCI.

COURAGE Extended Follow Up

The initial data from the COURAGE study demonstrates that PCI improves angina, but does NOT improve survival or risk of MI. The notion that PCI for stable CAD does not prevent MIs makes physiological sense. MIs are due to plaque rupture, which does not correlate with degree of luminal stenosis. A recently published study follows up on the initial COURAGE study. These patients were followed for 15 years and 381 additional deaths occurred during the extended period. There were a total of 284 deaths (25%) in PCI group and 277 (24%) in OMT. So at even 15 years out, PCI did not demonstrate a survival benefit.

FFR-guided PCI versus OMT

FAME-2 was a multi-center international, non-blinded RCT occurring primarily in United States and Europe. This trial looked to address whether using fractional flow reserve (FFR) guidance to target hemodynamically significant stenosis in stable ischemic disease was of benefit. The primary end point was a composite of all-cause mortality, non-fatal MI, and unplanned hospitalization with urgent revascularization. The follow up for this study was much shorter than for COURAGE at a mere 7-months. 881 patients with stable ischemic heart disease were randomized to either OMT + FFR-guided PCI (n=447) or OMT alone (n=441). Patients who had tortuous or calcified arteries non-amenable to FFR were excluded. Optimal medical therapy was defined as the use of aspirin, beta-1 selective beta blocker, ACEI or ARB, statin +/- ezetemibe titrated to LDL <70, and PCI group also received clopidogrel 75mg for at least a year. Patients undergoing PCI received aspirin and clopidogrel load prior to the intervention.

Patients were primarily male and about 1/4th were diabetic. More than half only had single vessel disease, but more than half had at least one significant lesion in the pLAD or mLAD.

At 7-months, 12.7% of patients suffered the primary end point in the OMT alone group, while only 4.3% in the FFR + OMT group had the primary outcome occur. However, this difference was largely driven by the need for urgent revascularization, while there was no difference in the death or MI. In post-hoc analysis, the authors found a decrease in the rate of death and MI the period between 8 days post intervention and the end of the follow up period. Also there was significant cross-over the study where 44% of patients in the OMT group received a stent and 9% received an additional stent in the FFR group.


  • Optimal medical therapy is equivalent to revascularization in regards to mortality and CV events, particularly MI
  • Both medical therapy and revascularization improve angina
  • Revascularization offers better relief of angina then medical therapy
  • Initial revascularization had decreased need for future revascularization
  • FFR guided therapy may improve death and MI after the immediate periprocedural period, i.e. greater than 7 days.


Shared decision making tools from the Mayo Clinic


  1. National Institutes of Health NH, Lung, and Blood Institute. Morbidity & Mortality: 2012 Chart Book on Cardiovascular, Lung, and Blood Diseases. Bethesda, MD: National Heart, Lung, and Blood Institute; 2012
  2. N Engl J Med 2007; 356:1503-1516
  3. N Engl J Med 2015; 373:1937-1946
  4. N Engl J Med 2012; 367:991-1001
  5. Mayo Clinic Shared Decision Making National Resource Center. Link.