Do We Have the COURAGE to Accept the ISCHEMIA Results?

Stable Ischemic Heart Disease (SIHD) is just that a “Stable” pattern of cardiac ischemia.  Yet for decades we treated SIHD with a strategy similar to acute coronary syndrome treatment.¹ This strategy occurred despite the COURAGE (Clinical Outcomes Utilization Revascularization and Aggressive Drug Evaluation) trial results published in 2007.² In short, the COURAGE trial was a prospective, randomized trial of 2287 patients who had objective evidence of myocardial ischemia with significant coronary artery disease.  Patients were randomized to undergo percutaneous coronary intervention (PCI) or optimal medical therapy (medical-therapy group: anti-ischemic drugs, aggressive LDL-C lowering [target level 60-85 mg/dL], and vigorous exercise program).  The 4.6 year follow-up period yielded a HR or 1.05 [95% CI: 0.87 to 1.27) for the composite primary outcome of death, myocardial infarction and stroke. 

Twelve years later the results of the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial were presented at the 2019 AHA meetings.³  The goal of the ISCHEMIA trial was to evaluate routine invasive therapy compared to optimal medical therapy in patients with SIHD and moderate to severe myocardial ischemia on non-invasive stress testing. A total of 5179 persons were randomized with a duration of follow-up of 3.3 years.  The primary composite outcome was cardiovascular death, myocardial infarction, resuscitated cardiac arrest, or hospitalization for unstable angina or heart failure.  The composite outcome occurred in 13.3% of the invasive group versus 15.5% in the medical therapy group (p = 0.34).  Invasive therapy was associated with an absolute increase in harm (≈ 2% absolute increase in the first 6 months and benefit within 4 years (≈ 2% absolute decrease).  Cardiovascular death or myocardial infarction (secondary outcome) occurred in 11.7% of the invasive group compared with 13.9% in the medical therapy group (p = 0.21). 

The second study in 12 years continues to reinforce that aggressive medical therapy is equivalent to an invasive strategy in patients with SIHD to reduce major adverse cardiac events.  In fact, routine invasive therapy is associated with short-term harm.  In patients who have not maximized medical therapy, aggressive up-titration of goal-directed medical therapy (quality of life based on reduction of daily/weekly/monthly angina; lowering of LDL-C with normalizing HDL-C to 2018 ACC/AHA Guidelines⁴; and vigorous exercise program) should be undertaken.  In patients who have maximized goal-directed medical therapy with ongoing angina burden and there is a low likelihood of procedural complications, then an invasive strategy could be explained to the patient.  If the latter strategy is offered then the associated early harms should be explained and confirmed by the patient.  These studies offer pharmacists a greater opportunity to become more involved in SIHD therapy.

Mark A. Munger, PharmD, FCCP, FACC, is a professor of pharmacotherapy and adjunct professor of internal medicine, at the University of Utah, where he also serves as the associate dean of Academic Affairs for the College of Pharmacy.  

References:

1. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients with Stable Ischemic Heart Disease: Executive Summary. Accessed 12/2019
2. Boden WE, O’Rourke RA, Teo KK, et al for the COURAGE Trial Research Group.  Optimal medical therapy with or without PCI for stable coronary disease. NEJM 2007;356(15):1503-16.
3. ISCHEMIA: Early Invasive TX on Par with Meds for Stable CAD. https://www.medpagetoday.com/meetingcoverage/aha/83393 Accessed 12/2019.
4. 2018 Guideline on the Management of Blood Cholesterol. https://www.acc.org/~/media/Non-Clinical/Files-PDFs-Excel-MS-Word-etc/Guidelines/2018/Guidelines-Made-Simple-Tool-2018-Cholesterol.pdf Accessed 12/2019.