COURAGEOVMC LANDMARK TRIALS SERIES

Boden WE, et al. "Optimal medical therapy with or without PCI for stable coronary disease". The New England Journal of Medicine. 2007. 356:1503-16.

2007 Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE)

BACKGROUND PCI has become prominent strategy in

management of stable CAD PCI has been shown to reduced rate of

death, MI, hospitalization from acute coronary syndrome (ACS)

However, prior to the COURAGE trial, it remained unclear whether PCI would have an added benefit to optimal medical therapy

Optimal medical therapy is defined as pharmacologic therapy and lifestyle intervention

CLINICAL QUESTION

In patients with stable CAD, how does optimal medical therapy plus PCI compare to optimal medical therapy alone in improving survival?

DESIGN

Analysis: Intention-to-treat Multicenter, open-label, parallel-group, randomized, controlled trial N=2,287

PCI plus OMT (n=1,149) OMT alone (n=1,138)

Setting: 50 centers in US and Canada Enrollment: June 1999 to January 2004 Median follow-up: 4.6 years Primary outcome: Composite of death from any cause and nonfatal MI

POPULATION

Inclusion Criteria Stable CAD Canadian Cardiovascular Society (CCS)

class I, II, III or stabilized class IV angina ≥70% stenosis in at least one coronary

artery Evidence of MI, defined as:

ST segment depression T wave inversion on the resting EKG Inducible ischemia with either exercise or

pharmacologic stress test 80% stenosis with classic angina without

provocative testing

Exclusion Criteria Persistent CCS class IV angina Markedly positive treadmill test (significant ST

segment depressions and/or hypotensive response during stage I of Bruce protocol)

LVEF <30% Refractory CHF Cardiogenic shock ≥50% left main disease Revascularization within the previous 6 months Coronary lesions deemed unsuitable for PCI

INTERVENTIONS Randomly assigned to PCI plus OMT vs. OMT alone Both arms received OMT, which included:

Antiplatelet: aspirin 81-325mg or clopidogrel 75mg daily (if aspirin intolerant); PCI arm received both

Antiischemic: metoprolol, amlodipine, Isosorbide mononitrate, alone or in combination Lisinopril or losartan regardless of LVEF or history of prior MI Lipid-lowering: Statins ±ezetimibe to goal LDL 60-85 mg/dl Niacin ±fibrates to goal HLD >40 mg/dl and TG <150 mg/dl Exercise recommended

For PCI arm: Target-lesion revascularization always attempted PCI success seen as normal coronary flow and <50% stenosis in luminal diameter after balloon

angioplasty and <20% after stent, based on visual estimation of angiogram Clinical success defined as PCI success without in-hospital MI, emergent CABG, or death

CRITICISMS

Query generalizability given high number of males Most patients received bare metal stents because DES not yet approved during

study High rate of excluded patients No stratification by ischemic burden Unclear how long patients took clopidogrel or if extended duration of therapy would

improve outcomes in the PCI group Unclear use of GP IIb/IIIa inhibitors

BOTTOM LINE

For patients with stable CAD, addition of PCI to optimal medical therapy DID NOT reduced risk of

death, MI, or other major cardiovascular events compared to

optimal medical therapy alone.

DISCUSSION QUESTIONS

For a patient with stable angina, according to the COURAGE trial, what is the best treatment?

What type of cardiac stent did the majority of patients in the COURAGE trial receive?

Why is the COURAGE trial not generalizable to half the population?

DISCUSSION QUESTIONS/ANSWERS

For a patient with stable angina, according to the COURAGE trial, what is the best treatment? ANSWER: Optimal medical therapy (pharmacologic and lifestyle). PCI not recommended.

What type of cardiac stent did the majority of patients in the COURAGE trial receive? ANSWER: Bare metal stents because Drug-eluting stents did not get approved until the last 6

months of the study Why is the COURAGE trial not generalizable to half the population?

ANSWER: The majority of the patients in the study were male

BOARD-LIKE QUESTION61yo F, evaluated for substernal chest pain that occurs with walking up 1 flight of stairs. Exercise stress nuclear myocardial perfusion study showed no ST-segment changes but did show small area of inducible ischemia at the apex with EF 40%. PMHx includes HTN, HLD, DM2. Meds are Lisinopril, Aspirin 81, Simvastatin 40, Metformin, Metoprolol, NTG PRN.Physical exam:Afebrile, HRN 61, BP 128/71, RR 14 bpm. BMI 25. Heart: RRR, no m/r/gLungs: Clear

EKG: normal sinus. No ST changes

What is the next step in management of this patient?A. Continue optimal medical therapyB. CT a for possible PEC. Cardiac catheterizationD. Add another anti-angina drug

BOARD-LIKE QUESTIONEducational Objective: Manage a diabetic patient with stable angina not controlled with optimal medical therapy

Key Point:- Although Courage Trial showed that PCI

in addition to optimal medical therapy does not offer any benefit over optimal medical therapy alone, this ONLY applies to patients with stable symptoms

- Patients with uncontrolled angina should still undergo cardiac cath to evaluate for possible revascularization

ANSWERWhat is the next step in management of this patient?A. Continue optimal medical therapyB. CT a for possible PEC. Cardiac catheterizationD. Add another anti-angina drug