View source for Chronic stable angina COURAGE trial

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{{Chronic stable angina}}
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==Overview==
The COURAGE (Clinical Outcomes Utilizing Revascularization and AGgressive Drug Evaluation) trial <ref name="pmid17387127">Boden WE, O'Rourke RA, Teo KK, Hartigan PM, Maron DJ, Kostuk WJ et al. (2007) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17387127 Optimal medical therapy with or without PCI for stable coronary disease.] ''N Engl J Med'' 356 (15):1503-16. [http://dx.doi.org/10.1056/NEJMoa070829 DOI:10.1056/NEJMoa070829] PMID: [http://pubmed.gov/17387127 17387127]</ref>, was a large-scale, randomized, multicenter, multinational trial conducted between 1999 and 2004. The trial compared the benefits of [[PCI]] versus optimal medical therapy as the initial treatment strategy in patients with [[Chronic stable angina pathophysiology|stable angina]] and significant underlying [[coronary artery disease]] on cardiac catheterization.

==Study Population==
A total of '''2,287''' patients were randomized to either '''PCI''' (1,149 patients) which consisted of [[PCI]] with optimal medical therapy or '''medical therapy''' (1,138 patients) which consisted of upfront optimal medical therapy alone. It should be noted that medical therapy patients could cross over to [[PCI]]. 

==Treatment Strategies==
===PCI===
The trial has been criticized because the [[PCI]] patients were treated predominantly with [[bare metal stents]] and only 15% of the patients were treated with [[drug eluting stents]].

===Optimal Medical Therapy===
All patients who were randomized to optimal medical therapy alone were treated with [[Chronic stable angina beta blocker therapy|beta blockers]], [[Chronic stable angina calcium channel blocker therapy|calcium channel blockers]], [[Chronic stable angina nitrate therapy|nitrates]], [[antiplatelet]] therapy (either [[Chronic stable angina treatment aspirin|aspirin]] or [[Chronic stable angina treatment clopidogrel|clopidogrel]]), and aggressive [[Chronic stable angina treatment anti-lipid agents|lipid-lowering therapy]] with [[statin]] (attained median [[LDL]]-[[cholesterol]] was 72 mg/dL at five years). [[Chronic stable angina treatment physical activity|Exercise]] was recommended to achieve further improvements in the lipid profile when necessary. 

===Both Groups===
Both groups received [[aspirin]] along with aggressive lipid and [[Chronic stable angina treatment blood pressure control|blood pressure]] lowering as a part of optimal medical therapy.

==Study Entry Criteria==

===Inclusion Criteria===
Patients were required to have both objective evidence of [[ischemia]] and significant [[coronary heart disease]] in a least one vessel (87% were symptomatic and 58% had [[Canadian Cardiovascular Society Classifications of Angina Pectoris|Canadian Cardiovascular Society CCS class II or III angina]]). Approximately, two thirds of the patients had multi-vessel disease.

===Exclusion Criteria===
Patients were excluded if they had [[Canadian Cardiovascular Society Classifications of Angina Pectoris|CCS class IV angina]], ≥50 percent left main disease, a markedly positive treadmill test (significant [[ST segment depressions]] and/or a [[hypotensive]] response during stage I of the Bruce protocol), an [[LVEF]] less than 30 percent, or coronary lesions deemed unsuitable for [[PCI]]. 

==Results==
===Primary Endpoint===
The '''primary endpoint''' of the study was the composite endpoint of death from any cause or non-fatal [[MI]]. There was no significant difference reported in the primary endpoint event rate between the two treatment groups during the median follow-up of 4.6 years (range 2.5 to 7 years): 19% in the PCI group and 18.5% in the medical therapy group, P=0.62.

===Secondary Endpoints===
*There was no significant difference observed between the incidence of hospitalization for [[acute coronary syndrome]], [[stroke]], rates of [[MI]] and death.

*However, patients in the PCI group underwent significantly fewer subsequent revascularization procedures (21 versus 33 percent, HR 0.60, 95% CI 0.51-71).  

*The COURAGE trial also addressed the issue of whether patients who receive [[PCI]] plus optimal medical therapy have a '''better quality of life and less angina''' than those who receive optimal medical therapy alone.

:*The rate of patients who were free from [[angina]] between the 2 groups at 1 and 3 years was statistically significant (74% patients who underwent [[PCI]] were angina free at 5 years in comparison to the 72% patients who received medical therapy alone, P=0.35).
:*However, there was no statistically significant difference noted at baseline, or at 3 year follow up.
::*22% patients who underwent [[PCI]] were angina free at baseline.
::*53% patients who underwent [[PCI]] were angina free versus 42% patients who received medical therapy alone noted at 3-month.
::*However, there was no significant difference between the 2 groups observed at 36 months (59% patients who underwent [[PCI]] versus 56% who received medical therapy alone).

:*Patients in both groups showed significant improvements from baseline values in various measures of quality of life. 
::*At 6-month follow up, the percent of patients with clinically significant improvement in the parameters such as physical limitation, angina stability, angina frequency, and overall quality of life was significantly higher in the PCI group in comparison to that of the medical group. 
::*However, there was no significant difference in these rates at 36 months.

*The '''results of COURAGE trail''' demonstrate that no benefit was observed with revascularization by PCI over aggressive medical management when performed in patients with chronic stable angina and suggest that [[PCI]] may be deferred as long as medical therapy is optimized and maintained in patients with chronic stable disease.

==Meta-analyses Including the COURAGE trial that Compare Medical and PCI Therapy==
A meta-analysis of 25,388 patients with stable coronary artery disease <ref name="pmid19286090">Trikalinos TA, Alsheikh-Ali AA, Tatsioni A, Nallamothu BK, Kent DM (2009) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19286090 Percutaneous coronary interventions for non-acute coronary artery disease: a quantitative 20-year synopsis and a network meta-analysis.] ''Lancet'' 373 (9667):911-8. [http://dx.doi.org/10.1016/S0140-6736(09)60319-6 DOI:10.1016/S0140-6736(09)60319-6] PMID: [http://pubmed.gov/19286090 19286090]</ref> who were enrolled in 61 randomized trials comparing at least two of the four interventions ([[PTCA]], [[BMS]], [[DES]], and medical therapy) demonstrated no statistically significant difference in the rates of death and [[MI]] among patients treated with either [[PCI]] or medical therapy.

Another recent meta-analysis <ref name="pmid20231568">Wijeysundera HC, Nallamothu BK, Krumholz HM, Tu JV, Ko DT (2010) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=20231568 Meta-analysis: effects of percutaneous coronary intervention versus medical therapy on angina relief.] ''Ann Intern Med'' 152 (6):370-9. [http://dx.doi.org/10.1059/0003-4819-152-6-201003160-00007 DOI:10.1059/0003-4819-152-6-201003160-00007] PMID: [http://pubmed.gov/20231568 20231568]</ref> compared the angina relief in 7,818 patients with stable [[coronary artery disease]] who were enrolled in 14 randomized trials comparing [[PCI]] and  medical therapy alone. Similar to COURAGE, [[PCI]] was associated with greater angina relief than medical therapy (odds ratio, 1.69 [95% CI, 1.24 to 2.30]), particularly in recent trials.

==References==
{{reflist|2}}

[[Category: Disease state]]
[[Category: Ischemic heart diseases]]
[[Category: Cardiology]]
[[category: Emergency medicine]]
[[Category: Intensive care medicine]]