Dissemination and Adoption of Comparative Effectiveness Research Findings When Findings Challenge Current Practices. Study Results

01/01/2013

The primary COURAGE trial results were published in 2007 (see Table 3.1). As an initial management strategy in patients with stable CAD, PCI did not reduce the risk of death, MI, or other major cardiovascular events when added to OMT. These findings reinforced existing practice guidelines, which stated that PCI can be safely deferred in patients with stable CAD, even in those with extensive, multivessel involvement and inducible ischemia, provided intensive, multifaceted OMT is instituted and maintained.

Both treatment groups—those who had PCI and those who did not—had marked improvements in health status during follow-up. The PCI group had small, but significant, lowering of angina prevalence and improved quality of life for about 24 months, but the relative advantage of PCI disappeared by 36 months (Weintraub, Spertus, et al., 2008). A cost-effectiveness analysis using patient-level data from the trial found that the addition of PCI to OMT cost from $168,000 to $300,000 per life-year or quality-adjusted life-year gained and thus offered little value based on standard benchmarks for cost-effectiveness (Weintraub, Boden, et al., 2008). In the trial’s nuclear substudy, patients assigned to the PCI group had a greater reduction in ischemia, and patients with moderate or severe pretreatment ischemia appeared to have better outcomes for the primary end point (death or MI), although the results were not statistically significant.

The COURAGE trial was not alone in suggesting that more-aggressive procedure-based treatment approaches might provide no greater benefit than OMT. The Occluded Artery Trial (OAT) published in 2006 (Hochman, Lamas, et al., 2006) and the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial published in 2009 also suggested that interventional procedures might not be better than OMT (Frye, August, et al., 2009). The OAT trial showed that patients in whom revascularization was attempted 3 to 28 days after MI (traditionally considered beyond the time frame for myocardial salvage) had no better outcomes (and potentially fared worse) than patients who were treated with OMT. In the BARI 2D study, stable CAD patients with diabetes were randomized to cardiac bypass surgery, PCI, and intensive medical therapy, and the authors found no difference in survival or cardiac events between treatments.

An alternative interpretation of the trial results suggested that the nuclear substudy finding suggesting superiority of PCI over OMT among patients with higher levels of baseline ischemia was actually the most important finding, as this result partially confirmed similar findings from observational studies. While the impact of the substudy findings on practice is still unclear, they have the potential to promote better tailoring of PCI use to patients’ underlying risk of future cardiac events.

Table 3.1

Results of the COURAGE Trial

Outcome

Results

Primary Outcome

 

Composite: death from any cause and
nonfatal MI

No difference: 19% (PCI) versus 18.5% (OMT), p = NS.

Secondary Outcomes

 

Composite: death, nonfatal MI, stroke, and hospitalization for unstable angina with negative biomarkers

No difference: 20% (PCI) versus 19.5% (OMT), p = NS.

Hospitalization for ACS

No difference: 12.4% (PCI) versus 11.8% (OMT), p = NS.

MI

No difference: 13.2% (PCI) versus 12.3% (OMT), p = NS.

Stroke

No difference: 2.1% (PCI) versus 1.8% (OMT), p = NS.

Other

 

Additional revascularizationa

21.1% (PCI) versus 32.6% (OMT), p < 0.001.

Percentage angina-free

Higher in the PCI group through 24 months but not statistically different at 36 months (final measurement).

 

 

 

 

Seattle Angina Questionnaire

Physical limitations

Change in angina severity

Frequency of angina

Satisfaction with treatment

Quality of life

Scores improved in both groups; scores were higher in the PCI group from 6 to 24 months for most domains, but by 36 months, the PCI group no longer provided a significant advantage for any domain.

The PCI group had more “clinically significant improvements” in physical function, angina frequency, and quality of life for the first 6 months, but these differences were no longer significant by 12 months.

RAND-36

Physical functioning

Role limitations due to emotional problems

Vitality

Emotional well-being

Social functioning

Pain

General Health

Scores improved in both groups; scores were higher in the PCI group at 3 months for most domains, but after 12 months, PCI provided no significant advantage for any domain.

The PCI group had more “clinically significant improvements” in physical functioning and role limitation due to physical problems at 6 months, but these differences were no longer significant by 12 months.

Sensitivity analysis: effect of crossovers

Patients assigned to the OMT group who crossed over had changes in quality-of-life outcomes similar to those of patients who did not cross over.

Sensitivity analysis: complete cases

328 (PCI) and 303 (OMT) patients had complete data at 36 months; there were no differences in results.

Subgroup analyses (efficacy outcomes)

There were no significant interactions by subgroup.

Subgroup analyses (quality-of-life outcomes)

There was interaction between the treatment and baseline tertile of Seattle Angina Questionnaire scores for the following domains: physical limitation, angina frequency, and quality of life (in favor of PCI).

aRevascularization was performed for angina that was unresponsive to OMT or when there was objective evidence of worsening ischemia on noninvasive testing, at the discretion of the patient’s physician.

View full report

Preview
Download

"rpt_RANDFinal.pdf" (pdf, 2.01Mb)

Note: Documents in PDF format require the Adobe Acrobat Reader®. If you experience problems with PDF documents, please download the latest version of the Reader®