Download this article's Factoid (PDF & PPT for Gold Subscribers) 

Contrary to findings from randomized trials, revascularization appears to reduce mortality compared with routine medical therapy in ‘real world’ patients with stable ischemic heart disease, according to a large registry study published online March 8, 2014, ahead of print in the Journal of General Internal Medicine. The study also suggests that use of percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) leads to fewer myocardial infarctions (MIs) and less need for subsequent revascularization. 

Investigators led by Harindra C. Wijeysundera, MD, PhD, of Sunnybrook Health Sciences Centre (Toronto, Canada), looked at outcomes of 39,131 patients with stable ischemic heart disease who underwent angiography at 18 hospitals and were enrolled in the Cardiac Care Network of Ontario, Canada, between October 2008 and September 2011. The cohort was stratified into those who received an initial strategy of medical therapy (n = 15,139) or revascularization (n = 15,604 for PCI, n = 8,388 for CABG). The median time to PCI was 0 days, while the median time to CABG was 28 days.

Revascularization Shows Multiple Benefits

Over a median 2.5 years, patients who underwent revascularization had lower rates of mortality, MI, and need for subsequent revascularization compared with those who received medical therapy (table 1).

Table 1. Kaplan-Meier Outcomes^a

^aP < 0.001 for PCI or CABG vs medical therapy, for all outcomes.

In time-varying multivariable models, revascularization was associated with lower risk of death (HR 0.76; 95% CI 0.68-0.84), MI (HR 0.78; 95% CI 0.72-0.85), and repeat PCI/CABG (HR 0.59; 95% CI 0.50-0.70; all P < 0.001) compared with medical therapy. There was an interaction between age and the effect of treatment strategy on mortality (P = 0.0373) with the benefit of revascularization attenuated with advancing age. 

In sensitivity analyses, compared with medical therapy, PCI and CABG consistently reduced the risk of death (HR 0.73 and HR 0.70, respectively) and repeat revascularization (HR 0.90 and HR 0.10, respectively), while only CABG decreased the risk of nonfatal MI (HR 0.42; all P < 0.001).

Analysis of 12,362 pairs of propensity-matched medical therapy and revascularization patients also showed that the invasive strategy reduced mortality (HR 0.75; 95% CI 0.69-0.81), MI (HR 0.84; 95% CI 0.77-0.93), and repeat revascularization (HR 0.67; 95% CI 0.63-0.71; all P < 0.001). 

Similar patterns of benefit were seen when analysis was restricted to patients who survived at least 90 days and to the 4,838 propensity-matched pairs (22.6% of the overall cohort) who would have met the eligibility criteria for the randomized COURAGE trial. 

Results Question ‘Conventional Wisdom’ 

In a telephone interview with TCTMD, Ajay J. Kirtane, MD, SM, of Columbia University Medical Center (New York, NY), called the results provocative. “The unique aspect of this [study] is that it was able to look at all patients who had diagnostic catheterization and then to see what ended up happening with them,” he said. “We are often told that revascularization should not change outcomes for patients with stable ischemic heart disease. But these types of results demonstrate that, lo and behold, there actually is a benefit to revascularization.”

Dr. Kirtane added that even when analysis was restricted to “patients for whom the benefit of revascularization might be less—that is, the COURAGE population—the fact that they still found benefit is pretty interesting.

“I think the take-home message is that we ought to continue to question the conventional wisdom that revascularization is not associated with improvement in outcomes in patients with stable ischemic heart disease,” Dr. Kirtane said. “After all, COURAGE is now 8 years old and did not include [many patients] that we see in [contemporary] clinical practice.”

Moreover, he noted, “This paper is consistent with a lot of data,” including a recent study based on the New York State Registry (Hannan EL, et al Circulation. 2012;125:1870-1879), also suggesting high-risk patients may benefit from revascularization. “We ought to understand that there are data on both sides of the fence,” he concluded.

Registry Yields ‘Interesting Hypothesis’

Sripal Bangalore, MD, of New York University School of Medicine (New York, NY), observed that registries have advantages over clinical trials, such as large sample sizes and the ability to capture real world practices. However, he told TCTMD in a telephone interview, the nonrandomized design makes it “very difficult to answer the question of whether revascularization is better than medical therapy for stable ischemic patients.”

Residual confounding could still play a decisive role in the results, he explained, “because there is a reason why a patient who received an angiogram did not go to the next step of receiving revascularization.” For example, he suggested, a patient may have had diffuse disease that was judged difficult to treat, the anatomy may not have been suitable, or the patient may have been too sick for invasive treatment. “We simply don’t know what the decision process was for not [performing] revascularization,” he said.

With regard to the differences in evidence-based medical therapy received by revascularized compared with medically managed patients seen in the trial, Dr. Bangalore said he was “not fully convinced” that those could account for a difference in mortality and other outcomes. Even in the medical therapy arm, use of cardioprotective drugs was “pretty robust,” he remarked, adding that the absolute difference in medication use between the groups was small. 

However, Dr. Bangalore called the authors’ suggestion that in the real world, receiving revascularization may be a marker for superior overall care including more frequent follow-up and more aggressive lifestyle management, “an interesting hypothesis that needs further exploration.” He agreed with the authors that if it is confirmed, it has important implications for clinical practice and quality improvement efforts.

“This study generates an interesting hypothesis” regarding the benefit of revascularization, Dr. Bangalore concluded. “That is all the more reason, given that the COURAGE and BARI-2D trials were negative and now observational studies are showing opposite results, to do the [randomized] ISCHEMIA and ISCHEMIA-CKD trials to address this question.” Aiming for enrollment of 8,000 patients, ISCHEMIA will be adequately powered, he noted.

Study Details

Over the year after the index angiogram, revascularization patients were more likely than medical therapy patients to receive cardioprotective medications such as beta-blockers and statins (both P < 0.001), while medical therapy patients were more likely to be prescribed anti-ischemic drugs such as calcium channel blockers and long-acting nitrates (both P < 0.001) as well as ACE inhibitors or angiotensin receptor blockers (P = 0.004).

Related Stories:

• Crossover Rate Clouds COURAGE Findings in High Risk, Stable CAD
• Does COURAGE Model for Optimal Medical Therapy Apply to Today’s Practice?
• NY Registry Shows Improved Outcomes with PCI vs. Medical Therapy in Stable Patients