‘Complete’ PCI Linked to Lower Mortality in Stable, Multivessel CAD: Registry

In stable patients with multivessel coronary disease, complete revascularization with PCI is associated with better long-term outcomes compared with a more-selective intervention, a Canadian registry study shows.

Patients who had all significant lesions treated during the index procedure were less likely to die (6.2% vs 10.7%) or to undergo repeat revascularization (12.7% vs 18.4%) through 5 years of follow-up compared with those who received incomplete revascularization, according to researchers led by M. Bilal Iqbal, MD, PhD (Victoria Heart Institute Foundation, Canada).

The findings, recently published online in Catheterization & Cardiovascular Interventions, were consistent in an analysis that accounted for patients who might have received complete revascularization in a staged fashion.

Moreover, the study might provide some insight into what was seen in the ISCHEMIA trial, which showed that an invasive strategy did not reduce the risk of major CV events compared with optimal medical therapy alone in patients who had stable, moderate-to-severe CAD. In the current analysis, complete revascularization was associated with a lower rate of 5-year mortality in higher-risk patients who would not have qualified for the ISCHEMIA trial, but this was not seen in an ISCHEMIA-like cohort.

“Our study indicates that in the real world, some of the stable patients are much higher risk, and in those higher-risk stable patients, there may be a benefit of complete revascularization,” Iqbal told TCTMD, acknowledging that the findings should be considered hypothesis-generating. “These data should be interpreted in that context,” he said.

Stefan James, MD, PhD (Uppsala University Hospital, Sweden), agreed, pointing to the possibility of bias introduced by unmeasured confounding. But, he said, considering the more-robust randomized evidence supporting multivessel PCI in the setting of ACS, “it’s reasonable to believe that their findings are true: that for stable patients it is of importance to achieve complete revascularization.”

Questions About Multivessel PCI in Stable Disease

More than half of patients undergoing PCI have multivessel disease, which is known to be associated with worse clinical outcomes in both stable and ACS populations. Although there are limited randomized data addressing the impact of complete revascularization with PCI in non-ACS cohorts, some evidence suggests that it would be of benefit, Iqbal said, pointing to analyses from the MASS II and SYNTAX trials and a recent network meta-analysis.

The release of the ISCHEMIA results renewed the heated debate over whether PCI in general has a prognostic benefit in patients with stable coronary disease, but the trial did not specifically address questions around the potential utility of complete revascularization.

The current analysis was based on real-world data from the British Columbia Cardiac Registry, which collects information from all five tertiary cardiac centers in the province. It included 8,436 patients (mean age 68 years; 21.2% women) who had stable multivessel disease and underwent PCI between 2008 and 2015; 16.6% underwent complete revascularization during the index procedure.

It’s reasonable to believe that their findings are true: that for stable patients it is of importance to achieve complete revascularization. Stefan James

On multivariate adjustment, complete versus incomplete revascularization was associated with lower 5-year risks of all-cause mortality (HR 0.73; 95% CI 0.58-0.91) and repeat revascularization (HR 0.78; 95% CI 0.66-0.93), with similar findings in propensity-score-adjusted analyses and in a sensitivity analysis that excluded patients with subsequent repeat revascularization to address potential confounding due to staged procedures.

In subgroup analyses, the presence of renal disease significantly influenced the mortality results (P = 0.007 for interaction), such that complete revascularization was associated with a benefit in patients with normal kidney function but not in those with renal disease. That’s not surprising “given their susceptibility [to] deterioration in renal function following greater contrast load,” the investigators say in their paper.

James noted that renal disease is a good proxy for arterial calcification, so this finding, which he called hypothesis-generating, “may suggest that for patients with severe calcifications or complex disease, there may be an increased risk associated with multivessel PCI, because if the lesions are too complex you may add risk of complications.”

Reconciling With ISCHEMIA

At first glance, the findings appear to conflict with those of the ISCHEMIA trial, although Iqbal argues the two studies are in harmony. The ISCHEMIA trial had a selected patient population, excluding patients with severe LV dysfunction, renal disease, and higher levels of angina and heart failure symptoms. In contrast, the risk level was higher in the real-world registry population, reflected in a higher 5-year mortality rate (10% vs 6.4%).

In the registry, only 56% of the patients would have been eligible for the ISCHEMIA trial, with the rest being too high-risk. Among ISCHEMIA-like registry patients, 5-year mortality did not differ between the complete and incomplete revascularization groups (4.7% vs 5.9%; P = 0.196). In the higher-risk patients who would not have been eligible for ISCHEMIA, however, complete revascularization was associated with less mortality (8.7% vs 16.6%; P < 0.001).

“Therefore, our findings confirm and support the results from the ISCEHMIA trial, but also indicate that some higher-risk patients with stable angina may derive prognostic benefit from complete revascularization,” Iqbal et al write.

Both Iqbal and James agreed that a dedicated randomized trial would be needed to definitively assess the utility of complete revascularization with PCI in stable patients. Such a trial would be challenging, Iqbal said, because enrolling a higher-risk cohort of stable patients would increase the likelihood of crossover between arms that would muddy interpretation of the results.

James pointed out, too, that it’s more difficult to identify the lesion causing symptoms in patients with stable disease than to pinpoint the culprit lesion in ACS patients, which would complicate a trial comparing complete versus incomplete revascularization in a stable cohort.

For now, the registry study provides “a good hypothesis-generating finding perhaps suggesting that if it’s possible without an excessive risk to doing the additional PCI, it may be [favorable] to the patients to try to do that,” James said.

Iqbal’s takeaway was that “in lower-risk stable patients, there’s a clear role for medical therapy,” with no difference in long-term mortality between treatment groups. “However, in the higher-risk cohort of stable patients,” he said, “there may be prognostic benefit with complete revascularization.”