New Analysis Fails to Find Link Between Successful CTO PCI and Lower Mortality

Adding to an already inconsistent body of evidence, a new Korean analysis shows that successful recanalization of a chronic total occlusion (CTO) using DES is not associated with a reduction in long-term mortality. Failed interventions are, however, tied to substantially higher rates of subsequent TVR and CABG, which might explain the lack of a mortality difference.

Prior studies have shown that successful CTO PCI is related to improved symptoms, better LV function, and less need for CABG, but results have been conflicting for survival, note lead authors Pil Hyung Lee, MD, and Seung-Whan Lee, MD, PhD (Asan Medical Center, Seoul, South Korea), and colleagues.

The lack of high-quality data has left the issue of whether to intervene on CTOs up for debate, they say.

“Following the continuous improvement in procedural techniques, coronary stent systems, and optimal medical therapy in coronary artery disease, reassessment of the effect of the success or failure of CTO PCI in a population with a relatively high success rate of contemporary stent treatment is essential,” they write.

Commenting on the study, Gerald Werner, MD (Klinikum Darmstadt, Germany), told TCTMD in an email that it is at odds with prior analyses, including a UK study with more than 13,000 patients, showing lower mortality with successful CTO PCI.

Asked why the current report does not show a lower mortality rate with successful recanalization, he pointed to the single-center design, the small sample size, and the high rate of CABG in the patients with failed PCI. If those patients underwent surgery, he said, “then revascularization was achieved anyway.”

J. Aaron Grantham, MD (Saint Luke’s Health System, Kansas City, MO), told TCTMD in an email that observational studies like the current one “do nothing to add clarity to the controversy” about the mortality effect of CTO PCI.

“The results of these types of studies are at best hypothesis-generating and do not contribute anything to our knowledge of the best practice for patients with asymptomatic CTOs—ie, those patients whose only potential benefit would be survival,” he said.

Ultimately, Grantham said, there are two main goals of performing CTO PCI: to extend life and to improve quality of life.

“Whether or not successful CTO PCI can provide the former [benefit] will be debated for decades to come, since properly designed RCTs are not yet underway,” he said. On the other hand, “there is no doubt that successful CTO PCI can improve the quality of life for patients with this common clinical problem.”

Additionally, he said, “the avoidance of CABG, cardiac transplantation, and defibrillator devices, improvements in LV function, and cost savings of care have all been shown to be potential benefits of CTO PCI.”

Single-Center Study

The current study, published online March 2, 2016, ahead of print in JACC: Cardiovascular Interventions, included 1,173 patients with a CTO in a native coronary vessel requiring PCI between March 2003 and May 2014 at Asan Medical Center. All of the successful interventions (85.6% of cases) included DES implantation.

Complications were relatively rate. Coronary perforation occurred in two patients in the successful group and five in the failed group (P = 0.001). There were no cases of in-hospital death, but emergency CABG was required on the same day as the index procedure in four patients who had failed recanalization.

The patients were followed for a median of 4.6 years, and during that time there was no difference in the rate of all-cause mortality between patients undergoing successful versus failed procedures (8.0% vs 7.1%; adjusted HR 1.04; 95% CI 0.53-2.04). Similarly, the groups did not differ on a composite of death or Q-wave MI, cardiac death, Q-wave MI alone, or stroke.

Successful PCI was associated with lower risks of TVR, CABG, and any coronary revascularization.

In a landmark analysis starting 6 months after the procedures, there was no longer a difference between groups in TVR, although patients with failed interventions were still more likely to undergo CABG.

Why No Mortality Reduction?

The study authors propose multiple explanations as to why successful recanalization was not associated with lower mortality, including both the low rate of serious complications and the high rate of CABG in the failed PCI group.

“Patients referred to an elective CABG following failed PCI can be considered as a ‘treated’ group, and analyses conducted with these patients in the failed PCI group may attenuate the possible long-term mortality benefit of patients in the successful PCI group,” they note.

It is also possible that the revascularization strategy used for non-CTO vessels influenced the results, they say. “Considering that the function of collateral circulation is proportional to donor epicardial artery patency, maintaining patency of non-CTO vessels may have a prognostic impact via maintenance of myocardial perfusion at both non-CTO and CTO artery-related territories,” they write, noting that in patients who underwent complete revascularization in the current study, outcomes did not differ based on the success of PCI. “Thus, if feasible, strategies to achieve patency of non-CTO vessels may be necessary, even in patients with failed CTO-PCI.”

In an accompanying editorial, George Vetrovec, MD (Virginia Commonwealth University; Richmond), points to the high success rate for CTO PCI and the high rate of early surgical revascularization in the failed group to explain the lack of a mortality difference between groups.

“The smaller size of the failed PCI group leads to a contracted population size in the failure group in comparison to the much larger success group, potentially confounding a comparative analysis,” he writes.

As for the surgical revascularization, “one supposes CABG was performed in either the most symptomatic patients or those with the greatest potential for ischemia. If this supposition is correct, this fact could help explain apparent discordant results compared to other CTO PCI studies showing better outcomes for successful CTO patients,” he writes.

“Importantly, greater revascularization regardless of PCI or CABG is consistent with the growing emphasis on the importance of complete revascularization, likely achieved in this study by effective use of adjunctive CABG in the failed PCI group,” he continues. “While Lee’s study does not completely answer the question of the importance of eliminating ischemia, greater completeness of revascularization increased by CABG for failed CTO PCI would be in keeping with the growing emphasis on the importance of complete revascularization.”

Definitive Studies Needed

Vetrovec says that more conclusive studies are needed. “Given the expense, risk, and management issues related to CTO PCI in optimal coronary disease management, continued retrospective comparative trials of successful vs unsuccessful CTO PCI seem unlikely to define the value of this technology,” he writes. “It appears time to seriously initiate plans for a randomized trial.”

The study authors agree that “further well-designed studies are required to define optimal treatment strategies for these patients,” pointing out that some physicians have advocated for using medical therapy alone for CTOs.

They note that the DECISION-CTO trial, a randomized comparison of optimal medical therapy and PCI with DES in patients with CTOs, is underway. Werner pointed out that the EuroCTO trial, which has a similar design, is also currently recruiting patients.

Referring to the DECISION-CTO trial, however, Grantham said “the enrollment has been disappointingly slow, the trial is a noninferiority design, and the techniques and success rates for CTO PCI have changed dramatically since the initiation of the trial [so] one wonders what relevance it will have if it is ever completed.”

Moving forward, there remains a need to define success rates, safety, benefits, and cost-effectiveness of CTO PCI in the contemporary era, he said.

“We are in need of an audited, events adjudicated, core lab-adjudicated registry using a single systematic approach to describe the true rates of procedure-related complications so that we can accurately inform our patients as to the risks of the procedure and determine the sample sizes needed for a rigorous RCT,” Grantham said.

He noted that just such a registry—the 1,000-patient OPEN-CTO registry, for which he is the principal investigator—completed enrollment on July 22, with first reports out of the study nearing submission.

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Sources: 
1. Lee PH, Lee S-W, Park H-S, et al. Successful recanalization of native coronary chronic total occlusion is not associated with improved long-term survival. J Am Coll Cardiol Intv. 2016;Epub ahead of print.
2. Vetrovec GW. Chronic total occlusion PCI: is this the ultimate test of the important of complete revascularization? J Am Coll Cardiol Intv. 2016;Epub ahead of print.

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