10.1 Latest Techniques and Devices for CTO Intervention: Will They Expand Indications?

These proceedings summarize the educational activity of the 16th Biennial Meeting of the International Andreas Gruentzig Society held January 31-February 3, 2022 in Punta Cana, Dominican Republic

Faculty Disclosures     Vendor Acknowledgments

2022 IAGS Summary Document

Statement of the problem or issue

In the latest ACC/AHA/SCAI guidelines, percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) was downgraded from a Class IIa to Class IIb recommendation, based on poorly executed clinical trials.¹ On the other hand, it is admittedly difficult to conduct large randomized clinical trials (RCTs) for CTO-PCI to inform our guidelines appropriately.

Gaps in our knowledge

Most large RCTs comparing PCI vs medical therapy either excluded patients with CTO, or the CTO was frequently left unrevascularized. The largest 2 randomized clinical trials of CTO-PCI vs medical therapy, DECISION-CTO and EUROCTO, both suffered from slow enrollment and failed to enroll the prespecified number of patients.^2,3 Furthermore, in addition, there is a lack of information about the impact of successful CTO-PCI on the long-term outcomes of patients in several specific settings of interest: post STEMI, patients with acute coronary syndromes (NSTEMI/unstable angina), patients with left main (LMCA) disease, and patients with low left ventricular ejection fraction (LVEF). The role of CTO-PCI in achieving complete revascularization has not been investigated in an RCT.

The decision to downgrade the recommendation for CTO-PCI in the latest ACC/AHA/SCAI guidelines was heavily based on the DECISION-CTO trial.² The primary endpoint of DECISION-CTO was a composite of death, myocardial infarction, stroke, or any revascularization. Health-related quality of life (QoL) was assessed at baseline and at 1, 6, 12, 24, and 36 months. The intention-to-treat analysis of DECISION-CTO showed no reduction in the primary endpoint at 4 years in the group that received CTO-PCI vs the group that received medical therapy (22.3% vs 22.4%; HR, 1.03; 95% CI, 0.77-1.37; P=.86). Both the CTO-PCI and no-CTO-PCI strategies were associated with significant improvements in health-related QoL indices, but without between-group differences sustained through 36 months. The DECISION-CTO trial suffered from multiple design flaws. First, because the study did not enroll the targeted number of patients the statistical power was reduced to only 64%. Secondly, 20% of patients assigned to the medical therapy arm crossed over to the CTO-PCI arm within 3 days of randomization. The slow enrollment in the trial indicates that investigators did not enroll highly symptomatic patients; in fact, 13%-14% of the enrolled patients were asymptomatic and had “silent ischemia.” Most importantly, the DECISION-CTO trial did not isolate the effect of a CTO on the patients’ QoL because two-thirds of the patients who were randomized to medical therapy received PCI of non-CTO coronary lesions. In reality, DECISION-CTO compared revascularization of all non-CTO lesions plus medical therapy (an incomplete revascularization strategy) to complete revascularization plus medical therapy (ie, a complete revascularization strategy). The results of DECISION-CTO do not reliably add to our knowledge about CTO-PCI effects on hard endpoints and health-related QoL measures.

The EUROCTO trial showed different outcomes than DECISION-CTO, because it randomized patients to CTO-PCI vs optimal medical therapy (OMT) alone, only if they continued to have angina after both OMT and revascularization of all non-CTO lesions was achieved.³ The primary endpoint was the change in health status QoL assessed by the Seattle angina questionnaire (SAQ) between baseline and 12-month follow-up. This trial showed significant improvement in the QoL (SAQ) in the CTO-PCI arm compared with the OMT arm. However, clinical adverse events (major cardiovascular and cerebrovascular adverse events; MACCE) were no different between the 2 groups at 12 months (6.7% vs 5.2%; P=0.55). This trial also suffered from slow enrollment and had to be stopped early; however, this trial retained better statistical power than the DECISION-CTO trial.

Possible solutions and future directions

CTO-PCI continues to be technically challenging, perceived as high risk, and understudied in RCTs comparing revascularization vs medical therapy. CTO-PCI has been shown to improve QoL in real-world registries, while only 3 relatively small randomized trials demonstrated a QoL improvement after CTO-PCI.^3–5 The difference between registries of CTO-PCI and clinical trials might be explained by an inherent bias to only enroll less symptomatic and lower-risk patients in the clinical trials, which will bias the outcomes of the trials toward the null hypothesis. In addition to this bias against randomizing severely symptomatic patients, several other barriers prevent conducting a large RCT to investigate efficacy and safety of CTO-PCI. First, CTO-PCI is technically challenging, with high failure rates outside of expert centers, which if these non-expert centers participate will bias the results toward the null hypothesis in any intention-to-treat analysis. Secondly, because of generally low adverse clinical event rates, a large number of patients need to be enrolled to achieve sufficient statistical power. This can be challenging too. Finally, only a few expert PCI operators can achieve high success and safety rates with CTOs. As a result of all these factors, a meaningful CTO-PCI trial will be costly and very slow to enroll the required number of patients. Despite these difficulties, a sham-controlled CTO-PCI trial will be necessary to demonstrate the real effect of CTO-PCI on QoL in patients who are highly symptomatic at baseline.

References

1. Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI Guideline for coronary artery revascularization: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022;79(2):e21-e129. Epub 2021 Dec 9. doi:10.1016/j.jacc.2021.09.006

2. Lee SW, Lee PH, Ahn JM, et al. Randomized trial evaluating percutaneous coronary Intervention for the treatment of chronic total occlusion. Circulation. 2019;139:1674-1683. doi:10.1161/CIRCULATIONAHA.118.031313

3. Werner GS, Martin-Yuste V, Hildick-Smith D, et al. A randomized multicentre trial to compare revascularization with optimal medical therapy for the treatment of chronic total coronary occlusions. Eur Heart J. 2018;39(26):2484-2493. doi:10.1093/eurheartj/ehy220

4. Obedinskiy AA, Kretov EI, Boukhris M, et al. The IMPACTOR-CTO trial. JACC Cardiovasc Interv. 2018;11(13):1309-1311. doi:10.1016/j.jcin.2018.04.017

5. Badoian AG, Krestyaninov OV, Khelimskii DA, Ibragimov RU, Naydenov RA. Predictors to quality of life improvements in patients with chronic coronary total occlusion depending on the selected treatment strategy. Comp Iss Cardiovasc Dis. 2021;10(2):72-83. doi:10.17802/2306-1278-2021-10-2-72-83