Current evidence on the safety and efficacy of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) procedures from randomized controlled trials (RCTs) may not be representative of real-world patients and should be interpreted with caution, according to a new meta-analysis of data.
The analysis, published online Monday and in the July 25 issue of JACC: Cardiovascular Interventions, noted that enrolling patients in RCTs comparing CTO PCI versus medical therapy has been challenging – especially for highly symptomatic and higher-risk patients.
“This challenge has plagued coronary interventional research and is often reflected in poor enrollment, termination of trials before complete enrolment, and very high screening-to-enrollment ratios,” said the team, led by Michael Megaly, MD, MS, from Henry Ford Hospital, Detroit, noting the potential for subsequent selection bias in RCTs.
“Our study is the first to compare characteristics of patients undergoing CTO PCI in the real world and those randomized in the few CTO PCI RCTs,” they said, noting that few RCTs have compared CTO PCI versus medical therapy, with all performed outside the United States.
“RCT patients have fewer comorbidities with lower risk profiles compared with real-world registries. They also underwent CTO PCI for less complex CTOs compared with those included in dedicated CTO PCI registries,” added the authors, warning that procedural complications of CTO PCI might be under-reported in registries.
Megaly and colleagues evaluated the differences between real-world CTO patients and those enrolled in RCTs through a meta-analysis of national and dedicated CTO PCI registries and compared patient characteristics and outcomes with those of RCTs that randomized patients to CTO PCI versus medical therapy.
The team analyzed data from six published RCTs of CTO PCI versus medical therapy (1,047 patients) and compared the trials with 15 registries: five national registries (110,349 patients) and 10 dedicated CTO PCI registries (76,067).
Given the large sample size differences between RCTs and registries, the study focused on the absolute numbers and their clinical significance, said the authors, adding that a 5% relative difference between groups was considered to be potentially clinically relevant.
Reporting on baseline characteristics of the RCTs and registries, Megaly and colleagues noted that RCT patients were more likely to be men (84.3% vs 76.4% – a relative difference of 9.3%), and tended to have fewer comorbidities, including: diabetes, hypertension, peripheral arterial disease, previous myocardial infarction (MI), previous PCI and previous coronary artery bypass grafting.
The team reported that overall, RCT patients had shorter mean CTO length (29.6 ± 19.7 mm vs 32.6 ± 23.0 mm; relative difference of 9.2%) and lower Japan–Chronic Total Occlusion Score (2.0 ± 1.1 vs 2.3 ± 1.1; relative difference of 13%) compared with those enrolled in dedicated CTO registries.
Furthermore, RCT patients had longer fluoroscopy times and more contrast than patients in national registries.
Procedural success was also found to be significantly lower in national registries compared with RCT patients (63.9% vs 84.5%; relative difference of 24.4%), said the authors, noting that success rates were similar between RCTs and dedicated CTO registries (84.5% vs 81.4%).
However, they noted that RCT patients also had a higher risk of in-hospital events, including death (1.3% vs 0.6%; a relative difference of 52.3%), major adverse cardiac events (7.9% vs 1.5%; a relative difference of 81.0%), MI (5.9% vs 1.0%; a relative difference of 83.1%) and tamponade (0.9% vs 0.3%, a relative difference of 66.7%).
“Decision making in current medical practice should be based on evidence, with RCTs providing the highest-quality data. In certain areas, the evidence from RCTs is limited; hence, leveraging high-quality observational studies is needed to evaluate the impact of treatment strategies,” said Megaly and colleagues.
Writing in an accompanying editorial, Carlo Di Mario, MD, PhD, and Niccolò Ciardetti, MD, from Careggi University Hospital, Florence, Italy, stressed that evidence-based medicine relies on RCT data to approve new drugs, devices and procedures.
The editorialists added that the new analysis “indirectly confirms” the importance of experienced operators using advanced equipment, noting that the procedural success of CTO-PCI in national registries was significantly lower than in dedicated registries (63.9% vs 81.4%), and that although still very low, mortality was twice as high in national registries (0.62% vs 0.30%).
“It is not surprising that the experience of both operators and centers correlates with patients’ outcome, which is the reason why the Global Expert Consensus on CTO PCI recommends that the CTO recanalization procedure should be performed in high-volume centers by dedicated operators,” they said.
“CTO randomized trials and registries offer complementary information if you are able to dive deep into the reasons for their apparent conflicting results, answering different but equally important questions on the clinical usefulness of CTO recanalization.”
Megaly M, Buda K, Mashayekhi K, et al. Comparative Analysis of Patient Characteristics in Chronic Total Occlusion Revascularization Studies: Trials vs Real-World Registries. JACC Cardiovasc Interv 2022;15:1441-1449.
Di Mario C, Ciardetti N. The Ultimate Trial of CTO Recanalization. JACC Cardiovasc Interv 2022;15:1450-1452.
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