OPTIMIZE IDE: A randomized trial of a novel, ultra low profile fixed-wire DES
Reported from the TCT Congress 2020
At TCT Connect 2020, Late-Breaking Trial Session IV, the primary results of the OPTIMIZE IDE were presented by Dean J. Kereiakes. Daniele Giacoppo provides a summary of the trial.
Objective
The OPTIMIZE IDE trial sought to prove the noninferiority of a novel sirolimus-eluting stent (Svelte) compared to validated everolimus-eluting stents (XIENCE or Promus).
The methodology
The OPTIMIZE IDE is a prospective, single-blind, noninferiority, randomised clinical trial in which 1629 patients with coronary artery disease were assigned to the Svelte drug-eluting stent or the XIENCE/Promus drug-eluting stent at 74 centres across United States, Europe, and Japan.
The Svelte is a novel, thin-strut, ultra-low profile, cobalt chromium, bioresorbable-polymer, sirolimus-eluting stent. The device is primarily available as premounted on a fixed-wire integrated delivery system developed with the aim to facilitate a systematic transradial direct stenting. The XIENCE and Promus are validated durable-polymer, everolimus-eluting stents.
Key inclusion criteria were the following: de novo native-vessel coronary disease, ≥50% to <100% stenoses with Thrombolysis in Myocardial Infarction flow >1 of which 50-70% stenoses had to be physiologically assessed, up to 2 lesions in a single vessel and up to 3 lesions in 2 target vessels, maximum lesion length ≤34 mm, reference vessel diameter ≥2.25 mm and ≤4.00 mm. Left main stenosis and ST-segment elevation myocardial infarction were among key exclusion criteria.
The primary endpoint was 12-month target lesion failure, defined as a composite of cardiac death, target vessel myocardial infarction, or clinically-driven target lesion revascularisation. The primary hypothesis was the noninferiority of the Svelte drug-eluting stent compared to the XIENCE/Promus drug-eluting stent.
What were the results?
A total of 827 patients (1018 lesions) were assigned to the Svelte drug-eluting stent and 812 patients (970 lesions) to the XIENCE/Promus drug-eluting stent. Baseline clinical characteristics were well balanced. Patients enrolled in the trial had mean age of approximately 65 years, were prevalently men (about 72%), suffering from diabetes in about 30%, and admitted for acute coronary syndrome in more than half of cases. Angiographic characteristics showed longer lesions and more frequent treatment of 3 lesions in the Svelte drug-eluting stent group, thought more than three quarters of patients received treatment for single-lesion coronary artery disease. Direct stenting was performed in about 30% of patients and device success was observed in approximately 96%.
At 12 months, the primary intention-to-treat analysis with respect to the primary endpoint of target lesion failure showed that the Svelte drug-eluting stent did not result noninferior to the XIENCE/Promus drug-eluting stent (10.3% vs. 9.5%, pnoninferiority=0.034 with 1-sided p value of 0.025 required to prove noninferiority); the prespecified absolute noninferiority margin was 3.58%, while the observed upper confidence limit was 3.8%.
No significant differences between stents were observed in terms of cardiac death (0.3% vs. 0.3%, p>0.99), target vessel myocardial infarction (9.3% vs. 8.2%, p=0.48) and clinically-indicated target lesion revascularization (1.5% vs. 1.9%, p=0.57).
However, target vessel myocardial infarction was unexpectedly high in both groups (8.8%) and predominantly periprocedural (90%). This finding was primarily driven by the use high-sensitivity troponin and resulted to be associated with concomitant electrocardiographic changes only in 3.8% of patients. Sensitivity analyses showed that by using a relative noninferiority margin of 1.55 or defining target vessel myocardial infarction according to the Society for Cardiovascular Angiography and Interventions, the Svelte drug-eluting stent was noninferior to the XIENCE/Promus drug-eluting stent.
Stent thrombosis was comparably low between the Svelte and XIENCE / Promus groups (0.4% vs. 0.5%, p=0.72).
My take on this study
The OPTIMIZE IDE trials did not formally prove that the Svelte drug-eluting stent is noninferior to the XIENCE/Promus drug-eluting stent. The appealing design of the Svelte drug-eluting stent facilitating a minimalistic radial approach and a direct stenting-based percutaneous revascularization did not accrue enough supporting evidence against validated, conventional-strut, durable-polymer, drug-eluting stents. This finding highlights the excellent levels of performance and biocompatibility of contemporary device technology and the reduced margin for further advances. In addition, the Svelte drug-eluting stent was tested overall in low-complexity patterns of coronary artery disease and ordinary clinical conditions. The use of a direct stenting-based percutaneous revascularization in more complex clinical scenarios and coronary artery disease patterns would be likely unfeasible.
On the other hand, the results of the OPTIMIZE IDE trial were undoubtedly influenced by the original statistical assumptions and the substantial incidences of target vessel myocardial infarction observed in both treatment groups. Indeed, the higher than expected rates of target vessel myocardial infarction translated into target lesion failure rates nearly double than originally assumed when the trial was designed. The incidences of target lesion failure observed in the OPTIMIZE IDE trial would have required a 3-fold increase of the sample size to ensure a meaningful statistical analysis.
These findings add fuel to the fire in the debate surrounding the definition of periprocedural myocardial infarction in contemporary myocardial revascularization and provocatively indicate the possible consequences of using restrictive thresholds in the era of high-sensitivity troponin. Further analysis to identify a reasonable definition of periprocedural myocardial infarction for percutaneous coronary interventions and coronary artery bypass grafting and delineate the real prognostic implications across the different proposed thresholds is highly advocated.
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