Rationale and design of the TUXEDO-2 India study: Ultra-Thin strUt Supraflex Cruz versus XiencE in a Diabetic pOpulation with multi-vessel disease-2.

BACKGROUND: The role of percutaneous coronary interventions (PCI) in patients with diabetes mellitus and multi-vessel disease has been questioned by the results of the FREEDOM trial, which showed superiority of coronary artery bypass graft(CABG) over first generation drug-eluting stents (DES) including a reduction in mortality. In the light of safer and more efficacious stents and significantly better medical management, those results that date back to 2012 need to be revisited. TUXEDO-2 is a study designed to compare two contemporary stents in Indian diabetic patients with multi-vessel disease. AIMS: The primary objective of the TUXEDO-2 study is to compare the clinical outcomes of PCI with ultra-thin Supraflex Cruz vs Xience when combined with contemporary optimal medical therapy (OMT) in diabetic patients with multi-vessel disease. The secondary objective is to compare clinical outcomes between a pooled cohort from both arms of the study (Supraflex Cruz + Xience; PCI arm) vs CABG based on a performance goal derived from the CABG arm of the FREEDOM trial (historical cohort). The tertiary objective is a randomized comparison of ticagrelor vs prasugrel in addition to aspirin for the composite of ischemic and bleeding events. METHODS: In this prospective, open-label, multi-centre, 2 × 2 factorial, randomized, controlled study, 1,800 patients with diabetes mellitus and multi-vessel disease (inclusion criteria similar to FREEDOM trial) with indication for coronary revascularization will be randomly assigned to Supraflex Cruz or Xience stents and also to ticagrelor- or prasugrel- based antiplatelet strategies. All patients will receive guideline directed OMT and optimal PCI including image- and physiology-guided complete revascularization where feasible. The patients will be followed through five years to assess their clinical status and major clinical events. The primary endpoint is a non-inferiority comparison of target lesion failure at one-year for Supraflex Cruz vs Xience (primary objective) with an expected event rate of 11% and a non-inferiority margin of 4.5%. For PCI vs CABG (secondary objective), the primary endpoint is major adverse cardiac events (MACE), defined as a composite of all cause death, nonfatal myocardial infarction, or stroke at one-year and yearly up to five years, with a performance goal of 21.6%. For ticagrelor vs prasugrel (tertiary objective), the primary endpoint is composite of death, myocardial infarction, stroke, and major bleeding as per the Bleeding Academic Research Consortium (BARC) at one-year with expected event rate of 15% and a non-inferiority margin of 5%. CONCLUSIONS: The TUXEDO-2 study is a contemporary study involving state-of-the-art PCI combined with guideline directed OMT in a complex subset of patients with diabetes mellitus and multi-vessel disease. The trial will answer the question as to whether a biodegradable polymer coated ultra-thin Supraflex Cruz stent is an attractive option for PCI in diabetic patients with multi-vessel disease. It will also help address the question whether the results of FREEDOM trial would have been different in the current era of safer and more efficacious stents and modern medical therapy. In addition, the comparative efficacy and safety of ticagrelor vs prasugrel in addition to aspirin will be evaluated. (CTRI/2019/11/022088).

Fractional flow reserve [FFR] guided stenting of left main coronary artery in acute coronary syndrome: A single centre experience.

The present study assesses the clinical outcomes after left main coronary stenting, using clinical evaluation, angiography, and Fractional Flow Reserve (FFR). A prospective observational study was conducted on 72 patients undergoing left main coronary artery (LMCA) stenting, transthoracic echocardiography, coronary angiography, and percutaneous coronary intervention were done and FFR was recorded. At the end of 6 months, follow up check angiography, FFR study were performed. The stent was placed from LMCA to left anterior descending artery (LAD) artery among 45.83% of patients and 9.72% had from LMCA to Left circumflex artery. The mortality rate was 8.33%. The fractional flow reserve was 0.81 on an average ranging from 0.58 to 0.90. Relatively low incidence of major cardiac event was noted among patients with single vessel disease and ostial LMCA disease.

One-year outcomes of a BioMime™ Sirolimus-Eluting Coronary Stent System with a biodegradable polymer in all-comers coronary artery disease patients: The meriT-3 study.

OBJECTIVES: The aim of the merit-3 study was to determine the safety and performance of the BioMime Sirolimus-Eluting Coronary Stent System (SES) in all-comer patients with coronary artery disease (CAD) in one-year clinical follow-up period. METHODS: The meriT-3 was a multi-centre, observational, post-marketing study conducted in 1161 patients with CAD who were implanted with BioMime SES at 15 sites in India. The primary endpoint was major adverse cardiac event (MACE) at one year defined as the composite of cardiac death, myocardial infarction (MI) and target lesion revascularization (TLR). Clinical follow-up was performed at 1, 6, and 12 months. Major adverse cardiac event occurred at 30 days and subsequently at 6 months and at long-term follow-up of 1 year was analyzed. RESULTS: MACE observed at 1 and 6 months follow-up was 16 (1.38%) and 21 (1.83%) respectively. Cumulative 1 year MACE was 26 (2.35%) with 16 (1.39%) all cause death, 4 (0.35%) MI and 6 (0.52%) TLR. In addition, ST was observed in 1 (0.09%) patient. CONCLUSIONS: The present study suggests that the BioMime SES is safe and effective in a "real-world", all-comers CAD patients, indicating low rates of MACE. CTRI ACKNOWLEDGEMENT NO: REF/2016/07/011808.

Clinical performance of biodegradable polymer-coated sirolimus-eluting stents in unselected real-world population with coronary artery disease: results from the multicenter CORE Registry.

BACKGROUND: The main aim of the CORE Registry was to evaluate clinical performance of the Supralimus-Core® biodegradable polymer-coated sirolimus-eluting cobalt-chromium stent (Sahajanand Medical technologies Pvt. Ltd., Surat, India) in unselected real-world patients. METHODS: This was a multicenter, retrospective, non-randomized, single-arm study. A total of 376 consecutive patients treated with the Supralimus-Core® between April 2010 and June 2014 were enrolled. The primary-end point of the registry was major adverse cardiac events (MACE), which is a composite of cardiac death, target lesion revascularization (TLR), target vessel revascularization (TVR), myocardial infarction (MI) and stent thrombosis (ST). Clinical follow-up were scheduled at 30-day and 6-month. RESULTS: The mean age of enrolled patients was 54.6±10.3 years. A total of 444 lesions were treated successfully with 457 stents (1.0±0.2 per lesion). The average stent length and diameter was 24.0±8.0 mm and 3.0±0.33 mm, respectively. Out of total patients, 300 (79.8%) were male. Diabetes, hypertension and chronic totally occluded lesions were found in 95 (25.3%), 102 (27.1%) and 125 (28.2%) patients, respectively, reflecting high-risk patients involvement. The incidence of MACE at 30-day and 6-month was found to be in 4 (1.1 %) and 4 (1.1%) patients, respectively. The TLR and ST was found in 1 (0.3 %) and 1 (0.3 %) patient respectively at 6-month follow-up. CONCLUSIONS: The lower incidence of MACE, TLR and ST clearly delineates safety and efficacy of Supralimus-Core sirolimus-eluting stent in "real-world" patients with complex coronary lesions.

Paclitaxel-Eluting versus Everolimus-Eluting Coronary Stents in Diabetes.

BACKGROUND: The choice of drug-eluting stent in the treatment of patients with diabetes mellitus and coronary artery disease who are undergoing percutaneous coronary intervention (PCI) has been debated. Previous studies comparing paclitaxel-eluting stents with stents eluting rapamycin (now called sirolimus) or its analogues (everolimus or zotarolimus) have produced contradictory results, ranging from equivalence between stent types to superiority of everolimus-eluting stents. METHODS: We randomly assigned 1830 patients with diabetes mellitus and coronary artery disease who were undergoing PCI to receive either a paclitaxel-eluting stent or an everolimus-eluting stent. We used a noninferiority trial design with a noninferiority margin of 4 percentage points for the upper boundary of the 95% confidence interval of the risk difference. The primary end point was target-vessel failure, which was defined as a composite of cardiac death, target-vessel myocardial infarction, or ischemia-driven target-vessel revascularization at the 1-year follow-up. RESULTS: At 1 year, paclitaxel-eluting stents did not meet the criterion for noninferiority to everolimus-eluting stents with respect to the primary end point (rate of target-vessel failure, 5.6% vs. 2.9%; risk difference, 2.7 percentage points [95% confidence interval, 0.8 to 4.5]; relative risk, 1.89 [95% confidence interval, 1.20 to 2.99]; P=0.38 for noninferiority). There was a significantly higher 1-year rate in the paclitaxel-eluting stent group than in the everolimus-eluting stent group of target-vessel failure (P=0.005), spontaneous myocardial infarction (3.2% vs. 1.2%, P=0.004), stent thrombosis (2.1% vs. 0.4%, P=0.002), target-vessel revascularization (3.4% vs. 1.2%, P=0.002), and target-lesion revascularization (3.4% vs. 1.2%, P=0.002). CONCLUSIONS: In patients with diabetes mellitus and coronary artery disease undergoing PCI, paclitaxel-eluting stents were not shown to be noninferior to everolimus-eluting stents, and they resulted in higher rates of target-vessel failure, myocardial infarction, stent thrombosis, and target-vessel revascularization at 1 year. (Funded by Boston Scientific; TUXEDO-India Clinical Trials Registry-India number, CTRI/2011/06/001830).

Impact of catalytic iron on mortality in patients with acute coronary syndrome exposed to iodinated radiocontrast-The Iscom Study.

BACKGROUND: Catalytic iron (CI) mediates vascular injury by generating reactive oxygen species. We evaluated role of CI in predicting mortality in patients with acute coronary syndrome (ACS) and studied association of contrast nephropathy with CI levels. METHODS: We investigated 806 patients with ACS undergoing contrast exposure for a cardiac procedure who were followed up for 30 days. RESULTS: Overall mortality was 1.6% at 30 days. Catalytic iron at baseline predicted mortality with CI levels significantly higher in those who died, 0.45 µmol/L (0.37, 0.68) compared with survivors 0.31 µmol/L (0.21, 0.40); P = .004. Catalytic iron was associated with increased risk of death in the highest quartile compared with lower 3 quartiles (hazard ratio 7.88, P = .001) after adjustment for age, diabetes, ST deviation, Killip class, ejection fraction, baseline creatinine, hemoglobin level, and troponin. Fifty-five patients (6.8%) developed contrast nephropathy. Patients with contrast nephropathy had a 27% increase in median CI levels from baseline up to 48 hours compared with a marginal 2.9% increase in those without contrast nephropathy (0.37, 0.14 µmol/L to 0.47, 0.20 µmol/L versus 0.35, 0.12 µmol/L to 0.36, 0.14 µmol/L, P < .0001). Patients with contrast nephropathy had significantly higher mortality compared with those without contrast nephropathy (9.1% vs 1.1%, P = .001). CONCLUSION: High baseline CI levels predicted mortality in patients with ACS. Occurrence of contrast nephropathy was associated with rise in CI levels and higher mortality. Therapeutic options to buffer or chelate CI may have beneficial effects on mortality in this setting.

Systemic exposure of sirolimus after coronary stent implantation in patients with de novo coronary lesions: Supralimus-Core® pharmacokinetic study.

OBJECTIVES: This study was conducted to assess the systemic drug release and distribution of sirolimus-eluting coronary stents. METHODS: Twenty patients with coronary artery disease (CAD) were treated with 1, 2, or 3 a newly designed metallic stents. Blood samples were drawn at 14 time points to determine the pharmacokinetic of sirolimus. Whole blood concentrations of sirolimus were determined by using a sensitive validated high-performance liquid chromatography mass spectrometry/mass spectrometry method. RESULTS: Minimal measurable blood levels were detectable at 7 days. Across all dose levels, individual T(max) values ranged from 1.00 hour and 12.00 hours; individual C(max) ranged from 0.73 ng/mL and 4.13 ng/mL. CONCLUSION: This study confirms the limited exposure of the systemic circulation of the eluted drug with the use of the Supralimus-Core® Sirolimus-Eluting Coronary Stent System (Sahajanand Medical Technologies Pvt. Ltd., Surat, India). In this study, sirolimus concentration in systemic circulation is to be safe, well-tolerated and short-lived.