Everolimus Eluting Stents in Patients with Diabetes Mellitus and Chronic Kidney Disease: Insights from the TUXEDO Trial

Cardiovasc Revasc Med. 2019 Dec;20(12):1075-1080. doi: 10.1016/j.carrev.2019.02.017. Epub 2019 Feb 28.

Abstract

Background: Patients with diabetes and those with chronic kidney disease (CKD) are at increased risk of cardiovascular events. Everolimus eluting stents (EES) have been shown to be superior to paclitaxel eluting stents (PES) in patients with diabetes. However, it is not known if EES is as beneficial in diabetic patients with CKD compared with those without CKD.

Methods and results: Patients enrolled in the TUXEDO-India trial, which is a clinical trial of patients with diabetes and coronary artery disease (CAD) randomly assigned to EES vs. thin-strut PES (Taxus Element), with data on baseline renal function were selected. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 using the Cockcroft-Gault formula. Primary outcome was target vessel failure (TVF-defined as cardiac death, TV myocardial infarction (MI) or ischemia driven TV revascularization) at 1 year. Various secondary outcomes including stent thrombosis were evaluated. Among the 1821 patients with diabetes included in this analysis, 344 (19%) had CKD. In a propensity score adjusted analysis, patients with CKD had a significant increase in MACE (HR = 2.02; 95% CI 1.17-3.50; P = 0.01); death/MI/TVR (HR = 1.99; 95% CI 1.18-3.34; P = 0.009); death/MI (HR = 2.31; 95% CI 1.30-4.08; P = 0.004); cardiac death/MI (HR = 2.40; 95% CI 1.31-4.42; P = 0.005); death (HR = 2.88; 95% CI 1.35-6.13; P = 0.006) driven by an increase in cardiac death (HR = 3.33; 95% CI 1.42-7.83; P = 0.006) when compared with those without CKD. However, stent related events (TV-MI, TVR, TLR and stent thrombosis) were not different between CKD and non CKD groups. A significant interaction between CKD status and stent type (EES vs. PES) was noted for the outcomes of TVF (Pinteraction = 0.046), MACE (Pinteraction = 0.02), cardiac death or MI (Pinteraction = 0.05), non-target vessel related MI (Pinteraction = 0.04), non-Q-wave MI (Pinteraction = 0.03) and deaths/MI/TVR (Pinteraction = 0.04) such that EES was superior to PES in the non-CKD cohort but not in the CKD cohort.

Conclusions: In subjects with diabetes, CKD is an independent predictor of adverse cardiovascular outcomes including increased risk of death driven largely by non-stent related events. While EES was superior to PES in patients without CKD, this was not the case in those with CKD (Clinical Trials Registry-India number, CTRI/2011/06/001830).

Keywords: Chronic kidney disease; Diabetes; Everolimus eluting stent; Paclitaxel eluting stent.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Cardiovascular Agents / administration & dosage*
  • Cardiovascular Agents / adverse effects
  • Coronary Artery Disease / complications
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / mortality
  • Coronary Artery Disease / therapy*
  • Coronary Thrombosis / etiology
  • Diabetes Mellitus* / diagnosis
  • Diabetes Mellitus* / mortality
  • Drug-Eluting Stents*
  • Everolimus / administration & dosage*
  • Everolimus / adverse effects
  • Female
  • Glomerular Filtration Rate
  • Humans
  • India
  • Kidney / physiopathology
  • Male
  • Middle Aged
  • Myocardial Infarction / etiology
  • Paclitaxel / administration & dosage*
  • Paclitaxel / adverse effects
  • Percutaneous Coronary Intervention / adverse effects
  • Percutaneous Coronary Intervention / instrumentation*
  • Percutaneous Coronary Intervention / mortality
  • Prosthesis Design
  • Renal Insufficiency, Chronic / complications*
  • Renal Insufficiency, Chronic / diagnosis
  • Renal Insufficiency, Chronic / mortality
  • Renal Insufficiency, Chronic / physiopathology
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Substances

  • Cardiovascular Agents
  • Everolimus
  • Paclitaxel