#5647 EFFECT OF STATINS ON THE INCIDENCE OF CARDIOVASCULAR EVENTS AFTER KIDNEY TRANSPLANTATION
Authors: Batteux Benjamin , Nazoiri Charifa , Brazier François , Nowak Alban , Benis Youssef , Laville Solene , Bodeau Sandra , Gras-Champel Valérie , Masmoudi Kamel , Choukroun Gabriel , Liabeuf Sophie 
Published: June 2023

Abstract

Background and Aims
Based on intervention thresholds [1], statins are recommended in kidney transplant recipients (KTRs) who are at high risk for major cardiovascular (CV) events. However, in this population, evidence of statin effectiveness is sparse and non-conclusive. The objective of this study is to assess the effect of statins on CV events in KTRs.

Method
613 consecutive KTRs from a single-center cohort were retrospectively included between 2006 and 2019. Exposure to statins (indicated in primary or secondary CV prevention) and atherosclerotic CV events during the study period were comprehensively documented. The primary outcome was the incidence of CV events in all statin users compared to that of non-users, based on the Cardiovascular and Stroke Endpoint Definitions for Clinical Trials [2]. In this study, only atherosclerotic events were selected (peripheral vascular stenosis, stroke, myocardial infarction, angina pectoris and transitional ischemic attack). The secondary outcomes were the incidence of CV events (i) in KTRs using statins indicated in primary CV prevention and (ii) in KTRs using statins indicated in secondary CV prevention compared to that of non-users. Cox proportional hazard models including statin exposure as a time-dependent covariate and fitted with inverse probability treatment weighting (IPTW) were used, as well as a multivariable Cox proportional hazard model.

Results
During a median [interquartile range (IQR)] follow-up period of 4.6 [2.7–10.0] years, CV events occurred in 88 KTRs: 48 (55.5%) KTRs had peripheral vascular stenosis, 24 (27.3%) had myocardial infarction, 12 (13.6%) had stroke, three (3.5%) had angina pectoris and one (1.1%) had a transitional ischemic attack. The incidence of CV events was 24.8 per 1000 person-years. In the Cox models fitted with IPTW, exposure to statins, regardless of the indication or indicated in primary and secondary CV prevention, was not associated with a decrease in CV events: Hazard Ratio (HR) [95% confidence interval (CI)]: 1.22 [0.73–2.03] (P = .435), HR: 1.12 [0.66–1.89] (P = .672), and HR: 2.78 [1.19–6.53] (P = .018), respectively. In the multivariable Cox model, diabetes mellitus was strongly associated with CV events (HR: 4.39 [2.79–6.90], p&lt;0.001), and statin exposure was not (HR: 1.25 [0.78–2.03]). In a subgroup of KTRs exposed to statins after kidney transplantation but not before (n=314), the median [IQR] levels of LDL-c was 3.48 [2.89–4.08] mmol/L when starting statins and 2.74 [2.14–3.35] mmol/L after one year of statin exposure, i.e. a significant decrease of 0.74 [0.60–0.85] mmol/L (p&lt;0.001). The median [IQR] levels of triglyceride was 1.99 [1.47–2.91] mmol/L when starting statins and 1.72 [1.20–2.50] mmol/L after one year of statin exposure, i.e. a significant decrease of 0.27 [0.17–0.42] mmol/l (p&lt;0.001). There were no significant changes in HDL-c levels.

Conclusion
Despite an improvement in the lipid profile including a reduction of LDL-c and triglyceride levels, statin exposure was not associated with a decrease in CV events in a long-term KTR cohort. Other CV risk factors than dyslipidemia, such as diabetes mellitus, were more likely related to such events.