PMID- 36890643 OWN - NLM STAT- MEDLINE DCOM- 20230602 LR - 20240201 IS - 1533-3450 (Electronic) IS - 1046-6673 (Print) IS - 1046-6673 (Linking) VI - 34 IP - 6 DP - 2023 Jun 1 TI - Statins in Kidney Transplant Recipients: Usage, All-Cause Mortality, and Interactions with Maintenance Immunosuppressive Agents. PG - 1069-1077 LID - 10.1681/ASN.0000000000000112 [doi] AB - SIGNIFICANCE STATEMENT: Cardiovascular diseases account for 32% of deaths among kidney transplant recipients. Statin therapy is common in this population. However, its effect on mortality prevention remains unclear among kidney transplant recipients, whose clinical risk profile might be unique because of concomitant immunosuppressive therapy. In this national study of 58,264 single-kidney transplant recipients, statin use was associated with a 5% decrease in mortality. More importantly, this protective association was stronger among those who used a mammalian target of rapamycin (mTOR) inhibitor for immunosuppression (27% decrease in mTOR inhibitor users versus 5% in nonusers). Our results suggest that statin therapy may reduce mortality in kidney transplant recipients and that the strength of this protective association may vary by immunosuppression regimen. BACKGROUND: Cardiovascular diseases are the leading cause of mortality in kidney transplant (KT) recipients, accounting for 32% of deaths. Statins are widely used in KT recipients, but effectiveness for preventing mortality remains unclear in this population, especially because of interaction between statins and immunosuppressive agents. We analyzed a national cohort to assess the real-world effectiveness of statins for reducing all-cause mortality in KT recipients. METHODS: We studied statin use and mortality among 58,264 adults (18 years or older) who received single kidneys between 2006 and 2016 and had Medicare part A/B/D. Statin use was ascertained from Medicare prescription drug claims and deaths from Center for Medicare and Medicaid Services records. We estimated the association of statin use with mortality using multivariable Cox models, with statin use as a time-varying exposure and immunosuppression regimen as effect modifiers. RESULTS: Statin use increased from 45.5% at KT to 58.2% at 1-year post-KT to 70.9% at 5-year post-KT. We observed 9785 deaths over 236,944 person-years. Overall, statin use was significantly associated with lower mortality (adjusted hazard ratio [aHR], 0.95; 95% confidence interval [CI], 0.90 to 0.99). The strength of this protective association varied by calcineurin inhibitor use (among tacrolimus users, aHR, 0.97; 95% CI, 0.92 to 1.03 versus among calcineurin nonusers, aHR, 0.72; 95% CI, 0.60 to 0.87; interaction P =0.002), mammalian target of rapamycin (mTOR) inhibitor use (among mTOR inhibitor users, aHR, 0.73; 95% CI, 0.57 to 0.92 versus among nonusers, aHR, 0.95; 95% CI, 0.91 to 1.00; interaction P =0.03), and mycophenolate use (among mycophenolate users, aHR, 0.96; 95% CI, 0.91 to 1.02 versus among nonusers, aHR, 0.76; 95% CI, 0.64 to 0.89; interaction P =0.002). CONCLUSION: Real-world evidence supports statin therapy for reducing all-cause mortality in KT recipients. Effectiveness might be greater when combined with mTOR inhibitor-based immunosuppression. CI - Copyright (c) 2023 by the American Society of Nephrology. FAU - Bae, Sunjae AU - Bae S AUID- ORCID: 0000-0003-0098-8816 AD - Department of Surgery, NYU Grossman School of Medicine, New York, New York. AD - Department of Population Health, NYU Grossman School of Medicine, New York, New York. FAU - Ahn, JiYoon B AU - Ahn JB AD - Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland. FAU - Joseph, Corey AU - Joseph C AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. FAU - Whisler, Ryan AU - Whisler R AD - Department of Pharmacy, Johns Hopkins Medicine, Baltimore, Maryland. FAU - Schnitzler, Mark A AU - Schnitzler MA AD - Department of Surgery, Saint Louis University, St. Louis, Missouri. FAU - Lentine, Krista L AU - Lentine KL AD - Department of Internal Medicine, Saint Louis University, St. Louis, Missouri. FAU - Kadosh, Bernard S AU - Kadosh BS AD - Department of Medicine, NYU Grossman School of Medicine, New York, New York. FAU - Segev, Dorry L AU - Segev DL AD - Department of Surgery, NYU Grossman School of Medicine, New York, New York. AD - Department of Population Health, NYU Grossman School of Medicine, New York, New York. FAU - McAdams-DeMarco, Mara A AU - McAdams-DeMarco MA AD - Department of Surgery, NYU Grossman School of Medicine, New York, New York. AD - Department of Population Health, NYU Grossman School of Medicine, New York, New York. LA - eng GR - K02 AG076883/AG/NIA NIH HHS/United States GR - K24 AI144954/AI/NIAID NIH HHS/United States GR - R01 DK120518/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20230309 PL - United States TA - J Am Soc Nephrol JT - Journal of the American Society of Nephrology : JASN JID - 9013836 RN - 0 (Immunosuppressive Agents) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Adult MH - Humans MH - Aged MH - United States/epidemiology MH - Immunosuppressive Agents/therapeutic use MH - *Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use MH - *Cardiovascular Diseases MH - *Kidney Transplantation MH - Medicare MH - TOR Serine-Threonine Kinases MH - Transplant Recipients PMC - PMC10278772 EDAT- 2023/03/10 06:00 MHDA- 2023/06/02 06:42 PMCR- 2024/06/01 CRDT- 2023/03/09 00:03 PHST- 2022/07/28 00:00 [received] PHST- 2023/01/17 00:00 [accepted] PHST- 2024/06/01 00:00 [pmc-release] PHST- 2023/06/02 06:42 [medline] PHST- 2023/03/10 06:00 [pubmed] PHST- 2023/03/09 00:03 [entrez] AID - 00001751-202306000-00015 [pii] AID - JASN-2023-000262 [pii] AID - 10.1681/ASN.0000000000000112 [doi] PST - ppublish SO - J Am Soc Nephrol. 2023 Jun 1;34(6):1069-1077. doi: 10.1681/ASN.0000000000000112. Epub 2023 Mar 9.