PMID- 33476406
OWN - NLM
STAT- MEDLINE
DCOM- 20210702
LR  - 20220531
IS  - 1399-0012 (Electronic)
IS  - 0902-0063 (Linking)
VI  - 35
IP  - 4
DP  - 2021 Apr
TI  - Mtor inhibitors associated with higher cardiovascular adverse events-A large 
      population database analysis.
PG  - e14228
LID - 10.1111/ctr.14228 [doi]
AB  - There are limited real-world data available regarding adverse events (AEs) of 
      immunosuppressants. We utilized the FDA Adverse Event Reporting System (FAERS) 
      database from 2004 to 2018 to perform a retrospective database analysis. We 
      analyzed AE reports due to the individual agents tacrolimus, sirolimus, or 
      everolimus and compared reporting odds ratios of the mTOR inhibitors to 
      tacrolimus. The mTOR inhibitors arm had 1282 reports with 4176 AEs, while the 
      tacrolimus arm had a total of 7587 reports with 20 940 individual AEs. mTOR 
      inhibitors had significantly higher incidences of cardiovascular (ROR 1.95, 95% 
      CI 1.70, 2.23), dermatologic (ROR 1.34, 95% CI 1.04, 1.73), endocrine (ROR 1.52, 
      95% CI 1.26, 1.82), gastrointestinal (ROR 1.15, 95% CI 1.01, 1.30), infectious 
      disease (ROR 1.35, 95% 1.20, 1.52), musculoskeletal (ROR 1.39, 95% CI 1.13, 
      1.70), pulmonary (ROR 3.46, 95% 2.97, 4.03), renal (ROR 1.27, 95% CI 1.10, 1.46), 
      and vascular AEs (ROR 3.10, 95% CI 2.14, 4.49). Across every organ type, mTOR 
      inhibitors had greater cardiovascular AEs compared to tacrolimus, specifically in 
      arteriosclerosis, heart failure, hypotension, tachycardia, chest pain, edema, and 
      pericardial disorders. mTOR inhibitors may be associated with higher 
      cardiovascular AEs. Further investigation is required to determine the potential 
      mechanism of this effect.
CI  - (c) 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Nguyen, Vi N
AU  - Nguyen VN
AD  - Department of Pharmacy, University of California San Diego, La Jolla, CA, USA.
FAU - Abagyan, Ruben
AU  - Abagyan R
AUID- ORCID: 0000-0001-9309-2976
AD  - Skaggs School of Pharmacy and Pharmaceutical Sciences, La Jolla, CA, USA.
FAU - Tsunoda, Shirley M
AU  - Tsunoda SM
AUID- ORCID: 0000-0002-3974-8038
AD  - Skaggs School of Pharmacy and Pharmaceutical Sciences, La Jolla, CA, USA.
LA  - eng
PT  - Journal Article
DEP - 20210202
PL  - Denmark
TA  - Clin Transplant
JT  - Clinical transplantation
JID - 8710240
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
MH  - *Adverse Drug Reaction Reporting Systems
MH  - Cardiovascular Diseases/*chemically induced
MH  - Everolimus/*adverse effects
MH  - Humans
MH  - Retrospective Studies
MH  - Sirolimus/*adverse effects
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
MH  - Tacrolimus/*adverse effects
MH  - United States/epidemiology
MH  - United States Food and Drug Administration
OTO - NOTNLM
OT  - adverse drug reaction
OT  - immunosuppression
OT  - mammalian target of rapamycin inhibitor
OT  - sirolimus
OT  - tacrolimus
EDAT- 2021/01/22 06:00
MHDA- 2021/07/03 06:00
CRDT- 2021/01/21 17:14
PHST- 2021/01/04 00:00 [revised]
PHST- 2020/11/13 00:00 [received]
PHST- 2021/01/12 00:00 [accepted]
PHST- 2021/01/22 06:00 [pubmed]
PHST- 2021/07/03 06:00 [medline]
PHST- 2021/01/21 17:14 [entrez]
AID - 10.1111/ctr.14228 [doi]
PST - ppublish
SO  - Clin Transplant. 2021 Apr;35(4):e14228. doi: 10.1111/ctr.14228. Epub 2021 Feb 2.