Mtor inhibitors associated with higher cardiovascular adverse events-A large population database analysis

Area of Science:

• Pharmacovigilance
• Immunosuppression Therapy
• Real-world Evidence

Background:

• Limited real-world data exists on adverse events (AEs) associated with immunosuppressant medications.
• Tacrolimus, sirolimus, and everolimus are commonly used immunosuppressants.
• Sirolimus and everolimus are mechanistic target of rapamycin (mTOR) inhibitors.

Purpose of the Study:

• To compare the real-world adverse event profiles of mTOR inhibitors (sirolimus, everolimus) versus tacrolimus.
• To identify specific types of adverse events associated with mTOR inhibitors.

Main Methods:

• Retrospective analysis of the FDA Adverse Event Reporting System (FAERS) database from 2004 to 2018.
• Comparison of reporting odds ratios (ROR) for AEs between mTOR inhibitors and tacrolimus.
• Analysis included 1282 reports (4176 AEs) for mTOR inhibitors and 7587 reports (20,940 AEs) for tacrolimus.

Main Results:

• mTOR inhibitors were associated with significantly higher incidences of cardiovascular, dermatologic, endocrine, gastrointestinal, infectious disease, musculoskeletal, pulmonary, renal, and vascular AEs compared to tacrolimus.
• Specifically, mTOR inhibitors showed higher reporting odds ratios for pulmonary (ROR 3.46) and vascular (ROR 3.10) AEs.
• Cardiovascular AEs, including arteriosclerosis, heart failure, and hypotension, were notably more frequent with mTOR inhibitors.

Conclusions:

• Real-world data suggests mTOR inhibitors are linked to a higher burden of adverse events, especially cardiovascular and pulmonary.
• The findings highlight a potential increased cardiovascular risk with mTOR inhibitors compared to tacrolimus.
• Further research is warranted to elucidate the mechanisms underlying these observed safety differences.