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Musculoskeletal Adverse Events Associated with PCSK9 Inhibitors: Disproportionality Analysis of the FDA Adverse Event
Lingqing Ding1, Congqin Chen1, Yongkuan Yang2
1Department of Pharmacy, Xiamen Cardiovascular Hospital, Xiamen University, Xiamen 361024, China.
Background:
Some studies suggest that potential safety issues about PCSK9 inhibitors have not been sufficiently explored in clinical trials, including musculoskeletal adverse events (MAEs).
Objective:
To examine the association between use of PCSK9 inhibitors with and without concurrent statins and risk of MAEs. Patients and Methods. FDA Adverse Event Reporting System (FAERS) dataset of PCSK9 inhibitors and statins from October 2015 to June 2021 was queried. The reporting odds ratio (ROR) with relevant 95% confidence interval (95% CI) was calculated as the index of disproportionality. Outcome of MAEs of different PCSK9 inhibitors regimens was also investigated.
Results:
3,185 cases of PCSK9 inhibitor-associated MAEs were recorded. PCSK9 inhibitor class alone demonstrated a strong link to MAEs (ROR 5.92; 95% CI 5.70-6.15), and evolocumab was associated with more reports of MAEs than alirocumab. Concomitant use with statins leaded to an increased occurrence of MAEs (ROR 32.15 (25.55-40.46)), and the risk differed among different statins. The PCSK9 inhibitors were safer than statins in terms of hospitalization rate and death rate (15.64% vs. 36.83%; 0.72% vs. 3.53%).
Conclusions:
This pharmacovigilance investigation suggests that PCSK9 inhibitors are associated with MAEs. The risk significantly increases when combined with statins. Increased laboratory and clinical monitoring are required to timely diagnose and manage MAEs.
Insights
PCSK9 inhibitors are linked to musculoskeletal adverse events (MAEs). Combining them with statins significantly increases MAE risk, requiring vigilant monitoring for patient safety.
Area of Science:
- Pharmacovigilance
- Cardiovascular Medicine
- Drug Safety
Background:
- Potential safety concerns of PCSK9 inhibitors, particularly musculoskeletal adverse events (MAEs), warrant further investigation.
- Clinical trials may not have fully explored the safety profile of PCSK9 inhibitors regarding MAEs.
Purpose of the Study:
- To investigate the association between PCSK9 inhibitors, with and without concurrent statin use, and the risk of MAEs.
- To analyze MAE reporting trends within the FDA Adverse Event Reporting System (FAERS).
Main Methods:
- Utilized the FAERS database for PCSK9 inhibitors and statins from October 2015 to June 2021.
- Calculated the reporting odds ratio (ROR) to assess disproportionality and identify safety signals.
- Examined MAE outcomes across different PCSK9 inhibitor regimens and statin combinations.
Main Results:
- A total of 3,185 PCSK9 inhibitor-associated MAEs were reported.
- PCSK9 inhibitors alone showed a strong association with MAEs (ROR 5.92).
- Concomitant use with statins markedly increased MAE risk (ROR 32.15), varying by statin type. PCSK9 inhibitors demonstrated lower hospitalization and death rates compared to statins.
Conclusions:
- PCSK9 inhibitors are associated with an increased risk of MAEs.
- The combination of PCSK9 inhibitors and statins significantly elevates MAE risk.
- Enhanced clinical and laboratory monitoring is crucial for early detection and management of MAEs.
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