Abstract
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.
Highlights
For statin-intolerant patients, or those who have been prescribed with high-intensity statins but failed to reach their low-density lipoprotein cholesterol (LDL-C) target levels, it is especially difficult for them to gain therapeutic efficacy.One of the potential ways is the use of the recently approved proprotein convertase subtilisin/kexin type 9 (PCSK9)inhibitors, alirocumab and evolocumab
It has been a consensus that musculoskeletal adverse events (MAEs) were the welldescribed side effects of statin therapy which were dominated by myalgia, myopathy, and rhabdomyolysis, etc., the underlying mechanism remains elusive that may be attributed to the novel immunogenetic factors, gender, etc
Since the aim of our study is to detect the possible occurrence of MAEs in patients exposed to PCSK9 inhibitors alone and further, compare the reports of PCSK9 inhibitors together with statins with the condition where they are prescribed alone; the target population is categorized into three groups [20]: reports of patients prescribed
Summary
They have been proven to notably reduce LDL-C levels alone or on a background of statin therapy and are changing the therapeutic landscape of dyslipidemia [1, 2]. Some studies suggest that potential safety issues about PCSK9 inhibitors have not been sufficiently explored in clinical trials, including musculoskeletal adverse events (MAEs). To examine the association between use of PCSK9 inhibitors with and without concurrent statins and risk of MAEs. Patients and Methods. 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. 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
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