Efficacy and safety of alirocumab in statin-intolerant patients over 3 years: open-label treatment period of the ODYSSEY ALTERNATIVE trial

Moriarty, Patrick M.; Thompson, Paul D.; Cannon, Christopher P.; Guyton, John R.; Bergeron, Jean; Zieve, Franklin J.; Bruckert, Éric; Jacobson, Terry A.; Baccara‐Dinet, Marie T.; Zhao, Jian; Donahue, Stephen; Ali, Shazia; Manvelian, Garen; Pordy, Robert

doi:10.1016/j.jacl.2020.01.001

Cited by 13 publications

(5 citation statements)

References 19 publications

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“…Musculoskeletal and connective tissue disorders were common in patients receiving alirocumab or evolocumab. The muscle-related AE signals were mainly manifested as back pain, myalgia, pain in extremity, arthralgia, and muscle spasms, which was consistent with evidence from previous clinical trials ( Robinson et al, 2015 ; Moriarty et al, 2020 ). In addition, the post-marketing pharmacovigilance studies also suggested the relation between PCSK9 inhibitors and muscle symptoms in clinical practice ( Gurgoze et al, 2019 ; Ding et al, 2022 ).…”

Section: Discussionsupporting

confidence: 88%

Real-world safety of PCSK9 inhibitors: A pharmacovigilance study based on spontaneous reports in FAERS

Feng

Tong

et al. 2022

Front. Pharmacol.

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Objective: We aimed to evaluate alirocumab- and evolocumab-related adverse events (AEs) in real-world compared with all other drugs, overall and by gender and age subgroups; we also aimed to compare their risks of cognitive impairment, musculoskeletal disorders and diabetes with various statins and ezetimibe.Methods: We retrospectively extracted AE reports from the FDA Adverse Event Reporting System (FAERS) database during July 2015-June 2021. Disproportionality analyses were performed using reporting odds ratios (RORs) to detect AE signals of alirocumab and evolocumab in the overall population and in different age and gender subgroups, respectively.Results: Compared with all other drugs, both alirocumab and evolocumab had a significant signal in “musculoskeletal and connective tissue disorders” (ROR1 = 2.626, 95% CI 2.552–2.702; ROR2 = 2.575, 95% CI 2.538–2.613). The highest ROR value of 2.311 (95% CI 2.272–2.351) was for “injury, poisoning and procedural complications” and was found in patients aged ≥65 years on evolocumab. The most frequent AEs were “general disorders and administration site conditions” and “musculoskeletal and connective tissue disorders” for all subpopulations. At the preferred term level, the most frequent AE signal was myalgia for alirocumab and injection site pain for evolocumab, overall and by subgroups. Compared with statins/ezetimibe, PCSK9 inhibitors exhibited lower ROR values for adverse events associated with SOC “nervous system disorders”, “psychiatric disorders” and “metabolism and nutrition disorders” (all RORs < 1), but mixed results for musculoskeletal disorders. Compared with all other drugs, undocumented AEs, such as acute cardiac event (ROR = 30.0, 95% CI 9.4–95.3) and xanthoma (ROR = 9.3, 95% CI 3.4–25.5), were also reported.Conclusion: Real-world evidence showed that PCSK9 inhibitors were associated with an increased risk of musculoskeletal and connective tissue disorders and general disorders and administration site conditions, overall and by subgroups. Muscle toxicity, injection site reactions, and influenza-like illness were significant AE signals. Compared with various statins and ezetimibe, PCSK9 inhibitors have shown a favorable safety profile in muscle-related events, cognitive impairment and diabetes. Some undocumented AE signals were also reported. Due to the limitations of spontaneous reporting databases, further studies are still needed to establish causality and validate our results.

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Section: Discussionsupporting

confidence: 88%

Real-world safety of PCSK9 inhibitors: A pharmacovigilance study based on spontaneous reports in FAERS

Feng

Tong

et al. 2022

Front. Pharmacol.

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“…This meta-analysis included 100,193 patients across 28 RCTs, evaluating four lipid-lowing therapies: bococizumab (Boc) ( 22 ), evolocumab (Evo) ( 23 – 38 ), alirocumab (Ali) ( 30 , 39 – 46 ), and inclisiran (Inc) ( 47 ). Basic information for each study, including the first author, publication date, lipid-lowering treatment type, patient sex ratio, age, follow-up duration, NCT number, and patient profile is provided in Supplementary Table S1 .…”

Section: Resultsmentioning

confidence: 99%

PCSK9 inhibitors and inclisiran with or without statin therapy on incident muscle symptoms and creatine kinase: a systematic review and network meta-analysis

Li,

Sun,

Yan

2024

Front. Cardiovasc. Med.

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BackgroundAtherosclerotic cardiovascular disease (ASCVD), a leading cause of global fatalities, has inconsistent findings regarding the impact of muscle symptoms despite promising clinical trials involving PCSK9 inhibitors (PCSK9i) and siRNA as potential therapeutic options.MethodsThe databases EMBASE, PubMed, Web of Science, Cochrane, and ClinicalTrials.gov were thoroughly searched without any restrictions on language. Review Manager 5.3 software was utilized to calculate relative risks with 95% confidence intervals (CIs) for dichotomous data and mean differences or standardized mean differences with 95%CIs for continuous data. To evaluate publication bias, Egger's test was employed using Stata/SE software.ResultsThis analysis included 26 studies comprising 28 randomized controlled trials (RCTs) involving a total of 100,193 patients, and 4 different lipid-lowering therapy combinations. For events with creatine kinase >3ULN, evolocumab and alirocumab demonstrated significant advantages compared to inclisiran. Evolocumab showed the best results in terms of both new muscle symptom events and creatine kinase >3ULN.ConclusionsBased on this network meta-analysis (NMA) results, evolocumab has emerged as a promising treatment option for patients with hyperlipidemia and muscle disorders compared to other PCSK9 inhibitors and inclisiran.Systematic Review RegistrationPROSPERO [CRD42023459558].

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“…The Moriarty et al open-label trial on the efficacy and safety of alirocumab in statin-intolerant patients over three years showed a 45% reduction in LDL-C levels when used alone, compared to a 14.6% reduction when ezetimibe was used in 2019 [15]. The study shows the ability to improve cardiovascular events when used alone to manage dyslipidemia [15].…”

Section: Pcsk9 Inhibitors and Chronic Kidney Disease: Safety Adherenc...mentioning

confidence: 98%

A Systematic Review on the Safety and Efficacy of PCSK9 Inhibitors in Lowering Cardiovascular Risks in Patients With Chronic Kidney Disease

Igweonu-Nwakile¹,

Ali²,

Paul³

et al. 2022

Cureus

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Cardiovascular events caused by dyslipidemia are one of the leading causes of death in patients with Chronic Kidney Disease (CKD). Statins are the first line of treatment for patients with hyperlipidemia and in the treatment regimen for patients with CKD. Therefore, the introduction of Proprotein Convertase Subtilisin-Kexin type 9 inhibitors (PCSK9 inhibitors) is a viable and possibly effective treatment option for patients who, despite high doses of statins, struggle to lower their low-density lipoprotein cholesterol (LDL-C) levels. Our paper's objective is to explore the safety of these biological agents, particularly in patients with varying stages of impaired kidney function, and the correlating effectiveness in lowering their LDL-C levels, thereby reducing cardiovascular risks in these patients.We methodically retrieved relevant articles from PubMed, PubMed Central, Medline, and Google scholar in April 2022. We used the Medical Subject Heading (MeSH) Strategy and used the relevant keyword, then applied our inclusion and exclusion criteria; the initial search gave 10,542 results; with the removal of duplicates, irrelevant articles, and application of quality assessments done, we finally included 15 papers for our review with 37,188 patients. PCSK9 inhibitors are reliable, safe, and efficient therapy in lowering LDL-C levels in patients with CKD. However, its safety and efficacy in severe and end-stage kidney disease are grey, as other factors such as infections lead to morbidity and mortality. Future trials on chronic kidney disease and PCSK9 inhibitors should investigate the inhibitors' ability to improve kidney functions at all stages of kidney disease while lowering lipid levels and finally analyze the safety in patients with end-stage kidney disease.

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Efficacy and safety of alirocumab in statin-intolerant patients over 3 years: open-label treatment period of the ODYSSEY ALTERNATIVE trial

Cited by 13 publications

References 19 publications

Real-world safety of PCSK9 inhibitors: A pharmacovigilance study based on spontaneous reports in FAERS

Real-world safety of PCSK9 inhibitors: A pharmacovigilance study based on spontaneous reports in FAERS

PCSK9 inhibitors and inclisiran with or without statin therapy on incident muscle symptoms and creatine kinase: a systematic review and network meta-analysis

A Systematic Review on the Safety and Efficacy of PCSK9 Inhibitors in Lowering Cardiovascular Risks in Patients With Chronic Kidney Disease

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