PCSK9 Inhibitors’ New Users: Analysis of Prescription Patterns and Patients’ Characteristics from an Italian Real-world Study

Piccinni, Carlo; Antonazzo, Ippazio Cosimo; Maggioni, Aldo P.; Pedrini, Antonella; Calabria, Silvia; Ronconi, Giulia; Dondi, Letizia; Martini, Nello; Roberto, Giuseppe; Sampietro, Tiziana; Sbrana, Francesco; Pino, Beatrice Dal; Bigazzi, Federico; Surdo, Giuseppa Lo; Volpi, Elisabetta; Biagini, Stefania; Gini, Rosa

doi:10.1007/s40261-019-00877-3

Cited by 23 publications

(21 citation statements)

References 25 publications

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“…The increase in ADR reporting is probably related to the increased utilization of both PCSK9Is. Indeed, these drugs obtained marketing authorization in 2015, becoming gradually available across EU and non-EU countries for use in clinical practice, and their use has constantly increased, as demonstrated by several studies [19,[28][29][30][31]. We found that the median age of patients who experienced ADRs was 66 years, and 55% were female.…”

Section: Discussionmentioning

confidence: 70%

PCSK9 Inhibitors and Neurocognitive Adverse Drug Reactions: Analysis of Individual Case Safety Reports from the Eudravigilance Database

et al. 2020

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Introduction Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9Is) were associated with a risk of neurocognitive adverse drug reactions (ADRs). Objective We aimed to investigate the occurrence of neuropsychiatric ADRs related to PCSK9Is. Methods We analyzed Individual Case Safety Reports (ICSRs) sent through the European pharmacovigilance database that reported alirocumab or evolocumab as the suspected drug and at least one neurological or psychiatric ADR. The reporting odds ratio (ROR) was computed to compare the probability of reporting ICSRs with neuropsychiatric ADRs between alirocumab, evolocumab and statins. Results Overall, 2041 ICSRs with alirocumab and/or evolocumab as the suspected drug described the occurrence of neuropsychiatric ADRs. The most reported preferred terms for both drugs were headache, insomnia and depression. No difference between alirocumab and evolocumab was observed for the RORs of ICSRs with ADRs belonging to the System Organ Classes (SOCs) ‘Nervous system disorders’ or ‘Psychiatric disorders’ (ROR 1.02, 95% confidence interval 0.91–1.14; and 1.12, 95% CI 0.94–1.34, respectively), while evolocumab and alirocumab had a higher reporting probability of ICSRs with ADRs belonging to the SOC ‘Nervous system disorders’ compared with atorvastatin and fluvastatin. A lower reporting probability was instead found for ICSRs with ADRs belonging to the SOC ‘Psychiatric disorders’ for evolocumab and alirocumab versus simvastatin, pravastatin and rosuvastatin. Conclusion Our results demonstrated that 22.7% of all ICSRs reporting alirocumab or evolocumab as suspect drugs described the occurrence of neuropsychiatric ADRs. The ROR showed that evolocumab and alirocumab had a higher reporting probability of neurological ADRs compared with statins. Further data from real-life contexts are needed. Electronic supplementary material The online version of this article (10.1007/s40264-020-01021-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 70%

PCSK9 Inhibitors and Neurocognitive Adverse Drug Reactions: Analysis of Individual Case Safety Reports from the Eudravigilance Database

et al. 2020

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“…As a result, treatment was limited to ezetimibe allowing no more than 15–20% reduction of LDLc levels. Nonetheless, treatment intensification with a PCSK9-inhibitor was not considered even though these agents have been available since 2015 for medical use and reimbursed in Italy since 2017, where the rate of prescription of PCSK9 inhibitors still appears below expectations ( 20 ). A sub-analysis of the ODYSSEY OUTCOMES, although, this trial was not specifically designed for the older population, showed that alirocumab improved outcomes irrespective of age ( 21 ) with no differences in adverse events between alirocumab and placebo.…”

Section: Discussionmentioning

confidence: 99%

Breaking Therapeutic Inertia With Alirocumab in an 80-Year-Old Patient With Severe Hypercholesterolemia: A Case Report

et al. 2021

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Background: Therapeutic inertia, defined as the failure to initiate or intensify therapy in a timely manner as per evidence-based clinical guidelines, is an important barrier limiting optimal care in the elderly. Therefore, overcoming therapeutic inertia is the core challenge when dealing with geriatric patients.Case Description: The patient was an 80-year-old man that attended our Outpatient Lipid Clinic (Pisa University Hospital) because of persistent high LDL cholesterol (LDLc) levels in a setting of a statin contraindication. He underwent five percutaneous coronary angioplasties with drug-eluting stents. In 2014, upon starting treatment with rosuvastatin for LDLc level of 7.59 mmol/L, the patient was admitted to the Emergency Room for a presumptive diagnosis of rhabdomyolysis (creatine kinase 6685 U/L) secondary to statin. Patient developed acute kidney injury treated with dialysis. After resolution, he was discharged with ezetimibe (10 mg daily). This treatment however failed to effectively reduce LDLc levels that ranged between 5.9 and 6.6 mmol/L for the ensuing 4-years. In 2018, at the time of our evaluation, in consideration of the age, we performed a comprehensive geriatric assessment that showed good functional and mental status supporting a reliable treatment with a proprotein convertase subtilisin–kexin type 9 inhibitor. Therefore, alirocumab was prescribed as add-on to ezetimibe. At 24-month follow-up, the geriatric assessment showed no significant changes, and alirocumab was well-tolerated. LDLc was 82% lower as compared to baseline values (from 6.6 to 1.2 mmol/L).Conclusions: This report describes a case of therapeutic inertia despite a very high-risk profile. It is also instrumental in highlightening that appropriate intensification of therapy in an elderly patient at high cardiovascular risk, by means of a patient-centered approach, may allow reaching therapeutic targets and overcoming the condition of therapeutic inertia.

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“…69,72 The outcome of these concerns about the affordability of PCSK-9 inhibitors has been a tendency towards underuse of these drugs compared with specialist society guideline recommendations at 1-2% of the population concentrated on the highest risk groups. [73][74][75] However, significant differences are likely to arise between payerderived guidelines [e.g. UK National Institute for Health and Clinical Excellence (NICE)] and specialist societies that do not need to consider reimbursement.…”

Section: Health Economics Of Pcsk-9 Therapymentioning

confidence: 99%

The history of proprotein convertase subtilisin kexin-9 inhibitors and their role in the treatment of cardiovascular disease

Kim

Wierzbicki

2020

Therapeutic Advances in Chronic Disease

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A consensus has formed based on epidemiological studies and clinical trials that intervention to reduce low density lipoprotein cholesterol (LDL-C) will reduce cardiovascular disease (CVD) events. This has progressively reduced the thresholds for intervention and targets for treatment. Whist statins are sufficient for many people in primary prevention, they only partially achieve the newer targets of secondary prevention for established CVD. Increasing use of statins has highlighted that 1–2% cannot tolerate these drugs. Other cholesterol-lowering drugs such as ezetimibe add to the benefits of statins but have limited efficacy. The discovery of activating mutations in proprotein convertase subtilisin kexin-9 (PCSK9) as a cause of familial hypercholesterolaemia while inactivating mutations lower LDL-C led to the idea to develop PCSK9 inhibitors as drugs. This article reviews the history of lipid-lowering therapies, the discovery of PCSK9 and the development of PCSK9 inhibitors. It reviews the key trials of the current antibody-based drugs and how these have influenced new guidelines. It also reviews the controversy caused by their cost and the increasing application of health economics to determine the optimum strategy for implementation of novel therapeutic pathways and surveys other options for targeting PCSK9 as well as other LDL-C lowering compounds in late development.

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PCSK9 Inhibitors’ New Users: Analysis of Prescription Patterns and Patients’ Characteristics from an Italian Real-world Study

Cited by 23 publications

References 25 publications

PCSK9 Inhibitors and Neurocognitive Adverse Drug Reactions: Analysis of Individual Case Safety Reports from the Eudravigilance Database

PCSK9 Inhibitors and Neurocognitive Adverse Drug Reactions: Analysis of Individual Case Safety Reports from the Eudravigilance Database

Breaking Therapeutic Inertia With Alirocumab in an 80-Year-Old Patient With Severe Hypercholesterolemia: A Case Report

The history of proprotein convertase subtilisin kexin-9 inhibitors and their role in the treatment of cardiovascular disease

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