Evolocumab for Early Reduction of LDL Cholesterol Levels in Patients With Acute Coronary Syndromes (EVOPACS)

Koskinas, Konstantinos C.; Windecker, Stephan; Pedrazzini, Giovanni; Müeller, Christian; Cook, Stéphane; Matter, Christian M.; Müller, Olivier; Häner, Jonas; Gencer, Baris; Crljenica, Carmela; Amini, Poorya; Deckarm, Olga; Iglesias, Juan F.; Räber, Lorenz; Heg, Dik; Mach, François

doi:10.1016/j.jacc.2019.08.010

Cited by 177 publications

(151 citation statements)

References 22 publications

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“…The EVOPACS study was an investigator-initiated study of evolocumab in the setting of acute coronary syndrome (Koskinas et al, 2019). 308 patients hospitalized for acute coronary syndrome were included if their LDL-C was ≥70 mg/dL despite high-intensity statin therapy for 4 weeks, ≥90 mg/dL despite low-or moderate-intensity statin, or ≥125 mg/dL with no statin pre-treatment.…”

Section: Addition To Statinsmentioning

confidence: 99%

PCSK9 Inhibition: Insights From Clinical Trials and Future Prospects

2020

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In 2003, clinical observations led to the discovery of the involvement of proprotein convertase subtilisin/kexin type 9 (PCSK9) in lipid metabolism. Functional studies demonstrated that PCSK9 binds to the low-density lipoprotein (LDL) receptor directing it to its lysosomal degradation. Therefore, carriers of gain-of-function mutations in PCSK9 exhibit decreased expression of LDL receptors on the hepatocyte surface and have higher LDL cholesterol (LDL-C) levels. On the contrary, loss-of-function mutations in PCSK9 are associated with low LDL-C concentrations and significantly reduced lifetime risk of cardiovascular disease. These insights motivated the search for strategies to pharmacologically inhibit PCSK9. In an exemplary rapid development, fully human monoclonal antibodies against PCSK9 were developed and found to effectively reduce LDL-C. Administered subcutaneously every 2–4 weeks, the PCSK9 antibodies evolocumab and alirocumab reduce LDL-C by up to 60% in a broad range of populations either as monotherapy or in addition to statins. Two large cardiovascular outcome trials involving a total of ∼46,000 cardiovascular high-risk patients on guideline-recommended lipid-lowering therapy showed that treatment with evolocumab and alirocumab led to a relative reduction of cardiovascular risk by 15% after 2.2 and 2.8 years of treatment, respectively. These findings expanded the armamentarium of pharmacological approaches to address residual cardiovascular risk associated with LDL-C. Furthermore, the unprecedented low LDL-C concentrations achieved (e.g., 30 mg/dL in the FOURIER study) suggest that the relationship between LDL-C and cardiovascular risk is without a lower threshold, and without associated adverse events during the timeframe of the studies. The side effect profile of PCSK9 antibodies is favorable with few patients exhibiting injection-site reactions. Currently, the access to PCSK9 antibodies is limited by high treatment costs. The development of novel approaches to inhibit PCSK9 such as the use of small interfering RNA to inhibit PCSK9 synthesis seems promising and may soon become available.

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Section: Addition To Statinsmentioning

confidence: 99%

PCSK9 Inhibition: Insights From Clinical Trials and Future Prospects

2020

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“…Evolocumab 140 mg Q2W or 420 mg QM on top of atorvastatin 5 or 20 mg reduced LDL-C by an average of 67–76%. When studied in patients during hospitalization due to acute coronary syndrome (ACS) in the EVOPACS 55 study ( n = 308), evolocumab 420 mg QM for 2 doses added to high-dose statin resulted in a difference in mean percentage change from baseline of −40.7% ( p < .001). In the evolocumab group, around 95.7% of patients achieved LDL-C levels < 1.8 mmol/L (70 mg/dL) by Week 8 versus 37.6% in the placebo group.…”

Section: Efficacy Of Pcsk9 Monoclonal Antibodiesmentioning

confidence: 99%

Efficacy and safety of PCSK9 monoclonal antibodies: an evidence-based review and update

Kaddoura

Orabi

Salam

2020

Journal of Drug Assessment

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Objective: Treatment of dyslipidemia lowers cardiovascular (CV) risk. Although statin use is a cornerstone therapy, many patients are not achieving their risk-specific low-density lipoprotein cholesterol (LDL-C) goals. The proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies have been extensively studied as lipid-lowering therapy (LLT). Herein, we present an updated evidencebased review of the efficacy and safety of PCSK9 monoclonal antibodies in the treatment of familial and non-familial hypercholesterolemia. Methods: PubMed database was searched to review Phase III studies on PCSK9 monoclonal antibodies. Then, the US National Institutes of Health Registry and the WHO International Clinical Trial Registry Platform were searched to identify and present the ongoing research. Results: PCSK9 monoclonal antibodies were investigated for the treatment of dyslipidemia, as a single therapeutic agent or as an add-on therapy to the traditional LLT. They proved effective and safe in the treatment of familial and non-familial hypercholesterolemia, and in the prevention of adverse CV events. Conclusions: The use of PCSK9 monoclonal antibodies in the treatment of dyslipidemia is currently recommended to achieve risk-specific LDL-C goal to reduce adverse CV events. Future results of the ongoing research might expand their clinical generalizability to broader patient populations.

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“…The EVOPACS (Evolocumab for Early Reduction of LDL Cholesterol Levels in Patients with Acute Coronary Syndromes) trial randomized 308 patients with elevated LDL -C levels who were hospitalized for ACS to evolocumab 420 mg (n = 155) or placebo (n = 153) initiated in the hospital and then administered every 4 weeks. 55 All patients received atorvastatin 40 mg and most of them (78.2%) had not been on statin treatment previously. At 8 weeks, mean LDL -C levels decreased from 3.6 mmol/l (140 mg/dl) to 0.8 mmol/l (31 mg/dl) with evolocumab and from 3.4 mmol/l (132 mg/dl) to 2.1 mmol/l (80 mg/dl) with placebo.…”

Section: Prescription Barriers and Possible Solutionsmentioning

confidence: 99%

“…Furthermore, 90% of the dual -therapy group achieved the new ESC / EAS guideline -recommended target of an LDL -C level below 55 mg/dl compared with 11% of patients randomized to high--intensity atorvastatin at a dose of 40 mg/d + placebo injections. 55 The EVOPACS findings highlight the significance of starting early, aggressive lipid -lowering therapy for rapid reduction in LDL -C levels in patients at very high risk. The clinical impact of very early LDL -C lowering with PCSK-9 inhibitors initiated in the acute ACS setting now warrants further investigation in a dedicated cardiovascular outcome trial.…”

Section: Prescription Barriers and Possible Solutionsmentioning

confidence: 99%

Statins plus ezetimibe in the era of proprotein convertase subtilisin/ kexin type 9 inhibitors

Luca¹,

Corsini²,

Uguccioni³

et al. 2020

Kardiol Pol

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therapies in the form of single pills and tailoring treatment to individual patients based on their ASCVD risk profile. This review examines the rationale and evidence with regard to adding ezetimibe and proprotein convertase subtilisin / kexin type 9 (PCSK-9) inhibitors as second-and third-line treatments, respectively, to statins, and to analyze in whom these agents should be prescribed in light of recent updates to international guidelines on cholesterol lowering. The role of low-density lipoprotein cholesterol reduction in cardiovascular events and the current therapeutic armamentarium The role of elevated atherogenic lipoprotein levels in the development of ASCVD and its clinical manifestations is firmly established. Data from

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Evolocumab for Early Reduction of LDL Cholesterol Levels in Patients With Acute Coronary Syndromes (EVOPACS)

Cited by 177 publications

References 22 publications

PCSK9 Inhibition: Insights From Clinical Trials and Future Prospects

PCSK9 Inhibition: Insights From Clinical Trials and Future Prospects

Efficacy and safety of PCSK9 monoclonal antibodies: an evidence-based review and update

Statins plus ezetimibe in the era of proprotein convertase subtilisin/ kexin type 9 inhibitors

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