Cost-Effectiveness of Alirocumab in Patients With Acute Coronary Syndromes

Bhatt, Deepak L.; Briggs, Andrew; Reed, Shelby D.; Annemans, Lieven; Szarek, Michael; Bittner, Vera; Dı́az, Rafael; Goodman, Shaun G.; Harrington, Robert A.; Higuchi, Keiko; Joulain, Florence; Jukema, J. Wouter; Li, Qian H; Mahaffey, Kenneth W.; Sanchez, Robert J.; Roe, Matthew T.; Lopes, Renato D.; White, Harvey D.; Zeiher, Andreas M.; Schwartz, Gregory G.; Steg, Ph. Gabriel; Tricoci, Pierluigi; Edelberg, Jay M.; Hanotin, Corinne; Lecorps, Guillaume; Moryusef, Angèle; Pordy, Robert; Sasiela, William J.; Tamby, Jean-François

doi:10.1016/j.jacc.2020.03.029

Cited by 52 publications

(50 citation statements)

References 27 publications

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“…The log linear association between LDL-C and ASCVD risk reduction results in diminishing cardiovascular risk reduction benefits from intensifying LDL-C lowering below 100 mg/dl unless ASCVD risk is extremely high due to an extensive burden of atherosclerosis and poorly controlled risk factors. This has important implications for clinical practice, cost effectiveness, and clinical trial planning [ 35 , 36 ]. The findings from this analysis support an evidence-based approach based on LDL-C and risk levels, which can be used to guide choice of the next therapy when considering multiple LDL-C lowering and other risk reduction therapies for a high risk patient.…”

Section: Discussionmentioning

confidence: 99%

“…This translates into improved cost-effectiveness when LDL-C ≥100 mg/dl [ 35 ]. In a recent cost-effectiveness analysis of the ODYSSEY OUTCOMES trial of alirocumab versus in patients with an acute coronary syndrome in the previous year, at an acquisition price of US$5850, the incremental cost effectiveness ratio of alirocumab was US$41,000 per quality adjusted life-year (QALY) for those with LDL-C ≥100 mg/dl on maximal statin therapy, compared to US$ 299,400 per QALY when LDL-C was <100 mg/dl [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, when LDL-C levels are <100 mg/dl on maximally tolerated statin therapy, mortality benefits are less likely to accrue from further LDL-C lowering, and there is an attenuation of the relative risk reduction in CHD events due to being in the flat part of the log linear curve [ 7 ]. As a result, cost-effectiveness worsens in this patient group compared to those with LDL-C ≥100 mg/dl [ 36 ]. In both large scale PCSK9 mAb trials involving very high risk secondary prevention patients, despite a large reduction in LDL-C to LDL-C levels of 30–50 mg/dl, the reduction in ASCVD endpoints was only 20% in the trial population overall [ 13 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

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Clinical implications of the log linear association between LDL-C lowering and cardiovascular risk reduction: Greatest benefits when LDL-C >100 mg/dl

et al. 2020

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Background The log linear association between on-treatment LDL-C levels and ASCVD events is amplified in higher risk patient subgroups of statin versus placebo trials. Objectives Update previous systematic review to evaluate how the log linear association influences the magnitude of cardiovascular risk reduction from intensifying LDL-C lowering therapy. Methods MEDLINE/PubMED, Clinical trials.gov, and author files were searched from 1/1/2005 through 10/30/2019 for subgroup analyses of cardiovascular outcomes trials of moderate versus high intensity statin, ezetimibe, and PCSK9 mAbs with an ASCVD endpoint (nonfatal myocardial infarction or stroke, cardiovascular death). Annualized ASCVD event rates were used to extrapolate 5-year ASCVD risk for each treatment group reported in subgroup analyses, which were grouped into a priori risk groups according to annualized placebo/control rates of ≥4%, 3–3.9%, or <3% ASCVD risk. Data were pooled using a random-effects model. Weighted least-squares regression was used to fit linear and log-linear models. Results Systematic review identified 96 treatment subgroups from 2 trials of moderate versus high intensity statin, 2 trials of a PCSK9 mAb versus placebo, and 1 trial of ezetimibe versus placebo. A log linear association between on-treatment LDL-C and ASCVD risk represents the association between on-treatment LDL-C levels and ASCVD event rates, especially in higher risk subgroups. Greater relative and absolute cardiovascular risk reductions from LDL-C lowering were observed when baseline LDL-C was >100 mg/dl and in extremely high risk ASCVD patient groups. Conclusions Greater cardiovascular and mortality risk reduction benefits from intensifying LDL-C lowering therapy may be expected in those with LDL-C ≥100 mg/dl, or in extremely high risk patient groups. When baseline LDL-C <100 mg/dl, the log linear association between LDL-C and event rates suggests that treatment options other than further LDL-C lowering should also be considered for optimal risk reduction.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Clinical implications of the log linear association between LDL-C lowering and cardiovascular risk reduction: Greatest benefits when LDL-C >100 mg/dl

et al. 2020

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“…Имеются данные о возможности повышения концентрации антиатерогенных маркеров -АпоА1, за счет комплексного липидмодифицирующего эффекта ингибиторов PCSK9 [7,12,13]. Применение ингибиторов PCSK9 в госпитальном периоде лечения ОКС имеет дополнительное патофизиологическое обоснование, поскольку у таких пациентов с первых суток развития атеротромботического события повышается уровень активно изучаемого в настоящее время проатерогенного фактора ССР -PCSK9, который ассоциирован с риском повторных кардиоваскулярных событий [3,4,[15][16][17][18][19][20]. Так, в исследовании Okada K, et al продемонстрировано повышение у пациентов с ОКС уровня PCSK9 в течение 12 нед.…”

Section: Discussionunclassified

PCSK9 inhibitors for in-hospital treatment of patients with acute coronary syndrome and severe lipid metabolism disorders

Барбараш¹,

Федорова²,

Седых³

et al. 2020

Russ J Cardiol

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Aim. To assess the efficacy and safety of PCSK9 inhibitor alirocumab as part of a combination lipid-lowering therapy in patients with acute coronary syndrome (ACS).Material and methods. This prospective, open-label, single-center activetreatment study included 13 patients hospitalized due to ACS. The main inclusion criterion was nonachievement of target low-density lipoprotein cholesterol (LDL-C) values (<1,4 mmol/L) with high-intensity statin therapy prior to ACS. During the first 30 days after ACS, all patients received therapy with atorvastatin 40-80 mg/day or rosuvastatin 20-40 mg/day in combination with alirocumab 150 mg/ml (Praluent) administered by subcutaneous injection. Lipid and biochemical profiles were monitored. The first injection of the PCSK9 inhibitor was performed on days 3-5 of hospitalization, the second — after 2 weeks.Results. On admission, the median LDL-C was 4,3 [3,5;5,3] mmol/L. A day after administration, there was a decrease in LDL-C by 41,9% (median 2,5 [1,8;3,2] mmol/L; p=0,001) without a negative effect on high-density lipoproteins (HDL-C) (median 1,2 [0,8;1,4] mmol/L; p=0,270). Before the next injection, LDL-C decreased by another 8% (median 2,3 [1,1;4,1] mmol/L). A day after the second injection, a decrease in LDL-C from the baseline values was 69,8% (median 1,3 [0,7;1,5] mmol/L; p=0,010). Strengthening lipid-lowering therapy with a PCSK9 inhibitor within 30 days after ACS did not lead to clinical and biochemical deterioration.Conclusion. The use of subcutaneous 150-mg injections of alirocumab 2 times a week 30 days after ACS in patients who did not reach target LDL-C values with statin therapy, leads to a 69% decrease in LDL-C from baseline values and is safe.

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“…These results were further demonstrated with the cost-effectiveness of alirocumab shown using data from ODYSSEY OUTCOMES. 84…”

Section: Odyssey Outcomes -Subanalyses In High-risk Patientsmentioning

confidence: 99%

<p>Cardiovascular Outcomes and Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors: Current Data and Future Prospects</p>

Duprez¹,

Handelsman²,

Koren³

2020

VHRM

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Cardiovascular (CV) disease remains the leading cause of morbidity and mortality worldwide and poses an ongoing challenge with the aging population. Elevated lowdensity lipoprotein cholesterol (LDL-C) is an established risk factor for atherosclerotic cardiovascular disease (ASCVD), and the expert consensus is the use of statin therapy (if tolerated) as first line for LDL-C reduction. However, patients with ASCVD may experience recurrent ischemic events despite receiving maximally tolerated statin therapy, including those whose on-treatment LDL-C remains ≥70 mg/dL, patients with familial hypercholesterolemia, high-risk subgroups with comorbidities such as diabetes mellitus, and those who have an intolerance to statin therapy. Optimal therapeutic strategies for this unmet need should deploy aggressive lipid lowering to minimize the contribution of dyslipidemia to their CV risk, particularly for very high-risk populations with additional risk factors beyond hypercholesterolemia and established ASCVD. To understand the current clinical climate and guidelines regarding ASCVD, we primarily searched PubMed for articles published in English regarding lipid-lowering therapies and CV risk reduction, including emerging therapies, and CV outcomes trials with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. This review discusses the findings of recent clinical trial evidence for CV risk reduction with cholesterol-lowering therapies, with a focus on CV outcomes trials with PCSK9 inhibitors, and considers the impact of the study results for secondary prevention and future strategies in patients with hypercholesterolemia and CV risk despite maximally tolerated statin therapy.

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Cost-Effectiveness of Alirocumab in Patients With Acute Coronary Syndromes

Cited by 52 publications

References 27 publications

Clinical implications of the log linear association between LDL-C lowering and cardiovascular risk reduction: Greatest benefits when LDL-C >100 mg/dl

Clinical implications of the log linear association between LDL-C lowering and cardiovascular risk reduction: Greatest benefits when LDL-C >100 mg/dl

PCSK9 inhibitors for in-hospital treatment of patients with acute coronary syndrome and severe lipid metabolism disorders

<p>Cardiovascular Outcomes and Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors: Current Data and Future Prospects</p>

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