scholarly journals The incremental net benefit of lipid-lowering therapy with PCSK9 inhibitors: A Systematic Review and Meta-analysis of cost-utility studies

2021 ◽  
Author(s):  
Bhavani Shankara Bagepally ◽  
Akhil Sasidharan

Introduction: Proprotein convertase subtilisin/kexin 9 inhibitors (PCSK9i) are monoclonal antibodies that lower lipid levels by inhibiting PCSK9. Although several cardiovascular outcome trials reported beneficial clinical effectiveness of PCSK9i, the evidence on cost-effectiveness is mixed. We systematically reviewed the evidence on cost-effectiveness and synthesized incremental net benefit (INB) to quantify the pooled cost-effectiveness of PCSK9i lipid-lowering therapy. Methods: We systematically searched for full economic evaluation studies reporting outcomes of PCSK9 inhibitors compared with any other lipid-lowering pharmacotherapies. We searched PubMed, Embase, Scopus, and Tufts Registry for eligible studies up-to September 2020, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. We pooled the INB with a 95% confidence interval using a random-effects model. We assessed the Heterogeneity using the Cochrane-Q test and I2 statistic. We used the modified economic evaluations bias (ECOBIAS) checklist to evaluate the quality of the selected studies.Results: A total of 20 studies were eligible, mainly from high-income countries (HIC). The pooled INB of PCSK9i versus other lipid-lowering pharmacotherapies were estimated from n=21 comparisons; with high heterogeneity (I2=98.04). The INBp (95% CI) was US$ -46,665 (-196,203; 102,874), PCSK9i was found to be not cost-effective when compared with other standard therapies; however, this finding was not statistically significant. On subgroup analysis PCSK9i was significantly not cost-effective [US$ -25,686 (-26,085;-25,287), I2=0] compared to other lipid-lowering pharmacotherapies among HICs, with payers perspective [US$ -25,686 (-26,086;-25,287), I2=0] and with higher discount rates of 5% for cost [US$ -25,686 (-26,086;-25,287), I2=0]. The sensitivity analysis revealed the subgroup findings are not robust.Conclusion: PCSK9is’ are not cost-effective compared to other lipid-lowering pharmacotherapies in HICs. Further, current pieces of evidence are predominantly from HICs with largely lacking evidence from other economies. Prospero registration: ID CRD42020206043

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Jorge A. H. Arroz ◽  
Baltazar Candrinho ◽  
Chandana Mendis ◽  
Melanie Lopez ◽  
Maria do Rosário O. Martins

Abstract Objective The aim is to compare the cost-effectiveness of two long-lasting insecticidal nets (LLINs) delivery models (standard vs. new) in universal coverage (UC) campaigns in rural Mozambique. Results The total financial cost of delivering LLINs was US$ 231,237.30 and US$ 174,790.14 in the intervention (302,648 LLINs were delivered) and control districts (219,613 LLINs were delivered), respectively. The average cost-effectiveness ratio (ACER) per LLIN delivered and ACER per household (HH) achieving UC was lower in the intervention districts. The incremental cost-effectiveness ratio (ICER) per LLIN and ICER per HH reaching UC were US$ 0.68 and US$ 2.24, respectively. Both incremental net benefit (for delivered LLIN and for HHs reaching UC) were positive (intervention deemed cost-effective). Overall, the newer delivery model was the more cost-effective intervention. However, the long-term sustainability of either delivery models is far from guaranteed in Mozambique’s current economic context.


Author(s):  
Mandana Zanganeh ◽  
Peymane Adab ◽  
Bai Li ◽  
Emma Frew

Many suggested policy interventions for childhood and adolescent obesity have costs and effects that fall outside the health care sector. These cross-sectorial costs and consequences have implications for how economic evaluation is applied and although previous systematic reviews have provided a summary of cost-effectiveness, very few have conducted a review of methods applied. We undertook this comprehensive review of economic evaluations, appraising the methods used, assessing the quality of the economic evaluations, and summarising cost-effectiveness. Nine electronic databases were searched for full-economic evaluation studies published between January 2001 and April 2017 with no language or country restrictions. 39 economic evaluation studies were reviewed and quality assessed. Almost all the studies were from Western countries and methods were found to vary by country, setting and type of intervention. The majority, particularly “behavioural and policy” preventive interventions, were cost-effective, even cost-saving. Only four interventions were not cost effective. This systematic review suggests that economic evaluation of obesity interventions is an expanding area of research. However, methodological heterogeneity makes evidence synthesis challenging. Whilst upstream interventions show promise, an expanded and consistent approach to evaluate cost-effectiveness is needed to capture health and non-health costs and consequences.


2020 ◽  
Vol 41 (40) ◽  
pp. 3900-3909 ◽  
Author(s):  
Ali Allahyari ◽  
Tomas Jernberg ◽  
Emil Hagström ◽  
Margrét Leosdottir ◽  
Pia Lundman ◽  
...  

Abstract Aims To estimate the proportion of patients with a recent myocardial infarction (MI) who would be eligible for additional lipid-lowering therapy according to the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines for the management of dyslipidaemias, and to simulate the effects of expanded lipid-lowering therapy on attainment of the low-density lipoprotein cholesterol (LDL-C) target as recommended by the guidelines. Methods and results Using the nationwide SWEDEHEART register, we included 25 466 patients who had attended a follow-up visit 6–10 weeks after an MI event, 2013–17. While most patients (86.6%) were receiving high-intensity statins, 82.9% of the patients would be eligible for expanded lipid-lowering therapy, as they had not attained the target of an LDL-C level of <1.4 mmol and a ≥50% LDL-C level reduction. When maximized use of high-intensity statins followed by add-on therapy with ezetimibe was simulated using a Monte Carlo model, the LDL-C target was reached in 19.9% using high-intensity statin monotherapy and in another 28.5% with high-intensity statins and ezetimibe, while 50.7% would still be eligible for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. When use of alirocumab or evolocumab was simulated in those who were eligible for PCSK9 inhibitors, around 90% of all patients attained the LDL-C target. Conclusion  Our study suggests that, even with maximized use of high-intensity statins and ezetimibe, around half of patients with MI would be eligible for treatment with PCSK9 inhibitors according to the 2019 ESC/EAS guidelines. Considering the current cost of PCSK9 inhibitors, the financial implications of the new guidelines may be substantial.


2020 ◽  
Vol 4 (7) ◽  
pp. 437-444
Author(s):  
O.L. Barbarash ◽  
◽  
V.V. Kashtalap ◽  
N.V. Fedorova ◽  
D.Yu. Sedykh ◽  
...  

The article presents current data on the prevalence of dyslipidemia worldwide and in the Russian Federation as the main cardiovascular risk factor of developing diseases associated with atherosclerosis. The article identifies the problems of low-level detection of dyslipidemia in the population and insufficient efficacy of lipid-lowering therapy to achieve the lipid profile target values depending on the established risk. It also presents the possibilities of modern lipid-lowering therapy with the use of innovative drugs — PCSK9 inhibitors and the use of evolocumab in accordance with evidence-based medicine. Adding that, the article shows the experience of two lipid control centers (in Kemerovo and Surgut) with the postulation of the need to expand the lipid control center chain to improve methods for providing medical care to patients with severe forms of dyslipidemia. The possibilities of intensifying lipid-lowering therapy in real clinical practice are outlined on the example of patients undergoing treatment in the lipid control center of Kemerovo. Evolocumab has been shown to be highly effective: reduction of atherogenic cholesterol fractions by 67% from the baseline and high safety of such therapy.KEYWORDS: lipid metabolism disorders, statins, lipid-lowering therapy, familial hypercholesterolemia, PCSK9 inhibitors, evolocumab.FOR CITATION: Barbarash O.L., Kashtalap V.V., Fedorova N.V. et al. Intensification of lipid-lowering therapy in patients with severe lipid metabolism disorders in specialized lipid control centers. Possibilities of using evolocumab. Russian Medical Inquiry. 2020;4(7):437–444. DOI: 10.32364/2587-6821-2020-4-7-437-444.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
F Noack ◽  
B Schwaab ◽  
H Voeller ◽  
K Eckrich ◽  
M Guha ◽  
...  

Abstract Background In the current guideline of the ESC, in patients with very high cardiovascular risk such as coronary heart disease (CHD) a treatment target for LDL-C <1.4mmol/l and/or a halving of the initial value are defined. It is unclear whether these treatment targets are achievable with standard therapy including statins and/or ezetemibe. Methods The primary objective of this prospective, multi-centre register study was the question of the guidance-based adaptation and adherence to lipid-lowering therapy during and after a cardiac rehabilitation in 1,100 patients with CHD up to 12 months after discharge from the six rehabilitation clinics involved. Patients were included from 2016 to 2018. Results The median age of the 1,100 patients was 63.4±10.4 years, the mean BMI was 28.5±4.7kg/m2, and 24.1% of patients were female. 12.2% were active smokers, 91.6% reported dyslipoproteinemia, 33.9% suffered from diabetes mellitus and 86.5% from hypertension. The majority of patients were included with the main indications NSTEMI (31.6%), STEMI (29.6%) and after CABG surgery (26.4%). The proportion of patients treated with statins was more than 94% when admitted and discharged from the rehabilitation clinic, as well as in 3- and 12-months follow-ups. Approximately 9% of patients were treated with ezetemibe at baseline. On discharge from the rehabilitation clinic 23% of patients were treated with ezetemibe, which remains stable at 3 and 12 months. PCSK9 inhibitors were used in 0.1–0.3% of patients at all times. The adjustment of LLT during three week cardiac rehabilitation resulted in median LDL-C values of 2.27mmol/l (1.80/2.84) at baseline, 1.97mmol/l (1.57/2.47) on discharge (p<0.001 compared to baseline), 1.94mmol/l (1.57/2.49) after three months and 1.94mmol/l (1.53/2.40) after 12 months. The proportion of patients with LDL-C <1.4mmol/l was 9% at baseline, 15.7% on discharge (p<0.001 compared to baseline), 15.6% at three-month follow-up and 15.1% at 12-month follow-up (Figure 1). Discussion In the context of cardiac rehabilitation, an effective adjustment of LLT is carried out, which resulted in a significant reduction of LDL-C. However, despite a high percentage of patients on statins and ezetemibe, the proportion of patients in the new target range <1.4mmol/l was only achievable in a small percentage and the question arises whether these treatment targets can be achieved without additional administration of PCSK9 inhibitors in majority of patients with CHD. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): This study was supported by an unrestricted grant from Sanofi-Aventis Germany.


2020 ◽  
Vol 878 ◽  
pp. 173114 ◽  
Author(s):  
Enrique Gallego-Colon ◽  
Aner Daum ◽  
Chaim Yosefy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B Hirsh-Raccah ◽  
A Yanovsky ◽  
V Rotshild ◽  
H Danenberg ◽  
R Eliaz ◽  
...  

Abstract Background Lipid lowering therapy may be associated with impaired cognitive function. The association between the use of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors and the risk of neurocognitive adverse effects remains unclear. Purpose To assess the neurocognitive safety of PCSK9 inhibitors using meta-analysis and meta-regression of randomized controlled trials (RCTs). Methods PubMed (MEDLINE), Embase and Cochrane library were searched. RCTs that reported assessments of neurocognitive outcomes of participants using PCSK9 inhibitors, with a duration of follow up of at least six months were included. The results of the search were screened by two independent reviewers. Any disagreements were resolved by consensus. The research was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension statement for meta-analyses. Results were pooled using random-effects models. The primary safety outcome of this analysis was defined as the reported incidence of neurocognitive adverse effects. Results Results of 21 trials were included in the analysis. Among 59,733 patients, 31,611 were treated with PCSK9 inhibitors. No significant difference in the incidence of neurocognitive side effects between the treatment and control groups was identified (RR=1.01, 95% CI: 0.86–1.19, I2=3%). Same results were seen in separate analysis for each of the medicines (Alirocumab- RR=0.88, 95% CI: 0.72–1.08, I2=0%, Evolocumab- RR=1.42, 95% CI: 0.74–2.73, I2=55%). In a meta-regression analysis there was no statistically significant association between the assessed and the risk for neurocognitive side effects. Conclusions Pooled results of our meta-analysis and meta-regression clearly show that the exposure to PCSK9 inhibitors is not associated with an increased risk of neurocognitive adverse events. Due to the increasing proportion of patients using lipid-lowering therapy these results are positively reassuring. However, more data from long-term outcomes studies is needed to further evaluate the effect of longer exposure to PCSK9 inhibitors Funding Acknowledgement Type of funding source: None


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