PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease

Schmidt, Amand F.; Carter, John-Paul; Pearce, Lucy S; Wilkins, John T.; Overington, John P.; Hingorani, Aroon D.; Casas, JP

doi:10.1002/14651858.cd011748.pub3

Cited by 62 publications

(63 citation statements)

References 94 publications

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“…Updated analysis shows that there is evidence for treating patients with PCSK9i, who are not eligible for other drugs or who cannot reduce LDL-C on traditional therapies. However, the evidence base of PCSK9i against other active treatments is weaker 25 .…”

Section: Introductionmentioning

confidence: 99%

Incremental net benefit of lipid-lowering therapy with PCSK9 inhibitors: a systematic review and meta-analysis of cost-utility studies

Bagepally

Sasidharan

2021

Eur J Clin Pharmacol

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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 I 2 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 (I 2 =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 085;287), I 2 =0] compared to other lipid-lowering pharmacotherapies among HICs, with payer's perspective 086;287), I 2 =0] and with higher discount rates of 5% for cost 086;287), I 2 =0]. The sensitivity analysis revealed that 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.

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Section: Introductionmentioning

confidence: 99%

Incremental net benefit of lipid-lowering therapy with PCSK9 inhibitors: a systematic review and meta-analysis of cost-utility studies

Bagepally

Sasidharan

2021

Eur J Clin Pharmacol

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“…These results agreed with the analysis of secondary prevention in our network meta-analysis. Whether PCSK9i can reduce mortality, however, is controversial ( Schmidt et al, 2020 ). Our findings showed that PCSK9i added to background high-intensity statins was associated with a reduced risk of all-cause mortality and cardiovascular mortality.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Lipid-Lowering Drugs of Different Intensity on Clinical Outcomes: A Systematic Review and Network Meta-Analysis

Pan

et al. 2021

Front. Pharmacol.

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There have been many meta-analyses for statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) to evaluate clinical outcomes, but the efficacy and safety of different intensity of these three drugs on clinical outcomes was absent. PCSK9i, ezetimibe, and statins were divided into seven interventions as follows: including PCSK9i + high-intensity statins (P9i+HT), PCSK9i + moderate-intensity statins (P9i+MT), ezetimibe + high-intensity statins (Eze+HT), ezetimibe + moderate-intensity statins (Eze+MT), high-intensity statins (HT), moderate-intensity statins (MT), and low-intensity statins (LT). The risk ratios (RR) and 95% confidence intervals (CI) were calculated to evaluate the clinical outcomes in all randomized controlled trials included. In traditional meta-analysis, the more intensive treatment had a lower risk of all-cause mortality (RR 0.91, 95% CI 0.88–0.95), cardiovascular mortality (RR 0.89, 95% CI 0.86–0.92), myocardial infarction (RR 0.79, 95% CI 0.77–0.81), coronary revascularization (RR 0.80, 95% CI 0.76-0.84), and cerebrovascular events (RR 0.84, 95% CI 0.80–0.88) compared with the less intensive treatment. However, the more intensive treatment had a higher risk of new-onset diabetes (RR 1.08, 95% CI 1.04-1.12). The network meta-analysis demonstrated that P9i+HT, P9i+MT, HT, and MT were significantly associated with a risk reduction in coronary revascularization and cerebrovascular events compared with PLBO. LT could effectively reduce the risk of cardiovascular mortality (RR 0.71, 95% CI 0.54–0.92), MI (RR 0.67, 95% CI 0.54-0.82), and coronary revascularization (RR 0.77, 95% CI 0.65–0.91) compared with PLBO. P9i+HT was superior to HT in reducing the risk of MI (RR 0.78, 95% CI 0.68–0.90), coronary revascularization (RR 0.84, 95% CI 0.73–0.96), and cerebrovascular events (RR 0.78, 95% CI 0.64–0.95). However, compared with PLBO, P9i+HT, HT, and MT could increase the risk of new-onset diabetes (RR 1.23, 95% CI 1.11–1.37; RR 1.23, 95% CI 1.14–1.33; RR 1.09, 95% CI 1.02–1.15, respectively). In conclusion, PCSK9i added to background statins may be recommended as preferred lipid-lowering therapy, and did not increase the additional risk of new-onset diabetes. The safety and efficacy of ezetimibe was not superior to that of statins. LT can be recommended as the initial therapy.

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“…Therefore, Lp(a) should now be considered a therapeutic target, especially after ACS [82]. There was a tremendous advantage when comparing alirocumab or evolocumab with placebo or ezetimibe plus a statin in another trial; however, the benefit difference between the two groups was not significant when comparing the two groups utilizing the combination of ezetimibe and statin [83].…”

Section: Treatment Of High Lipoprotein (A)mentioning

confidence: 99%

Residual Cardiovascular Risk Factors in Dyslipidemia

Nguyen¹,

Tran²,

Vo³

et al. 2022

Risk Factors for Cardiovascular Disease

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Cardiovascular disease poses a major challenge for the 21st century. Although good control of blood pressure and type 2 diabetes and reducing low-density lipoprotein-cholesterol levels can improve cardiovascular outcomes, a substantial residual risk remains existed after treatment in most patient populations. Recently, many efforts have been directed at finding the important role of low high-density-lipoprotein cholesterol, high triglycerides, especially triglyceride-rich lipoproteins and lipoprotein (a) in the metabolism of atherosclerotic plaque formation Therefore, based on the recent evidence, identification and treatment of these risk factors may play a role in optimizing therapeutic strategy, particularly in high risk subjects along with conventional treatment. In clinical practice, adequate attention should be paid when screening and managing residual cardiovascular risk factors in dyslipidemia in term of individualized approach. The ongoing trials will give more answers to elucidate this important area.

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PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease

Cited by 62 publications

References 94 publications

Incremental net benefit of lipid-lowering therapy with PCSK9 inhibitors: a systematic review and meta-analysis of cost-utility studies

Incremental net benefit of lipid-lowering therapy with PCSK9 inhibitors: a systematic review and meta-analysis of cost-utility studies

Efficacy and Safety of Lipid-Lowering Drugs of Different Intensity on Clinical Outcomes: A Systematic Review and Network Meta-Analysis

Residual Cardiovascular Risk Factors in Dyslipidemia

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