PCSK9 inhibition, atherosclerotic cardiovascular disease, and health economics: Challenges at the crossroads

Abstract

BACKGROUND: Improved survival after a cardiovascular event has led to an expanding patient population at very high risk of recurrent events. Reduction in low-density lipoprotein cholesterol, and thus implicitly non-high-density lipoprotein cholesterol, to guideline-recommended goals is a key tenet of secondary prevention. Yet, standard-of-care treatment with statin (with or without ezetimibe) often leaves a high risk of preventable cardiovascular events. Inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9), highly efficacious lipid-lowering treatments that confer reduction in cardiovascular events and death, clearly have a role in the personalized management of these very-high-risk patients. Given budget constraints, however, their integration into the health care pathway merits health economic considerations. Consequently, it is important to identify challenges at the crossroads of the clinical and economic dimensions.FINDINGS AND CONCLUSION: Health economic analyses involve application of modeling scenarios integrating multiple parameters to ultimately yield values for quality-adjusted life-years and cost-effectiveness ratios. To date, these analyses have led to widely variable estimates of these benchmarks for PCSK9 inhibitors, causing confusion among stakeholders in the health care pathway. Clearly, a consensual approach to the conduct and reporting of health economic analyses involving all players, including noneconomists such as clinicians and patient advocates, is essential to bridge the gap between the clinical needs of patients and financial access to PCSK9 inhibition.

Adverse event profiles of PCSK9 inhibitors alirocumab and evolocumab: Data mining of the FDA adverse event reporting system

“…The 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines recommended proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors for the management of dyslipidemias 8 . According to recent clinical trials, the addition of PCSK9 inhibitors to statin therapy further reduced LDL‐C levels, as well as the risk of ASCVD 9–11 . PCSK9, as a proteolytic enzyme, can bind to LDL receptors (LDLRs) on cell surfaces and induce LDLR degradation, thereby upregulating serum LDL‐C indirectly.…”

“…8 According to recent clinical trials, the addition of PCSK9 inhibitors to statin therapy further reduced LDL-C levels, as well as the risk of ASCVD. [9][10][11] PCSK9, as a proteolytic enzyme, can bind to LDL receptors (LDLRs) on cell surfaces and induce LDLR degradation, thereby upregulating serum LDL-C indirectly. PCSK9 inhibitors bind to PCSK9 specifically, thus blocking the binding of PCSK9 to LDLRs.…”

Nonadherence to lipid‐lowering therapy and strategies to improve adherence in patients with atherosclerotic cardiovascular disease

“…Cost‐effectiveness rather than cost should be used to determine patient access to therapy. 46 The active engagement of professional societies to address these challenges and to advocate for patient access to therapy should also benefit patients (Figure 1 ).…”

“…One approach could be to assess the cost‐effectiveness of available LLTs using validated health economic models based on data from randomized clinical trials or postregistrational studies. Cost‐effectiveness rather than cost should be used to determine patient access to therapy 46 . The active engagement of professional societies to address these challenges and to advocate for patient access to therapy should also benefit patients (Figure 1).…”

Αναζήτηση Βιοδεικτών Σε Ασθενείς Με Επαναλαμβανόμενα Καρδιαγγειακά Περιστατικά Για Την Βέλτιστη Κλινική Πρακτική

“…Άλλη μελέτη των Talmud και συνεργατών ανέδειξε πως η συσσώρευση κοινών μονονουκλεοτιδικών πολυμορφισμών, που σχετίζονται με τα επίπεδα της LDL-c, μπορεί να οδηγήσει στην αύξηση των επιπέδων αυτής στο αντίστοιχο επίπεδο της οικογενούς υπερχολυστερολαιμίας και να προκαλέσει πολυγονιδιακή υπερχοληστερολαιμία (Talmud et al, 2013). Η αντιμετώπιση των υψηλών LDL-c επιπέδων με μια εύστοχη ανά άτομο θεραπευτική προσέγγιση είναι απαραίτητη για την πρόληψη των επαναλαμβανόμενων καρδιαγγειακών διαταραχών (Annemans et al, 2019).…”