Tools for Practice Outils pour la pratique


#215 PCSK9 Inhibitors: Cardiovascular prevention panacea or pesky, pricey pokes?


CLINICAL QUESTION
QUESTION CLINIQUE
Do pro-protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors decrease cardiovascular events, and if so, are they cost-effective?


BOTTOM LINE
RÉSULTAT FINAL
For patients with cardiovascular disease (CVD) already on maximally tolerated statins, adding evolocumab or alirocumab decreases new CVD events for an additional one in 65 patients compared to placebo over ~2.5 years. Routine use of these agents is not cost-effective at current prices.  



CFPCLearn Logo

Reading Tools for Practice Article can earn you MainPro+ Credits

La lecture d'articles d'outils de pratique peut vous permettre de gagner des crédits MainPro+

Join Now S’inscrire maintenant

Already a CFPCLearn Member? Log in

Déjà abonné à CMFCApprendre? Ouvrir une session



EVIDENCE
DONNÉES PROBANTES
  • Focusing on two largest, industry-sponsored, placebo-controlled trials evaluating clinical outcomes.1,Patients had existing CVD and LDL >1.8 mmol/L while on maximally tolerated statins.1,2  
    • Evolocumab: 27,564 patients randomized to evolocumab (140 mg every two weeks or 420 mg monthlyor placebo.1 At 2.2 years:  
      • New CVD eventsEvolocumab 9.8%, placebo 11.3%, statistically significant 
        • Number Needed to Treat (NNT)=67. 
        • CVD reduction: Independent of baseline LDL. 
      • Death (any cause): No difference. 
    • Alirocumab: (pending publication) 18,924 patients post-acute coronary syndrome randomized to alirocumab (75-150 mg every two weeks) or placebo.2 At 2.8 years statistically significant reduction in: 
      • New CVD events: Alirocumab 9.5%, placebo 11.1%, NNT=63. 
      • Death (any cause): Alirocumab 3.5%, placebo 4.1%, NNT=167. 
        • Note: Statistical difference in death based on six fewer deaths. 
  • Adverse events:1,2 
    • Primarily injection site reactions: Number Needed to Harm ~100. 
  • Other smaller randomized controlled trials limited by only reporting surrogate outcomes,3 lack of blinding,4,and enrolling familial hypercholesterolemia patientsor patients from previous studies.3,5 These studies found inconsistent effects on CVD.5,6 
Context:  
  • Bococizumab research and development stopped due to development of drug-neutralizing antibodies.7 
    • Development of neutralizing antibodies to alirocumab and evolocumab is rare and usually clinically insignificant.1,8 
  • No studies on statin intolerant patients have evaluated clinical outcomes.9 
  • Some guidelines recommend considering PCSK9 inhibitors for patients with familial hypercholesterolemia or CVD whose LDL remains above target despite maximum-tolerated statin +/- ezetimibe.10,11 
  • Routine use of PCSK9 inhibitors in CVD patients is not cost-effective at current Canadian prices (~$7,100/year).12 A >90% price reduction would be required for cost-effectiveness.12 


Latest Tools for Practice
Derniers outils pour la pratique

#359 Topical corticosteroids for atopic dermatitis - More than skin deep

What are the benefits/harms of topical corticosteroids for atopic dermatitis in adults/children?
Read Lire 0.25 credits available Crédits disponibles

#358: Any berry good solutions to preventing UTIs: Cranberries?

Do cranberry products prevent recurrent urinary tract infections (UTIs)?
Read Lire 0.25 credits available Crédits disponibles

#357: Overcoming Resistance: Antipsychotics for difficult to treat depression

In patients with treatment-resistant depression, is adding an atypical antipsychotic to current therapy safe and effective?
Read Lire 0.25 credits available Crédits disponibles

This content is certified for MainPro+ Credits, log in to access

Ce contenu est certifié pour les crédits MainPro+, Ouvrir une session


Author(s)
Auteur(s)
  • Michael R Kolber BSc MD CCFP MSc
  • Tony Nickonchuk BScPharm
  • Ricky D. Turgeon BSc(Pharm) ACPR PharmD

1. Sabatine MS, Giugliano RP, Keech AC, et al for the FOURIER Steering Committee and Investigators. N Engl J Med. 2017; 376:1713-22.


2. Alirocumab in Patients after Acute Coronary Syndrome; 2018. Available at: https://accscientificsession.acc.org/~/media/ScientificSessions/ACC18/PDFs/Sanofi-stream/Session-401-ODYSSEY-slides.pdf. Last Accessed: April 24, 2018.

3. Blom DJ, Hala T, Bolognese M, et al for the DESCARTES Investigators. N Engl J Med. 2014; 370:1809-19


4. Raal FJ, Honarpour N, Blom DJ, et al for the TESLA Investigators. Lancet. 2015; 385: 341-50.

5. Sabatine MS, Giugliano RP, Wiviott SD, et al for the Open-Label Study of Long-Term Evaluation against LDL Cholesterol (OSLER) Investigators. N Engl J Med. 2015; 372:1500-9.

6. Robinson JG, Farnier M, Krempf M, et al for the ODYSSEY LONG TERM Investigators. N Engl J Med. 2015; 372:1489-99.



7. Ridker PM, Revkin J, Amarenco P, et al for the SPIRE Cardiovascular Outcome Investigators. N Engl J Med. 2017; 376:1527-39.


8. Roth EM, Goldberg AC, Catapano AL, et al. Antidrug antibodies in patients treated with alirocumab. N Engl J Med. 2017; 376:1589-90.

9. Karatasakis A, Danek BA, Karacsonyi J, et al. J Am Heart Assoc. 2017; 6:e006910.

10. Anderson TJ, Gregoire J, Pearson GJ, et al. Can J Cardiol. 2016; 32:1263-82.

11. Lloyd-Jones DM, Morris PB, Ballantyne CM, et al. J Am Coll Cardiol. 2017; 70:1785-822.

12. CADTH Canadian Drug Expert Committee Recommendation. Evolocumab (REPATHA—AMGEN CANADA INC). Available at: https://www.cadth.ca/sites/default/files/cdr/complete/SR0515_Repatha_Resubmission_complete_Nov_24_17.pdf. Last Accessed: April 24, 2018.

Authors do not have any conflicts of interest to declare.

Les auteurs n’ont aucun conflit d’intérêts à déclarer.