Efficacy, Safety and Clinical Applicability of PCSK9 Inhibitors

Walter Masson, Mariano Giorgi


Proprotein convertase subtilisin kexin type 9 (iPCSK9) inhibitors represent a new group of lipid-lowering drugs that havegenerated a substantial change in lipid management. In a few years, a large number of studies have evaluated the lipid efficacyand safety of these drugs. More recently, large randomized clinical trials showed that the decrease in LDL-C achievedwith these drugs was associated with a lower incidence of cardiovascular events. Such evidence resulted in the approval andcommercialization of iPCSK9 in many countries. Consequently, various scientific societies and health reference agenciesincorporated these drugs into the therapeutic arsenal of dyslipidemia, with the aim of reducing residual cardiovascular risk.In this review, we will describe the efficacy and safety of these drugs, analyze the available evidence about cardiovascularbenefit, and discuss in which population their use might be most effective.


Goldstein JL, Brown MS. The LDL receptor. Arterioscler

Thromb Vasc Biol. 2009;29:431-8. https://doi.org/10.1161/ATVBAHA.108.179564.

Abifadel M, Varret M, Rabès JP, Allard D, Ouguerram K, Devillers

M, et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia.

Nat Genet 2003;34:154-6. https://doi.org/10.1038/ng1161

Cohen J, Pertsemlidis A, Kotowski IK, Graham R, Garcia CK,

Hobbs HH. Low LDL cholesterol in individuals of African descent

resulting from frequent nonsense mutations in PCSK9. Nat Genet.

;37:161-5. https://doi.org/10.1038/ng1509

Peterson AS, Fong LG, Young SG. PCSK9 function and physiology. J Lipid Res. 2008;49:1152-6. https://doi.org/10.1194/jlr.E800008-JLR200.

Leren TP. Sorting an LDL receptor with bound PCSK9 to intracellular degradation. Atherosclerosis 2014;237:76-81. https://doi.org/10.1016/j.atherosclerosis.2014.08.038.

Chowdhury SR, Rees A. Inhibition of PCSK9: is this the way forward for managing residual risk? Curr Opin Lipidol. 2012;23:509-10. https://doi.org/10.1097/MOL.0b013e328358246a.

Vogel RA. PCSK9 inhibition: the next statin? J Am Coll Cardiol.

;59:2354-5. https://doi.org/10.1016/j.jacc.2012.03.011.

Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD,

Murphy SA, et al. Evolocumab and clinical outcomes in patients with

cardiovascular disease. N Engl J Med. 2017;376:1713-22. https://doi.org/10.1056/NEJMoa1615664.

Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R,

et al. Alirocumab and cardiovascular outcomes after acute coronary

syndrome. N Engl J Med. 2018;379:2097-2107. https://doi.org10.1056/NEJMoa1801174.

Blom DJ, Hala T, Bolognese M, Lillestol MJ, Toth PD, Burgess

L, et al. A 52-week placebo-controlled trial of evolocumab in hyperlipidemia.N Engl J Med. 2014;370: 1809-19. https://doi.org/10.1056/NEJMoa1316222.

Giugliano RP, Desai NR, Kohli P, Rogers WJ, Somaratne R, HuangF, et al. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57): a randomised, placebo-controlled, dose-ranging, phase 2 study. Lancet 2012;380:2007-17. https://doi.org/10.1016/S0140-6736(12)61770-X.

Hirayama A, Honarpour N, Yoshida M, Yamashita S, Huang F,

Wasserman SM, et al. Effects of evolocumab (AMG 145), a monoclonal antibody to PCSK9, in hypercholesterolemic, statin-treated Japanese patients at high cardiovascular risk--primary results from the phase 2 YUKAWA study. Circ J 2014;78:1073-82. https://doi.org/10.1253/circj.cj-14-0130.

Koren MJ, Lundqvist P, Bolognese M, Neutel JM, Monsalvo ML,

Yang J, et al. Anti-PCSK9 monotherapy for hypercholesterolemia:

the MENDEL-2 randomized, controlled phase III clinical trial of evolocumab. J Am Coll Cardiol 2014;63:2531-40. https://doi.org/10.1016/j.jacc.2014.03.018.

Koren MJ, Scott R, Kim JB, Knusel B, Liu T, Lei L, et al. Efficacy,

safety, and tolerability of a monoclonal antibody to proprotein

convertase subtilisin/kexin type 9 as monotherapy in patients with

hypercholesterolaemia (MENDEL): a randomised, double-blind,

placebo-controlled, phase 2 study. Lancet 2012;380:1995-2006. https://doi.org/10.1016/S0140-6736(12)61771-1.

Raal F, Scott R, Somaratne R, Bridges I, Li G, Wasserman SM,

et al. Low-density lipoprotein cholesterol-lowering effects of AMG

, a monoclonal antibody to proprotein convertase subtilisin/

kexin type 9 serine protease in patients with heterozygous familial

hypercholesterolemia: the reduction of LDL-C with PCSK9 inhibition

in heterozygous familial hypercholesterolemia disorder (RUTHERFORD) randomized trial. Circulation 2012;126:2408-17. https://doi.org/10.1161/CIRCULATIONAHA.112.144055.

Raal FJ, Stein EA, Dufour R, Turner T, Civeira F, Burgess L, et

al. PCSK9 inhibition with evolocumab (AMG 145) in heterozygous

familial hypercholesterolaemia (RUTHERFORD-2): a randomised,

double-blind, placebo-controlled trial. Lancet. 2015;385:331-40.


Robinson JG, Nedergaard BS, Rogers WJ, Fialkow J, Neutel JM, Ramstad D, et al. Effect of evolocumab or ezetimibe added to moderate-or high-intensity statin therapy on LDL-C lowering in patients with hypercholesterolemia: the LAPLACE-2 randomized clinical trial. JAMA 2014;311:1870-82. https://doi.org/10.1001/jama.2014.4030.

Stroes E, Colquhoun D, Sullivan D, Civeira F, Rosenson RS, Watts GF, et al. Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo controlledphase 3 clinical trial of evolocumab. J Am Coll Cardiol 2014;63:2541-48. https://doi.org/10.1016/j.jacc.2014.03.019.

Sullivan D, Olsson AG, Scott R, Kim JB, Xue A, Gebski V, et al.

Effect of a monoclonal antibody to PCSK9 on low-density lipoprotein

cholesterol levels in statin-intolerant patients: the GAUSS randomized trial. JAMA. 2012;308:2497-2506. https://doi.org/10.1001/jama.2012.25790.

Stroes E, Robinson JG, Raal FJ, Dufour R, Sullivan D, Kassahun H, et al. Consistent LDL-C response with evolocumab among patient subgroups in PROFICIO: A pooled analysis of 3146 patients from phase 3 studies. Clin Cardiol. 2018;41:1328-35. https://doi.org/10.1002/clc.23049.

Roth EM, McKenney JM. ODYSSEY MONO: effect of alirocumab

mg subcutaneously every 2 weeks as monotherapy versus ezetimibe over 24 weeks. Future Cardiol. 2015;11:27-37. https://doi.org/10.2217/fca.14.82.

Moriarty PM, Thompson PD, Cannon CP, Guyton JR, Bergeron

J, Zieve FJ, et al. Efficacy and safety of alirocumab vs ezetimibe in

statin-intolerant patients, with a statin rechallenge arm: The ODYSSEY ALTERNATIVE randomized trial. J Clin Lipidol 2015;9:758-69. https://doi.org/10.1016/j.jacl.2015.08.006.

Roth EM, Moriarty PM, Bergeron J, Langslet G, Manvelian G,

Zhao J, et al. A phase III randomized trial evaluating alirocumab 300

mg every 4 weeks as monotherapy or add-on to statin: ODYSSEY

CHOICE I. Atherosclerosis 2016;254:254-62. https://doi.org/10.1016/j.atherosclerosis.2016.08.043.

Stroes E, Guyton JR, Lepor N, Civeira F, Gaudet D, Watts GF, et al.Efficacy and Safety of Alirocumab 150 mg Every 4 Weeks in Patients With Hypercholesterolemia Not on Statin Therapy: The ODYSSEY CHOICE II Study. J Am Heart Assoc 2016;5: e003421. https://doi.org/10.1161/JAHA.116.003421.

Kereiakes DJ, Robinson JG, Cannon CP, Lorenzato C, Pordy R,

Chaudhari U, et al. Efficacy and safety of the proprotein convertase

subtilisin/kexin type 9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: the ODYSSEYCOMBO I study. Am Heart J 2015;169:906-915.e913. https://doi.org/10.1016/j.ahj.2015.03.004.

El Shahawy M, Cannon CP, Blom DJ, McKenney JM, Cariou

B, Lecorps G, et al. Efficacy and Safety of Alirocumab Versus

Ezetimibe Over 2 Years (from ODYSSEY COMBO II). Am J Cardiol

;120:931-39. https://doi.org/10.1016/j.amjcard.2017.06.023.

Kastelein JJ, Ginsberg HN, Langslet G, Hovingh GK, Ceska R,

Dufour R, et al. ODYSSEY FH I and FH II: 78 week results with

alirocumab treatment in 735 patients with heterozygous familial

hypercholesterolaemia. Eur Heart J 2015;36:2996-3003. https://doi.


Bays H, Gaudet D, Weiss R, Ruiz JL, Watts GF, Gouni-Berthold

I, et al. Alirocumab as add-on to atorvastatin versus other lipid

treatment strategies: ODYSSEY OPTIONS I randomized trial. J

Clin Endocrinol Metab. 2015;100:3140-48. https://doi.org/10.1210/


Farnier M, Jones P, Severance R, Averna M, Steinhagen-Thiessen E, Colhoun HM, et al. Efficacy and safety of adding alirocumab to rosuvastatin versus adding ezetimibe or doubling the rosuvastatin dose in high cardiovascular-risk patients: the ODYSSEY OPTIONS II randomized trial. Atherosclerosis. 2016;244:138-46. https://doi.org/10.1016/j.atherosclerosis.2015.11.010.

Ginsberg HN, Rader DJ, Raal FJ, Guyton JR, Baccara-Dinet MT,

Lorenzato C, et al. Efficacy and Safety of Alirocumab in Patients

with Heterozygous Familial Hypercholesterolemia and LDL-C of 160

mg/dl or Higher. Cardiovasc Drugs Ther. 2016;30:473-83. https://doi.


Teramoto T, Kiyosue A, Ishigaki Y, Harada-Shiba M, Kawabata

Y, Ozaki A, et al. Efficacy and safety of alirocumab 150mg every 4

weeks in hypercholesterolemic patients on non-statin lipid-lowering

therapy or lowest strength dose of statin: ODYSSEY NIPPON. J

Cardiol. 2019;73:218-27. https://doi.org/10.1016/j.jjcc.2018.10.004.

Ray KK, Leiter LA, Müller-Wieland D, Cariou B, Colhoun HM,

Henry RR, et al. Alirocumab vs usual lipid-lowering care as add-on

to statin therapy in individuals with type 2 diabetes and mixed dyslipidaemia: The ODYSSEY DM-DYSLIPIDEMIA randomized trial.

Diabetes Obes Metab. 2018;20:1479-89. doi: 10.1111/dom.13257.

Moriarty PM, Parhofer KG, Babirak SP, Cornier MA, Duell PB,

Hohenstein B, et al. Alirocumab in patients with heterozygous familial hypercholesterolaemia undergoing lipoprotein apheresis: the

ODYSSEY ESCAPE trial. Eur Heart J. 2016;37:3588-95. https://doi.


Leiter LA, Cariou B, Müller-Wieland D3, Colhoun HM, Del Prato

S,Tinahones FJ, et al. Efficacy and safety of alirocumab in insulintreated

individuals with type 1 or type 2 diabetes and high cardiovascular

risk: The ODYSSEY DM-INSULIN randomized trial. Diabetes

Obes Metab. 2017;19:1781-92. https://doi.org/10.1111/dom.13114.

McCullough PA, Ballantyne CM, Sanganalmath SK, Langslet

G, Baum SJ, Shah PK, et al. Efficacy and Safety of Alirocumab in

High-Risk Patients With Clinical Atherosclerotic Cardiovascular

Disease and/or Heterozygous Familial Hypercholesterolemia (from 5

Placebo-Controlled ODYSSEY Trials). Am J Cardiol. 2018;121:940-48.https://doi.org/10.1016/j.amjcard.2017.12.040.

Robinson JG, Farnier M, Krempf M, Bergeron J, Luc G, Averna

M, et al. Efficacy and safety of alirocumab in reducing lipids and

cardiovascular events. N Engl J Med 2015;372:1489-99. https://doi.


López-Sendón J, Castro A, Dalmau R. Una historia resumida. Lainhibición de la PCSK9 y su desarrollo clínico. Rev Esp Cardiol Supl 2017;17(A):10-15. https://doi.org/10.1016/S1131-3587(19)30011-1.

Ridker PM, Tardif JC, Amarenco P, Duggan W, Glynn RJ, JukemaJW, et al. Lipid-Reduction Variability and Antidrug-Antibody Formation with Bococizumab. N Engl J Med. 2017;376:1517-26. https://doi.org/10.1056/NEJMoa1614062.

Ridker PM, Revkin J, Amarenco P, Brunell R, Curto M, Civeira F,

et al. Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients. N Engl J Med. 2017;376:1527-39. https://doi.org/10.1056/NEJMoa1701488.

Henry RR, Müller-Wieland D, Taub PR, Bujas-Bobanovic M, Louie MJ, Letierce A, et al. Effect of alirocumab on lipids and lipoproteins in individuals with metabolic syndrome without diabetes: Pooled data from 10 phase 3 trials. Diabetes Obes Metab 2018;20:1632-41.https://doi.org/10.1111/dom.13273.

Filippatos TD, Kei A, Rizos CV, Elisaf MS. Effects of PCSK9 Inhibitors on Other than Low-Density Lipoprotein Cholesterol Lipid

Variables. J Cardiovasc Pharmacol Ther. 2018;23:3-12. https://doi.


Cao YX, Liu HH1, Li S1, Li JJ. A Meta-Analysis of the Effect of

PCSK9-Monoclonal Antibodies on Circulating Lipoprotein (a) Levels.

Am J Cardiovasc Drugs. 2019;19:87-97. https://doi.org/10.1007/


Toth PP, Descamps O, Genest J, Sattar N, Preiss D, Dent R,

et al. Pooled Safety Analysis of Evolocumab in Over 6000 Patients

From Double-Blind and Open-Label Extension Studies.Circulation. 2017;135:1819-31. https://doi.org/10.1161/CIRCULATIONAHA.


Strilchuk L, Fogacci F, Cicero AF. Safety and tolerability of injectable lipid-lowering drugs: an update of clinical data. Expert Opin Drug Saf 2019;18:611-21. https://doi.org/10.1080/14740338.2019.1620730.

Robinson JG, Rosenson RS, Farnier M, Chaudhari U, Sasiela

WJ, Merlet L, et al. Safety of Very Low Low-Density Lipoprotein

Cholesterol Levels With Alirocumab: Pooled Data From Randomized Trials. J Am Coll Cardiol. 2017;69:471-82. https://doi.org/10.1016/j.jacc.2016.11.037.

Masson W, Lobo M, Huerín M, Molinero G, Lobo L, Nogueira JP.

Plasma proprotein convertase subtilisin/kexin type 9 inhibitors and

cataract risk: A systematic review and meta-analysis. Arch Soc Esp

Oftalmol 2019;94:75-80. https://doi.org/10.1016/j.oftal.2018.11.003.

Giugliano RP, Mach F, Zavitz K, Kurtz C, Im K, Kanevsky E, et

al. Cognitive Function in a Randomized Trial of Evolocumab. N Engl

J Med 2017;377:633-43. https://doi.org/10.1056/NEJMoa1701131.

Koren MJ, Sabatine MS, Giugliano RP, Langslet G, Wiviott SD,

Ruzza A, et al. Long-Term Efficacy and Safety of Evolocumab in Patients With Hypercholesterolemia. J Am Coll Cardiol. 2019;74:2132-46. https://doi.org/10.1016/j.jacc.2019.08.1024.

Nicholls SJ, Puri R, Anderson T, Ballantyne CM, Cho L, Kastelein JJ, et al. Effect of Evolocumab on Progression of Coronary Disease in Statin-Treated Patients: The GLAGOV Randomized Clinical Trial. JAMA 2016;316:2373-84. https://doi.org/10.1001/jama.2016.16951.

Ako J, Hibi K, Tsujita K, Hiro T, Morino Y, Kozuma K, et al. Effect

of Alirocumab on Coronary Atheroma Volume in Japanese Patients

With Acute Coronary Syndrome - The ODYSSEY J-IVUS Trial. Circ J 2019;83:2025-33. https://doi.org10.1253/circj.CJ-19-0412.

Giugliano RP, Pedersen TR, Park JG, De Ferrari GM, Gaciong ZA, Ceska R, et al.Clinical efficacy and safety of achieving very low LDLcholesterol concentrations with the PCSK9 inhibitor evolocumab: a prespecified secondary analysis of the FOURIER trial.Lancet 2017;390:1962-71. https://doi.org/10.1016/S0140-6736(17)32290-0.

Sinnaeve PR, Schwartz GG, Wojdyla DM, Alings M, Bhatt DL,

Bittner VA, et al.Effect of alirocumab on cardiovascular outcomes

after acute coronary syndromes according to age: an ODYSSEY

OUTCOMES trial analysis.Eur Heart J. 2019 Nov 16. pii: ehz809.


Steg PG, Szarek M, Bhatt DL, Bittner VA, Brégeault MF, Dalby

AJ, et al. Effect of Alirocumab on Mortality After Acute Coronary

Syndromes. Circulation 2019;140:103-12. https://doi.org/10.1161/


Bittner VA, Szarek M, Aylward PE, Bhatt DL, Diaz R, Edelberg

JM, et al. Effect of Alirocumab on Lipoprotein(a) and Cardiovascular

Risk After Acute Coronary Syndrome. J Am Coll Cardiol. 2020;75:133-44. https://doi.org/10.1016/j.jacc.2019.10.057.

Jukema JW, Szarek M, Zijlstra LE, de Silva HA, Bhatt DL,

Bittner VA, et al. Alirocumab in Patients With Polyvascular Disease

and Recent Acute Coronary Syndrome: ODYSSEY OUTCOMES

Trial. J Am Coll Cardiol. 2019;74:1167-76. https://doi.org/10.1016/j.


Ray KK, Colhoun HM, Szarek M, Baccara-Dinet M, Bhatt

DL, Bittner VA, et al. Effects of alirocumab on cardiovascular and

metabolic outcomes after acute coronary syndrome in patients with

or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial. Lancet Diabetes Endocrinol 2019;7:618-28. https://doi.org/10.1016/S2213-8587(19)30158-5.

Sabatine MS, Leiter LA, Wiviott SD, Giugliano RP, Deedwania P,

De Ferrari GM, et al. Cardiovascular safety and efficacy of the PCSK9 inhibitor evolocumab in patients with and without diabetes and the effect of evolocumab on glycaemia and risk of new-onset diabetes: a prespecified analysis of the FOURIER randomised controlled trial. Lancet Diabetes Endocrinol 2017;5:941-50. https://doi.org/10.1016/S2213-8587(17)30313-3.

Turgeon RD, Tsuyuki RT, Gyenes GT, Pearson GJ. Cardiovascular Efficacy and Safety of PCSK9 Inhibitors: Systematic Review and Meta-analysis Including the ODYSSEY OUTCOMES Trial. Can J Cardiol 2018;34:1600-05. https://doi.org/10.1016/j.cjca.2018.04.002.

http://pathways.nice.org.uk/pathways/cardiovascular-disease prevention

Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/

ADA/AGS/AphA/ASPC/ NLA/PCNA Guideline on the Management

of Blood Cholesterol: A Report of the American Collegeof Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;73:e285-e350. https://doi.org/10.1016/j.jacc.2018.11.003.

Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020;41:111-88. https://doi.org10.1093/eurheartj/ehz455.



Siniawski D, Masson W, Rossi E, Damonte J, Halsband A, Pizarro R. Elegibilidad para la indicación de inhibidores de PCSK9 según las recomendaciones de diferentes sociedades científicas. Medicina (B Aires). 2019;79:104-10.

Elamin AFM, Grafton-Clarke C, Wen Chen K, Obafemi T, Luvai

A, Katira R, et al. Potential use of PCSK9 inhibitors as a secondary

preventative measure for cardiovascular disease following acute coronary syndrome: a UK real-world study. Postgrad Med J. 2019;95:61-6.


Colivicchi F, Massimo Gulizia M, Arca M, Luigi Temporelli

P, Gonzini L, Venturelli V, et al. Lipid Lowering Treatment and

Eligibility for PCSK9 Inhibition in Post-Myocardial Infarction

Patients in Italy: Insight from Two Contemporary Nationwide

Registries. Cardiovasc Ther 2020 Jan 3;2020:3856242. https://doi.


Chamberlain AM, Gong Y, Shaw KM, Bian J, Song WL, Linton

MF, et al. PCSK9 Inhibitor Use in the Real World: Data From the

National Patient-Centered Research Network. J Am Heart Assoc

;8:e011246. https://doi.org/10.1161/JAHA.118.011246.

Santos RD, Bourbon M, Alonso R, Cuevas A, Vasques-Cardenas NA, Pereira AC, et al. Clinical and molecular aspects of familial hypercholesterolemia in Ibero-American countries. J Clin Lipidol 2017;11:160-66. https://doi.org/10.1016/j.jacl.2016.11.004.

Kaufman TM, Warden BA, Minnier J, Miles JR, Duell PB, Purnell

JQ,et al. Application of PCSK9 Inhibitors in Practice. Circ Res.

;124:32-7. https://doi.org/10.1161/CIRCRESAHA.118.314191.

Cordero A, Fácila L, Rodríguez-Mañero M, Gómez-Martínez MJ,

Bertomeu-Martínez V, González-Juanatey JR. Initial Real-World

Experience With PCSK-9 Inhibitors in Current Indications for Reimbursement in Spain. Rev Esp Cardiol. 2019;72:968-70. https://doi.org/10.1016/j.rec.2019.03.008.

Chapman FH, Benner JS, Petrilla AA, Tierce JC, Collins SR,

Battleman DS, et al. Predictors of adherence with antihypertensive

and lipid lowering therapy. Arch Intern Med. 2005;165:1147-52.


Giorgi MA, Volman S, Pereira L, Coca A. Análisis de la persistenciade pacientes bajo tratamiento antihipertensivo en programa de educación administración de medicación. Hipertens Riesgo Vasc.2011;28:137-42.

Maningat P, Gordon BR, Breslow JL. How do we improve

patient compliance and adherence to long-term statin therapy?.

Curr Atheroscler Rep. 2013;15:291. https://doi.org/10.1007/s11883-


Nielsen SF, Nordestgaard BG. Negative statin-related news

stories decrease statin persistence and increase myocardial infarction and cardiovascular mortality: a nationwide prospective

cohort study. Eur Heart J. 2016;37:908-16. https://doi.org/10.1093/


Rosenson RS, Miller K, Bayliss M, Sanchez RJ, Baccara-Dinet MT, Chibedi-De-Roche D, et al. The Statin-Associated Muscle Symptom Clinical Index (SAMS-CI): Revision for Clinical Use, Content Validation, and Inter-rater Reliability. Cardiovasc Drugs Ther 2017;31:179-86. https://doi.org/10.1007/s10557-017-6723-4.

Gupta A, Thompson D, Whitehouse A, Collier T, Dahlof B, Poulter N, et al. Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase. Lancet. 2017;389:2473-81. https://doi.org/10.1016/S0140-6736(17)31075-9.

Sculpher MJ, Pang FS, Manca A, Drummond MF, Golder S, Urdahl H, et al. Generalisability in economic evaluation studies in health care: a review and case studies.Health Technol Assess. 2004;8(49):iii-iv,1-192. https://doi.org/10.3310/hta8490.

Drummond M, Barbieri M, Cook J, Glick HA, Lis J, Malik F,

et al. Transferability of economic evaluations across jurisdictions:

ISPOR Good Research Practices Task Force Report. Value Health.

;12:409-18. doi: 10.1111/j.1524-4733.2008.00489.x.

Giorgi M. Conceptos generales de farmacoeconomía: el caso de los nuevos anticoagulantes orales en la prevención de eventos trombóticos en la fibrilación auricular en Argentina. Revista del CONAREC 2015;(131):228-33.

Giorgi MA, Boissonnet CP, Micone PV, Gallo M, Stuart P, Giglio

ND.PCV-38 - Budget impact of alirocumab in the management of

heterozygous familial hypercholesterolemia patients in Argentina.

Value in Health 2018;21 (suppl 3):S98-S99.

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