Results of FOURIER study – beginning of the new era in cardiovascular disease prevention?

Authors: Daniel Pella
Authors‘ workplace: I. interná klinika UPJŠ LF a UNLP, Košice
Published in: AtheroRev 2017; 2(2): 87-92
Category: clinical studies


Increased levels of LDL-cholesterol (LDL-C) represent serious risk factor in the pathogenesis of atherosclerosis and its complications. There were no new approaches how to reach target levels of LDL-C easier from the time when statins were discovered (the only exception is ezetimibe) in majority of patients. Despite use of the most potent statins and prescribed in the highest doses (frequently administered in combination with ezetimibe) a large number of patients in high or very high cardiovascular risk will never reach target levels of LDL-C. Discovery of PCSK9 inhibitors (proprotein convertase subtilisin kexin type 9 inhibitors dramatically changed this situation due to their ability to cause additional decrease in LDL-C levels approximately about 60 % (irrespective, whether patients are treated with statins or not). Majority from PCSK9 inhibitors treated patients are able to reach target levels of LDL-C and moreover, like it was shown in GLAGOV trial, this decrease of LDL-C is accompanied usually with atherosclerosis regression. Multicenter, randomized, double-blind study FOURIER confirmed awaiting evidence that evolocumab in comparison to placebo in statin treated patients with documented atherosclerosis significantly reduced predefined primary and secondary key endpoints. Thus, we could consider FOURIER study results for the beginning of the new era in the prevention of cardiovascular disease.

Key words:
cardiovascular disease, PCSK9 inhibitors, statins, FOURIER study


1. Naghavi M, Wang H, Lozano R et al. [GBD 2013 Mortality and Causes of Death Collaborators]. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015; 385(9963): 117–171. Dostupné z DOI: <–6736(14)61682–2>.

2. Townsend N, Wilson L, Bhatnagar P et al. Cardiovascular disease in Europe: epidemiological update 2016. Eur Heart J 2016; 37(42): 3232–3245.

3. Sniderman A, Thanassoulis G, Couture P et al. Is lower and lower better and better? A re-evaluation of the evidence from the Cholesterol Treatment Trialists‘ Collaboration meta-analysis for low-density lipoprotein lowering. J Clin Lipidol 2012; 6(4): 303–309. Dostupné z DOI: <>.

4. Giugliano RP, Sabatini MS. Are PCSK9 inhibitors the next breakthrough in the cardiovascular field ? J Am Coll Cardiol 2015; 65(24): 2638–2651. Dostupné z DOI: <>.

5. Blom DJ, Hala T, Bolognese M et al. A 52 week placebo-controlled trial of evolocumab in hyperlipidemia. N Eng J Med 2014; 370(19): 1809–1819. Dostupné z DOI: <>.

6. Robinson JG, Nedergaard BS, Rogers WJ 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(18): 1870–1882. Dostupné z DOI: <>.

7. Koren MJ, Lundqvist P, Bolognese M et al. Anti-PCSK9 monotherapy for hypercholesterolemia: the MENDEL-2 randomized, controlled phase III clinical trial of evolocumab. J Am Coll Cardiol 2014; 63(23): 2531–2540. Dostupné z DOI: <>.

8. Stroes E, Colquhoun D, Sullivan D et al. Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo-controlled phase 3 clinical trial of evolocumab. J Am Coll Cardiol 2014; 63(23): 2541–2548. Dostupné z DOI: <>.

9. Raal FJ, Stein EA, Dufour R et al. PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomized, double-blind, placebo-controlled trial. Lancet 2015; 385(9965): 331–340. Dostupné z DOI: <–6736(14)61399–4>.

10. Sabatine MS, Giugliano RP, Keech AC et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017; 376(18): 1713–1722. Dostupné z DOI: <>.

11. Giugliano RP, Mach F, Zavitz K et al. Design and rationale of the EBBINGHAUS trial: A phase 3, double-blind, placebo-controlled, multicenter study to assess the effect of evolocumab on cognitive function in patients with clinically evident cardiovascular disease and receiving statin background lipid-lowering therapy-A cognitive study of patients enrolled in the FOURIER trial. Clin Cardiol 2017; 40(2): 59–65. Dostupné z DOI: <>.

12. Giugliano RP. Ebbinghaus: No Effect on Neurocognition With Evolucumab. 66th Annual Scientific Session and Expo American College of Cardiology. Washington, March 18th, 2017.

13. Catapano AL, Graham I, De Backer G et al. [Authors/Task Force Members; Additional Contributor]. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. Eur Heart J 2016; 37(39): 2999–3058.

14. Pfizer discontinues global development of bococizumab, its investigational PCSK9 inhibitor. Press release from Pfizer, New York, Nov 1st, 2016. Dostupné z WWW: <>

15. Cannon CP, Braunwald E, McCabe CH et al. Intensive vs moderate lipid lowering with statins after acute coronary syndromes. N Eng J Med 2004; 350(15): 1495–1504. Erratum in N Engl J Med 2006; 354(7): 778.

16. LaRosa JC, Grundy SM, Waters DD et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Eng J Med 2005; 352(14): 1425–1435.

17. Cannon CP, Blazing MA, Giugliano RP et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Eng J Med 2015; 372(25): 2387–2397. Dostupné z DOI: <>.

18. [Scandinavian Simvastatin Survival Study Group]. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344(8934):1383–1389.

19. Silverman MG, Ference BA, Im K et al. Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: a systematic review and meta-analysis. JAMA 2016; 316(12): 1289–1297. Dostupné z DOI: <>.

20. Ference BA, Robinson JG, Brook RD et al. Variation in PCSK9 and HMGCR and risk of cardiovascular disease and diabetes. N Eng J Med 2016; 375(22): 2144–2153.

21. Koren MJ, Sabatine MS, Giugliano RP et al. Long-term low-density lipoprotein cholesterol-lowering efficacy, persistence, and safety of evolocumab in treatment of hypercholesterolemia: results up to 4 years from the open-label OSLER-1 extension study. JAMA Cardiol 2017 Mar 14. Dostupné z DOI: <>.

Angiology Diabetology Internal medicine Cardiology General practitioner for adults
Forgotten password

Don‘t have an account?  Create new account

Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.


Don‘t have an account?  Create new account