Clinical study ODYSSEY OUTCOMES
Authors:
J. Murín 1; J. Špinar 2
Authors‘ workplace:
I. interná klinika LF UK a UN Bratislava 2 Interní kardiologická klinika LF MU a FN Brno
1
Published in:
Kardiol Rev Int Med 2018, 20(2): 131-136
Overview
Patients suffering from acute coronary syndrome (ACS) have a very high cardiovascular (CV) risk of morbidity and mortality even with an optimal treatment of ACS and optimal secondary prevention treatment afterwards. A more intensive treatment of dyslipidaemia, with further reduction of serum LDL-cholesterol (LDL-c) levels, should improve prognosis of these patients – such was the hypothesis of this study with alirocumab (PCSK9 inhibitor) treatment vs. placebo treatment. There were 18,924 patients in this study, randomized for the above-mentioned treatment in the time period of 1–12 months after ACS. In the active arm treatment there was a further reduction of serum LDL-c level (from 2.62 to 1.37 mmol/l, reduction of 54.7%). This serum LDL-c reduction contributed to a reduction of the primary end-point (coronary mortality/nonfatal myocardial infarction and stroke/hospitalization for unstable angina pectoris) of 15% (significantly – S), and also to an improvement of the components of this end-point and 15% reduction of all-cause mortality (S). The best benefit was achieved in the subgroup of patients with the highest serum level of LDL-c ≥ 2.6 mmol/l – the primary end-point was reduced by 24% (S) and CV mortality by 31% (S). The treatment was safe. The output of this study is a great reduction of CV events (mortality, nonfatal myocardial infarctions and strokes, unstable angina pectoris) in patients with an ACS treated by alirocumab – all patients had an excellent standard treatment of the disease, including strong and high doses of statins. Patients with the highest basal serum LDL-c levels (≥ 2.6 mmol/l) profited most.
Key words:
hypercholesterolemia – alirocumab – cardiovascular events
Sources
1. Schwartz GG, Olsson AG, Abt M et al. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med 2012; 367(22): 2089– 2099. doi: 10.1056/ NEJMoa1206797.
2. Schwartz GG, Olsson AG, Ezekowitz MD et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA 2001; 285(13): 1711– 1718.
3. Cannon CP, Braunwald E, McCabe CH et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004; 350(15): 1495– 1504. doi: 10.1056/ NEJMoa040583.
4. Fox KA, Carruthers KF, Dunbar DR et al. Underestimated and underrecognized: the late concequences of acute coronary syndrome (GRACE UK-Belgian Study). Eur Heart J 2010; 31(22): 2755– 2764. doi: 10.1093/ eurheartj/ ehq326.
5. Stamler J, Wentworth D, Neaton JD. Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? Finding in 356,222 primary screenees of the Multiple Risk Factor Intervention. Trial (MRFIT). JAMA 1986; 256(20): 2823– 2828.
6. Baigent C, Blackwell L, Emberson J et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 2010; 376(9753): 1670– 1681. doi: 10.1016/ S0140-6736(10)61350-5.
7. Wiviott SD, Cannon CP, Morrow DA et al. Can low-density lipoprotein be too low? The safety and efficacy of achieving very low low-density lipoprotein with intensive statin therapy: a PROVE IT-TIMI 22 substudy. J Am Coll Cardiol 2005; 46(8): 1411– 1416. 10.1016/ j.jacc.2005.04.064.
8. Karalis DG, Victor B, Ahedor I et al. Use of lipid--lowering medications and the likelihood of ochieving optimal LDL-cholesterol goals in coronary artery disease patients. Cholesterol 2012; 2012: 861924. doi: 10.1155/ 2012/ 861924.
9. Kotseva K, Wood D, De Backer G et al. EUROASPIRE III: a survey on the lifestyle, risk factors and use of cardioprotective drug therapies in coronary patients from 22 European countries. Eur J Cardiovasc Prev Rehabil 2009; 16(2): 121– 137. doi: 10.1097/ HJR.0b013e3283294b1d.
10. Do RQ, Vogel RA, Schwartz GG. PCSK9 inhibitors: potential in cardiovascular therapeutics. Curr Cardiol Rep 2013; 15(3): 345. doi: 10.1007/ s11886-012-0345-z.
11. Cohen JC, Boerwinkle E, Mosley TH Jr et al. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 2006; 354(12): 1264– 1272.
12. Naoumova RP, Tosi I, Patel D et al. Severe hypercholesterolemia in four British families with the D374Y mutation in the PCSK9 gene: long-term follow-up and treatment response. Arterioscler Thromb Vasc Biol 2005; 25(12): 2654– 2660. doi: 10.1161/ 01.ATV.0000190668.94752.ab.
13. Welder G, Zineh I, Pacanowski MA et al. High-dose atorvastatin causes a rapid sustained increase in human serum PCSK9 and disrupts its correlation with LDL cholesterol. J Lipid Res 2010; 51(9): 2714– 2721. doi: 10.1194/ jlr.M008144.
14. Stein EA, Mellis S, Yancopoulos GD et al. Effect of a monodonal antibody to PCSK9 on LDL cholesterol. N Engl J Med 2012; 366(12): 1108– 1118. doi: 10.1056/ NEJMoa1105803.
15. McKenney JM, Koren MU, Kereiakes DJ et al. Safety and efficacy of a monoclonal antibody to proprotein convertase subtilisin/ kexin type 9 serine protease, SAR236553/ REGN727, in patients with primary hypercholesterolemia receiving ongoing stable atorvastatin therapy. J Am Coll Cardiol 2012; 59(25): 2344– 2353. doi: 10.1016/ j.jacc.2012.03.007.
16. Stein EA, Gipe D, Bergeron J et al. Effect of a monoclonal antibody to PCSK9, REGN727/ SAR236553, to reduce low-density lipoprotein cholesterol in patients with heterozygous familial hypercholesterolaemia on stable statin dose with or without ezetimibe therapy: a phase 2 randomised controlled trial. Lancet 2012; 380(9836): 29– 36. doi: 10.1016/ S0140-6736(12)60771-5.
17. Roth EM, McKenney JM, Hanotin C et al. Atorvastatin with or without an antibody to PCSK9 in primary hypercholesterolemia. N Engl J Med 2012; 367(20): 1891– 1900. doi: 10.1056/ NEJMoa1201832.
18. Martin SS, Blaha MJ, Elshazly MB et al. Friedewald-estimated versus directly measured low-density lipoprotein cholesterol and treatment implications. J Am Coll Cardiol 2013; 62(8): 732– 739. doi: 10.1016/ j.jacc.2013.01.079.
19. Dolan P. Modeling valuations for EuroQol health states. Med Care 1997; 35(11): 1095– 1108.
20. Schwartz GG, Bessac L, Berdan LG et al. Effect of alirocumab, a monoclonal antibody to PCSK9, on long-term cardiovascular outcomes following acute coronary syndromes: rationale and design of the ODDYSSEY OUTCOMES trial. Am Heart J 2014; 168(5): 682– 689.e1. doi: 10.1016/ j.ahj.2014.07.028.
21. Steg PG, Schwartz GG, Szarek M et al. The ODYSSEY OUTCOMES Trial: Topline results. Alirocumab in patients after acute coronary syndrome. American College of Cardiology – 67th Scientific Sessions, 2018, Orlando USA. Available at: https:/ / accscientificsession.acc.org/ .
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