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Clinical Trial
. 2015 Nov 14;36(43):2996-3003.
doi: 10.1093/eurheartj/ehv370. Epub 2015 Sep 1.

ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia

John J P Kastelein  1 , Henry N Ginsberg  2 , Gisle Langslet  3 , G Kees Hovingh  4 , Richard Ceska  5 , Robert Dufour  6 , Dirk Blom  7 , Fernando Civeira  8 , Michel Krempf  9 , Christelle Lorenzato  10 , Jian Zhao  11 , Robert Pordy  12 , Marie T Baccara-Dinet  13 , Daniel A Gipe  12 , Mary Jane Geiger  12 , Michel Farnier  14
Affiliations
Clinical Trial

ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia

John J P Kastelein et al. Eur Heart J. .

Abstract

Aims: To assess long-term (78 weeks) alirocumab treatment in patients with heterozygous familial hypercholesterolaemia (HeFH) and inadequate LDL-C control on maximally tolerated lipid-lowering therapy (LLT).

Methods and results: In two randomized, double-blind studies (ODYSSEY FH I, n = 486; FH II, n = 249), patients were randomized 2 : 1 to alirocumab 75 mg or placebo every 2 weeks (Q2W). Alirocumab dose was increased at Week 12 to 150 mg Q2W if Week 8 LDL-C was ≥1.8 mmol/L (70 mg/dL). Primary endpoint (both studies) was percentage change in calculated LDL-C from baseline to Week 24. Mean LDL-C levels decreased from 3.7 mmol/L (144.7 mg/dL) at baseline to 1.8 mmol/L (71.3 mg/dL; -57.9% vs. placebo) at Week 24 in patients randomized to alirocumab in FH I and from 3.5 mmol/L (134.6 mg/dL) to 1.8 mmol/L (67.7 mg/dL; -51.4% vs. placebo) in FH II (P < 0.0001). These reductions were maintained through Week 78. LDL-C <1.8 mmol/L (regardless of cardiovascular risk) was achieved at Week 24 by 59.8 and 68.2% of alirocumab-treated patients in FH I and FH II, respectively. Adverse events resulted in discontinuation in 3.4% of alirocumab-treated patients in FH I (vs. 6.1% placebo) and 3.6% (vs. 1.2%) in FH II. Rate of injection site reactions in alirocumab-treated patients was 12.4% in FH I and 11.4% in FH II (vs. 11.0 and 7.4% with placebo).

Conclusion: In patients with HeFH and inadequate LDL-C control at baseline despite maximally tolerated statin ± other LLT, alirocumab treatment resulted in significant LDL-C lowering and greater achievement of LDL-C target levels and was well tolerated.

Clinical trial registration: Cinicaltrials.gov (identifiers: NCT01623115; NCT01709500).

Keywords: Alirocumab; Cardiovascular risk; Heterozygous familial hypercholesterolaemia; LDL-C; PCSK9.

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Figures

Figure 1
Figure 1
Randomization and treatment. ITT, intention-to-treat. Completion of the study was defined as follows: last study-drug injection received (Week 76) and end-of-treatment visit (Week 78) occurred within 21 days of last injection and at least 525 days post-randomization.
Figure 2
Figure 2
Levels of calculated LDL-C over time (intention-to-treat analysis). ALI, alirocumab; PBO, placebo.
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References

    1. Nordestgaard BG, Chapman MJ, Humphries SE, Ginsberg HN, Masana L, Descamps OS, Wiklund O, Hegele RA, Raal FJ, Defesche JC, Wiegman A, Santos RD, Watts GF, Parhofer KG, Hovingh GK, Kovanen PT, Boileau C, Averna M, Boren J, Bruckert E, Catapano AL, Kuivenhoven JA, Pajukanta P, Ray K, Stalenhoef AF, Stroes E, Taskinen MR, Tybjaerg-Hansen A. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J 2013;34:3478–3490a. - PMC - PubMed
    1. Risk of fatal coronary heart disease in familial hypercholesterolaemia. Scientific Steering Committee on behalf of the Simon Broome Register Group. BMJ 1991;303:893–896. - PMC - PubMed
    1. Mortality in treated heterozygous familial hypercholesterolaemia: implications for clinical management. Scientific Steering Committee on behalf of the Simon Broome Register Group. Atherosclerosis 1999;142:105–112. - PubMed
    1. Huijgen R, Kindt I, Verhoeven SB, Sijbrands EJ, Vissers MN, Kastelein JJ, Hutten BA. Two years after molecular diagnosis of familial hypercholesterolemia: majority on cholesterol-lowering treatment but a minority reaches treatment goal. PLoS One 2010;5:e9220. - PMC - PubMed
    1. Pijlman AH, Huijgen R, Verhagen SN, Imholz BP, Liem AH, Kastelein JJ, Abbink EJ, Stalenhoef AF, Visseren FL. Evaluation of cholesterol lowering treatment of patients with familial hypercholesterolemia: a large cross-sectional study in The Netherlands. Atherosclerosis 2010;209:189–194. - PubMed

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