Alirocumab in patients with heterozygous familial hypercholesterolemia undergoing lipoprotein apheresis: Rationale and design of the ODYSSEY ESCAPE trial

Moriarty, Patrick M.; Parhofer, Klaus G.; Babirak, Stephan P.; deGoma, Emil M.; Duell, P. Barton; Hohenstein, Bernd; Ramlow, Wolfgang; Simha, Vinaya; Steinhagen‐Thiessen, Elisabeth; Thompson, Paul D.; Vogt, Anja; Stritzky, Berndt von; Du, Yunling; Manvelian, Garen

doi:10.1016/j.jacl.2016.02.003

Cited by 18 publications

(16 citation statements)

References 45 publications

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“…The study design has been published 14 . The main study criteria are detailed in Supplementary material online, Table S1 .…”

Section: Methodsmentioning

confidence: 99%

“…Eligible patients had HeFH (diagnosed by genotyping or clinical criteria 15 , 16 ), had undergone consistent lipoprotein apheresis weekly for ≥4 weeks or Q2W for ≥8 weeks, and had maintained a stable background medical LLT, diet, and exercise level for ≥8 weeks. Patients undergoing all lipoprotein apheresis techniques were recruited (for additional information, see Supplementary material online, Text S1 ) 14 . Patients with homozygous familial hypercholesterolaemia (FH) were excluded.…”

Section: Methodsmentioning

confidence: 99%

“…During the 2-week screening period, patients provided informed consent, were checked for eligibility, and underwent a lipid panel and other laboratory testing, safety evaluation, and dietary review 14 . LDL-C was calculated using the Friedewald formula (for information on laboratory analyses, as well as the well-being analysis, see Supplementary material online, Text S1 ) 17 …”

Section: Methodsmentioning

confidence: 99%

“…Apheresis was not performed when the LDL-C value at that visit was ≥30% lower than the baseline (pre-apheresis) LDL-C value, as described previously 14 . Site personnel and patients were blinded to the LDL-C value and treatment assignment, and only received an alert as to whether apheresis should be performed on the basis of coded and blinded point-of-care LDL-C results.…”

Section: Methodsmentioning

confidence: 99%

“…Patient drop-outs were accounted for as described in Supplementary material online, Text S1 . The median treatment difference was determined using the Hodges–Lehmann estimation and 95% confidence intervals (CIs) using Moses distribution-free CI (see Supplementary material online, Text S1 ) 14 …”

Section: Methodsmentioning

confidence: 99%

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Alirocumab in patients with heterozygous familial hypercholesterolaemia undergoing lipoprotein apheresis: the ODYSSEY ESCAPE trial

Moriarty

Parhofer²,

Babirak³

et al. 2016

Eur Heart J

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183

120

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Aim To evaluate the effect of alirocumab on frequency of standard apheresis treatments [weekly or every 2 weeks (Q2W)] in heterozygous familial hypercholesterolaemia (HeFH). Methods and results ODYSSEY ESCAPE (NCT02326220) was a double-blind study in 62 HeFH patients undergoing regular weekly or Q2W lipoprotein apheresis. Patients were randomly assigned (2:1, respectively) to receive alirocumab 150 mg (n = 41) or placebo (n = 21) Q2W subcutaneously for 18 weeks. From day 1 to week 6, apheresis rate was fixed according to the patient’s established schedule; from weeks 7 to 18, apheresis rate was adjusted based on the patient’s low-density lipoprotein cholesterol (LDL-C) response in a blinded fashion. Apheresis was not performed when the LDL-C value was ≥30% lower than the baseline (pre-apheresis) value. The primary efficacy endpoint was the rate of apheresis treatments over 12 weeks (weeks 7–18), standardized to number of planned treatments. In the alirocumab group the least square (LS) mean ± SE (95% confidence interval [CI]) per cent change in pre-apheresis LDL-C from baseline at week 6 was −53.7 ± 2.3 (−58.2 to − 49.2) compared with 1.6 ± 3.1 (–4.7 to 7.9) in the placebo group. The primary efficacy endpoint showed statistically significant benefit in favour of alirocumab (Hodges–Lehmann median estimate of treatment difference: 0.75; 95% CI 0.67–0.83; P < 0.0001). Therefore, alirocumab-treated patients had a 0.75 (75%) additional reduction in the standardized rate of apheresis treatments vs. placebo-treated patients. During this period, 63.4% of patients on alirocumab avoided all and 92.7% avoided at least half of the apheresis treatments. Adverse event rates were similar (75.6% of patients on alirocumab vs. 76.2% on placebo). Conclusions Lipoprotein apheresis was discontinued in 63.4% of patients on alirocumab who were previously undergoing regular apheresis, and the rate was at least halved in 92.7% of patients. Alirocumab was generally safe and well tolerated.

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“…The study design has been published 14 . The main study criteria are detailed in Supplementary material online, Table S1 .…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Alirocumab in patients with heterozygous familial hypercholesterolaemia undergoing lipoprotein apheresis: the ODYSSEY ESCAPE trial

Moriarty

Parhofer²,

Babirak³

et al. 2016

Eur Heart J

Self Cite

183

120

View full text Add to dashboard Cite

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Cardiovascular events in patients with familial hypercholesterolemia and hyperlipoproteinaemia (a): Indications for lipoprotein apheresis in Poland

Mickiewicz

Marlęga

Kuchta

et al. 2021

J of Clinical Apheresis

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Background Lipoprotein apheresis (LA) is a safe method of reducing atherogenic lipoproteins and improving cardiovascular (CV) outcomes. We aimed to assess the reductions in low‐density lipoprotein cholesterol (LDL‐C) and lipoprotein (a) [Lp(a)] levels in patients undergoing regular LA therapy and to evaluate its influence on the incidence rate of adverse cardiac and vascular events (ACVE) and major adverse cardiac events (MACE). Methods A longitudinal study in Poland evaluated the prospective and retrospective observational data of 23 patients with hyperlipoproteinaemia (a) [hyper‐Lp(a)] and familial hypercholesterolemia (FH), undergoing 1014 LA sessions between 2013 and 2020. Their pre‐ and post‐apheresis LDL‐C and Lp(a) levels were assessed to calculate the acute percent reductions. The time period used to evaluate annual rates of ACVE and MACE before and after initiation of LA was matched in each patient. Results The pre‐apheresis LDL‐C and Lp(a) concentrations were 155 (107‐228) (mg/dL) (median and interquartile range) and 0.56 (0.14‐1.37) (g/L), respectively. LA therapy resulted in a reduction of LDL‐C to 50 (30‐73.5) (mg/dL) and of Lp(a) to 0.13 (0.05‐0.34) (g/L), representing a percent reduction of 70.0% and 72.7% for LDL‐C and Lp(a), respectively. We found a significant reduction in the annual rate of ACVE (0.365[0.0‐0.585] vs (0.0[0.0‐0.265]; P = .047) and MACE (0.365[0.0‐0.585] vs 0.0[0.0‐0.265]; P = .031). Conclusions The findings of our study indicate that LA treatment in patients with hyperlipoproteinaemia (a) and FH on maximally tolerated lipid lowering therapies leads to a substantial reduction in LDL‐C and Lp(a) concentrations and lowers CV event rates in Polish patients.

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PCSK9-Inhibitoren

Müller‐Wieland

2016

Herz

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Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to low-density lipoprotein (LDL) receptors leading to their degradation in the liver. Inhibition of PCSK9 leads to an increase in LDL receptors and as a result to a reduction of LDL cholesterol in blood. Currently, two antibodies against PCSK9 are available for clinical treatment in Germany, evolocumab (Repatha®) and alirocumab (Praluent®). Clinical studies have shown that treatment with these antibodies, which must be subcutaneously injected by patients every 2 or 4 weeks, in addition to an already existing lipid therapy can lower the LDL cholesterol level in blood by an average of 50-60 %. Data from previous study programs show that this treatment is safe although long-term data are still lacking. The results of currently running cardiovascular endpoint studies are not yet available, whereby a beneficial effect is to be expected after the preliminary analyses. These novel effective therapy approaches open up new perspectives for the treatment of patients whose LDL cholesterol values are still in excess of the corresponding target values despite previous maximum lipid-reducing therapy and suffer from a preexisting cardiovascular disease, statin intolerance, genetic forms of familiar hypercholesterolemia and patients on LDL apheresis.

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Alirocumab in patients with heterozygous familial hypercholesterolemia undergoing lipoprotein apheresis: Rationale and design of the ODYSSEY ESCAPE trial

Abstract: The ODYSSEY ESCAPE trial will determine whether alirocumab reduces the frequency of lipoprotein apheresis in patients with HeFH.

Cited by 18 publications

References 45 publications

Alirocumab in patients with heterozygous familial hypercholesterolaemia undergoing lipoprotein apheresis: the ODYSSEY ESCAPE trial

Alirocumab in patients with heterozygous familial hypercholesterolaemia undergoing lipoprotein apheresis: the ODYSSEY ESCAPE trial

Cardiovascular events in patients with familial hypercholesterolemia and hyperlipoproteinaemia (a): Indications for lipoprotein apheresis in Poland

PCSK9-Inhibitoren

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