Author + information
- Charles J. Gluecka,b,
- Alan Browna,b,
- Anne Goldberga,b,
- James McKenneya,b,
- Louis Kantarosa,b,
- John Stewarta,b,
- Joseph Elassala,b and
- Andrew Korena,b
Background: The alirocumab (ALI) compassionate use program provided access to ALI prior to its commercial availability to patients with severe hypercholesterolemia not controlled with maximal tolerated dose (MTD) of standard-of-care lipid-lowering therapy (LLT). Findings from this program provide insight into characteristics of patients not meeting low density lipoprotein cholesterol (LDL-C) goals despite MTD of LLT, who are likely to be early users of PCSK9 inhibitors post-approval. Lipid-lowering efficacy and safety of ALI were also assessed.
Methods: Patients with heterozygous familial hypercholesterolemia (HeFH) and/or established/documented coronary heart disease (CHD) and baseline LDL-C ≥160 mg/dL on MTD of LLT were enrolled, and received ALI 150 mg every 2 weeks for 24 weeks. Distinct from the majority of ALI ODYSSEY clinical trials, patients with a statin MTD of zero could be enrolled.
Results: Of 100 patients enrolled at 25 US clinical sites, 93 were white and 62 were female, with an overall mean age of 58 years; 64 had HeFH, 66 had CHD, 26 had both, 66 had hypertension, 10 had diabetes, and 12 were smokers. Sixty-four patients were statin intolerant, of whom 47 were not on a statin; 36 were on non-statin LLT, of whom 28 were on ezetimibe. ALI reduced LDL-C on average from 220 mg/dL at baseline to 105 mg/dL by Week 4 (-55%); reductions were maintained over 24 weeks (n=83) and were similar in patients on and not on statin. ALI reduced total cholesterol (-40%) and triglycerides (-11%), and increased high-density lipoprotein cholesterol (+10%), from baseline to Week 24. Consistent with findings from ODYSSEY, treatment-emergent adverse events (TEAE) were experienced in 61% of patients and TEAEs leading to permanent treatment discontinuation in 3% of patients; no deaths occurred.
Conclusions: Findings from the ALI compassionate use program in patients with HeFH and/or CHD with baseline LDL-C ≥160 mg/dL suggest there are many patients in the real-world setting who, despite MTD of standard-of-care LLT, do not reach LDL-C goals. Efficacy and safety observations were consistent with those in the ODYSSEY trials.
Poster Hall, Hall C
Saturday, March 18, 2017, 9:45 a.m.-10:30 a.m.
Session Title: Advances in Lipid Management
Abstract Category: 3. Acute and Stable Ischemic Heart Disease: Therapy
Presentation Number: 1203-309
- 2017 American College of Cardiology Foundation