~90% of patients in Odyssey Outcomes were on high-intensity statins and 29% of them had diabetes at baseline (99.2% of these had type 2 diabetes run in)2.
In the placebo group, the risk of MACE at median follow-up 2.8 years was approximately twice the risk in patients with diabetes than in patients with normoglycaemia (HR 2.09, 95% CI 1.78–2.46, p<0.0001) or prediabetes (HR 1·90 95% CI 1·65–2·17, p<0.0001)1.
Study design: ODYSSEY OUTCOMES was a randomized, double-blind, placebo-controlled phase 3 study. Patients with a recent MI or unstable angina, and on high-intensity statin (40 or 80 mg atorvastatin or 20 or 40 mg rosuvastatin, or maximally tolerated dose of one of these agents) +/- other lipid-lowering therapy but not at predefined target LDL-C were enrolled. Patients were classified by glycaemic status at baseline (normoglycemia, prediabetes, or diabetes) defined on the basis of patient history, review of medical records, or baseline HbA1c or fasting serum glucose, and risk of new-onset diabetes among those without diabetes at baseline1,2.
PRALUENT® did not increase the risk of new-onset diabetes for patients with prediabetes or normoglycemia at baseline1.
Praluent® demonstrated a significant reduction in the risk of MACE for the overall trial population.1 In post-ACS patients, Praluent® demonstrated a greater absolute benefit in MACE in patients with LDL-C ≥2.6 mmol/L, compared to the overall trial population1,2
Adapted from Schwartz G, et al. 2018, and Schwartz G, et al. 2018 suppl appendix.
*Observed cumulative incidence of events over 4 years.
†Observed cumulative incidence of events over a median of 2.8 years.
§The effect of PRALUENT on the relative risk of the composite endpoint did not differ significantly between pre-specified LDL-C subgroups. Interaction P value, P=0.09.
¶The NNT of 16 is calculated in accordance with the formula NNT = 1/ARR, with a 4-year Kaplan-Meier estimate ARR of 6.1%.
**Observed cumulative incidence of events over a median of 2.8 years (post hoc analysis).
References:
1. Schwartz G, et al. N Engl J Med 2018;379:2097–2107.
2. Schwartz G, et al. N Engl J Med 2018;379:2097–2107. Supplementary Appendix.
3. Praluent Summary of Product Characteristics. Available at https://www.medicines.org.uk/emc/medicine/30956. Accessed December 2020.
4. Data on file. Clinical study report. Sanofi and Regeneron Pharmaceuticals. June 2018.
With PRALUENT, a reduction of all-cause mortality was observed with only nominal significance for the secondary endpoint
Adapted from Schwartz G, et al. 2018.
*This p value is considered nominally significant based on the pre-specified hierarchical analysis of secondary endpoints
†At end of trial after median follow-up of 2.8 years
References:
1. Schwartz G, et al. N Engl J Med 2018;379:2097–2107.
2. Steg G, et al. Circulation 2019; doi: 10.1161/CIRCULATIONAHA.118.038840. [Epub ahead of print].
3. Schwartz G, et al. N Engl J Med 2018;379:2097–2107. Supplementary Appendix.
CV outcomes with Praluent® in the overall population in ODYSSEY OUTCOMES1
*MACE defined as a composite of: coronary heart disease (CHD) death, nonfatal myocardial infarction (MI), fatal and nonfatal ischaemic stroke, or unstable angina (UA) requiring hospitalisation.
†Unstable angina requiring hospitalisation.
‡CHD event defined as: major CHD event,§ UA requiring hospitalisation, ischaemia-driven coronary revascularisation procedure.
§Major CHD event defined as: CHD death, nonfatal MI.
||Cardiovascular event defined as follows: CV death, any nonfatal CHD event, and nonfatal ischaemic stroke.
References:
1. Praluent Summary of Product Characteristics. Available at https://www.medicines.org.uk/emc/medicine/30956. Accessed December 2020.
MACE=major adverse cardiac events (primary composite endpoint of CHD death, nonfatal myocardial infarction, fatal and nonfatal ischaemic stroke, or unstable angina requiring hospitalization; CV=cardiovascular; RRR=relative risk reduction; ARR=absolute risk reduction; CI=confidence interval; HR=hazard ratio; MI=myocardial infarction; LDL-C=low-density lipoprotein cholesterol.
- Ray KK, et al. Lancet Diabetes Endocrinol 2019; 7:618-628
- Schwartz G, et al. N Engl J Med 2018;379(22):2097