PCSK9 inhibition reduces atherogenic lipid levels in T2DM patients with mixed dyslipidemia

Background

Mixed dyslipidemia increases the CV risk of patients with type 2 diabetes (T2DM) and is characterized by elevated triglycerides (TGs), low levels of high-density lipoprotein cholesterol (HDL-c), while low-density lipoprotein cholesterol (LDL-c) may be normal [2,3]. It is not known whether proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibition is beneficial in this context.

In the ODYSSEY DM-DYSLIPIDEMIA trial, the efficacy and safety of alirocumab versus usual lipid-lowering care (UC) was assessed in high-risk T2DM patients with mixed dyslipidemia.

ODYSSEY DM-DYSLIPIDEMIA was a randomized, open-label, parallel group, multi-center trial, which included individuals, aged ≥18 years, with T2DM and mixed dyslipidemia, whose non-HDL-c was not adequately controlled despite maximally tolerated statin therapy for ≥4 weeks, without other lipid-lowering therapy, or who were statin-intolerant, and who had either a documented history of CVD or at least 1 additional CV risk factor, and a glycated hemoglobin (A1C) level <9% [13].

413 patients were included in this analysis. Mixed dyslipidemia was defined as non-HDL-c ≥2.59 mmol/L (≥100 mg/dL) and TGs ≥1.70 mmol/L (150 mg/dL) but <5.65 mmol/L (500 mg/dL). CVD was defined as coronary heart disease, peripheral arterial disease or ischemic stroke. Participants were stratified based on the need not to add lipid-lowering therapy or add lipid-lowering therapy that included fenofibrate, omega-3-fatty acids, ezetimibe, nicotinic acid, and were randomized in a 2:1 ratio to receive additionally either open-label alirocumab 75/150 mg every 2 weeks (Q2W), or UC for 24 weeks. The primary efficacy endpoint was the percentage change in non-HDL-c from baseline to week 24.

Main results

The mean percentage changes from baseline to week 24 with alirocumab vs. UC were:

• non-HDL-c: -37.3 (SE: 3.0)% vs. –4.7 (SE: 3.3)%; –32.5% difference; P<0.0001
• LDL-c: -43.3% vs. -0.3%; -43% difference; P<0.0001
• Total cholesterol: -27.4% vs. -2.8%; -24.6% difference; P<0.0001
• TGs: -13.0% vs. -8.8%; -4.2% difference; P=0.2191
• HDL-c: +14.5% vs. +8.2%; 6.2% difference; P=0.0026
• ApoB: -33.8% vs. -1.6%; -32.3% difference; P<0.0001
• Lp(a): -23.7% vs. +3.7%; -27.4% difference; P<0.0001
• LDL-p number: -41.6% vs. -3.9%; -37.8% difference; P<0.0001
• LDL-p size: -1.5% vs. +0.3%; -1.8% difference; P<0.0001

Results for the UC strata were similar to the overall analysis.

At week 24, more than two-thirds of alirocumab-treated individuals achieved levels of non-HDL-c <2.59 mmol/L (<100 mg/dL), LDL-c <1.81 mmol/L (<70 mg/dL) and ApoB <80 mg/dL. In addition, a greater proportion of individuals in the alirocumab group versus UC achieved a reduction in LDL-c from baseline of ≥50% (55.2% vs 3.8%).

Conclusion

References

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