Effects of ezetimibe, simvastatin and ezetimibe/simvastatin on correlations between apolipoprotein B, LDL cholesterol and non-HDL cholesterol in patients with primary hypercholesterolemia.

Farnier M, Guyton JR, Jensen E, et al.
Atherosclerosis. 2013 Aug;229(2):415-22. doi: 10.1016/j.atherosclerosis.2013.05.010

Background

In addition to LDL-c, non-HDL-c and apolipoprotein B (apoB) have been proposed as targets of drug therapy, and levels of the latter two may provide a more accurate assessment of future coronary risk than does LDL-c [1-6]. Many statin-treated patients still have a remaining increased risk , partly due to elevated apoB-containing lipoprotein particles [7,8], particularly in patients with metabolic syndrome, hypertriglyceridemia, and/or type 2 diabetes mellitus (T2DM). In patients who do not reach recommended LDL-c levels, additional lipid-lowering agents may be required.
Ezetimibe (EZE) blocks cholesterol absorption and can give additional lipid and lipoprotein reductions when added to statin therapy [9-12]. LDL-c, non-HDL-c and apoB are not affected to a similar extent by both statins and EZE. It is unclear how different combination therapies affect the correlations between apoB and LDL-c or non-HDL-c. This posthoc analysis therefore compares the correlations between apoB:LDL-c and apoB:non-HDL-c in a large population (n=2990) of untreated hypercholesterolemic patients, both at baseline and following 12 weeks of treatment with placebo, EZE, simvastatin (SIMVA) or EZE/SIMVA.

Main results

• EZE/SIMVA was more efficient than SIMVA alone with regard to lowering LDL-c, non-HDL-c and apoB at each dose comparison.
• ApoB was less strongly reduced than were LDL-c and non-HDL-c, after EZE, SIMVA or EZE/SIMVA.
• LDL-c and non-HDL-c strongly correlated with apoB in all treatment groups, at both baseline and endpoint, with the strongest correlation for non-HDL-c and apoB.
• Correlations between apoB:LDL-c (r>0.88) and apoB:non-HDL-c (r>0.94) were generally stronger after treatment with lipid-lowering therapy, as compared to baseline (r>0.76 for LDL-c and r>0.86 for non-HDL-c), specifically with SIMVA and EZE/SIMVA, and with increasing dose.
• Predicted values of LDL-c and non-HDL-c for a known apoB level (80 mg/dl) were calculated from a linear regression model. In untreated patients these predicted values were similar across treatment groups. After treatment with SIMVA and EZE/SIMVA, LDL-c and non-HDL-c were lower than after EZE and placebo. In a comparison based on triglyceride levels (higher or lower than 200 mg/dL), predicted LDL-c values were generally lower in patients with high TG levels, both at baseline and after treatment, irrespective of treatment. In contrast, non-HDL-c levels were often higher in high TG vs low TG patients, mostly at baseline.
• 63-79% of people in the SIMVA group and 51-68% in the EZE/SIMVA group achieved LDL-c and non-HDL-c recommendations as well as an apoB < 80 mg/dL. However, a large part of the patients who received SIMVA or EZE/SIMVA kept apoB>80 mg/dL, despite reaching LDL-c <70 mg/dL and non-HDL-c <100mg/dL.

Conclusion

The type and potency of treatment affects the correlations between apoB and LDL-c or non-HDL-c, and correlations were generally stronger in patients with low TG levels, irrespective of type of treatment. Many patients who achieved the most stringent LDL-c and non-HDL-c levels still had apoB>80 mg/dL, while the majority of patients who reached the apoB target had also met LDL-c and non-HDL-c recommendations. LDL-c may thus not be the best indicator of treatment-induced changes. Patients may remain at increased risk due to insufficient apoB-lowering even when receiving high doses of SIMVA or combination therapy.

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