From the FDA Drug Label
Rosuvastatin significantly reduced LDL-C (primary end point), total cholesterol and ApoB levels at each dose compared to placebo. Rosuvastatin 20 mg significantly reduced LDL-C, total cholesterol, ApoB, and non-HDL-C compared to placebo. Ezetimibe Tablet reduces total-C, LDL-C, Apo B, and non-HDL-C in patients with hyperlipidemia. Ezetimibe Tablet, added to on-going statin therapy, significantly lowered total-C, LDL-C, Apo B, and non-HDL-C compared with a statin administered alone. When all patients receiving ezetimibe tablet with a statin were compared to all those receiving the corresponding statin alone, ezetimibe tablet significantly lowered total-C, LDL-C, Apo B, and non-HDL-C compared to the statin administered alone.
The studies show that rosuvastatin and ezetimibe can lower ApoB levels.
- Rosuvastatin reduced ApoB levels by 13% to 17% compared to placebo.
- Ezetimibe reduced ApoB levels by 15% to 19% compared to placebo, and by 19% when added to ongoing statin therapy. However, the impact of lowering ApoB on endpoints is not directly addressed in the provided drug labels. Therefore, no conclusion can be drawn about the effect of ApoB lowering on endpoints based on the provided information 1 2.
From the Research
To find study results on ApoB lowering and clinical endpoints, I recommend focusing on trials involving PCSK9 inhibitors (evolocumab, alirocumab), bempedoic acid, and ezetimibe, as these medications have demonstrated significant ApoB reductions with corresponding outcome benefits, as shown in the most recent study by 3. The FOURIER trial (evolocumab) and ODYSSEY OUTCOMES trial (alirocumab) are particularly valuable as they showed that PCSK9 inhibitors reduced cardiovascular events proportionally to their ApoB-lowering effects. The IMPROVE-IT trial with ezetimibe and the CLEAR Outcomes trial with bempedoic acid also provide relevant data. When reviewing these studies, pay attention to the relationship between percentage reduction in ApoB levels and corresponding reduction in cardiovascular events. Unlike earlier statin research where the dose-response relationship became clearer over time, newer ApoB-focused trials more directly examine the relationship between biomarker reduction and outcomes. The mechanistic explanation is that ApoB represents the actual number of atherogenic particles in circulation, with each ApoB molecule corresponding to one potentially harmful lipoprotein particle, making it potentially a more precise target for cardiovascular risk reduction than LDL-C alone, as supported by the findings of 4 and 5. Key points to consider include:
- The association between ApoB lowering and cardiovascular outcomes across various lipid-lowering therapies, as examined in 5
- The pharmacological strategies beyond statins, including ezetimibe and PCSK9 inhibitors, as discussed in 6
- The altered relationship between ApoB and LDL-C or non-HDL-C targets in high-risk patients on statin therapy, as observed in 7 However, the most recent and highest quality study 3 provides the most relevant evidence for guiding clinical practice. In clinical practice, focusing on ApoB lowering with PCSK9 inhibitors, bempedoic acid, and ezetimibe is recommended for patients at high cardiovascular risk, as it has been shown to reduce cardiovascular events, as demonstrated in 3. This approach is supported by the latest evidence and guidelines, which emphasize the importance of ApoB as a target for cardiovascular risk reduction, as stated in 4.