Meta Analysis of apoB Lowering and CV Risk Reduction Among Different LLTs
Galimberti F, et al. Poster presented at the 91st European Atherosclerosis Society congress (EAS) 2023.
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Key Takeaway
This meta-analysis included 254,828 participants from 20 RCTs Reported the association of 6 different classes (statins, ezetimibe, PCSK9-inhibitors, CETP-inhibitors, fibrates, and niacin) of LLT with apoB levels and major CV events and showed that:
- All 6 classes of LLT were associated with similar reduction in risk of major CV events for the same magnitude and duration of apoB lowering
- For 30 mg/dL absolute reduction in plasma apoB levels, 6 classes of LLTs were associated with a consistent reduction in major CV events:
- 10%, 15%, 19% and 20% proportional reduction after 1, 2, 3, and 4 or 5 years of therapy, respectively
- Regardless of changes in other lipids, the therapeutic benefit of LLT was determined by changes in plasma apoB levels
Why This Matters
- LDL-C reduction therapies (statins, ezetimibe, and PCSK9 inhibitors) have demonstrated consistent reduction of major CV events in several RCTs
- However, therapies that do not involve up-regulation of LDL-receptor pathway* or that lower triglycerides† did not show a consistent reduction in risk of CV events
- Trapping of apoB molecule within the artery wall can cause progression of atherosclerotic plaque
- This study compared the association between the proportional reduction in major CV events and different classes of LLT for the same magnitude and duration of apoB lowering
Key Highlights
Methods:
- Meta-analysis of RCTs evaluating 6 different classes of LLTs
- Databases: MEDLINE and EMBASE were searched from inception to November 2022
Inclusion criteria:
- Placebo-controlled, double-blind RCTs reporting adjudicated clinical CV outcomes and enrolled ≥1,000 participants with a median follow-up duration of ≥1 year
- Reported absolute achieved differences in plasma apoB levels between treatment and control groups
- Provided cumulative event curves figure for the treatment and control groups that included number of participants remaining at risk at beginning of each year of follow-up
Analysis:
- Association between 30 mg/dL reduction in plasma apoB levels and risk of major CV events across classes of LLTs
- Summary estimates of the effect for an individual class of therapy were combined in an inverse variance-weighted random-effects meta-analysis iteratively after each year of follow-up
- Heterogeneity of effect among different LLT classes was assessed using the I2 statistics
Results:
254,828 participants from 20 trials with major CV events (30,175) were included
- Mean age = 63 years
- Females = 26%
Association of Reduction in Plasma Apo-b Levels with Llt and Reduction in Major Cv Events
For each 30 mg/dL absolute reduction in plasma apoB levels, the 6 classes of LLT (statins, ezetimibe, PCSK9-inhibitors, CETP-inhibitors, fibrates, and niacin) were associated with a consistent reduction in major CV events after therapy
Duration of therapy | Proportional reduction in major CV events for each 30 mg/dL absolute reduction in plasma apoB levels |
HR (95% CI) |
After 1 year | 10% | 0.90 (0.86–0.94) |
After 2 years | 15% | 0.85 (0.82–0.88) |
After 3 years | 19% | 0.81 (0.78–0.85) |
After 4 or 5 years | 20% | 0.80 (0.77–0.83) |
(I2 = 6.9%; P = 0.364)
Additional results on association of reduction in plasma apoB levels with LLT and reduction in major CV events
Therapy | HR (95% CI) | Heterogeneity; HR (95% CI) |
1 year | I2 = 0.00%, H2 = 1.00; 0.90 (0.86–0.94) |
|
Statins | 0.89 (0.82–0.96) | |
PCSK9mAB | 0.89 (0.84–0.96) | |
Ezetimibe | 0.90 (0.77–1.05) | |
CETP - Inhibitiors | 0.97 (0.77–1.24) | |
Fibrates | 0.87 (0.53–1.43) | |
Niacin | 0.99 (0.68–1.43) | |
2 years | I2 = 0.00%, H2 = 1.00; 0.85 (0.82–0.88) |
|
Statins | 0.83 (0.78–0.88) | |
PCSK9mAB | 0.86 (0.81–0.90) | |
Ezetimibe | 0.85 (0.75–0.97) | |
CETP - Inhibitiors | 0.93 (0.77–1.12) | |
Fibrates | 0.93 (0.66–1.31) | |
Niacin | 0.89 (0.68–1.17) | |
3 years | I2 = 0.00%, H2 = 1.00; 0.81 (0.78–0.85) |
|
Statins | 0.80 (0.76–0.84) | |
Ezetimibe | 0.83 (0.74–0.92) | |
CETP - Inhibitiors | 0.87 (0.74–1.02) | |
Fibrates | 0.78 (0.58–1.04) | |
Niacin | 0.86 (0.68–1.09) | |
4 years | I2 = 0.00%, H2 = 1.00; 0.80 (0.77–0.83) | |
Statins | 0.80 (0.76–0.83) | |
Ezetimibe | 0.81 (0.73–0.90) | |
CEPT - Inhibitors | 0.81 (0.70–0.94) | |
Fibrates | 0.77 (0.59–0.99) | |
Niacin | 0.84 (0.68–1.05) | |
5 years | I2 = 0.00%, H2 = 1.00; 0.80 (0.77–0.83) |
|
Statins | 0.80 (0.77–0.83) | |
Ezetimibe | 0.80 (0.73–0.88) | |
Fibrates | 0.81 (0.64–1.03) |
ABBREVIATIONS:
CETP, cholesteryl ester transfer protein; CI, confidence interval; HR, hazard ratio; PCSK9, proprotein convertase subtilisin/ kexin 9; PCSK9mAb, PCSK9 monoclonal antibodies.
*LDL-receptor pathway (CETP-inhibitors and niacin); †Lower triglycerides (fibrates).
Abbreviations
ApoB, apolipoprotein-B; CETP, cholesteryl ester transfer protein; CI, confidence interval; CV, cardiovascular; HR, hazard ratio; LDL-C, low-density lipoprotein cholesterol; LLTs, lipid-lowering therapies; PCSK9, proprotein convertase subtilisin/kexin 9; RCTs, randomized controlled trials.
Reference
- Galimberti F, et al. Meta-analysis of randomized controlled trials evaluating the association between magnitude and duration of apolipoprotein-b lowering and cardiovascular risk reduction among different lipid-lowering therapies. Poster presented at the 91st European Atherosclerosis Society congress (EAS 2023). May 21–24, 2023.