From the Guidelines
Lipoprotein(a) levels generally do not change significantly with statin therapy, and may even be raised in some cases. While statins are effective at lowering LDL cholesterol, they typically have minimal to no effect on Lp(a) concentrations, with most studies showing either no change or only very modest reductions (usually less than 10%) 1. This lack of effect occurs because statins primarily work by inhibiting HMG-CoA reductase to reduce cholesterol synthesis and upregulate LDL receptors, but Lp(a) metabolism follows different pathways that are largely independent of LDL receptor activity.
Some key points to consider when evaluating the effect of statins on Lp(a) levels include:
- The mechanisms through which therapeutic regimens affect Lp(a) levels are not well understood, and may involve complex interactions between different lipid pathways 1
- Other interventions, such as PCSK9 inhibitors, niacin, and newer therapies specifically targeting Lp(a), may be needed to reduce Lp(a) levels in patients with elevated Lp(a) who require intervention 1, 2
- Elevated Lp(a) remains an independent cardiovascular risk factor even when LDL is well-controlled with statins, which explains why some patients may continue to experience cardiovascular events despite achieving target LDL levels on statin therapy 1
It is also worth noting that some studies have suggested that statins may actually raise Lp(a) levels, although the mechanisms underlying this effect are not fully understood 1. Overall, the available evidence suggests that statins are not an effective treatment for reducing Lp(a) levels, and alternative approaches may be needed to address this important cardiovascular risk factor.
From the Research
Effect of Statins on Lipoprotein(a) Levels
- The effect of statins on lipoprotein(a) [Lp(a)] levels has been investigated in several studies, with varying results 3, 4, 5.
- A systematic review and meta-analysis of 39 studies found that statin therapy does not lead to clinically important differences in Lp(a) compared to placebo in patients at risk for cardiovascular disease (CVD) 3.
- Another study found that different types and dosages of statins showed no significant effect on Lp(a) levels, with no obvious difference between them 4.
- However, a real-world database research study found that the use of statins was associated with an increased risk of Lp(a) elevation compared with non-statin use counterparts 5.
Comparison of Statin Types and Dosages
- A network meta-analysis found that none of the types of statins changed Lp(a) significantly compared to placebo, and that intensities of statin therapy also had no significant effect on Lp(a) levels 3.
- Another study found that moderate-intensity pitavastatin tended to have the best effect on reducing Lp(a) levels, although this was not statistically significant 4.
- The dose intensity of statin was positively associated with the evaluated Lp(a) level in a real-world database research study 5.
Clinical Implications
- The findings of these studies suggest that statin therapy may not be effective in changing Lp(a)-associated CVD risk 3.
- However, the clinical relevance of the increases in Lp(a) levels associated with statin use needs to be addressed in surrogate marker trials and/or large, cardiovascular outcomes trials 5.
- Physicians should be aware of the potential for statins to have an unintended effect of elevated Lp(a) when using them in clinical practice 5.