From the Guidelines
Lowering lipoprotein(a) can be achieved through various methods, including the use of PCSK9 inhibitors, lipoprotein apheresis, and emerging therapies like antisense oligonucleotides, with the most recent and highest quality study suggesting that antisense therapy can lower plasma Lp(a) levels by up to 90% or more 1.
Current Treatment Options
- Niacin (vitamin B3) at doses of 1-3 grams daily can reduce Lp(a) by 20-30%, though side effects like flushing and liver concerns limit its use 2.
- PCSK9 inhibitors such as evolocumab (Repatha) and alirocumab (Praluent) may lower Lp(a) by 20-30% as a secondary effect 3.
- Lipoprotein apheresis, a specialized treatment, can temporarily remove Lp(a) from the blood, and is recommended for patients with very high levels of Lp(a) and those who do not achieve guideline-recommended LDL-cholesterol goals despite maximally tolerated combination drug therapy 4.
Emerging Therapies
- Antisense oligonucleotides have demonstrated an ability to lower plasma Lp(a) levels by up to 90% or more, even in subjects with greatly elevated Lp(a) levels, and are considered a promising emerging therapy for Lp(a) reduction 1.
Lifestyle Modifications
- Regular exercise, maintaining a healthy weight, avoiding smoking, and following a Mediterranean diet may help manage overall cardiovascular risk, though they have minimal direct impact on Lp(a) levels.
Recommendations
- The use of antisense therapy is recommended for patients with very high levels of Lp(a) who do not achieve guideline-recommended LDL-cholesterol goals despite maximally tolerated combination drug therapy, due to its ability to lower plasma Lp(a) levels by up to 90% or more 1.
- Lipoprotein apheresis is recommended for patients with very high levels of Lp(a) and those who do not achieve guideline-recommended LDL-cholesterol goals despite maximally tolerated combination drug therapy 4.
- PCSK9 inhibitors and niacin may be considered for patients with high levels of Lp(a), though their use is limited by side effects and variable efficacy 2, 3.
From the Research
Therapies to Lower Lipoprotein(a)
- PCSK9 inhibitors and lipoprotein apheresis are the only currently available therapeutic approaches that lower Lipoprotein(a) and reduce cardiovascular risk 5.
- PCSK9 inhibitors, such as alirocumab, decrease Lipoprotein(a) and cardiovascular events, particularly in high-risk patients with elevated Lipoprotein(a) 6.
- Antisense oligonucleotides and small interfering RNA agents targeting apolipoprotein(a) have the potential to reduce circulating Lipoprotein(a) concentrations by more than 70% 5.
Lifestyle Changes and Lipoprotein(a) Levels
- Relevant body weight loss, a relatively high intake of saturated fatty acids, the consumption of red wine, and intense physical exercise seem to be associated with significantly lower plasma Lipoprotein(a) levels 7.
- Foods rich in trans-unsaturated fatty acids are associated with increased Lipoprotein(a) levels 7.
- Dietary supplements such as coenzyme Q10, L-Carnitine, and flaxseed exert a mild but significant lowering effect on plasma Lipoprotein(a) 7.
Combination Therapies
- The addition of PCSK9 inhibitors to background niacin therapy is associated with a ∼15% reduction in Lipoprotein(a) beyond that achieved with background niacin monotherapy 8.
- PCSK9 inhibitors in combination with high-dose statins may reduce cardiovascular events and all-cause mortality in patients with clinical atherosclerotic cardiovascular disease 9.