Table 1.

Summary of pharmacology for lowering elevated plasma lipoprotein(a)

Agent/class	Target	Dose/administration	Major adverse effects	Contraindications	Extent of reduction
Statins [16, 17]	Inhibits HMG-CoA reductase	Varies, PO, daily	Arthralgia, diarrhea	Active liver disease, pregnancy	Ineffective
Fibric acid derivatives [18]	Induces PPAR-α; activates farnesoid X receptor	Varies, PO	Dyspepsia, GI pain, nausea, vomiting	Liver or severe kidney dysfunction	Limited reduction: WMD − 2.70 mg/dL; 95% CI − 4.56 to − 0.84; p = 0.004
Omega-3 fatty acids (fish oil) [21]	Decreases apoA synthesis; increases Lp(a) catabolism	8 gm PO, daily	AF, peripheral edema, atrial flutter, dysgeusia, constipation, gout, dyspepsia, hemorrhage	Hypersensitivity	Unpredictable effects
ER niacin [27]	Inhibits clearance of apoB, regulates Lp(a) turnover	≤2 to ≥ 2 g/day, PO	Flushing, myopathy, transaminitis, hyperglycemia	Active liver disease, peptic ulcer disease	Significant decrease: ≤ 2 g/day (WMD − 21.85%; 95% CI − 30.61 to − 13.10, p < 0.001); ≥ 2 g/day (WMD − 23.21%; 95% CI − 28.41 to − 18.01; p < 0.001)
Tamoxifen/raloxifene [31, 32]	Possible modulation apoA expression	Varies, PO	Gynecologic malignancies, bone marrow suppression	Hypersensitivities	Significant reduction: ~ 30%
Mipomersen [33]	Binds to apoB-100 mRNA	200 mg SC, weekly	Injection-site reactions, flu-like symptoms, elevated transaminases	Hypersensitivities, active liver disease (Child-Pugh class B or C)	Significant reduction: ~ 26%
Pelacarsen (AKCEA-APO(a)-LRx TQJ 230, ISIS 681257) [34]	Binds to apoB-100 mRNA	20, 40, 60 mg SC Q4W; 20 mg SC Q2W; 20 mg SC weekly	Injection-site reactions, flu-like symptoms, elevated transaminases, myalgias	Unknown	Significant reduction: 35–80%
Anacetrapib [39]a	Inhibits CETP	100 mg PO daily	Diarrhea, constipation, dyspepsia, myalgia	Unknown	Significant reduction: 25%
Obicetrapib (TA 8995, DEZ 001, AMG 899) [40]	Inhibits CETP	1,2.5, 5, 10 mg PO daily	Headaches	Unknown	Significant reduction: 26.7–36.9%
Evolocumab [46]	Inhibits PCSK9	140 mg SC Q2W; 420 mg SC Q4W	Injection-site reactions, flu-like symptoms, sore throat, hyperglycemia	Hypersensitivity	Significant reduction: 21.7–24.7%
Alirocumab [43, 44]	Inhibits PCSK9	10, 20, 40 mg SC Q2W; 50, 100, 150 mg SC Q2W; 200 or 300 mg SC Q4W	Injection-site reaction, chest pain, difficulty breathing or swallowing, hives, myalgias, reddening of skin	Hypersensitivity	Absolute reduction: 27%
Tocilizumab [47]	IL-6 receptor antagonist	8 mg/kg IV daily	Hypercholesterolemia, injection site reaction	Hypersensitivity	Modest reduction: 10–14.6 mg/dL at 1 and 3 months
Lomitapide [50]	Inhibits MTP	Median 40 mg PO daily	Fatigue, chest pain	Pregnancy, active liver disease (Child-Pugh class B or C)	Modest reduction: 15 and 19% at 26 and 56 weeks, respectively
Coenzyme Q10 [51]	Antioxidant	100–300 mg PO daily	Nausea, fatigue, headaches, insomnia	Anticoagulants	Modest reduction: WMD − 3.54 mg/dL; 95% CI − 5.50 to − 1.58; p < 0.001
Ezetimibe [52]	Anti-inflammatory effect, decreases LDL-C and apoB, through activation of LDL receptors	10 mg PO daily	Fatigue, diarrhea, increased serum transaminases (with HMG-CoA reductase inhibitors; ≥ 3 × ULN), arthralgia, limb pain	Hypersensitivity, concomitant use with statin with active liver disease, unexplained persistent elevations in serum transaminases, pregnancy, breastfeeding	Modest reduction: 7.06%

AF atrial fibrillation, apoA/B apolipoprotein A/B, CETP cholesteryl ester transfer protein, CI confidence interval, ER extended release, GI gastrointestinal, HMG-CoA hydroxymethylglutaryl coenzyme A (statin), IL interleukin, IV intravenous, LDL low-density lipoprotein, LDL-C LDL cholesterol, Lp(a) lipoprotein(a), mRNA messenger RNA, MTP microsomal triglyceride transport protein, PCSK9 proprotein convertase subtilisin/kexin type 9, PO oral administration, PPAR peroxisome proliferator activated receptor, Q2W every 2 weeks, Q4W every 4 weeks, SC subcutaneous, ULN upper limit of normal, WMD weighted mean difference

^aThe manufacturer has halted further development of anacetrapib