Top

Drugs

Published in:

01-05-2019 | Systematic Review

Efficacy and Safety of Mipomersen: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Authors: Federica Fogacci, Nicola Ferri, Peter P. Toth, Massimiliano Ruscica, Alberto Corsini, Arrigo F. G. Cicero

Published in: Drugs | Issue 7/2019

Abstract

Aim

Our aim was to assess the efficacy and safety of mipomersen through a systematic review of the literature and a meta-analysis of the available clinical studies.

Methods

A systematic literature search in SCOPUS, PubMed Medline, ISI Web of Science and Google Scholar databases was conducted up to January 20, 2019, in order to identify clinical trials assessing the effect of mipomersen on lipoproteins, and the safety profile of mipomersen. Effect sizes for lipid changes were expressed as weighted mean differences (WMD) and 95% confidence intervals (CI). For safety analysis, odd ratios (OR) and 95% CI were calculated using the Mantel–Haenszel method. Data were pooled from 13 clinical studies comprising 49 arms, which included 1053 subjects overall, with 729 in the active-treated arm and 324 in the control arm.

Results

Meta-analysis of data suggested that mipomersen significantly reduced low-density lipoprotein cholesterol (WMD − 1.52, 95% CI − 1.85 to − 1.19; p < 0.001), total cholesterol (WMD − 1.55, 95% CI − 1.97 to − 1.13; p < 0.001), non-high-density lipoprotein cholesterol (non-HDL-C) (WMD − 1.66, 95% CI − 2.06 to − 1.27; p < 0.001), lipoprotein(a) (WMD − 0.99, 95% CI − 1.37 to − 0.62; p < 0.001), apolipoprotein B (WMD − 1.66, 95% CI − 2.04 to − 1.27; p < 0.001), triglycerides (WMD –0.61, 95% CI − 0.76 to − 0.46, p < 0.001), very-low-density lipoprotein cholesterol (WMD − 0.58, 95% CI − 0.73 to − 0.43; p < 0.001) and apolipoprotein A-I (WMD − 0.25, 95% CI − 0.51 to − 0.001; p = 0.049) without affecting HDL-C levels (WMD 0.11, 95% CI − 0.03 to 0.26; p = 0.124). However, treatment with mipomersen was positively associated with an increased risk of discontinuation of treatment (OR 3.02, 95% CI 1.96–4.65; p < 0.001), injection-site reaction (OR 11.41, 95% CI 7.88–16.52; p < 0.001), hepatic steatosis (OR 4.96, 95% CI 1.99–12.39; p = 0.001), hepatic enzymes elevation (OR 3.61, 95% CI 2.09–6.24; p < 0.001) and flu-like symptoms (OR 2.02, 95% CI 1.45–2.81; p < 0.001).

Conclusion

Despite favourable effects on the lipid profile, some concerns are reinforced from the safety profile. As a matter of fact, mipomersen therapy is more likely discontinued and associated with increased risk of injection-site reactions, hepatic steatosis, hepatic enzyme elevation, and flu-like symptoms.

Available only for authorised users

Nordestgaard BG, Chapman MJ, Humphries SE, Ginsberg HN, Masana L, Descamps OS, Wiklund O, Hegele RA, Raal FJ, Defesche JC, Wiegman A, Santos RD, Watts GF, Parhofer KG, Hovingh GK, Kovanen PT, Boileau C, Averna M, Borén J, Bruckert E, Catapano AL, Kuivenhoven JA, Pajukanta P, Ray K, Stalenhoef AF, Stroes E, Taskinen MR, Tybjærg-Hansen A, European Atherosclerosis Society Consensus Panel. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J. 2013;34(45):3478-90a. https://doi.org/10.1093/eurheartj/eht273.CrossRefPubMed

Vallejo-Vaz AJ, Kondapally Seshasai SR, Cole D, Hovingh GK, Kastelein JJ, Mata P, Raal FJ, Santos RD, Soran H, Watts GF, Abifadel M, Aguilar-Salinas CA, Akram A, Alnouri F, Alonso R, Al-Rasadi K, Banach M, Bogsrud MP, Bourbon M, Bruckert E, Car J, Corral P, Descamps O, Dieplinger H, Durst R, Freiberger T, Gaspar IM, Genest J, Harada-Shiba M, Jiang L, Kayikcioglu M, Lam CS, Latkovskis G, Laufs U, Liberopoulos E, Nilsson L, Nordestgaard BG, O’Donoghue JM, Sahebkar A, Schunkert H, Shehab A, Stoll M, Su TC, Susekov A, Widén E, Catapano AL, Ray KK. Familial hypercholesterolaemia: a global call to arms. Atherosclerosis. 2015;243(1):257–9. https://doi.org/10.1016/j.atherosclerosis.2015.09.021.CrossRefPubMed

Cuchel M, Bruckert E, Ginsberg HN, Raal FJ, Santos RD, Hegele RA, Kuivenhoven JA, Nordestgaard BG, Descamps OS, Steinhagen-Thiessen E, Tybjærg-Hansen A, Watts GF, Averna M, Boileau C, Borén J, Catapano AL, Defesche JC, Hovingh GK, Humphries SE, Kovanen PT, Masana L, Pajukanta P, Parhofer KG, Ray KK, Stalenhoef AF, Stroes E, Taskinen MR, Wiegman A, Wiklund O, Chapman MJ, European Atherosclerosis Society Consensus Panel on Familial Hypercholesterolaemia. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. Eur Heart J. 2014;35(32):2146–57. https://doi.org/10.1093/eurheartj/ehu274.CrossRefPubMedPubMedCentral

Brautbar A, Leary E, Rasmussen K, Wilson DP, Steiner RD, Virani S. Genetics of familial hypercholesterolemia. Curr Atheroscler Rep. 2015;17(4):491. https://doi.org/10.1007/s11883-015-0491-z.CrossRefPubMed

Benn M, Watts GF, Tybjaerg-Hansen A, Nordestgaard BG. Familial hypercholesterolemia in the danish general population: prevalence, coronary artery disease, and cholesterol-lowering medication. J Clin Endocrinol Metab. 2012;97(11):3956–64. https://doi.org/10.1210/jc.2012-1563.CrossRefPubMed

Reiner Ž. Management of patients with familial hypercholesterolaemia. Nat Rev Cardiol. 2015;12(10):565–75. https://doi.org/10.1038/nrcardio.2015.92.CrossRefPubMed

Landmesser U, Chapman MJ, Stock JK, Amarenco P, Belch JJF, Borén J, Farnier M, Ference BA, Gielen S, Graham I, Grobbee DE, Hovingh GK, Lüscher TF, Piepoli MF, Ray KK, Stroes ES, Wiklund O, Windecker S, Zamorano JL, Pinto F, Tokgözoglu L, Bax JJ, Catapano AL. 2017 Update of ESC/EAS Task Force on practical clinical guidance for proprotein convertase subtilisin/kexin type 9 inhibition in patients with atherosclerotic cardiovascular disease or in familial hypercholesterolaemia. Eur Heart J. 2018;39(14):1131–43. https://doi.org/10.1093/eurheartj/ehx549.CrossRefPubMed

Raal FJ, Honarpour N, Blom DJ, Hovingh GK, Xu F, Scott R, Wasserman SM, Stein EA, TESLA Investigators. Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial. Lancet. 2015;385(9965):341–50. https://doi.org/10.1016/S0140-6736(14)61374-X.CrossRefPubMed

Raal FJ, Hovingh GK, Blom D, Santos RD, Harada-Shiba M, Bruckert E, Couture P, Soran H, Watts GF, Kurtz C, Honarpour N, Tang L, Kasichayanula S, Wasserman SM, Stein EA. Long-term treatment with evolocumab added to conventional drug therapy, with or without apheresis, in patients with homozygous familial hypercholesterolaemia: an interim subset analysis of the open-label TAUSSIG study. Lancet Diabetes Endocrinol. 2017;5(4):280–90. https://doi.org/10.1016/S2213-8587(17)30044-X.CrossRefPubMed

10.

Rader DJ, Kastelein JJ. Lomitapide and mipomersen: two first-in-class drugs for reducing low-density lipoprotein cholesterol in patients with homozygous familial hypercholesterolemia. Circulation. 2014;129(9):1022–32. https://doi.org/10.1161/CIRCULATIONAHA.113.001292.CrossRefPubMed

11.

Crooke ST, Geary RS. Clinical pharmacological properties of mipomersen (Kynamro), a second generation antisense inhibitor of apolipoprotein B. Br J Clin Pharmacol. 2013;76(2):269–76. https://doi.org/10.1111/j.1365-2125.2012.04469.x.CrossRefPubMed

12.

Cuchel M, Bloedon LT, Szapary PO, Kolansky DM, Wolfe ML, Sarkis A, Millar JS, Ikewaki K, Siegelman ES, Gregg RE, Rader DJ. Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. N Engl J Med. 2007;356(2):148–56.CrossRefPubMed

13.

Thomas T, Ginsberg H. Development of apolipoprotein B antisense molecules as a therapy for hyperlipidemia. Curr Atheroscler Rep. 2010;12(1):58–65. https://doi.org/10.1007/s11883-009-0078-7.CrossRefPubMed

14.

Levin AA. Treating disease at the RNA Level with oligonucleotides. N Engl J Med. 2019;380(1):57–70. https://doi.org/10.1056/NEJMra1705346.CrossRefPubMed

15.

Parham JS, Goldberg AC. Mipomersen and its use in familial hypercholesterolemia. Expert Opin Pharmacother. 2019;20(2):127–31. https://doi.org/10.1080/14656566.2018.1550071.CrossRefPubMed

16.

Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535. https://doi.org/10.1136/bmj.b2535.CrossRefPubMedPubMedCentral

17.

Higgins J, Green S. Cochrane handbook for systematic reviews of interventions. Version 5.0. 2. Chichester: Wiley; 2009 (Ref Type: Report; 2010).

18.

Fogacci F, Banach M, Mikhailidis DP, Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group; International Lipid Expert Panel (ILEP), et al. Safety of red yeast rice supplementation: a systematic review and meta-analysis of randomized controlled trials. Pharmacol Res. 2019;143:1–16.CrossRefPubMed

19.

Borenstein M, Hedges L, Higgins J, Rothstein H. Comprehensive meta-analysis version 3. Englewood: Biostat; 2005. p. 104.

20.

Follmann D, Elliott P, Suh I, Cutler J. Variance imputation for overviews of clinical trials with continuous response. J Clin Epidemiol. 1992;45(7):769–73.CrossRefPubMed

21.

Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014;19(14):135. https://doi.org/10.1186/1471-2288-14-135.CrossRef

22.

Melsen WG, Bootsma MC, Rovers MM, Bonten MJ. The effects of clinical and statistical heterogeneity on the predictive values of results from meta-analyses. Clin Microbiol Infect. 2014;20:123–9. https://doi.org/10.1111/1469-0691.12494.CrossRefPubMed

23.

Haenszel W, Hon NB. Statistical approaches to the study of cancer with particular reference to case registers. J Chronic Dis. 1956;4(6):589–99.CrossRefPubMed

24.

Fogacci F, Banach M, Cicero AFG. Resveratrol effect on patients with non-alcoholic fatty liver disease: a matter of dose and treatment length. Diabetes Obes Metab. 2018;20(7):1798–9. https://doi.org/10.1111/dom.13324.CrossRefPubMed

25.

Sahebkar A, Pirro M, Reiner Ž, et al. A systematic review and meta-analysis of controlled trials on the effects of statin and fibrate therapies on plasma homocysteine levels. Curr Med Chem. 2016;23(39):4490–503.CrossRefPubMed

26.

Duval S, Tweedie R. Trim and fill: a simple funnel-plot–based method of testing and adjusting for publication bias in meta-analysis. Biometrics. 2000;56:455–63.CrossRef

27.

Reeskamp LF, Kastelein JJP, Moriarty PM, Duell PB, Catapano AL, Santos RD, Ballantyne CM. Safety and efficacy of mipomersen in patients with heterozygous familial hypercholesterolemia. Atherosclerosis. 2019;280:109–17.CrossRefPubMed

28.

Waldmann E, Vogt A, Crispin A, Altenhofer J, Riks I, Parhofer KG. Effect of mipomersen on LDL-cholesterol in patients with severe LDL-hypercholesterolaemia and atherosclerosis treated by lipoprotein apheresis (the MICA-study). Atherosclerosis. 2017;259:20–5. https://doi.org/10.1016/j.atherosclerosis.2017.02.019.CrossRefPubMed

29.

Waldmann E, Vogt A, Crispin A, Altenhofer J, Riks I, Parhofer KG. Corrigendum to: “Effect of mipomersen on LDL-cholesterol in patients with severe LDL-hypercholesterolaemia and atherosclerosis treated by lipoprotein apheresis (The MICA-Study)” [Atherosclerosis 259 (2017 Apr) 20-25]. Atherosclerosis. 2018;275:461–2. https://doi.org/10.1016/j.atherosclerosis.2018.05.020.CrossRefPubMed

30.

Flaim JD, Grundy JS, Baker BF, McGowan MP, Kastelein JJ. Changes in mipomersen dosing regimen provide similar exposure with improved tolerability in randomized placebo-controlled study of healthy volunteers. J Am Heart Assoc. 2014;3(2):e000560. https://doi.org/10.1161/JAHA.113.000560.CrossRefPubMedPubMedCentral

31.

Thomas GS, Cromwell WC, Ali S, Chin W, Flaim JD, Davidson M. Mipomersen, an apolipoprotein B synthesis inhibitor, reduces atherogenic lipoproteins in patients with severe hypercholesterolemia at high cardiovascular risk: a randomized, double-blind, placebo-controlled trial. J Am Coll Cardiol. 2013;62(23):2178–84. https://doi.org/10.1016/j.jacc.2013.07.081.CrossRefPubMed

32.

McGowan MP, Tardif JC, Ceska R, Burgess LJ, Soran H, Gouni-Berthold I, Wagener G, Chasan-Taber S. Randomized, placebo-controlled trial of mipomersen in patients with severe hypercholesterolemia receiving maximally tolerated lipid-lowering therapy. PLoS One. 2012;7(11):e49006. https://doi.org/10.1371/journal.pone.0049006.CrossRefPubMedPubMedCentral

33.

Stein EA, Dufour R, Gagne C, Gaudet D, East C, Donovan JM, Chin W, Tribble DL, McGowan M. Apolipoprotein B synthesis inhibition with mipomersen in heterozygous familial hypercholesterolemia: results of a randomized, double-blind, placebo-controlled trial to assess efficacy and safety as add-on therapy in patients with coronary artery disease. Circulation. 2012;126(19):2283–92. https://doi.org/10.1161/CIRCULATIONAHA.112.104125.CrossRefPubMed

34.

Visser ME, Wagener G, Baker BF, Geary RS, Donovan JM, Beuers UH, Nederveen AJ, Verheij J, Trip MD, Basart DC, Kastelein JJ, Stroes ES. Mipomersen, an apolipoprotein B synthesis inhibitor, lowers low-density lipoprotein cholesterol in high-risk statin-intolerant patients: a randomized, double-blind, placebo-controlled trial. Eur Heart J. 2012;33(9):1142–9. https://doi.org/10.1093/eurheartj/ehs023.CrossRefPubMedPubMedCentral

35.

Akdim F, Tribble DL, Flaim JD, Yu R, Su J, Geary RS, Baker BF, Fuhr R, Wedel MK, Kastelein JJ. Efficacy of apolipoprotein B synthesis inhibition in subjects with mild-to-moderate hyperlipidaemia. Eur Heart J. 2011;32(21):2650–9. https://doi.org/10.1093/eurheartj/ehr148.CrossRefPubMed

36.

Akdim F, Stroes ES, Sijbrands EJ, Tribble DL, Trip MD, Jukema JW, Flaim JD, Su J, Yu R, Baker BF, Wedel MK, Kastelein JJ. Efficacy and safety of mipomersen, an antisense inhibitor of apolipoprotein B, in hypercholesterolemic subjects receiving stable statin therapy. J Am Coll Cardiol. 2010;55(15):1611–8. https://doi.org/10.1016/j.jacc.2009.11.069.CrossRefPubMed

37.

Akdim F, Visser ME, Tribble DL, Baker BF, Stroes ES, Yu R, Flaim JD, Su J, Stein EA, Kastelein JJ. Effect of mipomersen, an apolipoprotein B synthesis inhibitor, on low-density lipoprotein cholesterol in patients with familial hypercholesterolemia. Am J Cardiol. 2010;105(10):1413–9. https://doi.org/10.1016/j.amjcard.2010.01.003.CrossRefPubMed

38.

Raal FJ, Santos RD, Blom DJ, Marais AD, Charng MJ, Cromwell WC, Lachmann RH, Gaudet D, Tan JL, Chasan-Taber S, Tribble DL, Flaim JD, Crooke ST. Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial. Lancet. 2010;375(9719):998–1006. https://doi.org/10.1016/S0140-6736(10)60284-X.CrossRefPubMed

39.

Visser ME, Akdim F, Tribble DL, Nederveen AJ, Kwoh TJ, Kastelein JJ, Trip MD, Stroes ES. Effect of apolipoprotein-B synthesis inhibition on liver triglyceride content in patients with familial hypercholesterolemia. J Lipid Res. 2010;51(5):1057–62. https://doi.org/10.1194/jlr.M002915.CrossRefPubMedPubMedCentral

40.

Kastelein JJ, Wedel MK, Baker BF, Su J, Bradley JD, Yu RZ, Chuang E, Graham MJ, Crooke RM. Potent reduction of apolipoprotein B and low-density lipoprotein cholesterol by short-term administration of an antisense inhibitor of apolipoprotein B. Circulation. 2006;114(16):1729–35.CrossRefPubMed

41.

Panta R, Dahal K, Kunwar S. Efficacy and safety of mipomersen in treatment of dyslipidemia: a meta-analysis of randomized controlled trials. J Clin Lipidol. 2015;9(2):217–25. https://doi.org/10.1016/j.jacl.2014.12.006.CrossRefPubMed

42.

Santos RD, Duell PB, East C, Guyton JR, Moriarty PM, Chin W, Mittleman RS. Long-term efficacy and safety of mipomersen in patients with familial hypercholesterolaemia: 2-year interim results of an open-label extension. Eur Heart J. 2015;36(9):566–75. https://doi.org/10.1093/eurheartj/eht549.CrossRefPubMed

43.

Hashemi N, Odze RD, McGowan MP, Santos RD, Stroes ES, Cohen DE. Liver histology during Mipomersen therapy for severe hypercholesterolemia. J Clin Lipidol. 2014;8(6):606–11. https://doi.org/10.1016/j.jacl.2014.08.002.CrossRefPubMedPubMedCentral

44.

Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, Kirby A, Sourjina T, Peto R, Collins R, Simes R, Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366(9493):1267–78 (Epub 2005 Sep 27; Erratum in: Lancet. 2005 Oct 15-21;366(9494):1358. Erratum in: Lancet. 2008 Jun 21;371(9630):2084).CrossRefPubMed

45.

Catapano AL, Graham I, De Backer G, Wiklund O, Chapman MJ, Drexel H, Hoes AW, Jennings CS, Landmesser U, Pedersen TR, Reiner Ž, Riccardi G, Taskinen MR, Tokgozoglu L, Verschuren WMM, Vlachopoulos C, Wood DA, Zamorano JL, Cooney MT, ESC Scientific Document Group. 2016 ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J. 2016;37(39):2999–3058. https://doi.org/10.1093/eurheartj/ehw272.CrossRefPubMed

46.

Duell PB, Santos RD, Kirwan BA, Witztum JL, Tsimikas S, Kastelein JJP. Long-term mipomersen treatment is associated with a reduction in cardiovascular events in patients with familial hypercholesterolemia. J Clin Lipidol. 2016;10(4):1011–21. https://doi.org/10.1016/j.jacl.2016.04.013.CrossRefPubMed

47.

Cuchel M, Meagher EA, du Toit Theron H, Blom DJ, Marais AD, Hegele RA, Averna MR, Sirtori CR, Shah PK, Gaudet D, Stefanutti C, Vigna GB, Du Plessis AM, Propert KJ, Sasiela WJ, Bloedon LT, Rader DJ, Phase 3 HoFH Lomitapide Study investigators. Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study. Lancet. 2013;381(9860):40–6. https://doi.org/10.1016/S0140-6736(12)61731-0.CrossRefPubMed

48.

Blom DJ, Averna MR, Meagher EA, du Toit Theron H, Sirtori CR, Hegele RA, Shah PK, Gaudet D, Stefanutti C, Vigna GB, Larrey D, Bloedon LT, Foulds P, Rader DJ, Cuchel M. Long-term efficacy and safety of the microsomal triglyceride transfer protein inhibitor lomitapide in patients with homozygous familial hypercholesterolemia. Circulation. 2017;136(3):332–5. https://doi.org/10.1161/CIRCULATIONAHA.117.028208.CrossRefPubMed

49.

50.

51.

Stein EA, Honarpour N, Wasserman SM, Xu F, Scott R, Raal FJ. Effect of the proprotein convertase subtilisin/kexin 9 monoclonal antibody, AMG 145, in homozygous familial hypercholesterolemia. Circulation. 2013;128(19):2113–20. https://doi.org/10.1161/CIRCULATIONAHA.113.004678.CrossRefPubMed

52.

Lambert G, Chatelais M, Petrides F, Passard M, Thedrez A, Rye KA, Schwahn U, Gusarova V, Blom DJ, Sasiela W, Marais AD. Normalization of low-density lipoprotein receptor expression in receptor defective homozygous familial hypercholesterolemia by inhibition of PCSK9 with alirocumab. J Am Coll Cardiol. 2014;64(21):2299–300. https://doi.org/10.1016/j.jacc.2014.07.995.CrossRefPubMed

53.

Raal F, Panz V, Immelman A, Pilcher G. Elevated PCSK9 levels in untreated patients with heterozygous or homozygous familial hypercholesterolemia and the response to high-dose statin therapy. J Am Heart Assoc. 2013;2(2):e000028. https://doi.org/10.1161/JAHA.112.000028.CrossRefPubMedPubMedCentral

54.

Nordestgaard BG, Chapman MJ, Ray K, Borén J, Andreotti F, Watts GF, Ginsberg H, Amarenco P, Catapano A, Descamps OS, Fisher E, Kovanen PT, Kuivenhoven JA, Lesnik P, Masana L, Reiner Z, Taskinen MR, Tokgözoglu L, Tybjærg-Hansen A, European Atherosclerosis Society Consensus Panel. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J. 2010;31(23):2844–53. https://doi.org/10.1093/eurheartj/ehq386.CrossRefPubMedPubMedCentral

55.

Nandakumar R, Matveyenko A, Thomas T, Pavlyha M, Ngai C, Holleran S, Ramakrishnan R, Ginsberg HN, Karmally W, Marcovina SM, Reyes-Soffer G. Effects of mipomersen, an apolipoprotein B100 antisense, on lipoprotein (a) metabolism in healthy subjects. J Lipid Res. 2018;59(12):2397–402. https://doi.org/10.1194/jlr.P082834.CrossRefPubMed

56.

Burgess S, Ference BA, Staley JR, Freitag DF, Mason AM, Nielsen SF, Willeit P, Young R, Surendran P, Karthikeyan S, Bolton TR, Peters JE, Kamstrup PR, Tybjærg-Hansen A, Benn M, Langsted A, Schnohr P, Vedel-Krogh S, Kobylecki CJ, Ford I, Packard C, Trompet S, Jukema JW, Sattar N, Di Angelantonio E, Saleheen D, Howson JMM, Nordestgaard BG, Butterworth AS, Danesh J, European Prospective Investigation Into Cancer and Nutrition–Cardiovascular Disease (EPIC-CVD) Consortium. Association of LPA variants with risk of coronary disease and the implications for lipoprotein(a)-lowering therapies: a Mendelian randomization analysis. JAMA Cardiol. 2018;3(7):619–27. https://doi.org/10.1001/jamacardio.2018.1470.CrossRefPubMedPubMedCentral

57.

Furtado JD, Wedel MK, Sacks FM. Antisense inhibition of apoB synthesis with mipomersen reduces plasma apoC-III and apoC-III-containing lipoproteins. J Lipid Res. 2012;53(4):784–91. https://doi.org/10.1194/jlr.P021717.CrossRefPubMedPubMedCentral

58.

Pechlaner R, Tsimikas S, Yin X, Willeit P, Baig F, Santer P, Oberhollenzer F, Egger G, Witztum JL, Alexander VJ, Willeit J, Kiechl S, Mayr M. Very-low-density lipoprotein-associated apolipoproteins predict cardiovascular events and are lowered by inhibition of APOC-III. J Am Coll Cardiol. 2017;69(7):789–800. https://doi.org/10.1016/j.jacc.2016.11.065.CrossRefPubMedPubMedCentral

Title: Efficacy and Safety of Mipomersen: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
Authors: Federica Fogacci
Nicola Ferri
Peter P. Toth
Massimiliano Ruscica
Alberto Corsini
Arrigo F. G. Cicero
Publication date: 01-05-2019
Publisher: Springer International Publishing
Published in: Drugs / Issue 7/2019
Print ISSN: 0012-6667
Electronic ISSN: 1179-1950
DOI: https://doi.org/10.1007/s40265-019-01114-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Efficacy and Safety of Mipomersen: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Abstract

Aim

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Aim

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 7/2019

Pegaspargase: A Review in Acute Lymphoblastic Leukaemia

Solriamfetol: First Global Approval

New Drugs for Multidrug-Resistant Gram-Negative Organisms: Time for Stewardship

The Unique Pharmacological and Pharmacokinetic Profile of Teneligliptin: Implications for Clinical Practice

The Clinician’s Guide to Proton Pump Inhibitor Related Adverse Events

Correction to: Sarecycline: First Global Approval