Skip to main content

Advertisement

SpringerLink
Log in

Raloxifene Lowers Plasma Lipoprotein(a) Concentrations: a Systematic Review and Meta-analysis of Randomized Placebo-Controlled Trials

  • REVIEW ARTICLE
  • Published:
Cardiovascular Drugs and Therapy Aims and scope Submit manuscript

Abstract

Background and Aims

Lipoprotein(a) (Lp(a)) is a proatherogenic plasma lipoprotein and an independent risk factor for atherosclerotic cardiovascular disease. We investigated the effects of raloxifene, selective estrogen receptor modulator, on circulating Lp(a) levels in postmenopausal women using a systematic review and meta-analysis of randomized controlled trials (RCTs).

Methods

To identify relevant studies, electronic databases (PUBMED, Scopus, Web of Science, and Google Scholar) were searched by up to May 2015 to find controlled trials exploring the effects of oral raloxifene treatment on plasma Lp(a) levels in postmenopausal women. A random-effects model and generic inverse variance method were used for quantitative data synthesis.

Results

Overall, seven eligible RCTs with ten treatment arms were included in this meta-analysis. Meta-analysis suggested a significant reduction of Lp(a) levels after treatment with raloxifene (standardized mean difference (SMD) −0.42; 95% CI −0.65, −0.19; p < 0.001), which may be considered as a medium effect size. When the studies were categorized according to the administered dose, there was a significant effect in both subsets of studies with administered doses ≤60 mg/day (SMD −0.43; 95% CI −0.73, −0.13; p = 0.004) and >60 mg/day (SMD −0.36; 95% CI −0.68, −0.05; p = 0.025). No significant association between the changes in plasma concentrations of Lp(a) with dose and baseline Lp(a) levels was found in the random-effects meta-regression analysis. However, a significant inverse association was observed between the Lp(a)-lowering effect of raloxifene and duration of treatment (p = 0.001).

Conclusions

Results of the present meta-analysis showed a reduction in plasma Lp(a) concentrations of postmenopausal women with oral raloxifene treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

apo(a):

Apolipoprotein a

apoB:

Apolipoprotein B

BMI:

Body mass index

CVD:

Cardiovascular disease

HDL:

High-density lipoprotein

HDL-C:

High-density lipoprotein cholesterol

LDL:

Low-density lipoprotein

LDL-C:

Low-density lipoprotein cholesterol

Lp(a):

Lipoprotein(a)

OxPL:

Oxidized phospholipids

RCTs:

Randomized controlled trials

RLX:

Raloxifene

SERM:

Selective estrogen receptor modulators

TC:

Total cholesterol

References

  1. Bagger YZ, Rasmussen HB, Alexandersen P, Werge T, Christiansen C, Tanko LB. Links between cardiovascular disease and osteoporosis in postmenopausal women: serum lipids or atherosclerosis per se? Osteoporos Int. 2007;18(4):505–12.

    Article  CAS  PubMed  Google Scholar 

  2. Manson JE, Bassuk SS. Biomarkers of cardiovascular disease risk in women. Metabolism. 2015;64(3 Suppl 1):S33–9.

    Article  CAS  PubMed  Google Scholar 

  3. Sprini D, Rini GB, Di Stefano L, Cianferotti L, Napoli N. Correlation between osteoporosis and cardiovascular disease. Clin Cases Miner Bone Metab. 2014;11(2):117–9.

    PubMed  PubMed Central  Google Scholar 

  4. Maziere C, Louvet L, Gomila C, Kamel S, Massy Z, Maziere JC. Oxidized low density lipoprotein decreases Rankl-induced differentiation of osteoclasts by inhibition of Rankl signaling. J Cell Physiol. 2009;221(3):572–8.

    Article  CAS  PubMed  Google Scholar 

  5. Orozco P. Atherogenic lipid profile and elevated lipoprotein (a) are associated with lower bone mineral density in early postmenopausal overweight women. Eur J Epidemiol. 2004;19(12):1105–12.

    Article  CAS  PubMed  Google Scholar 

  6. Auro K, Joensuu A, Fischer K, Kettunen J, Salo P, Mattsson H, et al. A metabolic view on menopause and ageing. Nat Commun. 2014;5.

  7. Akahoshi M, Soda M, Nakashima E, Shimaoka K, Seto S, Yano K. Effects of menopause on trends of serum cholesterol, blood pressure, and body mass index. Circulation. 1996;94(1):61–6.

    Article  CAS  PubMed  Google Scholar 

  8. Campos H, McNamara JR, Wilson PW, Ordovas JM, Schaefer EJ. Differences in low density lipoprotein subfractions and apolipoproteins in premenopausal and postmenopausal women. J Clin Endocrinol Metab. 1988;67(1):30–5.

    Article  CAS  PubMed  Google Scholar 

  9. Jenner JL, Ordovas JM, Lamon-Fava S, Schaefer MM, Wilson PW, Castelli WP, et al. Effects of age, sex, and menopausal status on plasma lipoprotein(a) levels. The Framingham Offspring Study. Circulation. 1993;87(4):1135–41.

    Article  CAS  PubMed  Google Scholar 

  10. Berg G, Mesch V, Boero L, Sayegh F, Prada M, Royer M, et al. Lipid and lipoprotein profile in menopausal transition. Effects of hormones, age and fat distribution. Horm Metab Res. 2004;36(4):215–20.

    Article  CAS  PubMed  Google Scholar 

  11. Boffa MB, Koschinsky ML. Update on lipoprotein(a) as a cardiovascular risk factor and mediator. Curr Atheroscler Rep. 2013;15(10):360.

  12. Dube JB, Boffa MB, Hegele RA, Koschinsky ML. Lipoprotein(a): more interesting than ever after 50 years. Curr Opin Lipidol. 2012;23(2):133–40.

    Article  CAS  PubMed  Google Scholar 

  13. Erqou S, Kaptoge S, Perry PL, Di Angelantonio E, Thompson A, White IR, et al. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA. 2009;302(4):412–23.

  14. Kronenberg F. Human genetics and the causal role of lipoprotein(a) for various diseases. Cardiovasc Drugs Ther. 2016;30(1):87-100.

  15. Kostner KM, Marz W, Kostner GM. When should we measure lipoprotein (a)? Eur Heart J. 2013;34(42):3268–76.

    Article  CAS  PubMed  Google Scholar 

  16. Marcovina SM, Hegele RA, Koschinsky ML. Lipoprotein(a) and coronary heart disease risk. Current Cardiol Reports. 1999;1(2):105–11.

    Article  CAS  Google Scholar 

  17. Catapano AL, Graham I, De Backer G, Wiklund O, Chapman MJ, Drexel H, et al. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. Eur Heart J. 2016;37(39):2999–3058. doi:10.1093/eurheartj/ehw272.

    Article  PubMed  Google Scholar 

  18. Nordestgaard BG, Chapman MJ, Ray K, Boren J, Andreotti F, Watts GF, et al. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J. 2010;31(23):2844–53. doi:10.1093/eurheartj/ehq386.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Morishita R, Ishii J, Kusumi Y, Yamada S, Komai N, Ohishi M, et al. Association of serum oxidized lipoprotein(a) concentration with coronary artery disease: potential role of oxidized lipoprotein(a) in the vasucular wall. J Atheroscler Thromb. 2009;16(4):410–8.

    Article  CAS  PubMed  Google Scholar 

  20. Wei DH, Zhang XL, Wang R, Zeng JF, Zhang K, Yang J, et al. Oxidized lipoprotein(a) increases endothelial cell monolayer permeability via ROS generation. Lipids. 2013;48(6):579–86.

    Article  CAS  PubMed  Google Scholar 

  21. Francucci CM, Romagni P, Boscaro M. Raloxifene: bone and cardiovascular effects. J Endocrinol Invest. 2005;28(10 Suppl):85–9.

    CAS  PubMed  Google Scholar 

  22. Dayspring T, Qu Y, Keech C. Effects of raloxifene on lipid and lipoprotein levels in postmenopausal osteoporotic women with and without hypertriglyceridemia. Metabolism. 2006;55(7):972–9.

    Article  CAS  PubMed  Google Scholar 

  23. Higgins JPT, Green S. Handbook for systematic reviews of interventions. Version 5.0.2 ed. London: The Cochrane Collboration; 2009.

    Google Scholar 

  24. Borenstein M, Hedges L, Higgins JPT. Comprehensive meta-analysis. Version 2. Englewood: Biostat; 2005.

    Google Scholar 

  25. Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol. 2005;5:13.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Ferretti G, Bacchetti T, Sahebkar A. Effect of statin therapy on paraoxonase-1 status: a systematic review and meta-analysis of 25 clinical trials. Prog Lipid Res. 2015;60:50–73.

  27. Banach M, Serban C, Ursoniu S, Rysz J, Muntner P, Toth PP, Jones SR, Rizzo M, Glasser SP, Watts GF, Blumenthal RS, Lip GY, Mikhailidis DP, Sahebkar A. Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group. Statin therapy and plasma coenzyme Q10 concentrations--A systematic review and meta-analysis of placebo-controlled trials. Pharmacol Res. 2015;99:329–36.

  28. Banach M, Serban C, Sahebkar A, Mikhailidis DP, Ursoniu S, Ray KK, Rysz J, Toth PP, Muntner P, Mosteoru S, García-García HM, Hovingh GK, Kastelein JJ, Serruys PW. Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group. Impact of statin therapy on coronary plaque composition: a systematic review and meta-analysis of virtual histology intravascular ultrasound studies. BMC Med. 2015;13:229.

  29. Sahebkar A. Are curcuminoids effective C-reactive protein-lowering agents in clinical practice? Evidence from a meta-analysis. Phytother Res. 2014;28(5):633–42.

    Article  CAS  PubMed  Google Scholar 

  30. 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(2):455–63.

    Article  CAS  PubMed  Google Scholar 

  31. Mijatovic V, van der Mooren MJ, Kenemans P, de Walk-de Roo GW, Netelenbos C. Raloxifene lowers serum lipoprotein(A) in healthy postmenopausal women: a randomized, double-blind, placebo-controlled comparison with conjugated equine estrogens. Menopause. 1999;6(2):134–7.

    Article  CAS  PubMed  Google Scholar 

  32. Smolders RGV, Vogelvang TE, Mijatovic V, van Baal WM, Neele SJM, Netelenbos JC, et al. A 2-year, randomized, comparative, placebo-controlled study on the effects of raloxifene on lipoprotein(a) and homocysteine. Maturitas. 2002;41(2):105–14.

    Article  CAS  PubMed  Google Scholar 

  33. Vogelvang TE, Mijatovic V, Kenemans P, Teerlink T, van der Mooren MJ. HMR 3339, a novel selective estrogen receptor modulator, reduces total cholesterol, low-density lipoprotein cholesterol, and homocysteine in healthy postmenopausal women. Fertil Steril. 2004;82(6):1540–9.

    Article  CAS  PubMed  Google Scholar 

  34. Andersson B, Johannsson G, Holm G, Bengtsson BA, Sashegyi A, Pavo I, et al. Raloxifene does not affect insulin sensitivity or glycemic control in postmenopausal women with type 2 diabetes mellitus: a randomized clinical trial. J Clin Endocrinol Metab. 2002;87(1):122–8.

    Article  PubMed  Google Scholar 

  35. Insull W, Davidson MH, Kulkarni PM, Siddhanti S, Ciaccia AV, Keech CA. Effects of raloxifene and low-dose simvastatin coadministration on plasma lipids in postmenopausal women with primary hypercholesterolemia. Metab Clin Exp. 2005;54(7):939–46.

    Article  CAS  PubMed  Google Scholar 

  36. Lobo RA, Pinkerton JV, Gass MLS, Dorin MH, Ronkin S, Pickar JH, et al. Evaluation of bazedoxifene/conjugated estrogens for the treatment of menopausal symptoms and effects on metabolic parameters and overall safety profile. Fertil Steril. 2009;92(3):1025–38.

    Article  CAS  PubMed  Google Scholar 

  37. Walsh BW, Kuller LH, Wild RA, Paul S, Farmer M, Lawrence JB, et al. Effects of raloxifene on serum lipids and coagulation factors in healthy postmenopausal women. JAMA. 1998;279(18):1445–51.

  38. Riches K, Porter KE. Lipoprotein(a): cellular effects and molecular mechanisms. Cholesterol. 2012;2012:923289.

  39. Maranhao R, Arie S, Vinagre CG, Guimaraes JB, Strunz C, Pileggi F. Lipoprotein (a) plasma levels in normal subjects and patients with coronary disease confirmed by coronary cineangiography. Arq Bras Cardiol. 1991;56(2):121–5.

    CAS  PubMed  Google Scholar 

  40. Bos S, Yayha R, van Lennep JE. Latest developments in the treatment of lipoprotein (a). Curr Opin Lipidol. 2014;25(6):452–60.

    Article  CAS  PubMed  Google Scholar 

  41. Hoover-Plow J, Huang MG. Lipoprotein(a) metabolism: potential sites for therapeutic targets. Metab Clin Exp. 2013;62(4):479–91.

    Article  CAS  PubMed  Google Scholar 

  42. Bacchetti T, Campanati A, Ferretti G, Simonetti O, Liberati G, Offidani AM. Oxidative stress and psoriasis: the effect of antitumour necrosis factor-alpha inhibitor treatment. Br J Dermatol. 2013;168(5):984–9. doi:10.1111/bjd.12144.

    Article  CAS  PubMed  Google Scholar 

  43. Serban MC, Sahebkar A, Mikhailidis DP, Toth PP, Jones SR, Muntner P, et al. Impact of L-carnitine on plasma lipoprotein(a) concentrations: a systematic review and meta-analysis of randomized controlled trials. Scientific reports. 2016;6:19188. doi:10.1038/srep19188.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Sahebkar A, Simental-Mendia LE, Stefanutti C, Pirro M. Supplementation with coenzyme Q10 reduces plasma lipoprotein(a) concentrations but not other lipid indices: a systematic review and meta-analysis. Pharmacol Res. 2016;105:198–209. doi:10.1016/j.phrs.2016.01.030.

    Article  CAS  PubMed  Google Scholar 

  45. Kim CJ, Min YK, Ryu WS, Kwak JW, Ryoo UH. Effect of hormone replacement therapy on lipoprotein(a) and lipid levels in postmenopausal women—influence of various progestogens and duration of therapy. Arch Intern Med. 1996;156(15):1693–700.

    Article  CAS  PubMed  Google Scholar 

  46. Salpeter SR, Walsh JME, Ormiston TM, Greyber E, Buckley NS, Salpeter EE. Meta-analysis: effect of hormone-replacement therapy on components of the metabolic syndrome in postmenopausal women. Diabetes Obes Metab. 2006;8(5):538–54.

    Article  CAS  PubMed  Google Scholar 

  47. Sahebkar A, Reiner Z, Simental-Mendia LE, Ferretti G, Cicero AF. Effect of extended-release niacin on plasma lipoprotein(a) levels: a systematic review and meta-analysis of randomized placebo-controlled trials. Metabolism. 2016;65(11):1664–78. doi:10.1016/j.metabol.2016.08.007.

    Article  CAS  PubMed  Google Scholar 

  48. Kotani K, Sahebkar A, Serban C, Andrica F, Toth PP, Jones SR, et al. Tibolone decreases Lipoprotein(a) levels in postmenopausal women: a systematic review and meta-analysis of 12 studies with 1009 patients. Atherosclerosis. 2015;242(1):87–96.

    Article  CAS  PubMed  Google Scholar 

  49. Maranhao RC, Carvalho PO, Strunz CC, Pileggi F. Lipoprotein (a): structure, pathophysiology and clinical implications. Arq Bras Cardiol. 2014;103(1):76–83.

    PubMed  PubMed Central  Google Scholar 

  50. Kronenberg F, Steinmetz A, Kostner GM, Dieplinger H. Lipoprotein(a) in health and disease. Crit Rev Cl Lab Sci. 1996;33(6):495–543.

    Article  CAS  Google Scholar 

  51. Rader DJ, Cain W, Zech LA, Usher D, Brewer Jr HB. Variation in lipoprotein(a) concentrations among individuals with the same apolipoprotein (a) isoform is determined by the rate of lipoprotein(a) production. J Clin Invest. 1993;91(2):443–7. doi:10.1172/JCI116221.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Boffelli D, Zajchowski DA, Yang Z, Lawn RM. Estrogen modulation of apolipoprotein(a) expression. Identification of a regulatory element. J Biol Chem. 1999;274(22):15569–74.

    Article  CAS  PubMed  Google Scholar 

  53. Mitlak BH, Cohen FJ. In search of optimal long-term female hormone replacement: the potential of selective estrogen receptor modulators. Horm Res. 1997;48(4):155–63.

    Article  CAS  PubMed  Google Scholar 

  54. Barrett-Connor E, Grady D, Sashegyi A, Anderson PW, Cox DA, Hoszowski K, et al. Raloxifene and cardiovascular events in osteoporotic postmenopausal women: four-year results from the MORE (Multiple Outcomes of Raloxifene Evaluation) randomized trial. JAMA. 2002;287(7):847–57.

    Article  CAS  PubMed  Google Scholar 

  55. Barrett-Connor E, Mosca L, Collins P, Geiger MJ, Grady D, Kornitzer M, et al. Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N Engl J Med. 2006;355(2):125–37. doi:10.1056/NEJMoa062462.

    Article  CAS  PubMed  Google Scholar 

  56. Saitta A, Morabito N, Frisina N, Cucinotte D, Corrado F, D’Anna R, et al. Cardiovascular effects of raloxifene hydrochloride. Cardiovasc Drug Rev. 2001;19(1):57–74.

    Article  CAS  PubMed  Google Scholar 

  57. Saitta A, Altavilla D, Cucinotta D, Morabito N, Frisina N, Corrado F, et al. Randomized, double-blind, placebo-controlled study on effects of raloxifene and hormone replacement therapy on plasma NO concentrations, endothelin-1 levels, and endothelium-dependent vasodilation in postmenopausal women. Arterioscl Throm Vas. 2001;21(9):1512–9.

    Article  CAS  Google Scholar 

  58. Resch U, Mellauner V, Budinsky A, Sinzinger H. Inhibition of low-density lipoprotein and high-density lipoprotein oxidation by raloxifene. J Womens Health (Larchmt). 2004;13(4):404–11.

    Article  Google Scholar 

  59. Zuckerman SH, Bryan N. Inhibition of LDL oxidation and myeloperoxidase dependent tyrosyl radical formation by the selective estrogen receptor modulator raloxifene (LY139481 HCL). Atherosclerosis. 1996;126(1):65–75.

    Article  CAS  PubMed  Google Scholar 

  60. Figtree GA, Lu Y, Webb CM, Collins P. Raloxifene acutely relaxes rabbit coronary arteries in vitro by an estrogen receptor-dependent and nitric oxide-dependent mechanism. Circulation. 1999;100(10):1095–101.

    Article  CAS  PubMed  Google Scholar 

  61. Simoncini T, Genazzani AR. Raloxifene acutely stimulates nitric oxide release from human endothelial cells via an activation of endothelial nitric oxide synthase. J Clin Endocrinol Metab. 2000;85(8):2966–9. doi:10.1210/jcem.85.8.6853.

    Article  CAS  PubMed  Google Scholar 

  62. Fu Z, Luo B, Li M, Peng B, Wang Z. Effects of raloxifene on the proliferation and apoptosis of human aortic valve interstitial cells. Biomed Res Int. 2016;2016:5473204. doi:10.1155/2016/5473204.

    PubMed  PubMed Central  Google Scholar 

  63. Hansdottir H. Raloxifene for older women: a review of the literature. Clin Interv Aging. 2008;3(1):45–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Messalli EM, Scaffa C. Long-term safety and efficacy of raloxifene in the prevention and treatment of postmenopausal osteoporosis: an update. Int J Womens Health. 2010;1:11–20.

    PubMed  PubMed Central  Google Scholar 

  65. Jacobson TA. Lipoprotein(a), cardiovascular disease, and contemporary management. Mayo Clin Proc. 2013;88(11):1294–311.

    Article  CAS  PubMed  Google Scholar 

  66. Banach M, Serban C, Aronow WS, Rysz J, Dragan S, Lerma EV, et al. Lipid, blood pressure and kidney update 2013. Int Urol Nephrol. 2014;46(5):947–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Sahebkar A, Chew GT, Watts GF. Recent advances in pharmacotherapy for hypertriglyceridemia. Prog Lipid Res. 2014;56:47–66.

    Article  CAS  PubMed  Google Scholar 

  68. Sahebkar A, Chew GT, Watts GF. New peroxisome proliferator-activated receptor agonists: potential treatments for atherogenic dyslipidemia and non-alcoholic fatty liver disease. Expert Opin Pharmaco. 2014;15(4):493–503.

    Article  CAS  Google Scholar 

  69. Sahebkar A, Watts GF. New LDL-cholesterol lowering therapies: pharmacology, clinical trials, and relevance to acute coronary syndromes. Clin Ther. 2013;35(8):1082–98.

    Article  CAS  PubMed  Google Scholar 

  70. Sahebkar A, Watts GF. New therapies targeting apoB metabolism for high-risk patients with inherited dyslipidaemias: what can the clinician expect? Cardiovasc Drug Ther. 2013;27(6):559–67.

    Article  CAS  Google Scholar 

Download references

Author information

Author notes

    Authors and Affiliations

    1. Dipartimento di Scienze cliniche Specialistiche ed Odontostomatologiche, Università Politecnica delle Marche, Ancona, Italy

      Gianna Ferretti

    2. Dipartimento di Scienze della Vita e dell’Ambiente, Università Politecnica delle Marche, Ancona, Italy

      Tiziana Bacchetti

    3. Biomedical Research Unit, Mexican Social Security Institute, Durango, Mexico

      Luis E. Simental-Mendía

    4. Department of Internal Medicine, University Hospital Center Zagreb, University of Zagreb School of Medicine, Kišpatićeva 12, Zagreb, Croatia

      Željko Reiner

    5. Department of Hypertension, WAM University Hospital in Lodz, Medical University of Lodz, Zeromskiego 113, Lodz, Poland

      Maciej Banach

    6. Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

      Amirhossein Sahebkar

    7. Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

      Amirhossein Sahebkar

    8. School of Medicine, University of Western Australia, Perth, Iran

      Amirhossein Sahebkar

    Authors
    1. Gianna Ferretti
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Tiziana Bacchetti
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Luis E. Simental-Mendía
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Željko Reiner
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Maciej Banach
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Amirhossein Sahebkar
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Amirhossein Sahebkar.

    Ethics declarations

    Funding

    This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

    Conflict of Interest

    The authors declare that they have no competing interests.

    Ethical Approval

    This article does not contain any studies with human participants or animals performed by any of the authors.

    Additional information

    Gianna Ferretti and Tiziana Bacchetti contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Ferretti, G., Bacchetti, T., Simental-Mendía, L.E. et al. Raloxifene Lowers Plasma Lipoprotein(a) Concentrations: a Systematic Review and Meta-analysis of Randomized Placebo-Controlled Trials. Cardiovasc Drugs Ther 31, 197–208 (2017). https://doi.org/10.1007/s10557-017-6721-6

    Download citation

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s10557-017-6721-6

    Keywords

    Search

    Navigation