Tibolone decreases Lipoprotein(a) levels in postmenopausal women: A systematic review and meta-analysis of 12 studies with 1009 patients

Kotani, Kazuhiko; Sahebkar, Amirhossein; Şerban, Corina; Andrica, Florina; Tóth, Peter P.; Jones, Steven R.; Kostner, Karam; Blaha, Michael J.; Martin, Seth S.; Rysz, Jacek; Glasser, Stephen P.; Ray, Kausik K.; Watts, Gerald F.; Mikhailidis, Dimitri P.; Banach, Maciej

doi:10.1016/j.atherosclerosis.2015.06.056

Cited by 49 publications

(24 citation statements)

References 65 publications

(48 reference statements)

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“…In a recent systematic review and meta-analysis of 12 studies with 1009 patients, tibolone was shown to be effective in decreasing Lp(a) levels in postmenopausal women [47]. Tibolone has estrogenic, progestogenic, and weak androgenic actions, and together, the results of these two meta-analysis suggest that further investigation of estrogen receptor ligands may be fruitful in the treatment of elevated Lp(a).…”

Section: Discussionmentioning

confidence: 99%

The Effects of Tamoxifen on Plasma Lipoprotein(a) Concentrations: Systematic Review and Meta-Analysis

Sahebkar

Şerban

Penson

et al. 2017

Drugs

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IntroductionTamoxifen is a selective estrogen receptor modulator widely used in the treatment of breast cancer. Tamoxifen therapy is associated with lower circulating low-density lipoprotein cholesterol and increased triglycerides, but its effects on other lipids are less well studied.AimsWe aimed to investigate the effect of tamoxifen on circulating concentrations of lipoprotein(a) [Lp(a)] through a meta-analysis of available randomized controlled trials (RCTs) and observational studies.MethodsThis study was registered in the PROSPERO database (CRD42016036890). Scopus, MEDLINE and EMBASE were searched from inception until 22 March 2016 to identify studies investigating the effect of tamoxifen on Lp(a) values in humans. Meta-analysis was performed using an inverse variance-weighted, random-effects model with standardized mean difference (SMD) as the effect size estimate.ResultsMeta-analysis of five studies with 215 participants suggested a statistically significant reduction of Lp(a) levels following tamoxifen treatment (SMD −0.41, 95% confidence interval −0.68 to −0.14, p = 0.003). This effect was robust in the sensitivity analysis.ConclusionsMeta-analysis suggested a statistically significant reduction of Lp(a) levels following tamoxifen treatment. Further well-designed trials are required to validate these results.

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Section: Discussionmentioning

confidence: 99%

The Effects of Tamoxifen on Plasma Lipoprotein(a) Concentrations: Systematic Review and Meta-Analysis

Sahebkar

Şerban

Penson

et al. 2017

Drugs

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“…Anacetrapib, the only cholesteryl ester transfer protein inhibitor currently under investigation, has also been suggested to effectively reduce both LDL‐C and Lp(a) levels 38. In contrast, Lp(a)‐lowering agents such as tibolone,39 as well as recent antisense therapies could potentially be used as the primary approach to treat individuals with isolated high Lp(a) levels 36. A randomized trial with Lp(a)‐lowering antisense agents could also provide the final confirmatory test of causality for the role of Lp(a) in coronary artery disease and aortic valve disease 40…”

Section: Discussionmentioning

confidence: 99%

Lipoprotein(a) Interactions With Low‐Density Lipoprotein Cholesterol and Other Cardiovascular Risk Factors in Premature Acute Coronary Syndrome (ACS)

Afshar

Pilote

Dufresne

et al. 2016

JAHA

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BackgroundCurrent recommendations for lipoprotein(a) (Lp[a]) focus on the control of other risk factors, including lowering low‐density lipoprotein cholesterol (LDL‐C), with little evidence to support this approach. Identifying interactions between Lp(a) and other risk factors could identify individuals at increased risk for Lp(a)‐mediated disease.Methods and ResultsWe used a case‐only study design and included 939 participants (median age=49 years, interquartile range 46–53, women=33.1%) from the GENdEr and Sex determInantS of cardiovascular disease: from bench to beyond‐Premature Acute Coronary Syndrome (GENESIS‐PRAXY) study, a multicenter prospective cohort study of premature acute coronary syndrome. There was a higher prevalence of elevated Lp(a) levels (>50 mg/dL; 80th percentile) in PRAXY participants as compared to the general population (31% versus 20%; P<0.001). Lp(a) was strongly associated with LDL‐C (adjusted β 0.17; P<0.001). Individuals with high Lp(a) were more likely to have LDL‐C >2.5 mmol/L, indicating a synergistic interaction (adjusted odds ratio 1.51; 95% CI 1.08–2.09; P=0.015). The interaction with high Lp(a) was stronger at increasing LDL‐C levels (LDL‐C >3.5, adjusted odds ratio 1.87; LDL‐C >4.5, adjusted odds ratio 2.72). In a polytomous logistic model comparing mutually exclusive LDL‐C categories, the interaction with high Lp(a) became attenuated at LDL‐C ≤3.5 mmol/L (odds ratio 1.16; 95% CI 0.80–1.68, P=0.447). Other risk factors were not associated with high Lp(a).ConclusionsIn young acute coronary syndrome patients, high Lp(a) is more prevalent than in the general population and is strongly associated with high LDL‐C, suggesting that Lp(a) confers greater risk for acute coronary syndrome when LDL‐C is elevated. Individuals with high Lp(a) and LDL‐C >3.5 mmol/L may warrant aggressive LDL‐C lowering.

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“…In detail, tibolone at the usual dose of 2.5 mg/d was associated with a 29% mean reduction in Lp(a) concentrations, whereas the respective mean reduction with doses of <2.5 mg/d was 17%. Regarding the duration, treatment of ≥24 months or <24 months led to comparable decreases in Lp(a) concentrations (26.8% and 23.1%, respectively) . Others have shown a much lower (−5%) or no reduction in Lp(a) plasma concentrations with tibolone therapy.…”

Section: Therapeutic Strategiesmentioning

confidence: 95%

Lipoprotein(a) in postmenopausal women: assessment of cardiovascular risk and therapeutic options

et al. 2016

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Tibolone decreases Lipoprotein(a) levels in postmenopausal women: A systematic review and meta-analysis of 12 studies with 1009 patients

Cited by 49 publications

References 65 publications

The Effects of Tamoxifen on Plasma Lipoprotein(a) Concentrations: Systematic Review and Meta-Analysis

The Effects of Tamoxifen on Plasma Lipoprotein(a) Concentrations: Systematic Review and Meta-Analysis

Lipoprotein(a) Interactions With Low‐Density Lipoprotein Cholesterol and Other Cardiovascular Risk Factors in Premature Acute Coronary Syndrome (ACS)

Lipoprotein(a) in postmenopausal women: assessment of cardiovascular risk and therapeutic options

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