The Association between the Risk of Cardiovascular Disease and Androgen Deprivation Therapy in Patients with Prostate Cancer. A Meta-Analysis and systematic review.

Abstract Background : Androgen deprivation therapy (ADT) is widely being applied in men who suffered from prostate cancer, our aim is to evaluate whether ADT is associated with an excess risk of cardiovascular disease (CVD). Method : Studies comparing the the incidence of CVD between ADT group and control group were identified through literature search in electronic databases (Pubmed, Embase, Web of Science) until July 2019 and only observational studies and randomized controlled trials (RCT) were included. The estimating relative risk ratio (RR) and 95% confidence intervals (CI) were calculated through random effects meta-analyses. Result : A statistically significant association was detected for acute myocardial infarction (AMI) with RR = 1.22; 95% confidence interval CI, 1.05–1.43; P< 0.05. Significant relationship between coronary heart disease (CHD) and ADT was also observed, with summary RR=1.19; 95%CI, 1.03-1.38; P<0.05. ADT was associated with a risk increasement for heart failure (HF) with RR=1.15; 95% CI 1.01–1.33; P< 0.05. On the contrary, ADT was not associated with an increased risk of sudden cardiac death (SCD). Conclusions : From this study, ADT is associated with increased risk of AMI, CHD, and heart failure (HF); in contrast, this association is not detected in SCD; various modalities of ADT could significantly increase the risk of CHD, AMI, except for oral anti-androgen (AA). Our meta-analysis also suggests that the long-term application of ADT in prostate cancer patients would not result in a significant increase in AMI incidence compared with short-term. Moreover, the combined application of AA and GnRH agonists would lead to a similar risk of AMI compared with orchiectomy or GnRH agonists monotherapy whereas higher risk of CHD was detected when compared GnRH agonists plus AA with orchiectomy.

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The Association between the Risk of Cardiovascular Disease and Androgen Deprivation Therapy in Patients with Prostate Cancer. A Meta-Analysis and systematic review.

10.21203/rs.2.10884/v2 ◽

2019 ◽

Author(s):

Zhen Liang ◽

Jun Zhu ◽

Xiaoxin Duo ◽

Shangheng Shi ◽

Yawei Xu ◽

...

Keyword(s):

Prostate Cancer ◽

Cardiovascular Disease ◽

Androgen Deprivation Therapy ◽

Meta Analysis ◽

Androgen Deprivation ◽

Relative Risk Ratio ◽

Gnrh Agonists ◽

Combined Application ◽

Increased Risk

Abstract Background : Androgen deprivation therapy (ADT) is widely being applied in men who suffered from prostate cancer, our aim is to evaluate whether ADT is associated with an excess risk of cardiovascular disease (CVD). Method : Literature search in electronic databases was conducted until July 2019 for observational studies and randomized controlled trials (RCT) to select eligible studies. The relationship was evaluated through estimating relative risk ratio (RR) and 95% confidence intervals (CI). Result : A statistically significant association was detected for acute myocardial infarction (AMI) with RR = 1.22; 95% confidence interval CI, 1.05–1.43; P< 0.05 including a total of 142,012 cases and 174,099 controls. Significant relationship between coronary heart disease (CHD) and ADT was also observed, with summary RR=1.19; 95%CI, 1.03-1.38, from 157,165 ADT users and 375,754 non-ADT users. Conclusions : From this study, ADT is associated with increased risk of AMI, CHD, and heart failure (HF); in contrast, this association is not detected in sudden cardiac death (SCD); various modalities of ADT could significantly increase the risk of CHD, AMI, except for oral anti-androgen (AA). Our meta-analysis also suggests that the long-term application of ADT in prostate cancer patients would not result in a significant increase in AMI incidence compared with short-term. Moreover, the combined application of AA and GnRH agonists would lead to a similar risk of AMI compared with orchiectomy or GnRH agonists monotherapy whereas higher risk of CHD was detected when compared GnRH agonists plus AA with orchiectomy.

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Is Androgen Deprivation Therapy for Prostate Cancer Associated with Cardiovascular disease ? A Meta-Analysis and systematic review.

10.21203/rs.2.10884/v1 ◽

2019 ◽

Author(s):

Zhen Liang ◽

Longlong Chen ◽

Yawei Xu ◽

Yongjiao Yang ◽

Rui Hu ◽

...

Keyword(s):

Prostate Cancer ◽

Systematic Review ◽

Cardiovascular Disease ◽

Androgen Deprivation Therapy ◽

Disease Risk ◽

Meta Analysis ◽

Androgen Deprivation ◽

Increased Risk ◽

Significant Difference ◽

The Relationship

Abstract Background: Whether androgen deprivation therapy (ADT) is associated with an increased risk of developing cardiovascular related disease is poorly defined. The aim of the present meta‐analysis is to explore the relationship between ADT and the risk of cardiovascular disease (CVD). Method: For this systematic review and meta-analysis, we searched databases until April 2019 for randomized controlled trial (RCT) or observational studies that reported data on ADT administration and cardiovascular disease (CVD) incidence. The relationship was evaluated through estimate relative risk ratio (RR) and 95% confidence intervals (CIs) Result: A statistically significant difference was detected for acute myocardial infarction (AMI) (RR = 1.13; 95% CI, 1.10–1.15; P< 0.05) including a total of 142,186 cases and 174,404 controls. Significant difference between coronary heart disease (CHD) and ADT was also observed, with summary (RR=1.11; 95% confidence interval CI: 1.10-1.13), from 157,339 ADT users and 349,636 non-ADT users of 7 eligible studies. Conclusions: Pooled result demonstrated that ADT could significantly increase the risk of CHD, AMI and sudden cardiac death (SCD). Various ADT modalities have different impact on cardiovascular disease risk in different level. Our meta-analysis also suggests that the application of ADT in prostate cancer patients for over 5 years resulted in a significant increase in cardiovascular morbidity. Moreover, subgroup analyses for different types of ADT indicated that compared with the individual administration of ADT, GnRH plus AA (oral anti-androgens) is more likely significantly lead to AMI.

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Risk and Timing of Cardiovascular Disease After Androgen-Deprivation Therapy in Men With Prostate Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2014.59.1792 ◽

2015 ◽

Vol 33 (11) ◽

pp. 1243-1251 ◽

Cited By ~ 121

Author(s):

Sean O'Farrell ◽

Hans Garmo ◽

Lars Holmberg ◽

Jan Adolfsson ◽

Pär Stattin ◽

...

Keyword(s):

Prostate Cancer ◽

Cardiovascular Disease ◽

Androgen Deprivation Therapy ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Androgen Deprivation ◽

Gnrh Agonists ◽

Cvd Risk ◽

Comparison Cohort ◽

Using Data

Purpose Findings on the association between risk of cardiovascular disease (CVD) and the duration and type of androgen-deprivation therapy (ADT) in men with prostate cancer (PCa) are inconsistent. Methods By using data on filled drug prescriptions in Swedish national health care registers, we investigated the risk of CVD in a cohort of 41,362 men with PCa on ADT compared with an age-matched, PCa-free comparison cohort (n = 187,785) by use of multivariable Cox proportional hazards regression models. Results From 2006 to 2012, 10,656 men were on antiandrogens (AA), 26,959 were on gonadotropin-releasing hormone (GnRH) agonists, and 3,747 underwent surgical orchiectomy. CVD risk was increased in men on GnRH agonists compared with the comparison cohort (hazard ratio [HR] of incident CVD, 1.21; 95% CI, 1.18 to 1.25; and orchiectomy: HR, 1.16; 95% CI, 1.08 to 1.25). Men with PCa on AA were at decreased risk (HR of incident CVD, 0.87; 95% CI, 0.82 to 0.91). CVD risk was highest during the first 6 months of ADT in men who experienced two or more cardiovascular events before therapy, with an HR of CVD during the first 6 months of GnRH agonist therapy of 1.91 (95% CI, 1.66 to 2.20), an HR of CVD with AA of 1.60 (95% CI, 1.24 to 2.06), and an HR of CVD with orchiectomy of 1.79 (95% CI, 1.16 to 2.76) versus the comparison cohort. Conclusion Our results support that there should be a solid indication for ADT in men with PCa so that benefit outweighs potential harm; this is of particular importance among men with a recent history of CVD.

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Influence of age on incident diabetes (DM) and cardiovascular disease (CVD) among prostate cancer survivors receiving androgen deprivation therapy (ADT).

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.4_suppl.31 ◽

2014 ◽

Vol 32 (4_suppl) ◽

pp. 31-31

Author(s):

Alicia Katherine Morgans ◽

Kang-Hsien Fan ◽

Tatsuki Koyama ◽

Peter C. Albertsen ◽

Michael Goodman ◽

...

Keyword(s):

Prostate Cancer ◽

Cardiovascular Disease ◽

Cancer Survivors ◽

Androgen Deprivation Therapy ◽

Older Men ◽

Androgen Deprivation ◽

Age At Diagnosis ◽

Prostate Cancer Survivors ◽

Increased Risk ◽

The Relationship

31 Background: Androgen deprivation therapy (ADT) has been associated with an increased risk of developing diabetes (DM) and cardiovascular disease (CVD), though this is controversial, particularly for CVD. We prospectively assessed the relationship between ADT and incident DM and CVD in the Prostate Cancer Outcomes Study (PCOS), a population-based cohort of prostate cancer survivors followed longitudinally for 15 years from diagnosis. Methods: We identified men in the PCOS with non-metastatic prostate cancer diagnosed from 1994 to 1995 and followed through 2009 to 2010. We used multivariable logistic regression models to compare groups receiving short-term ADT (less than 2 years), prolonged ADT (2 years or more) and no ADT to assess the relationship between ADT exposure and subsequent diagnoses of DM and CVD (determined by patient report and cause of death data). We evaluated the effects of age at diagnosis, race, stage, and comorbidity on the development of DM and CVD. Results: Among 3,526 men with comorbidity and treatment data, 2,985 men without baseline DM and 3,112 men without baseline CVD constituted the DM and CVD cohorts, respectively. Regardless of duration of ADT exposure, there was not an increased risk of DM or CVD in men younger than 70 at diagnosis. Compared to no ADT exposure, prolonged ADT was associated with an increased risk of DM and CVD that increased steadily over age 76 at diagnosis for DM (OR 2.11 at age 74, 95% CI 1.02 – 4.36; OR 2.65 at age 80, 95% CI 1.09 – 6.47) and age 74 at diagnosis for CVD (OR 1.89 at age 74, 95% CI 1.02 - 3.49; OR 3.19 at age 80, 95% 1.25 – 8.17). Increasing comorbidity burden modified risk of DM and CVD (for 3 or more comorbidities vs. no comorbidities; for DM, OR 4.25, 95% CI 2.3 - 7.9; and for CVD, OR 8.1, 95% CI 4.3 -15.5 P<0.001). Conclusions: The relationship between ADT and development of CVD and DM may be dependent upon age at diagnosis in addition to length of ADT administration, with longer ADT exposure predominantly increasing risk among older men only. Men with greater comorbid burden had increased risk of developing DM and CVD. Closer monitoring for development of DM and CVD may be most important among older men receiving prolonged ADT, especially those with other comorbidities.

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Quantifying Observational Evidence for Risk of Fatal and Nonfatal Cardiovascular Disease Following Androgen Deprivation Therapy for Prostate Cancer: A Meta-analysis

European Urology ◽

10.1016/j.eururo.2014.11.039 ◽

2015 ◽

Vol 68 (3) ◽

pp. 386-396 ◽

Cited By ~ 130

Author(s):

Cecilia Bosco ◽

Zsolt Bosnyak ◽

Anders Malmberg ◽

Jan Adolfsson ◽

Nancy L. Keating ◽

...

Keyword(s):

Prostate Cancer ◽

Cardiovascular Disease ◽

Androgen Deprivation Therapy ◽

Meta Analysis ◽

Observational Evidence ◽

Androgen Deprivation

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Increased Risk of Metabolic Syndrome, Diabetes Mellitus, and Cardiovascular Disease in Men Receiving Androgen Deprivation Therapy for Prostate Cancer

Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy ◽

10.1592/phco.28.12.1511 ◽

2008 ◽

Vol 28 (12) ◽

pp. 1511-1522 ◽

Cited By ~ 59

Author(s):

Polly E Kintzel ◽

Sandra L Chase ◽

Lisa M Schultz ◽

Timothy J O'Rourke

Keyword(s):

Prostate Cancer ◽

Diabetes Mellitus ◽

Cardiovascular Disease ◽

Metabolic Syndrome ◽

Androgen Deprivation Therapy ◽

Androgen Deprivation ◽

Increased Risk

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Retrospective cohort study of androgen deprivation therapy and the risk of diabetes in men with prostate cancer in Lithuania

BMJ Open ◽

10.1136/bmjopen-2020-045797 ◽

2021 ◽

Vol 11 (7) ◽

pp. e045797

Author(s):

Mingaile Drevinskaite ◽

Ausvydas Patasius ◽

Marius Kincius ◽

Vincas Urbonas ◽

Giedre Smailyte

Keyword(s):

Prostate Cancer ◽

Type 2 Diabetes ◽

Cohort Study ◽

Androgen Deprivation Therapy ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Androgen Deprivation ◽

Gnrh Agonists ◽

Increased Risk

ObjectivesTo examine the risk of type 2 diabetes in patients with prostate cancer and its association with androgen deprivation therapy (ADT).Design and participantsWe performed a retrospective cohort study of patients diagnosed with prostate cancer in the Lithuanian male population between 1 January 2003 and 31 December 2012 who were identified through the Lithuanian Cancer registry. All prostate cancer cases were linked to the National Health Insurance Fund database to obtain information regarding the diagnosis of diabetes mellitus and information on prescriptions of antiandrogens and gonadotropin-releasing hormone (GnRH) agonists. Patients with prostate cancer were followed up until the diagnosis of type 2 diabetes, or 31 December 2017, or date of death, whichever came first. Cox proportional hazard models were used to estimate the risk of type 2 diabetes in patients with prostate cancer with or without ADT exposure.Results27 580 men were diagnosed with prostate cancer, out of whom 14 502 (52.6%) did not receive ADT and 13 078 (47.4%) were treated with ADT. The incidence of type 2 diabetes for all patients with prostate cancer was 7.4/1000 person-years, for men on GnRH agonists 9.0/1000 person-years and 5.8/1000 person-years for men on antiandrogens. There was an increased risk of developing type 2 diabetes comparing ADT users and non-users (HR=1.49, 95% CI 1.34 to 1.66).ConclusionThis study showed an increased risk of diabetes in patients with prostate cancer treated with ADT in comparison to ADT-free patient cohort. GnRH agonist users showed higher susceptibility, while the group on antiandrogen monotherapy showed no such increase.

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Androgen deprivation therapy in the treatment of prostate cancer and dementia risk: A systematic review and meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.5044 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 5044-5044

Author(s):

Kevin Thomas Nead ◽

Sumi Sinha ◽

Paul L. Nguyen

Keyword(s):

Prostate Cancer ◽

Systematic Review ◽

Androgen Deprivation Therapy ◽

Meta Analysis ◽

Androgen Deprivation ◽

Small Study ◽

Effect Estimate ◽

Neurocognitive Deficits ◽

Dementia Risk ◽

Increased Risk

5044 Background: Androgen deprivation therapy (ADT) to treat prostate cancer may be associated with an increased risk of dementia, but existing studies have shown conflicting results. Here we conduct a systematic review and meta-analysis on the association of ADT in the treatment of prostate cancer with the risk of dementia. Methods: We conducted a systematic review of articles reporting the outcome of dementia among individuals with prostate cancer in those exposed to ADT versus a lesser-exposed comparison group (e.g. no ADT, intermittent ADT) using the PRISMA statement guidelines. Two authors independently carried out searches in PubMed (1966–present), Web of Science (1945–present), Embase (1966–present), and PsycINFO (1806–present). The search was undertaken December 4th, 2016. We assessed the validity of each study per the Newcastle-Ottawa Scale criteria. We meta-analyzed studies reporting an effect estimate and controlling for confounding.Random- or fixed-effects meta-analytic models were used in the presence or absence of heterogeneity, respectively, per the I2statistic. Small study effects were evaluated using Egger and Begg’s tests. Results: Nine studies were included in the systematic review. Seven studies reported an adjusted effect estimate for dementia risk. A random-effects meta-analysis of studies reporting any dementia outcome, which included 50,541 individuals, showed an increased risk of dementia among ADT users (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.08–2.00; p = 0.02). We separately meta-analyzed studies reporting all-cause dementia (HR, 1.46; 95% CI, 1.05–2.02; p < 0.001) and Alzheimer’s disease (HR, 1.25; 95% CI, 0.99–1.57; p = 0.06). The I2statistic to evaluate the proportion of heterogeneity due to study variation was 76% (95% CI, 47–89; p < 0.001) for the primary analysis. There was no evidence of bias from small study effects (Egger, p = 0.19; Begg, p = 1.00). Conclusions: The currently available combined evidence suggests that ADT in the treatment of prostate cancer may be associated with an increased risk of dementia. The potential for neurocognitive deficits secondary to ADT should be discussed with patients and evaluated prospectively.

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