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

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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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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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

Andrology ◽

10.1111/andr.12731 ◽

2019 ◽

Vol 8 (3) ◽

pp. 559-574 ◽

Cited By ~ 2

Author(s):

Zhen Liang ◽

Jun Zhu ◽

Longlong Chen ◽

Yawei Xu ◽

Yongjiao Yang ◽

...

Keyword(s):

Prostate Cancer ◽

Systematic Review ◽

Cardiovascular Disease ◽

Androgen Deprivation Therapy ◽

Meta Analysis ◽

Androgen Deprivation

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Faculty Opinions recommendation of Comparison of Abiraterone Acetate and Docetaxel with Androgen Deprivation Therapy in High-risk and Metastatic Hormone-naïve Prostate Cancer: A Systematic Review and Network Meta-analysis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.732006685.793538242 ◽

2017 ◽

Author(s):

Michael Glode

Keyword(s):

Prostate Cancer ◽

Systematic Review ◽

High Risk ◽

Androgen Deprivation Therapy ◽

Meta Analysis ◽

Abiraterone Acetate ◽

Androgen Deprivation

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Effect of Salvage Radiotherapy and Endocrine Therapy on Patients with Biochemical Recurrence After Prostate Cancer Operation— a Meta‑Analysis

American Journal of Men s Health ◽

10.1177/15579883211024881 ◽

2021 ◽

Vol 15 (3) ◽

pp. 155798832110248

Author(s):

Yong Yuan ◽

Qiang Zhang ◽

Chaofan Xie ◽

Tao Wu

Keyword(s):

Prostate Cancer ◽

Systematic Review ◽

Endocrine Therapy ◽

Androgen Deprivation Therapy ◽

Biochemical Recurrence ◽

Meta Analysis ◽

Combined Treatment ◽

Androgen Deprivation ◽

Salvage Radiotherapy ◽

End Point

Context: Several studies reported the application of androgen deprivation therapy and radiotherapy in patients with biochemical recurrence after prostate cancer operation. Objective: To perform a systematic review and meta-analysis evaluating of endocrine therapy and radiotherapy in patients with biochemical recurrence after prostate cancer surgery. The primary end point was biochemical progression-free survival (bPFS). Secondary end point was overall survival (OS). Methods: A systematic review of PubMed/Medline, Embase, and Cochrane databases to identify relevant studies published in English up to March 2020. Twelve studies were selected for inclusion. Results: There were 11 studies included in the present study. Including two randomized controlled trials and nine cohort studies. The meta-analysis shows a significant bPFS benefit from androgen deprivation therapy and radiotherapy in patients with biochemical recurrence after prostate cancer operation. (hazard ratio [HR]: 0.57; 95% confidence interval CI, 0.52–0.63; p < .001). For patients with GS < 7 and low-risk patients, combined treatment can have a benefit for BPFs (HR: 0.53; 95% CI, 0.37–0.76; HR: 0.58; 95% CI, 0.36–0.93). Androgen deprivation therapy and radiotherapy in patients with biochemical recurrence was associated with a slightly OS improvement (HR: 0.73; 95% CI, 0.57–0.93; p = 0.01). Conclusions: Compared with salvage radiotherapy alone, This meta-analysis shows a significant bPFS benefit from endocrine therapy combined with salvage radiotherapy in patients with biochemical recurrence after prostate cancer operation. And benefit more for high-risk groups. However, there was no significant benefit in group GS ≥ 8. It shows a slightly OS benefit from endocrine therapy combined with salvage radiotherapy in patients with biochemical recurrence.

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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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