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CME / ABIM MOC / CE

Does Androgen Deprivation Therapy Increase Cardiovascular Risk?

  • Authors: News Author: Megan Brooks; CME Author: Laurie Barclay, MD
  • CME / ABIM MOC / CE Released: 7/15/2022
  • Valid for credit through: 7/15/2023
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  • Credits Available

    Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™

    ABIM Diplomates - maximum of 0.25 ABIM MOC points

    Nurses - 0.25 ANCC Contact Hour(s) (0.25 contact hours are in the area of pharmacology)

    Pharmacists - 0.25 Knowledge-based ACPE (0.025 CEUs)

    Physician Assistant - 0.25 AAPA hour(s) of Category I credit

    IPCE - 0.25 Interprofessional Continuing Education (IPCE) credit

    You Are Eligible For

    • Letter of Completion
    • ABIM MOC points

Target Audience and Goal Statement

This activity is intended for cardiologists, family medicine and primary care clinicians, nurses, pharmacists, hematologists/oncologists, physician assistants, internists, urologists, and other members of the health care team who treat and manage patients receiving androgen deprivation therapy who may be at increased cardiovascular risk.

The goal of this activity is for learners to be better able to describe the association between androgen deprivation therapy for nonmetastatic prostate cancer and subsequent myocardial infarction, stroke, other cardiovascular disease, and all-cause mortality, based on a Norwegian nationwide, longitudinal study.

Upon completion of this activity, participants will:

  • Assess the association between androgen deprivation therapy for nonmetastatic prostate cancer and subsequent cardiovascular disease and all-cause mortality, based on a Norwegian nationwide, longitudinal study
  • Evaluate the clinical implications of the association between androgen deprivation therapy for nonmetastatic prostate cancer and subsequent cardiovascular disease and all-cause mortality, based on a Norwegian nationwide, longitudinal study
  • Outline implications for the healthcare team


Disclosures

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All relevant financial relationships for anyone with the ability to control the content of this educational activity are listed below and have been mitigated according to Medscape policies. Others involved in the planning of this activity have no relevant financial relationships.


News Author

  • Megan Brooks

    Freelance writer, Medscape

    Disclosures

    Megan Brooks has no relevant financial relationships.

CME Author

  • Laurie Barclay, MD

    Freelance writer and reviewer
    Medscape, LLC

    Disclosures

    Laurie Barclay, MD, has the following relevant financial relationships:
    Formerly owned stocks in: AbbVie

Editor/Compliance Reviewer

  • Amanda Jett, PharmD, BCACP

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Amanda Jett, PharmD, BCACP, has no relevant financial relationships.

Compliance Reviewer

  • Yaisanet Oyola, MD

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Yaisanet Oyola, MD, has no relevant financial relationships.

Peer Reviewer

This activity has been peer reviewed and the reviewer has no relevant financial relationships.


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In support of improving patient care, Medscape, LLC is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

This activity was planned by and for the healthcare team, and learners will receive 0.25 Interprofessional Continuing Education (IPCE) credit for learning and change.

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  • Medscape, LLC designates this enduring material for a maximum of 0.25 AMA PRA Category 1 Credit(s)™ . Physicians should claim only the credit commensurate with the extent of their participation in the activity.

    Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 0.25 MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

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    For Nurses

  • Awarded 0.25 contact hour(s) of nursing continuing professional development for RNs and APNs; 0.25 contact hours are in the area of pharmacology.

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    For Pharmacists

  • Medscape designates this continuing education activity for 0.25 contact hour(s) (0.025 CEUs) (Universal Activity Number: JA0007105-0000-22-239-H01-P).

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  • For Physician Assistants

    Medscape, LLC has been authorized by the American Academy of PAs (AAPA) to award AAPA Category 1 CME credit for activities planned in accordance with AAPA CME Criteria. This activity is designated for 0.25 AAPA Category 1 CME credits. Approval is valid until 7/15/2023. PAs should only claim credit commensurate with the extent of their participation.

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This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity online during the valid credit period that is noted on the title page. To receive AMA PRA Category 1 Credit™, you must receive a minimum score of 75% on the post-test.

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CME / ABIM MOC / CE

Does Androgen Deprivation Therapy Increase Cardiovascular Risk?

Authors: News Author: Megan Brooks; CME Author: Laurie Barclay, MDFaculty and Disclosures

CME / ABIM MOC / CE Released: 7/15/2022

Valid for credit through: 7/15/2023

processing....

Clinical Context

Androgen deprivation therapy (ADT) has been a mainstay of prostate cancer treatment for decades, aiming to deprive androgen-dependent prostate cancer cells of circulating androgen and its precursors. ADT is currently recommended as monotherapy or combined with other therapeutics for aggressive and more advanced cancers. It has shown to be greatly beneficial at reducing cancer-related death, but also to cause significant adverse effects.

Patients with prostate cancer have increased cardiovascular disease (CVD) risk and are more likely to die from non-prostate-cancer-specific causes, mainly cardiovascular related, than from prostate cancer. Evidence suggests that ADT may increase risk for cardiovascular morbidity and mortality, and of all-cause mortality, but findings have been contradictory.

Study Synopsis and Perspective

ADT for localized prostate cancer increases the risk for myocardial infarction (MI), stroke, and other CVD events, as well as death, according to a study from Norway.

These risks appear more pronounced in men with preexisting CVD risk factors and those receiving therapy for longer durations.

Although more data are needed to put these findings in context with respect to overall benefit from ADT, for now, "[ healthcare team members should carefully weigh the risks and benefits of ADT when developing a treatment plan, with possible consideration of early intervention for CVD risk factors," lead author Rachel B. Forster, PhD, and colleagues.

Although some previous research has suggested that ADT can increase the risk for cardiovascular morbidity and mortality, other studies have not demonstrated such a link, leaving the relationship between prostate cancer treatment and CVD unclear.

To investigate further, Dr Forster and colleagues used Norwegian registry data to identify 30,923 men diagnosed with prostate cancer between 2008 and 2018. Of those patients, 8449 (27%) received primary ADT. Patients were followed up for a mean of 2.9 years for CVD events and 3.8 years for mortality.

In the fully adjusted model, ADT was associated with a 13% increased risk for any CVD event, which included MI, stroke, and heart failure (adjusted hazard ratio [HR], 1.13). This association persisted in men at low (HR, 1.17), moderate (HR, 1.11), and high (HR, 1.29) CVD risk. ADT was also associated with increased risk for each CVD event individually: MI (HR, 1.18), stroke (HR, 1.21), and heart failure (HR, 1.23).

The risk for all-cause mortality was significantly higher among those who received ADT (HR, 1.49), as well as for each CVD risk group (HR, 1.75 for low, 1.50 for moderate, and 1.17 for high risk). The authors found no association between ADT and atrial fibrillation.

Treatment duration was also a factor in CVD risk. The authors found no association between ADT that was administered for 7 months or less and CVD outcomes. But they did observe associations between treatment for 7 to 18 months and overall CVD outcomes (HR, 1.12) and for stroke (HR, 1.32) and heart failure (HR, 1.25). For ADT lasting more than 18 months, the risk for CVD events overall (HR, 1.23), as well as MI (HR, 1.31) and heart failure (HR, 1.28), were also higher.

Notably, all treatment durations were associated with an increased risk of dying from any cause (HR, 1.52 for ADT for <7 months; HR, 1.35 for ADT for 7-18 months; HR, 2.04 for >18 months).

"Although there is evidence of ADT being associated with increased risk of CVD and all-cause mortality, it cannot simply be removed as a treatment option," the authors write. "Rather, risk reduction and mitigation strategies should be explored, specifically for subgroups of people at moderate risk of CVD."

For instance, the authors suggest, a patient at higher risk for CVD who requires ADT may benefit from having the duration of treatment reduced. Other mitigation strategies could include careful monitoring and control of modifiable risk factors, such as blood pressure, cholesterol, and diabetes.

"Most importantly, there should be a focus on using clear guidelines to recommend ADT only to patients that have a demonstrated benefit from the treatment," the authors conclude.

The study had no specific funding. The authors have disclosed no relevant financial relationships.

Int J Cancer. Published online April 30, 2022.[1]

Study Highlights

  • This nationwide, longitudinal study used Norwegian registry data to identify patients with prostate cancer from 2008 to 2018 who received primary ADT in the first year after diagnosis.
  • Time-varying Cox regression models evaluated associations between ADT and composite cardiovascular events and individual components of MI, stroke, and heart failure; atrial fibrillation; and all-cause mortality.
  • Of 30,923 patients with prostate cancer, 8449 (27%) received primary ADT.
  • Mean follow-up was 2.9 years for CVD events and 3.8 years for mortality.
  • ADT was associated with composite CVD (fully adjusted HR, 1.13; 95% confidence interval [CI], 1.05-1.21), MI (adjusted HR, 1.18; 95% CI, 1.05-1.32), stroke (adjusted HR, 1.21; 95% CI, 1.06-1.38), heart failure (adjusted HR, 1.23; 95% CI, 1.13-1.35), and all-cause mortality (adjusted HR, 1.49; 95% CI, 1.39-1.61), but not with atrial fibrillation.
  • Associations of ADT with composite CVD persisted among patients with low (adjusted HR, 1.17), moderate (adjusted HR, 1.11), and high (adjusted HR, 1.29; not statistically significant) CVD risk and with all-cause mortality (adjusted HR, 1.75, 1.50, and 1.17, respectively).
  • ADT lasting 7 or fewer months was not associated with CVD outcomes.
  • ADT for 7 to 18 months was associated with composite CVD (adjusted HR, 1.12), stroke (adjusted HR, 1.32), and heart failure (adjusted HR, 1.25).
  • ADT for longer than 18 months was linked to higher risk for composite CVD (adjusted HR, 1.23), MI (adjusted HR, 1.31), and heart failure (adjusted HR, 1.28).
  • All treatment durations were associated with increased risk for all-cause mortality (aHR, 1.52 for ADT <7 months, 1.35 for 7-18 months, and 2.04 for >18 months).
  • Sensitivity analyses removing patients that were diagnosed in 2008, as some patients may have incomplete CVD risk factor data in the period before prostate cancer diagnosis or removing patients who received luteinizing hormone-releasing hormone antagonists, minimally affected the results.
  • The investigators concluded that ADT was associated with composite CVD and all-cause mortality, especially in those with low or moderate CVD risk and longer treatment duration.
  • Future studies with more detailed cancer data are needed to verify the clinical relevance of these findings, especially when considering all-cause mortality within the context of treatment guidelines and benefits of ADT.
  • Risk reduction and mitigation strategies should be considered, specifically for subgroups of people at moderate CVD risk.
  • Other mitigation strategies may include careful monitoring and control of blood pressure, cholesterol, diabetes, and modifiable risk factors.
  • Based on clear guidelines, ADT should be recommended only to patients that have demonstrated benefit from this therapy.
  • When developing a treatment plan, healthcare team members should carefully weigh ADT risks and benefits with possible consideration of early intervention for CVD risk factors.
  • Study limitations include possible effect modification by treatment duration, as patients receiving ADT for longer durations have more severe prostate cancer than those with shorter durations.
  • Increased CVD risk in this group may therefore reflect an unhealthier population rather than ADT effects, despite controlling for comorbidity and cardiovascular risk factors.
  • Another limitation is confounding by indication, as patients with prostate cancer with more advanced cancer, and thus poorer overall survival, are more likely to receive ADT and may also have a high burden of CVD risk factors.
  • Future studies should focus on a narrower population with advanced prostate cancer to create balanced exposure groups based on prostate cancer diagnostic variables including Gleason score, tumor-node-metastasis, and stage, as well as cardiovascular risk factors and multimorbidity scoring.

Clinical Implications

  • ADT was associated with composite CVD and all-cause mortality.
  • On the basis of clear guidelines, ADT should be recommended only to patients who have demonstrated benefit from this therapy.
  • Implications for the Health Care Team: Clinicians should carefully weigh ADT risks and benefits for prostate cancer and consider early intervention for CVD risk factors.

 

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