You are leaving Medscape Education
Cancel Continue
Log in to save activities Your saved activities will show here so that you can easily access them whenever you're ready. Log in here CME & Education Log in to keep track of your credits.
 

CME / ABIM MOC / CE

Is the Risk for Atrial Fibrillation With Cancer Drugs Higher Than We Think?

  • Authors: News Author: M. Alexander Otto, PA, MMS; CME Author: Charles P. Vega, MD
  • CME / ABIM MOC / CE Released: 5/5/2023
  • Valid for credit through: 5/5/2024
Start Activity

  • 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 primary care physicians, oncologists, cardiologists, nurses, pharmacists, physician assistants, and other members of the healthcare team who care for patients with cancer.

The goal of this activity is for learners to be better able to analyze the risk for atrial fibrillation (AF) associated with anticancer drugs.

Upon completion of this activity, participants will:

  • Analyze the impact of AF among patients with a history of cancer
  • Distinguish anticancer drugs associated with higher rates of incident AF
  • Outline implications for the healthcare team


Disclosures

Medscape, LLC requires every individual in a position to control educational content to disclose all financial relationships with ineligible companies that have occurred within the past 24 months. Ineligible companies are organizations whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

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


News Author

  • M. Alexander Otto, PA, MMS

    Freelance writer, Medscape

    Disclosures

    M. Alexander Otto, PA, MMS, has no relevant financial relationships.

CME Author

  • Charles P. Vega, MD

    Health Sciences Clinical Professor of Family Medicine
    University of California, Irvine School of Medicine
    Irvine, California

    Disclosures

    Charles P. Vega, MD, has the following relevant financial relationships:
    Consultant or advisor for: Boehringer Ingelheim Pharmaceuticals Inc.; GlaxoSmithKline; Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Editor/Nurse Planner

  • Leigh Schmidt, MSN, RN, CNE, CHCP

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Leigh Schmidt, MSN, RN, CNE, CHCP, has no relevant financial relationships.

Compliance Reviewer

  • Amanda Jett, PharmD, BCACP

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

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

Peer Reviewer

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


Accreditation Statements



In support of improving patient care, Medscape, LLC is jointly accredited with commendation 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.

    For Physicians

  • 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. Aggregate participant data will be shared with commercial supporters of this activity.

    The European Union of Medical Specialists (UEMS)-European Accreditation Council for Continuing Medical Education (EACCME) has an agreement of mutual recognition of continuing medical education (CME) credit with the American Medical Association (AMA). European physicians interested in converting AMA PRA Category 1 credit™ into European CME credit (ECMEC) should contact the UEMS (www.uems.eu).

    College of Family Physicians of Canada Mainpro+® participants may claim certified credits for any AMA PRA Category 1 credit(s)™, up to a maximum of 50 credits per five-year cycle. Any additional credits are eligible as non-certified credits. College of Family Physicians of Canada (CFPC) members must log into Mainpro+® to claim this activity.

    Through an agreement between the Accreditation Council for Continuing Medical Education and the Royal College of Physicians and Surgeons of Canada, medical practitioners participating in the Royal College MOC Program may record completion of accredited activities registered under the ACCME’s “CME in Support of MOC” program in Section 3 of the Royal College’s MOC Program.

    Contact This Provider

    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.

    Contact This Provider

    For Pharmacists

  • Medscape designates this continuing education activity for 0.25 contact hour(s) (0.025 CEUs) (Universal Activity Number: JA0007105-0000-23-155-H01-P).

    Contact This Provider

  • 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 5/5/2024. PAs should only claim credit commensurate with the extent of their participation.

For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact [email protected]


Instructions for Participation and Credit

There are no fees for participating in or receiving credit for this online educational activity. For information on applicability and acceptance of continuing education credit for this activity, please consult your professional licensing board.

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.

Follow these steps to earn CME/CE credit*:

  1. Read the target audience, learning objectives, and author disclosures.
  2. Study the educational content online or printed out.
  3. Online, choose the best answer to each test question. To receive a certificate, you must receive a passing score as designated at the top of the test. We encourage you to complete the Activity Evaluation to provide feedback for future programming.

You may now view or print the certificate from your CME/CE Tracker. You may print the certificate but you cannot alter it. Credits will be tallied in your CME/CE Tracker and archived for 6 years; at any point within this time period you can print out the tally as well as the certificates from the CME/CE Tracker.

*The credit that you receive is based on your user profile.

CME / ABIM MOC / CE

Is the Risk for Atrial Fibrillation With Cancer Drugs Higher Than We Think?

Authors: News Author: M. Alexander Otto, PA, MMS; CME Author: Charles P. Vega, MDFaculty and Disclosures

CME / ABIM MOC / CE Released: 5/5/2023

Valid for credit through: 5/5/2024

processing....

Clinical Context

Patients with cancer are at risk for a large number of potential adverse events (AEs) during treatment and even years thereafter, and the current study highlights the risk for atrial fibrillation (AF) among patients with a history of cancer. Atrial fibrillation accounts for nearly 5% of cardiovascular (CV) AEs in clinical trials of cancer treatment, and previous research has found that the diagnosis of cancer is associated with a 47% increase in the risk for incident AF. Another study of women with breast cancer found that the diagnosis of AF within 30 days of the diagnosis of cancer was associated with more than a 2-fold increase in the risk for death at 1 year.

Many factors can increase the risk for AF among patients with cancer, including higher levels of inflammation, immune dysregulation, and electrolyte abnormalities. Higher stages of cancer are also associated with higher risks for AF, but the application of anticancer drugs might also contribute to AF among patients with cancer, and the current study by Alexandre and colleagues uses clinical trial data to assess the significance of this potential association.

Study Synopsis and Perspective

Atrial fibrillation is a known and serious AE of some cancer treatments, but it is underreported in cancer drug trials, French investigators said in a new report.

As a result, oncologists likely underestimate the risk for AF when new cancer drugs come to market, they said.

The team came to these conclusions after conducting a meta-analysis of 191 phase 2 or 3 clinical trials that included 26,604 patients. The trials investigated 15 anticancer drugs used as monotherapy.

The meta-analysis showed that the annualized incidence rate of AF ranged from 0.26 cases per 100 person-years (PY): about the same as placebo to 4.92 cases, a nearly 20 times' higher risk.

Rates were the highest for ibrutinib, clofarabine, and ponatinib.

The study was published on March 28 in JACC: Cardio-Oncology, a journal of the American College of Cardiology.[1]

Actual rates of AF are probably higher than what they found in this meta-analysis, the authors suspected, because most oncology trials only identify and report severe cases of AF that require immediate medical attention. Less severe cases can also lead to serious complications, including strokes, but they go unreported, said investigators led by Joachim Alexandre, MD, PhD, a member of the cardio-oncology program at the University of Caen Normandie Hospital Center, Caen, France.

"These findings suggest a global and systemic underreporting and/or under-identification of cardiotoxicity among cancer clinical trial participants," and AF reporting is "particularly affected," they said.

Call for Routine Monitoring

The root of the problem is the lack of routine rhythm monitoring in cancer trials. This, in turn, "leads to a significant underestimation of AF incidence" and rates "markedly lower than those observed among real-life" patients, the authors pointed out.

To address the issue, Alexandre and his team called for routine cardiac monitoring in trials to capture the true incidence of AF and to "clearly define which anticancer drugs are significantly associated" with the condition.

Approached for comment, Michael Fradley, MD, medical director of cardio-oncology at the University of Pennsylvania, Philadelphia, Pennsylvania, agreed.

"It's incredibly important" to "identify the drugs most likely to cause arrhythmias and determine the best prevention and treatment strategies. Unfortunately, systematic evaluation of arrhythmias in cancer clinical trials has often been lacking," Fradley told Medscape Medical News.

The investigators said the issue is particularly pressing for drugs known to be associated with AF. For Bruton tyrosine kinase inhibitors, they called for standardize AF detection in trials "not only on 12-lead ECGs" for symptomatic AF but also with "longer-term ambulatory monitoring or insertable cardiac monitors to detect subclinical AF."

Fradley thought there might also be a role for newer wearable technologies that can detect arrhythmias through a skin patch or by other means.

Details of the Meta-Analysis

The investigators pulled the 191 studies they used in their meta-analysis from the ClinicalTrials.gov database.

The trials covered anticancer drugs used as monotherapy up to September 18, 2020. Almost half were randomized trials, but only 7 had placebo arms. Trials involving hematologic cancers outnumbered those involving solid tumors.

The 15 drugs examined were dacarbazine, abiraterone, clofarabine, azacitidine, ibrutinib, nilotinib, ponatinib, midostaurin, ipilimumab, aldesleukin, lenalidomide, pomalidomide, rituximab, bortezomib, and docetaxel.

The annualized incidence AF rates per 100 PY were 4.92 cases for ibrutinib, 2.38 cases for clofarabine, and 2.35 cases for ponatinib.

The lowest AF rates were for ipilimumab (0.26 cases), rituximab (0.27), and nilotinib (0.29).

For placebo, the annualized rate was 0.25 cases per 100 PY.

The team says caution is warranted regarding their estimations for clofarabine and midostaurin (0.65 cases) because no trials were registered after September 2009, when AE reporting became mandatory. As a result, estimates may be artificially low.

One of the limits of the study is that it focused on monotherapy in an age when combination treatment is generally the rule for cancer, the authors noted.

No external funding was reported for the study. Alexandre has received honoraria for presentations and consulting fees from Amgen Inc.; Bayer AG; Bioserenity; Bristol-Myers Squibb Company; and Pfizer Inc.

Study Highlights

  • Investigators drew study data from ClinicialTrials.gov, which has data on > 440,000 clinical trials.[2] The current study examined trials of chemotherapy agents posted before September 18, 2020.
  • The current analysis excluded case control and observational studies. The analysis also excluded clinical trials with < 20 participants.
  • Researchers examined the clinical data for the annualized incidence rate of AF associated with 19 anticancer drugs used as monotherapy in clinical trials. They compared these data with the data from placebo arms of these trials.
  • Researchers chose 191 studies with a total of 26,604 participants for full review. 47.1% of studies were randomized controlled trials.
  • Although there was a broad collection of anatomic sites of cancer in the included research, hematologic cancers were overrepresented compared with solid tumors.
  • The duration of follow-up varied across studies from 2.7 to 138 months.
  • There was no systemic approach to the detection of AF. It was only diagnosed among symptomatic participants with electrocardiography.
  • Because of study limitations, the annualized incidence rates of AF could be determined for only 15 of the 19 drugs of interest.
  • There were 485 cases of AF reported. The incidence rates varied from 0.26 to 4.92 cases of AF per 100 PY across different agents.
  • The top 3 summary annualized incidence rates of AF reporting were found for ibrutinib 4.92 (95% CI: 2.91, 8.31), clofarabine 2.38 (95% CI: 0.66, 8.55), and ponatinib 2.35 (95% CI: 1.78, 3.12) per 100 PY. The elevated risk for AF with ibrutinib was significant regardless of patient age.
  • In comparison, the annualized incidence rate of AF in the placebo group was 0.25 cases/100 PY.
  • Overall, anticancer drugs used in hematologic malignancies, and, particularly, leukemias, were associated with higher rates of AF.
  • There was a bias toward higher rates of unpublished data of studies with higher AF rates.

Implications for the Healthcare Team

  • Atrial fibrillation accounts for nearly 5% of CV AEs in clinical trials of cancer treatment, and previous research has found that the diagnosis of cancer is associated with a 47% increase in the risk for incident AF. Another study of women with breast cancer found that the diagnosis of AF within 30 days of the diagnosis of cancer was associated with more than a 2-fold increase in the risk for death at 1 year, and cancer stage correlates positively with the risk for AF.
  • Atrial fibrillation was generally more common after treatment with anticancer drugs vs placebo in the current analysis of clinical trials of cancer. The drugs associated with the highest rates of AF included ibrutinib, clofarabine, and ponatinib.
  • The healthcare team should have a low threshold for routine testing for AF among patients with a history of cancer, particularly if they were treated with specific anticancer drugs

 

Earn Credit

  • Print