DCRI’s Piccini Weighs in on Catheter Ablation in Cardiology Today

October 14, 2019 – Mixed results from the CABANA trial have led to debate about whether catheter ablation is an effective treatment option that provides benefit to patients with atrial fibrillation.

A Cardiology Today cover story published online today discussing results from the CABANA trial includes perspectives from several atrial fibrillation (AF) experts across the U.S., including the DCRI’s Jonathan Piccini, MD, MHS.

Jonathan Piccini, MDThe CABANA trial, which compared catheter ablation with drug therapy treatment to evaluate which option is better for patients with AF, culminated in inconclusive results. When compared with drug therapy, catheter ablation did not significantly reduce the risk of the primary endpoint, which included death, stroke, cardiac arrest, or major bleeding. The catheter ablation group did see lower all-cause mortality, but these results were not statistically significant. However, when examining the secondary endpoints for the study, the catheter ablation group had lower rates of death, cardiovascular hospitalization, and AF recurrence.

These mixed results have led to debate among clinicians about whether catheter ablation is an effective treatment option that provides benefit for patients with AF. In a conversation with Cardiology Today, Piccini said the results call for further studies in this area. “There are a lot of important findings from CABANA that have great relevance to our patients with AF,” he told Cardiology Today. “There are also some important findings that require further investigation.”

Many of the experts cited in the cover story emphasized that treatment for AF should not be approached with a one-size-fits-all mindset; instead, clinicians should take into account the patient’s goals and explain their options so the patient can help make an informed decision. For example, relatively young patients with minimal heart disease may be good candidates for catheter ablation, as the procedure can be helpful for symptom reduction.

Piccini suggests that catheter ablation should be considered when drug therapy fails, and for a small minority of patients who are concerned about the safety of taking antiarrhythmic drugs long-term.

To read more insights from Piccini and other AF experts, read the Cardiology Today story.

Minority Populations Enrolled in Heart Failure Trials May Not Represent Real-World Patients

October 10, 2019 – Differences exist between acute heart failure patients seen in real-world practice and clinical trials, and these differences may be largest among black patients and women.

Black patients and women are frequently underrepresented in clinical trials. However, aside from trials generally including lower proportions of patients from these groups, new findings from the DCRI and co-authors suggest that black patients and women who are enrolled may not fully reflect black patients and women seen in clinical practice.

Stephen GreeneAn analysis published yesterday in the Journal of the American College of Cardiology: Heart Failure compared outcomes of U.S. patients enrolled in a heart failure trial called ASCEND-HF with outcomes of those from a U.S. heart failure registry called Get With the Guidelines-Heart Failure who were eligible for ASCEND-HF. The study was led by former DCRI fellow Stephen Greene, MD, (pictured top), and the DCRI’s Robert Mentz, MD, (pictured bottom), also contributed.

The study results showed that trial-eligible patients in the registry had worse outcomes than individuals enrolled in the trial. This difference in outcomes was driven largely by differences in black and female patients. For example, 29.4 percent of black patients in the registry experienced 30-day hospital readmission, while only 13.9 percent of black patients in the trial experienced this outcome. The same was true for women; 28.0 percent of women in the registry and 16.5 percent of women in the trial experienced 30-day readmission. The differences between registry patients and trial participants were much greater in these populations than the differences for white patients and men.

Robert MentzThese findings suggest that unmeasured social and behavioral factors among patients and site investigators can significantly shape the profile of patients enrolled in heart failure clinical trials, independent of trial eligibility criteria. This selection bias may particularly influence black patients and women, and may result in enrollment of patients who are not necessarily typical of the black patients and women seen in real-world practice.

“Even among patients who meet all the trial eligibility criteria and have otherwise similar disease characteristics, there may be major differences between those who do and do not get enrolled,” Greene said. “Our study suggests that these differences may be greatest among black patients and women.”

“Because heart failure trials often include fewer black patients and women, this can lead to questions of whether trial results apply to these groups,” he continued. “However, our study adds another layer to this. Not only may there be fewer black patients and women in a study, but the ones who are enrolled may not be reflective of the typical black patients and women we see in routine practice. In contrast, white patients and men in the trial may be a closer reflection of these groups seen in practice.”

“Although we already knew underrepresentation was a problem—both in heart failure trials and in trials studying other conditions—these findings suggest that representativeness is also an issue at play,” Mentz said. “To make sure heart failure clinical trials meet the needs of patients with this condition, we will need concentrated efforts to improve both enrollment of black patients and women, and representativeness.”

PTN Receives NIH Funding to Advance Down Syndrome Research

October 9, 2019 – Research from DCRI investigators will help determine whether medications prescribed off-label to individuals with Down syndrome are safe and effective.

The Pediatric Trials Network (PTN) received funding to contribute to the NIH’s Investigation of Co-occurring conditions across the Lifespan to Understand Down syndrome (INCLUDE) project.

Mara Becker, MD, MSCEThe DCRI acts as a coordinating center for the PTN, a research network established to make drugs safer and more effective for pediatric patients. Investigators from the DCRI will work on the project; Mara Becker, MD, (pictured), will serve as the principal investigator of INCLUDE and will collaborate with Danny Benjamin, MD, PhD, MPH, principal investigator and chair of PTN.

The award will enable researchers to conduct work to characterize how drugs travel through the bodies of individuals with Down syndrome, as well as any potential effects. The research will focus on drugs that are already administered to children and young adults with Down syndrome, with an emphasis on including these individuals in ongoing clinical trials.

INCLUDE investigators will also work to develop a training program for clinical researchers to provide insight and guidance in trial design, recruitment, and engagement specifically for people with Down syndrome.

To learn more about the award, visit the PTN website.

.Danny Benjamin discusses INCLUDE project

New Faculty Member Joins the DCRI

October 8, 2019 – A new faculty member has joined the DCRI’s musculoskeletal group.

Christine Goertz, DC, PhD, joined the DCRI on October 1 as Professor of Orthopaedic Surgery and the Director of System Development and Coordination for Spine Health at Duke Health. She comes to Durham from Oskaloosa, Iowa, where she served as the CEO of The Spine Institute for Quality. She is also the former vice chancellor of research and health policy at the Palmer College of Chiropractic.

Goertz received her DC degree from Northwestern Health Sciences University and her PhD in health services research from University of Minnesota with a focus in policy and administration.

“It is my great pleasure to be joining the Duke faculty at DCRI,” Goertz said. “I can’t think of a better environment or a more outstanding team of collaborators to work with in order to address evidence gaps in spine care delivery.”

Goertz has a strong and diverse publication record that includes papers in JAMA, JAMA Network Open, Spine, Journal of Hypertension, Military Medicine, and Value Health. She is currently the principal investigator of a pragmatic trial funded by the National Institutes of Health and the National Center for Complementary and Integrative Health that is studying dosing affects for chronic lower back pain in veterans. In addition, Goertz was recently named the new chair for the Governing Board of the Patient Centered Outcomes Research Institute (PCORI) by the US Comptroller General.

“I am extremely excited to welcome Dr. Goertz to the faculty here at Duke,” said Steven George, PhD, PT, director of musculoskeletal research at the DCRI. “Christine is a perfect fit for the Department of Orthopaedic Surgery and our musculoskeletal therapeutic area given her strong track record in innovative clinical and health services research, including large-scale, pragmatic trials studying non-pharmacological treatments. In her role she will work towards creating an evidence base to support effective care pathways for individuals with spine pain at Duke and beyond.”


DCRI Contributes to FDA Guidance to Improve Medication Safety in Newborns

October 2, 2019 – Research guidance recently issued by the FDA provides clarity regarding clinical trial study design, drug dosing, and analysis in studies of newborns.

Years of research undertaken by the DCRI Pediatrics group recently contributed to the U.S. FDA’s publication of draft guidance on neonatal studies.

Pediatric researchers at the DCRI have been working on dosing studies in babies for over 10 years, in conjunction with the Pediatric Trials Network (PTN), a research network coordinated by the DCRI that studies drug safety and efficacy in pediatric populations. DCRI investigators shared new findings with the FDA as their research progressed, and this collaboration eventually developed into the publication of FDA guidance. The DCRI’s Kanecia Zimmerman, MD, MPH, who oversees the daily operations of the PTN, and Michael Cohen-Wolkowiez, MD, PhD, who serves as a PTN investigator, recently wrote about their work and the importance of the new FDA guidance in STAT News.

Baby in incubatorResearch from the DCRI and the PTN has shown that medications function differently in newborns than in other children, both because of their smaller size and because their organs are not fully developed. In response, researchers from both groups have developed methods to make studying infants easier. These methods include techniques to take smaller and fewer samples from infants, as well as innovative mathematical modeling that enables better predictions so that fewer babies can be enrolled in each study. All of these findings and more are included in the new FDA guidance for neonates, which the DCRI group began to draft in 2015.

“We knew from studies at the DCRI and within the PTN that accurate dosing is critical for safety and efficacy of medication,” said Danny Benjamin, MD, PhD, director of DCRI Pediatrics. “Just as the PTN was formed because we didn’t want to dose children like small adults, we also knew we had to drill down further and develop specific guidelines for studies in newborns.”

The guidance outlines clinical pharmacology considerations that should be taken into account when conducting neonatal studies for drugs and biological products, and it provides clarity regarding clinical trial study design, drug dosing, and analysis. One of the recommendations calls for input from multidisciplinary teams during the study design period, including parents.

“We are pleased that our work will now help to improve medication safety for newborns, one of our most vulnerable populations, across the clinical research enterprise,” Cohen-Wolkowiez said. “Along with the FDA, we expect that all organizations working on studies in newborns, from industry sponsors to the NIH, will rely on this guidance.”

The FDA also anticipates that clearer guidelines could help spur development of new therapies for newborns.

“The FDA is committed to gaining more information on the safety and efficacy of existing therapies given to our youngest patients,” the FDA’s Susan McCune, MD, director of the Office of Pediatric Therapeutics, said in a statement issued by the FDA. “We hope the recommendations will encourage drug development for newborns, and ultimately help families make more informed decisions about the care of their babies.”

Differences in Patient Beliefs May Play Role in Women’s Underuse of Statins

September 18, 2019 – Recently published results explore reasons behind the well-documented phenomenon of gendered differences in statin use.

Women are less likely than men to receive statins, and those who do receive statins are more likely to receive a prescription below recommended guidelines.

DCRI fellow Michael Nanna, MD (pictured), examined patient data from the PALM (Patient and Provider Assessment of Lipid Management) Registry in an effort to ascertain reasons for these differences. He and his team found that women are offered statins at lower rates but refuse or discontinue statins at higher rates than men.

A paper discussing the findings was recently published in Circulation: Cardiovascular Quality and Outcomes. Nanna and his colleagues also presented findings at the 2018 American Heart Association Scientific Sessions.

“We were able to identify some key differences in terms of patient beliefs and perceptions around statins, as well as willingness to try statins,” Nanna said. “Female patients were less likely to believe statins were safe and less likely to believe they were effective. In addition, female patients who had previously been on a statin were less willing to try another statin compared to male patients. These differences in beliefs suggest that providers can do more to educate their patients on the safety and efficacy of statins.”

Other DCRI contributors to this study include Tracy Wang, MD, MHS, MSc; Eric Peterson, MD; Ann Marie Navar, MD, PhD; Zhoukai Li and Qun Xiang (formerly of DCRI).

Implantable Cardioverter Defibrillators Still Important in Clinical Practice

September 10, 2019 – Evidence supports that implantable cardioverter defibrillators still provide life-saving benefits, but more research is needed to improve the selection of patients for this treatment.

Although it is incorrect to discount the potential benefit of implantable cardioverter defibrillators, it is also critical to improve selection criteria for patients who would derive the most benefit, writes the DCRI’s Sana Al-Khatib, MD, (pictured), in two recent pieces on the topic.

For many patients with heart failure with a reduced ejection fraction (HFrEF), implantable cardioverter defibrillators (ICDs) can prevent sudden cardiac death and save lives. However, some clinicians argue that evidence supporting the benefit of ICDs is more than 15 years old and perhaps not still applicable. In a paper co-authored by Al-Khatib, which was recently published in Circulation, she counters that newer evidence exists that links ICDs with a survival benefit and lists several examples of recent studies and their findings.

The paper also points out that the original randomized clinical trials that supported the use of ICDs did not include good numbers of traditionally underrepresented patient populations, such as women, racial minorities, and older patients. Newer studies have shown that ICDs are associated with survival benefit in these populations.

However, Al-Khatib also writes, in a recent editorial in The Lancet, that patient selection for ICDs needs to be improved because of high costs and potential for complications associated with the device. Attempts to improve selection criteria to determine which patients would live longer with an ICD have so far been unsuccessful.

Al-Khatib also provides analysis of the results of an observational sub-study published in The Lancet, which found that high repolarization dynamics were associated with the greatest reduction in mortality in patients treated with ICDs. Although these results are potentially important, Al-Khatib writes, they need to be verified with further study and randomized clinical trials before being implemented in clinical practice.

DCRI Study Applies ACC/AHA Guidelines on Cholesterol Management

September 3, 2019 – A study led by a DCRI faculty member provides additional clarification on which patients may benefit the most from additional lipid-lowering therapies, if their cholesterol levels remain elevated despite optimal statin therapy.

A new DCRI-led study applied recently published guidelines on cholesterol management from the American College of Cardiology (ACC) and the American Heart Association (AHA) and confirmed that patients at the highest risk may benefit from lipid-lowering treatments in addition to statins.

The ACC/AHA Guidelines on the Management of Blood Cholesterol, published in December 2018, updates the 2013 guidelines and provides more guidance on newer lipid-lowering therapies that can lower cholesterol levels beyond what can be achieved with statins. By recommending the use of these classes of lipid-lowering drugs, which include ezetimibe and PCSK9 inhibitors, for patients with established atherosclerotic cardiovascular disease (ASCVD) and at high risk, the new guidelines promote more personalized treatments for individual ASCVD patients.

Matthew Roe

The study, which was recently published in Circulation, applied the updated guidelines to patients included in the ODYSSEY OUTCOMES trial, for which the DCRI served as the academic coordinating center from 2012-2018. Results of this trial, which were presented at the ACC 2018 Scientific Sessions, showed that alirocumab, a PCSK9 inhibitor, reduced cardiovascular events when compared with placebo in ASCVD patients with a recent acute coronary syndrome (ACS) and residual dyslipidemia, meaning they had not reached target cholesterol levels with optimized statin therapy.

The study was led by Matthew T. Roe, MD, MHS, (pictured), who was the DCRI faculty leader for the ODYSSEY OUTCOMES trial. Because the updated cholesterol management guidelines were published after the trial results were released, Roe and colleagues were interested in conducting an exploratory analysis to apply the guidelines risk stratification recommendations and determine which patients received the most benefit from the randomized study drug (alirocumab).

The study included 18,924 patients, with 11,935 (63 percent) classified as very high risk based upon the updated guidelines’ risk categorizations. The frequency of cardiovascular events was highest in those patients classified as very high risk and these patients had a greater absolute reduction in the frequency of cardiovascular events from treatment with alirocumab compared with patients classified as not very high risk.

“Through these analyses, we have provided some key messages that will help clinicians decide how to apply the updated cholesterol management guidelines in clinical practice,” Roe said. “Namely, we should target the use of additional lipid-lowering therapies, such as PCSK9 inhibitors, for very-high risk ASCVD patients with residual elevated cholesterol levels despite statin therapy because this population was found to benefit the most.”

Other DCRI contributors to this study include Renato Lopes, MD, PhD.

Hyperlipidemia Not Associated With Cardiovascular Risk in Older Adults

August 20, 2019 – Recent findings suggest that elevations in low-density lipoprotein cholesterol levels may not confer additional risk in populations 75 or older.

Although hyperlipidemia is a well-established factor that indicates risk for cardiovascular events in younger adults, findings from a recent DCRI study show that this measure may not be an accurate predictor in adults 75 or older.

The study, led by DCRI fellow Michael Nanna, MD, (pictured), examined 2,667 older adults with no known cardiovascular disease to determine the association between hyperlipidemia, or elevated low-density lipoprotein cholesterol (LDL) levels, and cardiovascular events. The study team assessed events over a 5-year period in patients with and without hyperlipidemia and recently published results in the Journal of the American Geriatrics Society.

“We wanted to look at this population because although there is a robust body of evidence for the association in younger adults, there is not as much evidence for the older population,” Nanna said. “We are caring for more and more older adults in the clinical setting, so it is increasingly important for us to understand how to assess and stratify their risk.”

The study team split its participants into three groups: no other risk factors—which was defined as free of smoking, diabetes, and hypertension; one non-hyperlipidemia risk factor; and two or more non-hyperlipidemia risk factors. In the group with no other risk factors, cardiovascular event rates were similar between those with and without hyperlipidemia. In the other two groups, there was also no association between hyperlipidemia and cardiovascular events.

“These findings show that in older adults, we should be looking more at cardiovascular risk factors such as hypertension and diabetes rather than LDL levels to identify people for aggressive risk reduction strategies,” Nanna said.

Although the investigators did not find an association between hyperlipidemia and increased risk, Nanna emphasized that these findings should not be misinterpreted to imply that statins are ineffective. “In younger adults, statins have been shown to lower cardiovascular risk across a large range of LDL levels, and randomized trials of statins in older adults are on the horizon,” he said.

“These data highlight the importance of conducting well-done randomized clinical trials to investigate the safety and efficacy of statin therapy for both primary and secondary prevention in older adults,” said the DCRI’s Eric Peterson, one of the co-authors of the study.

Other DCRI contributors to this study include Ann Marie Navar, MD, PhD.

DCRI and Responsum Health Announce Collaboration to Connect Uterine Fibroids Patients

August 13, 2019 – Responsum Health, a company that creates patient platforms for chronic diseases, will create a patient-centered information portal and community hub that will synchronize with the DCRI’s COMPARE-UF patient registry.

The DCRI is partnering with Responsum Health, an innovative creator of personalized patient newsfeeds and support platforms, to improve the quality of life for patients with uterine fibroids. They are joined in this effort by The White Dress Project and CARE About Fibroids, two of the nation’s top uterine fibroids patient advocacy organizations. The announcement follows Fibroids Awareness Month, recognized in July.

Through the partnership, Responsum will commit to developing and promoting a unique, uterine fibroids patient-centered information portal, similar to its work in other therapeutic areas. This new platform will serve the dual goals of providing comprehensive, understandable, and trustworthy information while helping to connect a nationwide community of patients. The new web-based tool and app, Responsum for UF, will synchronize with the DCRI’s unique patient registry, COMPARE-UF (Comparing Options for Management: Patient-centered Results for Uterine Fibroids).

The COMPARE-UF registry is funded by the Agency for Healthcare Research and Quality (AHRQ), in collaboration with the Patient-Centered Outcomes Research Institute (PCORI). DCRI serves as the Data and Statistical Coordinating Center.

The registry has enrolled more than 3,000 women from nine medical centers. By sharing their experiences with uterine fibroids treatments, these women are helping doctors understand symptom relief patterns, impact on pregnancy, and the need for additional treatment. The goal of COMPARE-UF is to help patients and their doctors make informed decisions about treatment options.

COMPARE-UF will follow the patients in its registry, who are women between the ages of 18 and 54 who have been diagnosed with uterine fibroids and who are not in the transition to menopause.

“We are very excited to be working with Responsum, CARE About Fibroids, and The White Dress Project to develop innovative ways for women to share their experiences with uterine fibroids, as well as to get the best possible information about their choices for treatment,” said Dr. Evan Myers, principal investigator of COMPARE-UF at DCRI.

“We look forward to collaborating with the Duke Clinical Research Institute to help collect valuable insights from women with uterine fibroids,” said Andrew Rosenberg, founder of Responsum Health. “By bringing the patient experience to bear through our partnerships with The White Dress Project and CARE About Fibroids, we will create an online tool, newsfeed, and support platform that fills a vital information gap while simultaneously convening an authentic, welcoming online community for women with uterine fibroids.”

“We are thrilled to partner with the Duke Clinical Research Institute and Responsum Health as we continue to fulfill our mission of heightening public awareness and creating a greater sense of urgency around the toll and challenge of uterine fibroids,” said Jenny Rosenberg, executive director of CARE About Fibroids. “Combined with The White Dress Project’s incredible patient advocate network, we look forward to bringing the strategic communications capabilities along with the scientific and policy expertise of CARE About Fibroids to join this extraordinary opportunity to provide women with a trustworthy, online information platform to replace Dr. Google.”

“The White Dress Project is committed to growing, educating, and enriching a community of women who feel confident knowing they no longer have to suffer in silence with uterine fibroids,” said Tanika Gray Valbrun, executive director of The White Dress Project. “Our partnership with the Duke Clinical Research Institute and Responsum Health is a groundbreaking way to make sure women are better informed and equipped to be their own best advocates.”