New DCRI Registry Could Provide Path for Pediatric Migraine Drug Development

March 5, 2020 – A recently published paper details the development and design of the FDA-funded Pediatric Migraine Registry, which has enrolled around 200 patients between the ages of 4 and 17.

A new registry established by the DCRI seeks to answer critical questions for pediatric patients who experience migraines, while providing a potential pathway for future drug development to help these patients.

A recent paper in Headache: The Journal of Head and Face Pain, authored by the DCRI’s Christoph Hornik, MD, PhD, MPH, and colleagues, details the development and design of the Pediatric Migraine Registry. The FDA-funded registry progressed from concept to first patient enrolled in about six months, and is currently implemented at 20 sites in 15 states across the U.S. The registry met its initial goal to enroll 200 children between the ages of 4 and 17 in the span of 13 months, and creators of the registry say they are planning for potential international expansion.

Hornik said the team chose to focus on pediatric migraine because of the critical need in this area. About 5 percent of children are diagnosed with migraine by age 10, and this number only continues to increase as children progress through adolescence. However, evidence supporting treatments for pediatric migraine remains limited. In alignment with the FDA's Framework for Real-World Evidence Program, Hornik and colleagues began to work on a solution to this problem in the form of a real-world data from a registry. The team leaned on the registry’s co-primary investigator and steering committee co-chair, Amy Gelfand, MD, from University of California, San Francisco, as a subject matter expert in pediatric migraine. Combining Gelfand’s clinical expertise with the DCRI’s experience in developing and overseeing registries contributed to the success of the project’s implementation.

The DCRI's Christoph Hornik, MD, PhD, MPH, principal investigator for the Pediatric Migraine Registry, discusses the goals of the project with Monica Lemmon, MD, a child neurologist at Duke.

“Not only was the study team dedicated to launching the registry, but we are also fortunate to have engaged patients, families, and sites,” Hornik said. “Because of their commitment to advancing the science in this area and finding potential treatments, we were able to advance quickly through the process as we worked to get the registry off the ground.”

Patients enrolled in the registry will be followed for up to a year at three-month intervals, and the registry will include clinical data collected at study sites, data reported by patients and their parents in “headache diaries” through a mobile health app, and biological samples. The data collected are regulatory compliant and provide the infrastructure to support future drug development for pediatric migraine. Participating sites are encouraged to propose research projects that could leverage registry data. In addition, registry leaders are focusing on site training to prepare sites for potential involvement in clinical trials.

“The registry is able to generate the type of data that sponsors, investigators, and others may need to inform their future clinical trials in the space,” Hornik said. “It’s also an ideal platform to act as a springboard for other projects associated with pediatric migraine.”

The registry was developed in collaboration with DCRI Research Together, a group that helped engage patients and their families to ensure that the registry’s goals were aligned with their needs. Investigators also solicited feedback from the International Children’s Advisory Network, an organization committed to empowering pediatric patients, and Miles for Migraine, a nonprofit dedicated to improving quality of life for people with migraine and their families. “A highly collaborative approach with broad stakeholder engagement at all stages of the registry development was a key to our operational success,” the authors write.

Other DCRI contributors to the registry and the design paper include Danny Benjamin, MD, PhD, MPH; Michael Cohen-Wolkowiez, MD, PhD; and Amanda Utevsky (formerly of the DCRI), who helped lead the registry during the development phase.

Certain Risk Factors Could Predict High Costs for Patients with Musculoskeletal Pain

December 31, 2019 – A new analysis from the DCRI showed that 35 percent of direct costs related to musculoskeletal pain were attributable to about 4 percent of patients who were persistent high-cost utilizers.

Health care delivery models that take into consideration risk factors such as physical and mental health may help alleviate the burden of high costs for patients with musculoskeletal pain, according to recent DCRI-led research.

An analysis led by the DCRI’s Trevor Lentz, PT, PhD, MPH, and recently published in PLOS One, examined health care utilization costs and other patient characteristics in a sample of nearly 13,000 patients with musculoskeletal pain drawn from Medical Expenditure Panel Survey data between 2008 and 2013. Because musculoskeletal pain can be a chronic condition, the study team wanted to find out which factors contributed to high health care costs over time.

Findings showed that 35 percent of direct costs related to musculoskeletal pain were attributable to about 4 percent of patients. Persistent high cost utilization was related to non-modifiable variables such as age, race, poverty level, geographic region, insurance status, diagnosis type, and total number of diagnoses. However, modifiable variables also contributed to risk of high costs, including higher number of days missed at work, greater pain interference, and higher use of prescription medication for pain. Conversely, those who reported to have better mental and physical health were less likely to become high-cost utilizers over time.

Trevor Lentz, PT, PhD, MPH“Because we now better understand the factors that are associated with persistently high health care costs, we may be able to prospectively identify the individuals who are at great risk of carrying this burden by looking at demographic and health information for our patients, as well as pain-related characteristics,” Lentz said. “We also may be able to decrease costs for some of these patients by addressing modifiable risk factors within our health care delivery systems.”

“This analysis adds to the conversation because it is, to our knowledge, the first study that examines persistence of high costs for musculoskeletal pain in the U.S,” said Steven George, PT, PhD, FAPTA, who also contributed to the study. “Studies have been conducted in other countries with single-payer systems, but those data do not always translate well to the U.S., where we know that socioeconomic status and insurance status can have a significant impact on health care costs. Further research is needed to be able to ascertain when these high costs are necessary for good musculoskeletal outcomes, versus when they are indicative of low-value care.”

Federal Awards Funds Collaborative Child Health Effort Among Duke, UNC, NC DHHS

December 23, 2019 – The initiative, which will be led by a DCRI pediatrician, aims to create a new care and services model for children in five North Carolina counties.

A federal funding award of up to $16 million to Duke University, in partnership with the University of North Carolina at Chapel Hill and the N.C. Department of Health and Human Services, will help establish an innovative approach to providing health and wellness services to children in five N.C. counties.

The model, called North Carolina Integrated Care for Kids, was one of eight nationally to be awarded funding from the Centers for Medicare & Medicaid Services.

The initiative aims to integrate a variety of services that children receive from different agencies and providers, including those for physical and behavioral health, housing, food, early care and education, child welfare, mobile crisis response services and juvenile justice and safety.

“The NC Integrated Care for Kids model is a tremendous opportunity for us to transform how we support the well-being of children and their families by breaking down siloes and working together across the many systems, including health care, schools, child welfare and early child care settings,” said the DCRI’s Charlene Wong, MD, executive director of the new initiative and an adolescent medicine pediatrician at Duke.

“Our goal is to build relationships, link data and develop new connections between all the different sectors that are currently working to improve the welfare of children,” Wong said. “We believe we can demonstrate that this approach can better serve the children we all seek to help.”

The initiative’s leaders hope improved integration of services will address some of the root causes of poor health, reduce avoidable out-of-home placements, prevent hospitalizations for children, and create innovative and sustainable pediatric alternative payment models under the state’s Medicaid program.

“Children’s health and wellbeing are shaped by so much more than visits to the doctor,” said Mandy K. Cohen, MD, Secretary of North Carolina Department of Health and Human Services. “Do they have enough food to eat? Do they have safe housing? Do they have nurturing caregivers? This model builds on our commitment to caring for the whole person and will help us achieve the bold goals set in our state’s early childhood action plan.”

The model will serve Medicaid- and CHIP-insured children from birth to age 21 in Alamance, Orange, Durham, Granville, and Vance counties, which includes an estimated 80,000 eligible children. The CMS funding allocation begins Jan. 1, 2020 and covers two years for planning and program infrastructure development, followed by five years of implementation beginning in 2022.

The NC Integrated Care for Kid Partnership Council will serve as the governing body. It will include representation from families, youth and Medicaid payers as well as service providers in health care as well as other core areas.

“As the lead organizations at Duke, UNC, and NC DHHS work in collaboration, we are excited to join with many other state and local entities to make this approach a success, and really improve the lives of children by better addressing all of the factors that impact their health,” said Mike Steiner, MD, medical director of NC Integrated Care for Kids and pediatrician in chief of UNC Children’s.

The project described is supported by Funding Opportunity Number CMS 2B2-20-001 from the U.S. Department of Health & Human Services, Centers for Medicare & Medicaid Services. The contents provided are solely the responsibility of the authors and do not necessarily represent the official views of HHS or any of its agencies.

Year in Review 2019: DCRI Continues Study Support and Knowledge Sharing

December 19, 2019 – As the year—and the decade—draws to a close, we take a look back at some of our accomplishments and the ways in which we shared knowledge in 2019.

Road with years on itAs detailed in our DCRI Annual Report, 2019 was a busy and productive year. Our faculty and operational staff published more than 1,300 scholarly articles in FY19—the highest number on record for the DCRI. In addition to publishing science in scholarly journals, DCRI representatives shared their knowledge and expertise in plenty of other avenues, including through writing editorials on seminal topics in their respective fields, contributing research that helped shape FDA guidance and other regulatory documents, and presenting at large conferences. Take a look through this article to view some of the year’s highlights.

Providing Wraparound Study Support: Our Services and Capabilities

The DCRI continues to provide capabilities that are critical to the future of efficient and well-designed clinical research, such as taking pragmatic approaches to clinical trials. This year, the DCRI’s pragmatic approach of identifying and recruiting patients through electronic health records resulted in ADAPTABLE successfully meeting its enrollment goal of 15,000 participants. The DCRI also continues its services in areas like adjudication of clinical events from its Clinical Events Classification group and partnering with patients to provide diverse perspectives in research through DCRI Research Together. New this year to the DCRI was the Behavioral Research Intervention Science Center (BRISC), which implements behavioral incentives into studies and provides evidence for what motivates patients and providers to change their behavior.  Additional services and capabilities provided by the DCRI are discussed in the following articles:

  • The DCRI Arrhythmia Core Lab, which has longstanding expertise in evaluation and adjudication of electrograms and electrocardiograms, is now set to work on more studies that involve wearable devices.
  • The DCRI provides advice on best practices via white papers. For example, through the Global Pediatric Clinical Trials Research Network, the DCRI worked directly with sponsors to identify pain points and challenges to pediatric clinical research, and subsequently released a white paper providing recommendations to address these challenges.
  • Along with groundbreaking studies, the DCRI also generates new evidence through registries, such as the cv-MOBIUS registry that seeks to enroll and follow 8,500 high-risk patients to understand how lipid management treatments are used in real-world practice.
  • The DCRI hosts quarterly DCRI Think Tanks, which are designed to convene diverse stakeholders to tackle the greatest challenges and largest gaps in clinical research. Recently, the DCRI published a paper sharing findings from a think tank on tech-enabled trials.

Sharing Our Expertise: Contributions to Regulatory Documents and Other Recommendations

The DCRI also delivers on our mission to share knowledge through contributing to regulatory documents and other recommendations widely recognized by their fields. This year, work from DCRI pediatrics researchers helped to shape FDA guidance on how to conduct studies in newborns. Several collaborations among the DCRI and other organizations have also helped the FDA to map its strategy and recommendations for using real-world evidence in research. Other key examples of DCRI faculty sharing their expertise to impact their fields include:

Conducting Innovative Research: New Studies and Study Milestones

DCRI teams continued to work diligently on their respective studies. Some teams launched new trials, such as the PREVENTABLE trial, which was awarded $90 million to study the effects of statins on the cognitive function of older adults. Others celebrated the achievement of milestones years in the making; for example, expansive childhood research program ECHO, for which the DCRI acts as a coordinating center, received IRB approval and has already initiated studies. Additional new studies and study milestones included:

Working Together to Make an Impact: Collaborations and Strategic Partnerships

In addition to new studies, the DCRI has also entered into new collaborations over the last year. Some of these strategic partnerships have been study-related, such as a partnership with Cerner, the world’s largest electronic health record company, to leverage real-world data in clinical research. Others have been related to a general area of expertise, such as the DCRI’s entry into the Digital Therapeutics Alliance. Additional collaborations and partnerships include:

Owning Our Perspective: Editorials and Discussion Pieces

From a Viewpoint in JAMA Cardiology from Ann Marie Navar, MD, PhD, which likened medical misinformation surrounding vaccines to fears surrounding statins, to an editorial from Michael Felker, MD, in Circulation that called for more data on the benefits of newer cardio-metabolic drugs, our faculty shared many perspectives this year. A sampling of DCRI stories that covered other editorials and discussion pieces published within the last year include:

Presenting New Discoveries: Attendance at Major Conferences

Many DCRI faculty and operations staff attended both the American College of Cardiology Annual Scientific Session, held in March in New Orleans, and the American Heart Association Scientific Sessions, held in November in Philadelphia. Science shared at these two major cardiology conferences included:

In addition to ACC and AHA, our cardiology faculty, fellows, and staff attended and presented at several other key cardiology related conferences throughout the year, including: the Cardiovascular Clinical Trialists Forum; European Society of Cardiology Congress; the 23rd annual meeting of the Heart Failure Society of America; the Society for Cardiovascular Angiography & Interventions Scientific Sessions; and the Transcatheter Cardiovascular Therapeutics Symposium.

Our conference attendance isn’t reserved for our cardiovascular therapeutics team only, however. DCRI faculty and operational staff also attended and presented at: The American Association for the Study of Liver Diseases; Digestive Disease Week; the Infectious Diseases Society’s IDWeek; the American Society of Nephrology’s Kidney Week; the American Urological Association’s 2019 Annual Meeting; the American Medical Informatics Association’s Informatics Summit and its Annual Symposium; the professional society for health economics and outcomes research (HEOR) annual ISPOR conference; the Society for Clinical Data Management’s SCDM 2019 conference; the Pediatric Academy Societies Meeting; the American Thoracic Society’s International Conference; and the International Stroke Conference.

Survey Finds Older Cardiac Patients Have Different Goals, Lower Risk Tolerance

December 18, 2019 – The survey focused on invasive cardiac care and measured patient knowledge, goals, and concerns related to these procedures.

Findings from a survey conducted by researchers at the DCRI sheds new light on how age plays a role in invasive cardiac care and further emphasizes the need to take individual patient preferences into account when determining a treatment plan.

The study, which was led by DCRI Fellow Michael Nanna, MD, and recently published in the American Heart Journal, surveyed 628 patients hospitalized with acute coronary syndrome. This group included 373 patients younger than 75 and 255 patients who were 75 or older.

The survey sought to determine:

  • Knowledge, preferences, goals, and concerns related to cardiac care;
  • Risk tolerance for coronary artery bypass grafting (CABG) surgery; and
  • Whether willingness to consider different types of invasive cardiac care corresponds with whether patients actually received the procedures.

Prior to this survey being conducted, systematic studies of the knowledge, beliefs, and preferences of older patients as these factors relate to invasive cardiac care had been lacking. There had also been no quantitative assessment of risk tolerance for this type of care.

The survey found that when compared with younger patients, older patients had less knowledge of acute invasive cardiac care and were less willing to consider cardiac catheterization, percutaneous coronary intervention, and coronary artery bypass grafting (CABG). However, even in the older group, the majority of patients were willing to consider cardiac catheterization.

Even when they indicated they would not be willing to consider surgery, many patients across both groups did end up having a procedure done. Nearly half of those who wouldn’t consider cardiac catheterization did have the procedure, and 22 percent of patients who originally answered no underwent percutaneous coronary intervention or CABG.

To measure risk tolerance, the study team measured the patient’s highest risk prior to changing his or her preference away from CABG, a measure called a standard gamble score. Older patients were found to have lower risk tolerance (a median of 1 percent) than younger patients (a median of 20 percent).

Michael Nanna, MDBoth groups were concerned about the potential of death associated with invasive surgery, but other concerns varied between younger and older patients. For example, older respondents cited losing mental capacity as their top concern.

Goals for treatment also differed between the two groups. Younger patients were more likely to prioritize preserving life in the years to come, while older patients prioritized symptom relief. However, smaller proportions of older patients valued preserving life, while smaller proportions of younger patients valued symptom relief, indicating that it is important to consider individual preferences in treatment plans.

“These survey results are illuminating because they reveal the goals, concerns and priorities of older adults as they seek cardiac care later in life,” Nanna said. “While high quality evidence supports revascularization to improve chances of survival and quality of life, we know that one size does not fit all and that individualized treatment plans are important, especially when older adults were not included in many of the evidence-generating studies. Efforts to decrease the knowledge gap for older adults in regard to cardiac surgery have been successful, but more work can be done to ensure we are all well informed as we work together in shared decision-making.”

Other DCRI contributors to this study include Eric Peterson, MD, MPH; Karen Alexander, MD; Angie Wu, MS; Tina Harding, BSN; Anthony Galanos, MD; and Lisa Wruck, PhD.

ADHD Could Present Higher Risk for Nicotine Addiction

December 17, 2019 – A study showed that young adults with ADHD were more likely to self-administer nicotine in both relaxing and cognitively difficult scenarios.

Study results recently published in Neuropsychopharmacology indicate that young adults with ADHD are at higher risk of becoming addicted to nicotine after even the first exposure to the substance.

The study included 136 non-smokers between ages 18 to 25, about half of whom had a clinical diagnosis of ADHD. Participants were administered two different doses of nicotine and a placebo. Then, they were asked to choose a spray while engaged in two different scenarios: a relaxed setting and a setting in which they were asked to solve math problems.

Scott Kollins, PhDThe researchers hypothesized that participants with ADHD would be more likely to choose the nicotine while solving the math problems.

“We have known for a long time that nicotine does have some of the same properties that medicine used to treat ADHD has,” said the DCRI’s Scott Kollins, PhD, while discussing the findings in an interview with NPR. “It increases vigilance and attention.”

However, while participants without ADHD were more likely to choose nicotine when working on the math problems, those with ADHD were more likely to self-administer nicotine in both scenarios. Participants with ADHD were also more likely to report pleasurable effects from the nicotine.

Kollins, who was the lead author of the paper, said that these results indicate that young adults with ADHD could be at higher risk for nicotine addiction after only one exposure to the substance. Conversation, education, and prevention efforts surrounding nicotine use and addiction need to start early, he added.

Research Network Based at DCRI Awarded up to $102.5M for Work on Antibacterial Resistance

December 13, 2019 – The Antibacterial Resistance Leadership Group conducts clinical research to better understand how to diagnose, treat, and prevent antibacterial resistant infections.

 The Antibacterial Resistance Leadership Group (ARLG), a unique research network for which the DCRI acts as a coordinating center, received a federal award worth up to $102.5 million over seven years that will continue the ARLG mission to prioritize, design, and execute clinical research to reduce the public health threat of antibacterial resistance.

The funding, provided by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, supports the mission of the ARLG under award number UM1AI104681.

Antibacterial treatments are becoming less effective, resulting in an urgent threat to public health. A 2019 report from the Centers for Disease Control and Prevention estimates that antibiotic-resistant bacteria infect more than 2.8 million people annually, killing at least 35,000 in the U.S.

The ARLG, which received its inaugural funding from NIAID in 2013, is composed of more than 50 leading experts working together to innovate clinical trial design, inform guidelines, and improve clinical practice in infectious diseases.

The ARLG’s research team has collaborations in 19 countries and has initiated more than 40 clinical research studies involving more than 20,000 patients across more than 130 sites. Its three areas of research align with the CDC’s antibiotic resistance threats and include:

  • Infections caused by Gram-negative bacteria, such as Escherichia coli;
  • Infections caused by Gram-positive bacteria, such as Staphylococcus aureus; and
  • Diagnostics such as rapid point-of-care tests to detect drug resistance, guide antibacterial therapy, and support clinical trials.

Vance Fowler, MD, MHS“The renewal support from the NIAID will allow the ARLG to continue its collaborative work to advance science in antibacterial research, and to provide funding opportunities for the next generation of researchers dedicated to addressing this public health threat,” said Vance Fowler, M.D., ARLG co-principal investigator, member of the DCRI, and professor of medicine at the Duke University School of Medicine.

“We are delighted to be able to continue to support efforts to fight antibiotic resistance by generating data that is used to inform dosing guidelines and developing diagnostic testing for better detection and timely treatment,” Fowler said.

To learn more, read the news release from the NIAID.

Working at the Intersection of Expertise to Improve Patient Care

December 11, 2019 – With eight-plus clinical areas under one roof, the DCRI enables faculty members of various specialties to work together to draw deeper insights in clinical research and find better treatments for patients.

Working at the Intersection of Expertise to Improve Patient Care

Traditionally, patient care has taken a somewhat siloed approach, with specialists treating patients for organ-specific complaints. However, advancements in medicine have resulted in the need for a new paradigm: one in which specialists in different areas of medicine come together to address issues at the intersection of their expertise.

“We now have tools that we know are effective in keeping our patients healthier and helping them to live longer,” said Jennifer Green, MD, an endocrinologist at the DCRI. “We all need to partner and be engaged in ensuring our patients’ care aligns with current evidence-based guidelines. This will require communication with other specialty areas, but it is very important to understand that optimization of care is a shared responsibility. We can no longer only focus on our areas of expertise; instead, we have to focus on collaborating to care for the whole patient.”

With 140 faculty members across nine therapeutic areas who often come together to work on clinical trials, the DCRI is particularly well poised to work in this space.

DCRI faculty from various specialty areas discuss ongoing projects and future opportunities for collaboration in the cardiometabolic and cardiorenal spaces.

New Medications, New Opportunity

As health care advances, patients live longer and develop more comorbidities, calling for a new era of health care in which providers must think about clinical areas outside the one in which they work. For instance, a cardiologist now needs to consider how medications he or she prescribes affect other conditions like diabetes or renal disease. Simultaneously, new evidence is emerging that show many therapies can be used for multiple indications.

Some of this evidence was presented at the American Heart Association Scientific Sessions 2019, such as results from DAPA-HF, which was led by John McMurray, MD, of the BHF Cardiovascular Research Centre in Glasgow, Scotland. The study results showed that dapagliflozin, an SGLT2 inhibitor traditionally used to treat diabetes, can also be used to safely and effectively treat heart failure with reduced ejection fraction both in patients with and without diabetes.

“It’s changed how we think of dapagliflozin; we now consider it a foundational therapy for reduced ejection fraction, and I think many of us eagerly await the preserved ejection fraction data, as well,” said Robert Mentz, MD, a heart failure specialist at the DCRI.

Although the DAPA-HF study was not powered to look at renal outcomes, nephrologists were also struck by the results, which Daniel Edmonston, MD, a nephrologist at the DCRI, called “profound.”

“Results like these are exciting for work moving forward from a cardio-renal-metabolic standpoint as we expand the use of these medications in growing indications outside of diabetes,” he said.

Green also looks forward to the opportunities provided by expanded uses for these medications. She is the principal investigator for a trial called EMPA-Kidney, which is examining the effects of empagliflozin, another SGLT2 inhibitor, in patients who have chronic kidney disease. Although empagliflozin, like dapagliflozin, was initially approved to reduce glucose levels in patients with type 2 diabetes, the leaders of EMPA-Kidney expect that it will also reduce cardiovascular and kidney complications in patients with and without diabetes.

“Although these drugs are traditionally viewed as diabetes medications, we need to start thinking of them as drugs with much broader benefits for our patients,” Green said.

Closing the Gap via Implementation Science

Although advancements like DAPA-HF have resulted in more options for treatment of previously difficult-to-treat conditions, implementation of these therapies into clinical practice remains challenging.

A DCRI-led study called COORDINATE-Diabetes is making an effort to tackle this problem by working with cardiology clinics to improve care for patients who have cardiovascular disease and diabetes. Through the intervention arm of the trial, teams from the DCRI are helping clinics identify their challenges and create solutions that would boost prescribing rates of efficacious therapies. The teams that visit the sites are diverse in their expertise—each team includes a cardiologist, an endocrinologist, and a quality improvement specialist—in an effort to help sites coordinate their patients’ care among cardiologists, endocrinologists, and primary care doctors.

DCRI co-chief fellow and cardiologist Adam Nelson, MBBS, PhD, who is working on COORDINATE-Diabetes along with Green and others from the DCRI, contributed to a poster presented at AHA 2019 that outlined data from patients similar to the COORDINATE study illustrating the depth of the problem. In a population of over 150,000 patients with both atherosclerotic cardiovascular disease and diabetes, fewer than 5 percent of all patients were being prescribed all three agents that have proven to be effective including high intensity statins, ACE inhibitors or ARBs, and SGLT2 inhibitors or GLP-1 receptor agonists.

Neha Pagidipati, MD, MPH, a cardiovascular prevention specialist and one of the faculty leads for COORDINATE-Diabetes, noted that there are multiple barriers to prescribing guideline-recommended therapies, both at the provider level and at the system level. Some cardiologists report hesitancy to infringe on the diabetes care providers’ space, while others share they are uncomfortable with some of the metabolic side effects that can accompany the newer medications proven to be effective for cardiovascular conditions. She said she hopes to see a shift as medications move from being defined as primarily diabetes treatments to now being seen as cardiovascular risk reduction medications.

“We have been thinking a lot at the DCRI about how to actually get therapies implemented because we know it takes approximately 17 years for guideline therapies to make it into clinical practice,” Pagidipati said. “When you have therapies that are this effective and populations that are at such high risk, this is not acceptable.”

The AHA 2019 analysis that Nelson contributed to provides further insight into this divide. In the cohort his team examined, less than 30 percent were seen by an endocrinologist, while 70 percent were seen by a cardiologist. Nelson said these findings show that an intervention targeted toward cardiologists has the greatest potential impact to increase prescriptions of guideline-recommended therapies. Through COORDINATE’s intervention, the study team will be looking for ways to empower cardiologists to take a more active role in their patients’ overall health and feel comfortable prescribing medications beyond traditional cardiovascular medications.

Looking Toward a Future of Integrated Care

Although it previously would have been unusual to see cardiologists working alongside a nephrologist to improve patient care, these days it is commonplace at the DCRI, Nelson said.

Edmonston agrees. “There is increasing overlap in the Venn diagram of subspecialty care for our patients,” he said. “It’s exciting to see opportunities where we will be able to work together across differing specialties to provide the best care.”

Because the DCRI contains eight different therapeutic areas under one roof, along with numerous subspecialties within these therapeutic areas, Nelson said the institute provides an ideal environment for a new way of working that lays the groundwork for the future of health care.

“The DCRI is a one-stop shop that has experts in every clinical area running trials and collaborating on research,” Nelson said. “A model in which we can see the common threads in our research helps us to aggregate data, opinions, and ideas to inform more well-rounded patient care.”

Considerations for Assessing Open-Label, Comparative Effectiveness Trials

Matthew Roe, MD, MHS

Deepak Bhatt, MD, MPH

The DCRI’s Matthew Roe, MD, MHS, (pictured left), recently participated in a discussion with his colleague, Deepak Bhatt, MD, MPH, (pictured right), of Brigham and Women’s Hospital and Harvard Medical School. The two cardiologists discussed how to interpret results from head-to-head comparative effectiveness trials involving cardio-metabolic drugs. Listen to an audio recording of the conversation.





Conflicts of Interest for Dr. Matthew Roe from July, 2017 – June, 2019:
Research Grant Funding: Sanofi-Aventis, Astra Zeneca, Patient Centered Outcomes Research Institute, Ferring Pharmaceuticals, Myokardia, Familial Hypercholesterolemia Foundation, Bayer.
Consulting or Honoraria: Astra Zeneca, Amgen, Cytokinetics, Eli Lilly, Roche-Genentech, Janssen Pharmaceuticals, Regeneron, Novo Nordisk, Pfizer, Sanofi-Aventis, Signal Path, and Elsevier Publishers.
All conflicts of interest are listed at

Dr. Deepak L. Bhatt discloses the following relationships - Advisory Board: Cardax, Cereno Scientific, Elsevier Practice Update Cardiology, Medscape Cardiology, PhaseBio, Regado Biosciences; Board of Directors: Boston VA Research Institute, Society of Cardiovascular Patient Care, TobeSoft; Chair: American Heart Association Quality Oversight Committee; Data Monitoring Committees: Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo), Population Health Research Institute; Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News,; Vice-Chair, ACC Accreditation Committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Medtelligence/ReachMD (CME steering committees), Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Research Funding: Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Idorsia, Ironwood, Ischemix, Lilly, Medtronic, PhaseBio, Pfizer, PLx Pharma, Regeneron, Roche, Sanofi Aventis, Synaptic, The Medicines Company; Royalties: Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); Site Co-Investigator: Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott), Svelte; Trustee: American College of Cardiology; Unfunded Research: FlowCo, Merck, Novo Nordisk, Takeda.

New Quadruple Therapy Shows Promise, But More Data are Needed

December 4, 2019 – In a recent editorial in Circulation, the DCRI’s Michael Felker, MD, raises questions that the heart failure field should consider in light of new results from the DAPA-HF trial.

Recent results from DAPA-HF may be moving the treatment of heart failure into a new era of “quadruple therapy,” but further studies are needed to understand the benefits of using an SGLT2 inhibitor such as dapagliflozin in addition the guideline-recommended triple therapy, wrote the DCRI’s Michael Felker, MD, in a recent editorial in Circulation.

The editorial, which accompanied new results published from DAPA-HF on quality of life and the impact of patient age, points to the importance of these findings in understanding the role of dapagliflozin in patients with heart failure with reduced ejection fraction regardless of diabetes status. SGLT2 inhibitors had previously been found to prevent heart failure in patients with Type 2 diabetes.

Michael Felker, MD

More studies will need to be conducted, Felker notes, to determine whether these benefits are specific to dapagliflozin or whether they extend to the entire class of SGLT2 inhibitors. Additional study of the specific mechanisms that result in the benefits of the drug is also needed. Implementation of this new quadruple therapy will also be challenging in a landscape in which it is already difficult to get patients on guideline-directed medical therapy, especially in at-risk subsets of patients like older patients.

Felker points to two papers published in the same issue of Circulation that help provide some insight to answer these questions. A paper by Kosiborod et al. found that dapagliflozin resulted in an improvement in health-related quality of life that was sustained over six months. Another paper by Martinez et al. reports on the effects of dapagliflozin stratified by age group. Although adults over 75 were more likely to have adverse events, the study saw similar rates between the intervention group and the control group, suggesting that dapagliflozin is well tolerated even in older patients.

Although the results from DAPA-HF are promising, more data are needed to confirm the benefit of dapagliflozin and other SGLT2 inhibitors in the treatment of heart failure, Felker writes. This is especially important in other subsets of the population, such as patients with heart failure with preserved ejection fraction. In addition, physicians will have to focus on implementing these new findings into clinical practice to provide the best care for patients with heart failure.