New professional development program aims to advance women’s clinical research careers

May 2, 2019 – The program, offered by the American College of Cardiology, will see involvement from DCRI faculty in chairing, teaching, and participating.

Several DCRI faculty members are developing a new professional development program for early- to mid-career female clinical researchers offered by the American College of Cardiology.

The Clinical Trials Research Program is a training and networking program open to women cardiologists who have committed to a career in clinical research and have been nominated by their institution for further development in research leadership. The program, which will be held in May in Washington, D.C., is co-led by Pamela Douglas, MD, and Tracy Wang, MD, MHS, MSc, at the DCRI, as well as Mary Norine Walsh, MD, at St Vincent’s. Douglas brought the idea for a women-specific professional development program to the American College of Cardiology’s Diversity and Inclusion initiative, which she also chairs.

“Half of all medical students are women, and roughly 45 percent of internal medicine residents are women, but only 20 to 25 percent of cardiology fellows are women,” said Douglas (pictured left), who has served as director of the DCRI’s imaging program since 2006. “So among practicing cardiologists, it’s only about 10 to 12 percent women. This means we’re missing a huge amount of talent—we’re missing about 30 percent of the brainpower in our profession.”

Over the years, Douglas and Wang have had ongoing discussions about how to best provide career opportunities for women. It is an issue that is personal for Wang, who wanted to be an interventional cardiologist but ultimately ended up choosing a different path. Although this decision was influenced by many factors, she attributes it in part to the fact that there were few female interventional researcher mentors at Duke and elsewhere during her training.

Wang and Douglas hope to help solve the representation problem with women-specific offerings like the ACC Clinical Trials Research Program.

“We want to help women navigate some of the same challenges we saw when we were early-career faculty,” Wang said. “We want this program to act as a launching pad to help these promising researchers get to where they need to be — at the highest levels of research leadership.”

Wang (pictured right) said the program will do this in three ways: by building a solid foundation of knowledge, by creating peer networks that help women sponsor each other for opportunities and leadership roles, and by connecting women with study funders/leaders, role models and other resources.

Wang and Douglas hope there will be future iterations of the program. Approximately 50 women were accepted to this inaugural cohort, which is 10 percent underrepresented minorities and 15 percent international researchers.

The program’s primary goal is to elevate women’s careers, but promoting women will also have a positive impact on science and on patients, Douglas and Wang said. This is because women are more likely to conduct research that is relevant to female patients, more likely to attract female research participants, and therefore, more likely to return sex-specific results.

Two DCRI researchers will be attending the program — Melissa Daubert, MD, whose work focuses on women’s cardiac health, cardio-obstetrics, and cardiac imaging, and Chiara Melloni, MD, whose primary research interest is cardio-oncology.

Daubert, who has been at the DCRI since 2012, said she applied to the program because the agenda offered each participant the opportunity to create her own personal career action plan. She is looking forward to forecasting new opportunities and collaborations as her clinical research career continues to grow.

“It’s important to train women in a male-dominated field like cardiology so that we can take a balanced approach to care and ensure that gender disparities are adequately addressed,” she said.

Melloni, who has been at the DCRI since she arrived for a fellowship in 2005, said she is most excited about enhancing her skills in certain areas, such as engaging with stakeholders and forging relationships with sponsors. Although she has worked on many different trials, she said she has more to learn.

Both Daubert and Melloni also said they will find value in making connections with other female cardiologists and helping to create a network for professional advancement.

“I like clinical research because each trial is different and presents different challenges,” Melloni said. “But the road to becoming an expert is long.”

The DCRI’s Kevin Thomas, MD, and Kevin Anstrom, PhD, will also serve as faculty for the program.

DCRI receives CRO Leadership Awards for fourth year

April 30, 2019 – The DCRI was recognized in five categories, including Capabilities, Compatibility, Expertise, Phase IV, and Reliability.

The DCRI has again received several CRO Leadership Awards from Life Science Leader magazine and Industry Standard Research. The awards, presented annually by the magazine to contract and academic research organizations, were created to recognize excellence in several key categories. This year, the DCRI was recognized in the categories of Capabilities, Compatibility, Expertise, Phase IV, and Reliability. The organization also received Individual Attribute Awards for Data Quality, Project Timelines, Operational Excellence, and Responsiveness. The DCRI has received CRO Leadership Awards for four consecutive years.

The awards are based on surveys of biopharmaceutical and medical device companies conducted by Industry Standard Research. For this year’s awards, more than 70 research organizations were evaluated on more than 20 different performance metrics. Respondents only evaluated companies with which they have worked on an outsourced project in the last 18 months.

A complete list of winners was published in the May 2019 issue of Life Science Leader. A formal awards ceremony will be held June 24 in San Diego.

“These awards are evidence of the incredible work that our faculty, fellows, and staff do every day,” said DCRI Interim Executive Director Lesley Curtis, PhD. “The DCRI is honored to again be recognized for its efforts to improve patient health around the world.”

DCRI helps FDA map strategy to broaden use of real-world evidence

April 24, 2019 – Through projects such as ADAPTABLE, CTTI, and the NIH Collaboratory, the DCRI is defining how to use RWE in clinical research.

From electronic health records to insurance claims, patient registries, and mobile devices, modern technology has ushered in a wealth of real world data (RWD) that can complement traditional randomized clinical trials to help researchers understand more about a drug or treatment. Until recently, however, there was little agreement on how to transform this data into solid evidence that can guide patients to better decisions.

In 2018, the U.S. Food and Drug Administration (FDA) released a new Framework for Real-World Evidence (RWE). The document, which establishes a definitive roadmap for FDA’s development of standards for the use of RWD and RWE, is a product of insights gleaned from some of the nation’s most respected trailblazers in advancing the generation and use of RWE, including the DCRI.

Specifically, the Framework outlines various areas in which FDA will evaluate the use of RWD and RWE; FDA’s plan for evaluating how RWD can be incorporated into study designs and the regulatory considerations for such use of RWD; and FDA’s plan for developing guidance in a number of key areas, including on data standards and additional sources of RWD to help address current gaps in the capture of key information.

DCRI researchers were among those invited to participate in a 2016 Bipartisan Policy Center roundtable. That event, which focused on advancing the use of RWE, was an opportunity for the DCRI to share its perspective on how the right policy pathways are critical to shaping the future of real-world medicine.

Leading by example

Through several innovative programs, the DCRI continues to spearhead new and better ways of bringing RWE to the fore of research that will inform future regulatory policy.

As highlighted in the FDA’s framework document as a case example, the ADAPTABLE (Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-Term Effectiveness) Study is a patient-centered, pragmatic clinical trial assessing two different daily doses of aspirin to evaluate which dose is more effective for patients living with cardiovascular disease.

The DCRI is the Coordinating Center for ADAPTABLE, which is funded through a Patient-Centered Outcomes Research Institute (PCORI) award and is conducted through PCORnet– the National Patient-Centered Clinical Research Network.

Forty healthcare systems and two health plans use electronic health records (EHRs) and health insurance information to identify potential study participants. Effectively using EHRs as a recruitment strategy requires transparency and communication with clinicians.

“Finding ways to make research more practical is what ADAPTABLE and pragmatic clinical research is all about,” said ADAPTABLE principal investigator Schuyler Jones, MD. “ADAPTABLE integrates conversations about participation into the clinical work flow, helping both clinicians and patients become more aware of the research question, and better understand if participation is the right choice for that individual patient.”

It takes a team approach to establishing best practices for leveraging electronic health records, engaging patients as partners, and overcoming regulatory hurdles. The ADAPTABLE team consists of patient partners, clinicians, and researchers who regularly discuss study progress, challenges, and success. Team members frequently share lessons learned and insights within the ADAPTABLE community and beyond as they continue to set the bar and put in place measures to innovate clinical research.

The DCRI also serves as the Coordinating Center for the National Institutes of Health Health Care Systems Research Collaboratory (NIH Collaboratory), helping to realize the program’s mission to strengthen the national capacity to implement cost-effective large-scale research studies that engage healthcare delivery organizations as research partners. Led by DCRI’s Lesley Curtis, PhD, Adrian Hernandez, MD, MHS, and Kevin Weinfurt, PhD, the Coordinating Center supports and learns from innovative pragmatic trials to advance the field.

“Through the NIH Collaboratory program, we are discovering the best ways to embed research in everyday clinical care,” said DCRI’s Tammy Reece, MS, project director for the Coordinating Center. “Everything we learn is fed back to the research community to shape how the next generation of clinical trials will be conducted.”

One example is the Pragmatic Trial of Higher vs. Lower Serum Phosphate Targets in Patients Undergoing Hemodialysis (HiLo), led by the DCRI’s Myles Wolf, MD, MMSc. HiLo is testing the effects of different levels of phosphate control for patients with end-stage renal disease under real-world conditions. This clinically important question will be answered through partnership with dialysis organizations and their providers.

Another DCRI-affiliated project, the Clinical Trials Transformation Initiative (CTTI), is working on a collaborative project with the FDA, industry, patients, and other stakeholders to advance the use of RWD—which is also used and analyzed to create RWE—in planning for regulatory submission trials. As part of this work, CTTI is developing recommendations and supporting resources for using data from electronic health records (EHR) and insurance claims to evaluate trial eligibility criteria and recruit potential research participants. The work is based on in-depth interviews and meetings with representatives from academia, biopharmaceutical companies, health systems, and other organizations to identify challenges and opportunities for incorporating RWE in regulatory submission trials.

“RWD is a potentially powerful tool for enhancing the quality and efficiency of clinical trials,” said CTTI Executive Director Pamela Tenaerts, MD, MBA. “Clarifying the best approaches for incorporating RWD into clinical trials can accelerate recruitment and completion of these trials and lead to substantial benefits for all stakeholders in the clinical trials enterprise, including sponsors, sites, and participants.”

The next era of research

Each of these DCRI projects is laying the groundwork for something bigger: a new era of drug development that seamlessly employs RWD and RWE to bring patients meaningful insights at less cost and greater speed than ever before. In January 2019, former FDA Commissioner Scott Gottlieb emphasized the value of RWD and RWE in a speech at the Bipartisan Policy Center.

“Traditional postmarket studies typically require years to design and complete and cost millions of dollars. By using RWD and RWE, we may be able to provide patients and providers with important answers much sooner—identifying a broader range of safety signals more quickly, and following up on them much more effectively,” Gottlieb said.

As FDA continues making this case and mapping the right ways to enhance modern drug development with real world insights, it will be looking to the outcome of these DCRI efforts to guide its trajectory.

Many heart attack patients may be needlessly treated in ICU

April 15, 2019 – A new study finds that more than 80 percent of stable STEMI patients are treated in the ICU.

Many patients who suffer a type of heart attack known as an ST-elevation myocardial infarction (STEMI) are treated in the intensive care unit (ICU), despite a relatively low risk of developing a complication requiring ICU care, according to a new study published in JACC: Cardiovascular Interventions.

A STEMI is caused by a blocked blood supply to the heart and is the most severe type of heart attack.

“In recent years, treatment for STEMI patients has improved so much that cardiologists have seen the risk of developing a complication requiring care has significantly decreased,” said Jay S. Shavadia, MD, a cardiologist and researcher from the DCRI and the study’s lead author. “We wanted to quantify the risk and see whether ICUs are being overutilized for STEMI patients.”

The researchers analyzed data from the Chest Pain-MI Registry, which includes patients admitted to participating hospitals with STEMI or non-STEMI (NSTEMI). They examined patterns of ICU use among STEMI patients ages 65 years and older treated with PCI who were stable when they were first seen in the hospital. This meant they were not in cardiac arrest, were not in shock or had had a procedural complication.

“We know those patients [with shock] need to be in an ICU, so we didn’t include them in the study,” he said.

Of 19,507 stable STEMI patients treated at 707 hospitals, 82.3 percent were treated in an ICU with a median one-day ICU stay. Overall, 16.2 percent of patients developed complications requiring ICU care while hospitalized. The study found 3.7 percent died, 3.7 percent experienced cardiac arrest, 8.7 percent experienced shock, 0.9 percent suffered a stroke, 4.1 percent had a blockage of electrical signals between the heart’s upper and lower chambers (atrioventricular block) and 5.7 percent experienced respiratory failure. These complications were not limited to those related to heart problems.

“As patients get older, their risk of non-cardiovascular complications requiring an ICU stay increases, such as other causes of shock or respiratory failure, sepsis for instance,” Shavadia said.

Patients who waited longer to receive treatment were more likely to develop at least one complication. Those who received treatment within an hour of being evaluated by emergency medical service (EMS) personnel or going directly to the hospital without being seen by EMS, had a complication rate of 13.4 percent, compared with 18.7 percent for those who were not treated for at least 90 minutes.

“Although 16 percent is not a small number of STEMI patients who should be in the ICU, we found the majority of patients don’t need to be there,” Shavadia said.

He said that patients age 65 years and older are more likely to develop complications than younger patients, so the overall risk for STEMI patients of all ages who need ICU care may be even lower than 16 percent.

The study did not address which stable STEMI patients will need ICU care.

“We’re now trying to identify which patients are at greatest risk of complications, so we can predict who needs to be treated in the ICU,” Shavadia said.

In an accompanying editorial, Suartcha Prueksaritanond, MD, and Ahmed Abdel-Latif, MD, PhD, of the Gill Heart and Vascular Institute and division of cardiovascular medicine at the University of Kentucky, and the Lexington VA Medical Center in Lexington, Kentucky, wrote, “The high ICU utilization pattern despite declining complications following PPCI [primary percutaneous coronary intervention] calls for a new approach. This is particularly important as the overall health care cost continues to grow and calls for optimal resource utilization prevail.”

They noted that until a more comprehensive, simple-to-follow algorithm for stratifying risk in STEMI patients is developed, “the ICU admission decision for STEMI patients will continue to be based on individual judgment and traditional protocols rather than robust and evidence-based risk prediction models.”

Organizations join forces to create global alliance against antibiotic resistance

April 13, 2019 – The ARLG and COMBACTE will work together on a number of initiatives designed to fight drug-resistant infections.

The U.S.-based Antibacterial Resistance Leadership Group (ARLG), part of the DCRI, and the University Medical Center (UMC) Utrecht, the managing entity of the COMBACTE (Combatting Bacterial Resistance in Europe) consortium, will work together to solidify a comprehensive global community to combat the threat of antibiotic resistance around the world.

This collaboration is expected to take several forms, including joint design and implementation of clinical research, working meetings at scientific conferences like the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), and IDWeek, cross-entity working groups with diverse functional group participation, clinical trial innovations, data and protocol exchanges, and, contractual, regulatory, and systems harmonization.

ARLG logo“We at the ARLG have long admired the work being done by COMBACTE to increase the efficacy of antimicrobial drug development,” said Vance Fowler, MD, an investigator at the DCRI and co-principal investigator of the ARLG. “Combining our efforts will allow us to maximize the work we both do to stop the advancement of antibacterial resistance.”

Both organizations have been working toward the same mission since each launched in 2013, and now, the two groups will share their work to increase synergy and avoid duplicative efforts in clinical research.

“We have already made efforts to expand our reach across Europe, where an increasing number of people suffer from infections caused by antibiotic-resistant bacteria,” said Marc Bonten, MD, coordinator of COMBACTE and a professor at UMC Utrecht. “But by collaborating and sharing our progress with the ARLG, we can make a truly global impact beyond this population — an important consideration in a globally connected era in which epidemics travel across oceans quickly.”

As part of the agreement, the ARLG will have the opportunity to lead and coordinate U.S.-based studies for all clinical research initiated by COMBACTE, while COMBACTE will have the opportunity to lead and coordinate ARLG-initiated projects in Europe.

Earlier this year the European Clinical Research Alliance on Infectious Diseases (ECRAID) was formed, merging COMBACTE’s more than 850 clinical trial sites and 650 laboratories with the network of primary care sites coordinated by The Platform for European Preparedness Against (Re-)Emerging Epidemics (PREPARE) to form a European-wide sustainable clinical research organization for infectious diseases and antimicrobial resistance. The ARLG, with established collaborations in 19 countries, will help to expand these efforts outside of Europe. The alliance will enable innovative, flexible, and adaptive collaboration between the DCRI and UMC Utrecht.

“This is an exciting year for PREPARE to expand its work in reducing a serious public health threat,” said Herman Goossens, MD, coordinator of PREPARE and professor at University of Antwerp and UMC Utrecht. “First, we joined forces with COMBACTE by forming ECRAID, and now, we welcome a partnership with the ARLG, which will help all three organizations leverage a wider set of resources and a deeper pool of expertise.”

The ARLG is supported by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, under Award Number UM1AI104681. COMBACTE-NET, COMBACTE-CARE, and COMBACTE-MAGNET receive support from the Innovative Medicines Initiative Joint Undertaking under grant agreement n° 115523 | 115620 | 115737 resources of which are composed of financial contribution from the European Union Seventh Framework Programme (FP7/2007-2013) and EFPIA companies in kind contribution. COMBACTE-CDI receives support from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement n° 777362 resources of which are composed of financial contribution from the European Union’s Horizon 2020 research and innovation programme, and EFPIA. PREPARE is funded by the European Union’s FP7 Programme n° 602525. ECRAID is funded by the European Union’s Horizon 2020 Programme n° 825715.

ECHO program set to begin expansive child health research

April 9, 2019 – The DCRI serves as the Coordinating Center for the program, which received single IRB approval to proceed with its expansive observational research.

The National Institutes of Health’s (NIH’s) ECHO Program has received single Institutional Review Board (sIRB) approval for its ECHO-wide Cohort Data Collection Protocol, clearing the program to start answering high-impact research questions related to early influences on child health outcomes. The DCRI serves as ECHO’s coordinating center to help the program meet its mission to enhance the health of the nation’s children.

“The ECHO-wide Cohort Data Collection Protocol includes hundreds of interacting variables, and the DCRI played a central role in uniting collaborators to bring it to life,” said the DCRI’s P. Brian Smith, MD, MPH, MHS, who serves as a principal investigator for the ECHO coordinating center. “This sIRB approval gives us the green light to begin ECHO’s important research, delivering answers that will help our nation’s children live happier, healthier lives.”

ECHO is a seven-year NIH-supported program that is trying to better understand the effects of a broad range of influences—including physical, chemical, biological, social, behavioral, natural, and built environments—on child health outcomes. The ECHO-wide Cohort is made up of more than 70 individual cohorts of mothers and children from ongoing research projects. Researchers follow participants through different life stages, some starting before birth and through adolescence. Together, they form a massive virtual “cohort of cohorts” that includes more than 50,000 children from diverse backgrounds across the United States. By bringing together data collected under a single protocol, ECHO researchers can answer high-impact, complex research questions.

While many past research projects have looked at children through a single, narrow lens, the ECHO Program is taking a multidisciplinary approach that will offer a richer understanding of child health and development. Researchers from 44 states, Puerto Rico, and the District of Columbia are involved in the ECHO-wide Cohort Data Collection Protocol.

As ECHO’s coordinating center, the DCRI plays a crucial role in ECHO’s mission. The DCRI is responsible for organizing and managing activities and logistics for all collaborative components of the ECHO Program. Nearly 40 DCRI employees work on ECHO.

“ECHO has a huge scale and an ambitious vision, which is why it is such an important program for the DCRI,” said the DCRI’s Elisabeth Schweins, MS, who serves as project director for the ECHO Coordinating Center. “As ECHO’s Coordinating Center, the DCRI is poised to make a real difference in the lives of children across our nation, uncovering insights that can potentially improve their lives for generations to come. It is an exciting opportunity, and we are eager to get started.”

One of the first steps of protocol implementation is training site staff on the specific measurements in the ECHO-wide Cohort Data Collection Protocol. Consistency in data collection and measurement between cohorts will be critical to obtaining quality data. The coordinating center is committed to supporting the training of site staff and has created an integrated plan of training communications, online Learning Management System modules, and in-person training sessions for site staff to gain necessary protocol experience.

Few people with heart failure take guideline-recommended drug

April 8, 2019 – DCRI researchers found that heart failure patients are much more likely to take a guideline-recommended medication if they are started on the drug while still in the hospital.

Heart failure patients who could possibly benefit from a newer class of drug to lower their heart rate were more likely to take the medication if it was prescribed before hospital discharge rather than in a follow-up doctor’s visit, according to preliminary research presented at the American Heart Association’s Quality of Care and Outcomes Research Scientific Sessions in Arlington, Virginia.

“The hospitalization rate in heart failure patients is quite high despite a number of good therapies, yet we have ivabradine, a relatively new therapy that can reduce hospitalization, and we still aren’t using it to the extent possible,” said the DCRI’s Robert Mentz, MD, lead author of the study (pictured).

When people have heart failure and less than 35 percent of the blood in the heart is pumped out with each contraction (a reduced ejection fraction), having a lower heart rate (less than 70 beats per minute) is associated with better outcomes. Current standard care for heart failure with reduced ejection fraction is to use beta-blocker medications in most patients. Beta-blockers can lower heart rate and have many other beneficial effects that improve outcomes for patients with reduction ejection fraction. Research has shown that adding ivabradine, which works in a different way to lower heart rate, may also be helpful in those patients who have a faster heart rate despite being on the highest dose of beta-blockers they can tolerate.

In 2016, the American Heart Association and the American College of Cardiology issued a focused update to heart failure guidelines to reflect newer medication options, including ivabradine, more recently proven successful in helping improve outcomes for heart failure patients, including reduced re-hospitalization.

The current study, called PRIME-HF, evaluated 104 patients (average age 57.5 years, 36 percent women, 64 percent African American) who had been hospitalized at one of 23 U.S. hospitals with worsening heart failure and were appropriate candidates to receive ivabradine. In the randomized, open-label study, researchers compared rates of medication use six months later between those whose hospital physicians were asked to initiate ivabradine prior to discharge and those whose physicians were instructed to provide usual care with consideration of starting the medication during follow-up visits.

Six months after hospitalization, the researchers found that patients whose physicians were asked to initiate ivabradine prior to discharge:

  • Were far more likely to be using ivabradine (40.4 percent vs. 11.5 percent);
  • Had a greater reduction in heart rate (10 bpm vs. 0.7 bpm, average heart rate 77 bpm vs 86 bpm);
  • Had not reduced their dose of beta-blockers; and
  • Did not develop abnormally low blood pressure or heart rate.

“This was a small study, but it provides important evidence of the safety and efficacy of starting this medication in the hospital period,” Mentz said. “There’s often a tendency to just say, ‘Let’s wait until we see the patient back in the clinic in a couple of weeks after hospital discharge.’ But the reality is that so often things are incredibly busy in the outpatient setting and many patients never get started on the right medications if we delay. Our message is to act now and help patients get the greatest benefits as early as possible.”

Patients in both groups encountered barriers to obtaining ivabradine, with 30.6 percent having trouble getting their initial prescription and 58.1 percent having trouble getting ivabradine at some point during the six-month study. Frequent barriers were high price, insurers declining to pay, and physicians deciding to stop the drug.

“When we designed the trial, we thought that more people would be using this medication in routine practice. The reality has been that adoption of the therapy has been very slow and only a fraction of potential patients are receiving it.” Mentz said. “Some of this is related to cost while some is also related to providers’ lack of familiarity with the medication and how best to use it. We are looking into how we can better support the early adoption of novel therapies in patients with heart failure to improve their outcomes.”

Because of slow recruitment, the study was terminated early, so the sample is too small to assess outcomes such as survival and re-hospitalization.

In addition to Mentz, the study’s authors include Adam D. DeVore, MD; Gudaye Tasissa, PhD; John F. Heitner, MD; Ileana L. Pina, MD; Anuradha Lala, MD; Robert T. Cole, MD; David D. Lanfear, MD; Chetan B. Patel, MD; Mahazarin Ginwalla, MD; Wayne Old, MD; Abraham S. Salacata, MD; Robert Bigelow, PhD; Tim T. Peterson, BS; Gregg C. Fonarow, MD; and Adrian F. Hernandez, MD. Author disclosures are on the abstract.

Amgen funded this investigator-initiated study.

Study finds lower death rates for TAVR centers that do more procedures

April 4, 2019 – The findings could inform a CMS decision on volume as a criterion for Medicare coverage.

Hospitals that perform the highest volume of transcatheter-aortic valve replacement (TAVR) procedures have significantly lower mortality rates than centers that do fewer of the minimally invasive surgeries, according to an analysis by a collaboration that included the DCRI.

The finding, published April 3 in the New England Journal of Medicine, comes as the Centers for Medicare & Medicaid Services is reconsidering the procedure’s coverage parameters, which established a center’s volume as a key criterion for reimbursement.

Approved in 2011, TAVR is largely performed on older patients insured by Medicare, and has grown into a multi-billion-dollar annual industry. As the number of procedures has escalated and the technique and devices have evolved, questions arose over the necessity of volume standards for CMS coverage.

“What we found is that there is still a very real relationship with annual volume and 30-day mortality at the hospital level, even taking into account the new devices and the learning curve that new centers face in the first 12 months of initiating a program,” said lead author and DCRI cardiologist Sreekanth Vemulapalli, MD (pictured).

“TAVR is different from most other cardiac procedures – it’s not a single-person effort,” Vemulapalli said. The procedure involves putting a replacement valve over a damaged aortic valve using a catheter rather than open-chest surgery, similar to the way a stent is placed in coronary arteries. “Patients are evaluated by a surgeon and an interventional cardiologist, and there is usually also a cardiac imaging specialist involved in the procedure. That team approach is very important, which is why we looked at the data from a hospital level.”

Even so, the authors said, the relationship between higher TAVR volumes and lower mortality was also evident at the individual proceduralist level, suggesting that repeated practice does improve outcomes.

Vemulapalli and colleagues launched their analysis last summer after CMS announced it would reevaluate coverage criteria. Using a database called the Transcatheter Valve Registry — which includes all of the commercial procedures in the United States, including those covered by Medicare — the researchers focused on volumes and outcomes from 2015–2017.

This timeframe rooted out earlier procedures that used outdated techniques and devices. The researchers also removed a hospital’s first 12 months of cases to account for the learning curve. More than 500 hospitals were included and segmented into four groups based on volume, from lowest to highest.

Among nearly 100,000 transfemoral TAVR cases included in the analysis, the researchers found that hospitals in the group with the lowest volume had the highest 30-day mortality rate, at 3.19 percent, compared to hospitals in the group with highest volumes at 2.66 percent. This represents a relative reduction in patient mortality of 19.45 percent between the lowest- and highest-volume centers.

“This was the most comprehensive analysis of the outcomes of more than 100,000 people recently receiving TAVR in the U.S.,” said John Carroll, MD, professor of medicine at the University of Colorado School of Medicine and director of Interventional Cardiology at the UCHealth University of Colorado Hospital.

“The results definitively reaffirm an inverse relationship between the volume of procedures and the risk of death following the procedure,” added Carroll, who is also the vice-chair of the STS-ACC TVT Registry Steering Committee. “The study’s conclusive data should be incorporated by CMS in their final coverage policy to provide Americans with the best results from this transformative non-surgical therapy for the increasingly common condition of aortic stenosis, one of the most serious valve disease problems.”

“These findings suggest a clear relationship between the volume of TAVR procedures and death at 30 days, both at the hospital level and at the individual operator level, and should be factored into the CMS revised National Coverage Determination related to TAVR until a validated quality outcome metric can be established,” said co-author Michael Mack, MD. “This relationship held true even after eliminating the first 12 months, meaning this is not just a ‘learning curve.’”

In addition to Vemulapalli, Carroll and Mack, study authors include Zhuokai Li, David Dai, Andrzej S. Kosinski, Dharam J. Kumbhani, Carlos Ruiz, Vinod H. Thourani, George Hanzel, Thomas G. Gleason, Howard C Herrmann, Ralph G. Brindis and Joseph E. Bavaria.

Funding for the study was provided by the Society of Thoracic Surgeons and American College of Cardiology through the National Cardiovascular Data Registry.

Lack of physician guidance, fear of side effects lead to lower statin adherence

March 27, 2019 – Despite national guidelines indicating that statins can lower risk of heart attack and stroke, many patients who could benefit do not take them.

Despite national guidelines indicating that statins can lower risk of heart attack and stroke, many patients who could benefit do not take them. More than half of eligible patients say they were never offered the cholesterol-lowering drugs; the experience of side effects or fear of side effects were reasons for stopping or refusing statins, according to new research by Duke and DCRI researchers in Journal of the American Heart Association.

Corey BradleyAnn Marie NavarStatins lower the amount of low-density lipoprotein (LDL, or “bad” cholesterol) and have been shown to lower the risk of heart attack and strokes. Because statins are proven effective and have a low risk of side effects, guidelines from the American Heart Association/American College of Cardiology recommend doctors use an atherosclerotic and cardiovascular disease risk calculator to give a detailed assessment of a person’s 10-year risk for heart disease and to help create a personalized plan.

“We need to focus our efforts on improving how doctors identify patients who need to be on a statin, and how they present information to patients to ensure that no one is missing the opportunity to improve their heart health,” said Corey Bradley, MD, lead author of the study (pictured left).

To find out whether eligible patients use statins, and why they sometimes decline or discontinue the drugs, researchers surveyed 5,693 adults (average age 68) who participated in a registry for those receiving medical care at a cardiology, primary care, or endocrinology practice.

Researchers found:

  • Of the 1,511 (26.5 percent) who were not currently taking statins, 59.2 percent reported that they had never been offered them.
  • Patients were more likely to report never being offered a statin if they were female (22 percent higher than others), black (48 percent higher than others), or without insurance (38 percent higher than others).
  • Patients seen in cardiology practices were more likely to be offered a statin than those in primary care.

“It is possible that some people did not remember being offered a statin, so we may have over-estimated the percent who were never offered one. However, we believe that if the patient did not remember the conversation, the discussion likely was not an effective one,” Bradley said.

Of the patients who declined (10.1 percent) or discontinued (30.7 percent) statins, the most common reasons given were a fear of side effects and perceived side effects. Compared with statin users, non-users were less likely to believe statins are safe.

“Although there are risks associated with statins, the public fear of side effects is out of proportion to the actual risks,” said the DCRI’s Ann Marie Navar, MD, PhD, senior author of the study (pictured right). “Misconceptions about statins are everywhere and are fueled by false information on the internet. We need better tools to help combat this type of misinformation.”

Despite their concerns, in the survey 59.7 percent of patients who discontinued a statin would consider retrying it.

“Physicians should not hesitate to re-approach the conversation about starting or re-trying statin therapy in patients who could benefit but are currently not on the therapy,” Bradley said.

In addition to Bradley and Navar, the study’s authors included Tracy Y. Wang, MD, MHS, MSc; Shuang Li, MS; Jennifer G. Robinson, MD, MPH; Veronique L. Roger, MD; Anne C. Goldberg, MD; Salim S. Virani, MD; Michael J. Louis, MD, MPH, MSc; L. Veronica Lee, MD; and Eric D. Peterson, MD, MPH.

Sanofi, Regeneron, and the National Heart, Lung, and Blood Institute funded the study.

Large accountable care organizations committed to overhauled Medicare program

March 21, 2019 -Dropout rates for the program remain relatively low among ACOs, researchers found.

While most Accountable Care Organizations (ACOs) have committed to continue participating in the recently overhauled flagship Medicare Shared Savings Program (MSSP), physician-led ACOS are leaving at a higher rate than in 2017, new research from the Duke-Margolis Center for Health Policy and Leavitt Partners shows.

Highlights of this research were published this month in Health Affairs. The DCRI’s Donald Taylor, PhD, is one of the study’s authors.

The most recent tracking showed that more than 1,000 public and private ACOs provide health care coverage to approximately 33 million Americans. In 2018, more than half of these ACOs participated in the Centers for Medicare & Medicaid Services (CMS) MSSP program.

Late last year however, CMS released its Pathways to Success rule, overhauling MSSP, its largest ACO program. The new 2019 MSSP participant list showed that 74 ACOs dropped out of MSSP at the end of 2018, representing 13 percent of participating ACOs.

Duke and Leavitt researchers examined this data to determine the early impact of the new rule, and found:

  • Hospital-led ACOs, which tend to be large, as well as large ACOs of any type, had lower dropout rates at the end of 2018. This early look at new dropouts from the MSSP program suggest the rule is not driving large ACOs out of the program, but rather that they are willing to accept increasing risk for the cost of the care they provide, also known as downside risk.
  • Overall, the ACO dropout rate increased modestly at the end of 2018, in contrast to the two previous years when it decreased.
  • As part of its overhaul of MSSP, CMS assigned different downside risk requirements for high-revenue and low-revenue ACOs to reflect their different capacity to bear risk, and to encourage more small and physician-led ACOs to participate in the program. So far, revenue status does not appear to be consistently correlated with ACO dropout rates, and is not highly correlated with ACO size or physician ownership.
  • Physician-led ACOs, which tend to be smaller, had higher dropout rates than hospital-led ACOs, despite new policies to support low-revenue ACO.  Small physician-led ACOs had the highest dropout rate at the end of 2018, so how well “low revenue” status supports these particular types of ACOs bears close watching.

“If the ACOs leaving were not likely to succeed, or were not seriously engaged in changing care delivery to improve value, then lower participation is not a bad outcome,” said Mark McClellan, MD, PhD, director of the Duke-Margolis Center. “If organizations that were likely to succeed are exiting, especially smaller physician-led organizations that have had promising results to date, then further policy adjustments may be needed.”