Digital Health in Neurosciences

March 21, 2017 -The first Neurosciences Medicine Digital Health Clinical Trials Symposium was held last month in San Francisco.

The DCRI hosted the inaugural Neurosciences Medicine Digital Health Clinical Trials Symposium in San Francisco this February. The agenda included a wide-ranging discussion of the current state of clinical trials for games, apps, and electronic medical devices to diagnose or alleviate symptoms of psychiatric and neurological disorders.

“There are unique challenges in digital health applications for neurosciences medicine, and the genesis of this meeting was the concept of bringing together experts to identify and develop solutions to move the field forward,” said Andrew Krystal, MD, MS, (right) in opening remarks. Krystal is co-director of Neurosciences Medicine at the DCRI; adjunct professor of Psychiatry and Behavioral Sciences at Duke University School of Medicine; and Ray and Dagmar Dolby distinguished professor of psychiatry and vice chair for research in the Departments of Psychiatry and Neurology, University of California San Francisco.

“The DCRI is active in developing diagnostic and treatment interventions for neuropsychiatric conditions, including studies of digital health applications.” Krystal also gave a talk on designing appropriate control devices for trials.

Adam GazzaleyThe keynote presentation, “Neuroscience Meets Technology: A vision of the future of brain health,” was given by Adam Gazzaley, MD, PhD, (left) who is a professor in Neurology, Physiology and Psychiatry at UC San Francisco; founder and executive director of Neuroscape; co-founder and chief science advisor of Akili Interactive Labs; and co-founder and chief scientist of JAZZ Venture Partners. He noted that challenges include the need to better assess and enhance cognition – including elements such as attention, memory, mood, compassion, and empathy – in a meaningful and lasting way.

Other key takeaways from DCRI presentations at the meeting included:

  • There are currently no standard endpoints for psychiatry trials in digital health, and the endpoints used for drug trials may not be appropriate; academia, industry, the Food and Drug Administration, and the National Institute of Mental Health should all work together to address this.
  • There are unique challenges in designing control interventions for digital health apps such as games, since none have been definitively proven to be effective or ineffective. As a result, careful control design is essential to elucidate effects.
  • Many statistical challenges are unique to digital health, and these must be taken into account in innovative trial designs, since “there are no right answers to wrong questions.”
  • Computerized testing has potential in standardizing measurements of cognition. Today, these measurements are based on tests developed in the 1980s, often administered by testers with no psychometric experience, which poses a risk of inaccuracy and inconsistency. This can potentially be addressed via computerization.
  • Technology is moving forward rapidly, but medicine and research are still catching up, mainly due to regulatory issues and trial design limitations. Enhanced recruitment using the web will help reduce the effort required to collect data and the cost of trials, by allowing brick and mortar sites to be added where the patients are, instead of maintaining non-enrolling sites. The electronic medical record has potential as a viable tool for large-scale clinical research, though integration into clinical trial designs and validation of data flow remain issues. There are opportunities to provide standardization of protocol, decision support and automated data capture within the workflows of ongoing clinical care.

nsm crowd panelOther DCRI speakers on the agenda were: Scott H. Kollins, PhD, professor and vice chair for research strategy and development, and director of the Duke ADHD Program, Department of Psychiatry & Behavioral Sciences, Duke University School of Medicine, and global lead for ADHD and SUD, Neurosciences Medicine, DCRI, who examined standard and exploratory endpoints for psychiatry trials in digital health; Roseann White, MA, director, Pragmatic Clinical Trial Statistics, who described biostatistical trial design and the need to power studies properly; Richard Keefe, PhD, professor in Psychiatry and Behavioral Sciences, Duke Institute for Brain Sciences, and Global Cognition Sciences Lead, DCRI, who focused on where cognition fits into trial design; and Brad J. Kolls, MD, PhD, of the Department of Neurology, Duke University School of Medicine, and Clinical Informatics Global Trials Lead, DCRI Neurosciences Medicine, whose presentation focused on capturing data from systems and digital interfaces in clinical trials.

The business side of digital health was discussed by a panel including: Eddie Martucci, CEO, Akili Interactive Labs; Henry Mahnke, CEO, Posit Science; Zack Lynch, general partner, JAZZ Venture Partners; Craig Fischer, vice president of Medical Professional Markets, Pearson; Anand Iyer, chief strategy officer, Welldoc; and Carolyn Jasik, medical director, Omada Health.

A panel discussion addressed the question of “What do emerging digital health companies need to know about business decisions regarding clinical trials?” Key takeaways included:

  • There is no agreed blueprint for digital health clinical trials. A company must identify the most important question, then think two questions ahead and try to get preliminary answers to those, too.
  • Access to patients is a major issue. Many psychiatrists and psychologists are outside of the mainstream health care system.
  • Clinical outcomes open the door in discussions with payers, but the challenge is demonstrating what financial impact these outcomes have and what the intervention does from an efficacy standpoint.
  • The company must understand whom they are delivering the study results to: the needs may be different for the medical community vs. the psychology community. Potential customers should be asked what they need. It is vital to make sure that the study output includes tools and resources.
  • It is essential to understand the value of the product to your customer’s customer. The customer will need to “sell” the product to someone else – such as the government, employers, health care organizations, medical groups, health plans, or patients
  • From venture capital viewpoint, clinical trial results are table stakes. Investors are most concerned about reimbursement on a broad scale and how that will happen.

Participants also had a choice of two breakout sessions, on FDA Guidance on Digital Health, and Business Models 101: Direct-to-consumer, workplace wellness, and the payer model.

DCRI introduces novel app for patients with hypertrophic cardiomyopathy

March 21, 2017 – The app will provide patient information and educational materials about the genetic heart condition.

The DCRI has partnered with cardiology experts to find new ways to inform and engage patients with hypertrophic cardiomyopathy (HCM), a genetic heart condition with an estimated prevalence of 1 in 500 adults.

The new, patient-focused app, called HCM Care, is available for both mobile devices and as a web-based version.  The app features videos of leading HCM clinicians and engaging medical animation to answer common questions faced by HCM patients in key aspects of diagnosis, symptoms, risk assessment, and treatment. It also provides patient education about genetic testing and family screening, and other resources related to research and patient support. MyoKardia, Inc., a clinical stage biopharmaceutical company focusing on novel therapeutics for genetic cardiovascular disease, sponsored development of HCM Care.

Patients with HCM typically have abnormal thickening of the heart muscle. There is a wide spectrum of clinical symptoms, risk, and treatment considerations among HCM patients. Some patients may be asymptomatic, while others have severe symptoms such as shortness of breath, chest pain or fainting; a small percentage of patients have life threatening heart arrhythmias. Advancements in diagnosis and treatment have led to improved outcome for HCM patients.

“Many patients have important concerns and don’t know where to look for information about this condition,” said the DCRI’s Andrew Wang, MD, who led the app’s development team. “HCM Care is based on actual questions that are frequently asked by HCM patients. We hope that this will better inform patients and their families before and after they see a cardiologist about HCM.”

“MyoKardia is thrilled to support this fresh and innovative approach to patient education,” said Marc Semigran, MD, MyoKardia chief medical officer. “The clinicians at DCRI and leading HCM centers have created an exciting and empowering resource that is much needed in the HCM community.”

Patients can download the free app from the Apple or Android app stores or can use the web-based version at

ACC 2017: Surgically sealing heart pouch in AF patients appears to reduce strokes, death

March 19, 2017 – The procedure could help atrial fibrillation patients who cannot tolerate anticoagulants.

People with an irregular heart rhythm known as atrial fibrillation are prone to blood clots that form in the heart and travel to the brain, causing a stroke.

In about 90 percent of these thromboembolic strokes, clots originate in a small pouch on the heart wall called the left atrial appendage. Surgeons and cardiologists sometimes remove or close the appendage to eliminate this source of blood clots.

Although closure of the left atrial appendage has been shown to be safe, the procedure remains controversial and evidence of its effectiveness has been inconclusive.

Now a team led by DCRI researchers has found that surgically sealing the pouch at the time of other cardiovascular surgeries is associated with fewer strokes from blood clots in older patients with atrial fibrillation.

“While our study was not a randomized trial, it does demonstrate strong support for the benefits of closing the left atrial appendage at the time of cardiac surgery in patients with atrial fibrillation,” said Daniel J. Friedman, MD (pictured left), a cardiology research fellow at the DCRI and lead author of a study presented on March 19 at the American College of Cardiology 66th Annual Scientific Session meeting in Washington, D.C..

Atrial fibrillation affects between 3 million and 6 million U.S. adults. Anticoagulation drugs such as warfarin are effective in managing blood clots in these patients, but more than half of them do not take the drugs for a variety of reasons, including the risk of bleeding.

Low rates of oral anticoagulant use have driven interest in other ways to control clotting, including sealing off the left atrial appendage either with a catheter through a vein in the leg or surgically during a cardiac procedure.

In the Duke-led study, researchers focused on the surgical approach. They used the Society of Thoracic Surgeons National Database to identify more than 10,000 Medicare recipients with atrial fibrillation undergoing cardiac surgery. Patients were predominantly male (61 percent), had a median age of 76, and were at high risk for stroke.

In 37 percent of cases, patients underwent the additional surgery to close off the appendage in a procedure called left atrial appendage occlusion, or LAAO. This group of patients tended to be in better cardiovascular health than those who did not undergo the surgical LAAO.

After statistically adjusting for these differences, the research team found that the surgical LAAO procedure was associated with a 40-percent reduction in thromboembolism and a 15-percent reduction in all-cause death after one year. Additional analyses demonstrated that the lower risk of thromboembolism occurred predominantly among patients who were discharged from the hospital without blood thinners.

“Our study suggests that surgical left atrial appendage occlusion appears safe regardless of whether patients received anticoagulation therapy after discharge, and it could be particularly beneficial for patients who cannot take anticoagulation therapies for medical reasons,” Friedman said.

“Patients scheduled to undergo open heart surgery should talk with their surgical teams about closure of the left atrial appendage,” said principal investigator J. Matthew Brennan, MD, an interventional cardiologist in Duke’s Division of Cardiology and member of the DCRI (pictured right). “Particularly among patients with atrial fibrillation, this may be one of the most effective available treatments to prevent future strokes. Until randomized trials are available, this study will represent the strongest available data in this field.”

The authors note that the study was limited by its use of Medicare data, which included only older adults. It also had a non-randomized design, and was unable to identify the method used to seal the appendage or to gauge the success of the procedure. Randomized studies are needed to determine whether anticoagulation can be safely withheld in patients who have had successful surgical LAAO.

In addition to Friedman and Brennan, study authors include Jonathan P. Piccini, Tongrong Wang, S. Chris Malaisrie, David R. Holmes, Rakesh M. Suri, Michael J. Mack, Vinay Badhwar, Jeffrey P. Jacobs, Jeffrey G. Gaca, Shein-Chung Chow and Eric D. Peterson.

The study received funding support from the Food and Drug Administration (1U01FD004591-01), and an Innovation in Regulatory Science Award from Burroughs Welcome Fund (1014158). Friedman is funded by the National Institutes of Health T 32 training grant (HL069749).

ACC 2017: Common heart drug digoxin appears to heighten death risk in AF patients

March 19, 2017 – DCRI-led study concludes people with atrial fibrillation should not take the drug.

Amid growing uncertainty about the safety of digoxin — a commonly used heart drug — a study led by DCRI found that people with atrial fibrillation should avoid taking the drug because starting this medication is associated with higher death rates.

The finding was reported Sunday at the American College of Cardiology 66th Annual Scientific Session meeting in Washington, D.C..

“Although its general use has declined over the past 30 years, digoxin is still used by as many as one-third of atrial fibrillation patients worldwide,” said lead author Renato D. Lopes, MD, PhD, professor of medicine and member of the DCRI (pictured). “There have been several studies questioning the safety of this drug in patients with atrial fibrillation, and different analyses looking at different questions have shown conflicting results. Yet current guidelines still have digoxin as a treatment option for patients with atrial fibrillation.

“Our study provides a strong, comprehensive, and up to date evidence — short of a randomized, control trial — that starting digoxin is associated with an increased risk of death in patients with atrial fibrillation,” Lopes said. Digoxin is generally used to strengthen the heart’s contractions and to control the heart rate.

Lopes and colleagues analyzed data from a large, international clinical trial called ARISTOTLE, which was undertaken to compare warfarin to apixaban

as a stroke prevention for patients with atrial fibrillation.

In a subsequent analysis to examine whether digoxin was associated with mortality, the researchers examined deaths from all causes, including cardiovascular and non-cardiovascular deaths among a total of 17,897 atrial fibrillation patients in the database.

Of those patients, 5,824 (32.5 percent) were on digoxin at the start of the study, and 6,693 (37.4 percent) had heart failure. Another 873 patients (6.9 percent) started the drug at some point during the study.

The researchers found that in patients already receiving digoxin and, therefore more likely to tolerate it, the overall relationship between digoxin use and death was non-significant. However, even among those patients, the risk of death was related to digoxin concentration in the blood: for every 0.5 nanograms per milliliter increase in the blood level of digoxin, the risk of death rose by 19 percent. Among patients whose digoxin levels were greater than 1.2 ng/mL, the death rate significantly increased by 56 percent.

“Additionally, death risks — and particularly sudden death — were substantially higher in patients who began digoxin after the start of the study,” Lopes said. “Most of the deaths occurred in the first six months after digoxin was initiated.”

Lopes said the full scope of the study and its independent findings add up to the conclusion that the drug should not be used by patients with atrial fibrillation, particularly if symptoms can be alleviated with other treatments. He added that in atrial fibrillation patients already taking digoxin in whom treatment is deemed necessary, monitoring digoxin serum concentration is important to ensure that blood levels stay below 1.2ng/mL. 

“Although our study results speak in favor of causation between digoxin use and increased risk of death, this is an observational study, and causation cannot be definitively established,” Lopes said.

“Definitively determining the efficacy and safety of digoxin in patients with atrial fibrillation would require a large and well-powered randomized trial,” Lopes said. “Until then, our finding that digoxin may be causing more harm than good in patients with atrial fibrillation is important and could help guide physicians in their clinical decisions when managing these patients.”

In addition to Lopes, study authors include Roberto Rordorf, Gaetano M. De Ferrari, Sergio Leonardi, Laine Thomas, Daniel M. Wojdyla, Peter Ridefelt, Jack Lawrence, Raffaele De Caterina, Dragos Vinereanu, Michael Hanna, Greg Flaker, Sana M. Al-Khatib, Stefan Hohnloser, John H. Alexander, Christopher B. Granger and Lars Wallentin, for the ARISTOTLE committee and investigators.

Bristol-Myers Squibb and Pfizer funded the ARISTOTLE trial. The current analysis was supported by the DCRI, Bristol-Myers Squibb, and Pfizer.

ACC 2017: Quality of care may improve quality of life in AF patients in Japan, says first of its kind study

March 19, 2017: Adherence to updated AHA/ACC atrial fibrillation performance measures might lead to improvement of patients’ quality of life in Japan, but warrants further study, say researchers.

A recent study by DCRI researchers presented at the annual ACC conference in Washington, D.C. aimed to explore whether compliance to updated American Heart Association/American College of Cardiology (AHA/ACC) quality measures will lead to improved outcomes and better quality of life in patients with atrial fibrillation (AF) in Japan.

AF is the most common sustained arrhythmia in adults in the United States and around the world, impairing both functional status and quality of life of those affected. In countries like Japan, where no instruments or measures exist for evaluating the quality of care for patients with AF, it can be difficult to assess and implement means to improve the care of these patients.

“Being able to manage AF appropriately is a pressing public health challenge in Japan,” said DCRI Fellow Taku Inohara, MD, lead author of the study. “Due to a lack of indicators evaluating the quality of care for patients with AF in the country, we evaluated the 2016 AHA/ACC clinical performance and quality measures and their association with clinical outcomes and quality of life for AF patients in Japan.”

Measure sets developed by the ACC/AHA are intended to provide practitioners and institutions tools to measure the quality of care provided and identify opportunities for improvement. While they have been developed in the context of the U.S. health system, they can also be applied in other countries, since measures for high quality care do not vary based on the country they are studied or implemented in.

To assess the quality of AF care in Japan, investigators evaluated adherence with the AF performance measures based on the 2016 AHA/ACC criteria in the Japanese KiCS-AF multicenter outpatient AF registry.

“The Keio Inter-hospital Cardiovascular Studies for AF (KiCS-AF) is a clinician-initiated, prospective, 10-center, outpatient AF registry designed to collect clinical variables and outcome measures for AF patients,” Inohara said.

With its coordinating center at Keio University in Tokyo, it currently enrolls around 2000 patients, all diagnosed with AF within the last six months.

The researchers also assessed the association between adherence to these guidelines with clinical outcomes and quality of life using the Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire, which is a 20-item survey using 7-point response scales, which measures AF-specific quality of life.

In this study, the patient was deemed ‘adherent’ when all applicable components of the performance measures for outpatient settings were satisfied. The researchers found that among 1,874 patients with AF, a total of 863 patients were fully adherent to the AF performance measures. Adherence was more frequently achieved in patients managed with rhythm control compared with rate control alone.

After a one-year follow-up, it was also found that the AFEQT global scores were likely to be higher in adherent patients compared with non-adherent patients. The “Treatment Concern” and “Satisfaction” sub-domains in AFEQT were also significantly improved during the follow-up.

“This means that high quality of care according to performance measures might provide patients with a deeper understanding about their disease and facilitate shared decision-making,” Inohara said.

According to Inohara, there is an important opportunity to improve the quality of care in patients with AF in Japan and though this study demonstrates that adherence to the AF performance measures might lead to the improvement of patients’ quality of life, further and more in-depth studies are needed to evaluate its association with clinical outcomes.

In addition to Inohara, other researchers included Shun Kohsaka, Takehiro Kimura, Ikuko Ueda, Nobuhiro Ikemura, Mitsuaki Sawano, Kazuaki Nakajima, Shin Kashimura, Akira Kunitomi, Yoshinori Katsumata, Takahiko Nishiyama, Nobuhiro Nishiyama, Yoshiyasu Aizawa, Keiichi Fukuda and Seiji Takatsuki.

ACC 2017: Drug could reduce serious complication in cardiac bypass patients

March 19, 2017 – Researchers found that levosimendan did not reduce short-term incidences of death, but did reduce incidence of low cardiac output syndrome.

Patients undergoing cardiac surgery that requires use of a heart-lung machine can see complications afterwards. Some experience low cardiac output syndrome (LCOS), in which their heart is unable to pump enough blood to properly supply their organs, making them susceptible to heart attack, death and other risks.

John Alexander

A study led by researchers at the DCRI found that the drug levosimendan did not reduce the combined short-term incidences of death, kidney failure, myocardial infarction or use of a mechanical assist device among high-risk patients undergoing cardiac surgery on bypass machines. However, levosimendan did reduce the incidence of low cardiac output syndrome and could be a safe alternative to other drugs that aim to improve the heart’s pumping function. Levosimendan is widely used in Europe, but is not approved for use in the United States.

The findings were presented Sunday at a late-breaking session at the American College of Cardiology 66th Annual Scientific Session in Washington, D.C. and published simultaneously in the New England Journal of Medicine. They are based on a randomized study of 882 patients from 70 medical centers in the United States and Canada.

Prior to cardiac bypass surgery, each patient’s left ventricular ejection fraction, one measure of how much blood the heart is pumping, was 35 percent or less. Such levels indicate preexisting, reduced pumping function, which is associated with the development of LCOS.

“Given the substantial morbidity and mortality of patients who develop LCOS following surgery, understanding how to safely treat or prevent the condition is critically important,” said John Alexander, MD, the study’s senior author and member in the DCRI (pictured).

In addition to Alexander, study authors include Rajendra Mehta, Jeffrey D. Leimberger; Sean Van Diepen, James Meza, Alice Wang; Rachael Jankowich; Robert W. Harrison; Douglas Hay; Stephen Fremes; Andra Duncan; Edward G. Soltesz; John Luber; Soon Park; Michael Argenziano, MD; Edward Murphy; Randy Marcel; Dimitri Kalavrouziotis; Dave Nagpal; John Bozinovski; Wolfgang Toller; Matthias Heringlake; Shaun G. Goodman; Jerrold H. Levy; Robert A. Harrington; and Kevin J. Anstrom.

TENAX Therapeutics supported the study. The authors report no financial conflicts.

ACC 2017: Study supports safety and effectiveness of TAVR in real-world patients

March 18, 2017 – Patients with lung disease or who have undergone previous heart surgery may also derive additional benefits from TAVR.

A new study by DCRI researchers found no significant difference in rates of death, stroke, or days alive and out of hospital to one year in intermediate- and high-risk patients treated with transcatheter aortic valve replacement (TAVR) and those receiving surgical aortic valve replacement (SAVR).

The results of this study, based on data from the Transcatheter Valve Therapies Registry and Society of Thoracic Surgeons National Database linked to Medicare administrative claims for follow-up, were presented on Saturday at the 66th annual Scientific Sessions of the American College of Cardiology (ACC), in Washington, D.C..

Patients receiving TAVR, a minimally invasive surgical procedure for aortic stenosis, were more often discharged directly to home, reflecting a less demanding post-operative recovery. These findings were consistent across most patient subgroups, including those with the full spectrum of intermediate to high pre-operative surgical risk. The study – led by the DCRI’s J. Matthew Brennan, MD, MPH, assistant professor of medicine at the Duke University School of Medicine (pictured) – examined a broad cohort of 9,464 intermediate- and high-risk patients in the United States with severe aortic stenosis who were eligible for treatment with either TAVR or SAVR.

“Our primary finding was that TAVR does appear to be safe and effective in patients at moderate and high risk, which is consistent with randomized data,” Brennan said. “The overall risk of stroke was low, reflecting device improvements. Our analysis also found that patients with significant lung disease and prior cardiac surgery might derive additional benefit from TAVR, rather than SAVR, for selected outcomes. These highly credible findings underscore the importance of meticulous methodology when evaluating treatment effects using non-randomized data.”

The results largely echo those of three previous randomized clinical trials, and support the safety and effectiveness of TAVR in unselected real-world patients. They counter those of a German Aortic Valve Registry (GARY) study suggesting that patients treated with TAVR might have a higher one-year risk of mortality compared with those receiving SAVR.

The treatment of aortic valve disease is developing rapidly, with ongoing modifications in device technology for both minimally invasive SAVR and TAVR. As devices continue to evolve, the relative risks and benefits of the two procedures may change. Diligent monitoring of outcomes will continue to help direct future device innovation in this field.

This analysis was a part of a larger effort – the ADVICE Trial – to help patients, caregivers and their providers to understand the risks and benefits of these two treatment options in real-world clinical practice. An educational website ( and a decision assistance tool are being launched at the ACC meeting to use ‘big data’ to personalize the treatment of aortic valve disease. The decision assistance tool will give patients their individualized one-year risks of death, stroke, days alive and out of hospital, and likelihood of discharge to home with SAVR or TAVR. The tool is available as a mobile app and a web-based tool.

In addition to Brennan, Duke authors on the ACC paper were: David Dai, PhD; Laine Thomas, PhD; Alice Wang, MD; Sean O’Brien, PhD; Roland Matsouaka, PhD; Michael Pencina, PhD; and Eric Peterson, MD, MPH, FAHA, FACC.

This research was funded through a Patient-Centered Outcomes Research Institute (PCORI) Award (CER-1306-04350).

ACC 2017: Study compares use of fractional flow reserve with instantaneous wave-free ratio in PCI

March 18, 2017 – Compared with angiography alone, FFR-guided revascularization improves patient outcomes after PCI.

A new study involving a DCRI researcher found similar clinical outcomes in coronary revascularization guided by instantaneous wave-free ratio (iFR) and by fractional flow reserve (FFR), based on major adverse cardiac events at one year.

The study results were presented on Saturday at the 66th annual Scientific Sessions of the American College of Cardiology (ACC), in Washington, D.C., and published simultaneously in the New England Journal of Medicine.

Compared with angiography alone, FFR-guided revascularization improves patient outcomes after percutaneous coronary intervention (PCI). FFR helps assess whether narrowing in coronary arteries – which can interfere with blood flow and cause chest pain – require treatment.  However, this approach requires the administration of a drug, adenosine, which adds cost and time to the procedure, and may be unavailable in some countries. As a result, despite the clear health and healthcare costs benefits of FFR, this approach is currently used in fewer than 10 percent of revascularization procedures. As a new technique that does not require adenosine, iFR holds promise in delivering improved outcomes to a much larger patient population.

“This represents a substantial advance for the management of patients with coronary disease using an invasive technique that will better allow us to ensure that the right patient gets the right treatment,” said the DCRI’s Manesh R. Patel, MD, associate professor of medicine and chief of the Division of Cardiology (pictured). “The study was an international collaboration that showed our ability to rapidly enroll patients in clinical trial to compare iFR with FFR.”

In the Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation (DEFINE-FLAIR) study, 2,492 patients with coronary artery disease were randomized 1:1 to either iFR-guided or FFR-guided coronary revascularization. The primary end point was the composite of major adverse cardiac events, defined as the composite of all-cause mortality, non-fatal myocardial infarction or unplanned revascularization, at one year. The trial was designed to demonstrate non-inferiority of iFR to FFR.

At one year, the primary end point occurred in 78 patients (6.79 percent) in the iFR group and 84 patients (7.02 percent) in the FFR group. There were no statistically significant differences between groups for the components of the primary end point or for cardiovascular or noncardiovascular death. Rates of adverse procedural symptoms and clinical signs and procedural time were significantly lower in the iFR arm than the FFR arm, showing potential for improved efficiency with iFR.

ACC 2017: Study finds patients with new-onset AF following TAVR have worse outcomes

March 18, 2017 – Less than half of new AF patients were discharged with oral anticoagulation.

A study by DCRI researchers found that 8.4 percent of 13,559 patients who received transcatheter aortic valve replacement (TAVR), a minimally invasive surgical procedure for aortic stenosis, developed new-onset atrial fibrillation (AF), a common type of heart arrhythmia.

Additionally, only 28.9 percent of new AF patients were discharged on oral anticoagulation, which is often prescribed to reduce the risk of stroke associated with atrial fibrillation. In-hospital mortality and stroke were significantly higher among patients developing post-procedure AF compared with those who did not. At one year, rates of death, stroke, and bleeding were high among patients with post-TAVR AF, and the differences persisted even after multivariable adjustment.

These results were presented on Saturday at the 66th annual Scientific Sessions of the American College of Cardiology (ACC), held in Washington, DC.

“The study showed that new-onset atrial fibrillation after TAVR is common, with low rates of anticoagulation at discharge, and an increased risk of in-hospital and one-year mortality and stroke,” said lead author and DCRI cardiology fellow Amit N. Vora, MD, MPH (pictured). “Management strategies for these high-risk patents seem to be variable, highlighting the need for additional studies to define the optimal antithrombotic strategy to improve outcomes.”

The study used data from the Society for Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (STS/ACC TVT) Registry, linked with Medicare data for patients undergoing TAVR from 2011-2015, and who developed post-procedure AF. Patients with AF prior to TAVR were excluded. Outcomes of interest included in-hospital mortality and stroke and all-cause mortality, stroke, and bleeding at 12 months.

In addition to Vora, Duke researchers on the paper were: David Dai, PhD; Roland Matsouaka, PhD; J. Kevin Harrison, MD; G. Chad Hughes, MD; Matthew Sherwood, MD; Jonathan Piccini, MD; Eric Peterson, MD, MPH, FAHA, FACC; and Sreekanth Vemulapalli, MD.

ACC 2017: Blood thinner and aspirin show similar bleeding risk in coronary patients

March 18, 2017 – A new study is a first step in potentially expanding post-ACS treatment.

Substituting rivaroxaban for aspirin in patients with acute coronary syndromes (ACS) appears to cause no significant increase in bleeding risk, according to a study led by scientists from the DCRI and Harvard Medical School.

The findings of the Phase 2 GEMINI ACS 1 study — presented Saturday at the American College of Cardiology 66th Annual Scientific Session in Washington, D.C., and simultaneously published in the journal The Lancet — are based on a randomized study of 3,037 patients with ACS.

Acute coronary syndrome is characterized by reduced blood flow to the heart, including heart attack or unstable angina. Standard treatment includes a regimen of aspirin and antiplatelet drugs such as ticagrelor or clopidogrel. Some patients, however, cannot tolerate aspirin, and for others, the dual therapy doesn’t prevent complications.

“We wanted to examine if we could substitute a blood thinner for aspirin in the standard regimen and achieve better or similar outcomes. If so, it could open up new treatment avenues,” said E. Magnus Ohman, the study’s co-lead author and member of the DCRI (pictured). Ohman and Michael Gibson, MD, of Harvard Medical School, led the study.

Study patients were randomly assigned to take either rivaroxaban or aspirin in addition to an antiplatelet drug within 10 days of presenting with ACS. The therapy was continued for six to 12 months.

Researchers sought to determine whether rivaroxaban caused more bleeding than aspirin as a component of the dual therapy. They found no statistically significant difference in bleeding rates among the rivaroxaban group (5.3 percent) and the aspirin group (4.9 percent).

“This study is important because it is the first where aspirin has been removed within the first few days after patients experienced ACS and replaced with another anti-clotting drug,” Ohman said. “Finding that bleeding profiles were the same in both study groups is an exciting first step towards expanding post-ACS treatment.”

Ohman noted that the trial was exploratory and further studies are needed to evaluate how the regimens compare in preventing stroke, heart attack and death.

Study co-authors include Matthew T. Roe; Gabriel Steg; Stefan K. James; Thomas J. Povsic; Jennifer White; Frank Rockhold; Alexei Plotnikov; Hardi Mundl; John Strony; Xiang Sun; Steen Husted; Michal Tendera; Gilles Montalescot; M. Cecilia Bahit; Diego Ardissino; Héctor Bueno; Marc J. Claeys; Jose C. Nicolau; Jan H. Cornel; Shinya Goto; Robert Gabor Kiss; Ümit Güray; Duk-Woo Park; Christoph Bode; and Robert Welsh.

Janssen Research & Development, LLC (Janssen) and Bayer AG funded the study. Some authors report financial relationships with the sponsors. Full disclosures are available in the study’s manuscript.