DCRI Early Phase Unit tests broad-spectrum influenza vaccine

March 20, 2018 – Researchers say the vaccine could be effective against multiple strains of the virus for several years.

The Duke Early Phase Clinical Research (DEPRU) recently completed the first study cohort for a broad-spectrum investigational influenza vaccine that has the potential to be effective against multiple strains of the virus for five or more years at a time.

Thirty-seven adult study volunteers, 22 of whom were confined in the unit simultaneously for approximately one week, will be followed for 15 months after immunization as part of the multi-center, randomized, observer-blind phase I safety and immunogenicity study. The volunteers are part of a larger group of up to 55 volunteers spread across two clinical sites at the DEPRU and Cincinnati Children’s Hospital Medical Center. The study is sponsored by the international nonprofit PATH, and the investigational vaccine was developed through a partnership between the Icahn School of Medicine at Mount Sinai (ISMMS) and PATH, the study’s sponsor.

“There are several reasons why you get an influenza vaccine every year,” said Chip Walter, MD, Duke Clinical Vaccine Unit director and co-investigator on the study (pictured left). “One is that strains change from year to year and the protection isn’t durable. I think this is a step toward finding a vaccine that is broadly cross-protective. If the technology is successful, the vaccine will protect against seasonal influenza strains and pandemic influenza strains that jump species from animals to humans.”

The United States is in the midst of its worst influenza season in almost a decade. Although most people will make a recovery within a week, there has been a large number of hospitalizations and pediatric deaths this season. The annual influenza vaccine can provide protection to those who get it before they are exposed to the virus. However, the effectiveness of the vaccine depends on whether it is properly matched against the season’s circulating strains of the virus.

Current vaccines are designed to create antibodies to specific strains of the virus to build the body’s immunity before they strike. This is one of the reasons why the effectiveness of the annual vaccines can range from 60 percent to 10 percent. Once an individual has been exposed to the virus, it enters the respiratory tract cells via a protein on the surface known as the hemagglutinin molecule, the universal vehicle among influenza strains.

Developed at ISMMS, the investigational vaccine utilizes a technology which combines two different protein segments of the hemagglutinin to engineer a new protein. This new, chimeric hemagglutinin redirects the immune system to target sites that are conserved and do not change every year. The study has five treatment groups testing two different combinations of a live Jeff Guptillattenuated virus, which is a weaker form of the virus, and an inactivated split influenza vaccine with or without an adjuvant to potentially boost immune response.

“One of the potential benefits of this investigational vaccine is that at least in animal studies so far, it does generate a long-lasting immune response which means we may not have to get vaccinated every year,” said Jeff Guptill, MD, DEPRU associate faculty director (pictured right). “It could be much less frequently.”

“This study really is a testament to the outstanding coordinators and staff we have here,” Guptill said. “Their dedication and capability to manage the very detailed logistics required of such a complex study is commendable. This study would also not be possible without study volunteers who are willing to participate, and we are very fortunate to have a large study population eager to conduct clinical trials with the DEPRU.”

Participating volunteers will continue to check-in with the DEPRU over the next year so researchers can better understand outcomes following the investigational vaccine. They also receive a booster vaccine of the inactivated virus as part of their participation. Results of this study will inform future studies of the investigational vaccine, potentially leading to a broader spectrum or universal influenza vaccine.

ACC 2018: 30-day Risk-Standardized Mortality Rate may be useful hospital performance metric

March 12, 2018 – DCRI researchers call for increasing the focus on 30-day RSMR to improve long-term clinical outcomes for heart failure patients.

Adrian HernandezA late-breaking clinical trial presented today by DCRI researchers at this year’s annual American College of Cardiology conference in Orlando, Florida, evaluated the association of hospital-specific 30-day Risk-Standardized Mortality Rate (RSMR) with long-term mortality among patients hospitalized with heart failure (HF) in the American Heart Association Get With The Guidelines–HF registry.

The results were published simultaneously in JAMA Cardiology.

Get With The Guidelines (GWTG) is a hospital-based quality improvement initiative designed to close the treatment gap in cardiovascular disease, stroke, and resuscitation and includes modules in coronary artery disease, heart failure, atrial fibrillation, stroke and resuscitation. Created by the American Heart Association and American Stroke Association, GWTG collects millions of patient records from U.S. hospitals, creating vast databases for advancing scientific research.

GWTG-HF was created for improving care of patients with HF by promoting consistent adherence to the latest scientific treatment guidelines. HF is the leading cause of hospitalization among Medicare beneficiaries in the United States and is associated with considerable risk of morbidity and mortality.

According to researchers, among patients hospitalized with HF, the long-term clinical implications of hospitalization at hospitals based on 30-day RSMRs was not previously known. Hospital 30-day all-cause RSMR following HF hospitalization, is a measure that estimates a hospital-level, 30-day mortality rate for patients discharged from the hospital with a principal diagnosis of HF. Mortality is defined as death from any cause within 30 days from the start of admission.

“While the focus nationally has been on how to reduce hospital readmissions after heart failure, the greater gain may be towards improving survival,” said DCRI’s Adrian Hernandez, MD, director of Health Services and Outcomes Research. “With this study, our overall goal was looking at long-term survival after a hospital admission for heart failure, and if patients discharged from hospitals that have 30-day lower risk of mortality, also have better long-term outcomes,” he said.

Recent years have seen heightened focus on readmission of HF patients to the hospital, and hospitals with high 30-day readmission rates face financial penalties. However, readmissions are a complex metric, with many readmissions being avoidable, and their association with long-term patient outcomes questionable.

“There’s been a lot of efforts to reduce the variation in HF readmissions as a quality of care indicator,” said Hernandez, “The key question is whether there is any relationship to what hospitals do for the health of patients with heart failure 30 days after discharge has any impact on long-term outcomes.” According to Hernandez, this study reinforces that, “as opposed to only paying attention to readmissions, we should pay much more attention to early mortality as a performance metric.”

The longitudinal study included 106,304 HF patients 65 years and older, admitted to 317 centers participating in the GWTG-HF registry between January 2005 and December 2013 and had Medicare-linked follow-up data. The researchers calculated hospital-specific 30-day RSMR and assessed the association of 30-day RSMR-based hospital groups with long-term mortality using adjusted Cox models, which provide an estimate of the treatment effect on survival, after adjustment for other explanatory variables.

The study found that hospitals in the low 30-day RSMR group had greater availability of advanced HF therapies, cardiac surgery, and percutaneous coronary interventions. Compared with patients admitted to hospitals with low 30-day RSMRs, patients at hospitals with high 30-day RSMRs had 14 percent higher risk-adjusted relative risk of 5-year mortality, meaning that lower hospital-level 30-day RSMR was found to be associated with greater 1-year, 3-year, and 5-year survival for patients with HF.

According to researchers, these differences in 30-day survival continued to accumulate beyond 30 days and persisted long term, suggesting that 30-day RSMR may be a useful performance metric to incentivize quality care and improve long-term outcomes in patients hospitalized with HF.

The study found the survival advantage associated with treatment at hospitals with lower 30-day RSMR to be durable over time, independent of mortality differences within the first 30 days. The sum of these findings, according to researchers, highlight the need to increase the focus on 30-day RSMR as a performance metric to motivate quality care and to improve long-term clinical outcomes for patients with HF.

In addition to Hernandez, other researchers included Ambarish Pandey, Kershaw V. Patel, Li Liang, Adam D. DeVore, Roland Matsouaka, Deepak L. Bhatt, Clyde W. Yancy, Paul A. Heidenreich, James A. de Lemos and Gregg C. Fonarow.

ACC 2018: First study of staff CPR in dialysis clinics finds rates sub-optimal

March 12, 2018 – CPR by dialysis clinic staff was associated with a three-fold increase in odds of survival to hospital discharge.

Hemodialysis patients are one of the highest risk groups for out-of-hospital cardiac arrest (OHCA), which occurs 20 times more frequently than in the general population, accounting for more than 25 percent of all hemodialysis patient deaths. Sudden cardiac arrest events occur frequently within outpatient dialysis facilities, where up to 23 percent of all OHCAs take place. Earlier reports suggest that only 56 percent of patients with dialysis clinic OHCA survive to hospital admission, and only 8 percent are alive after one year.

Patrick PunIn a new analysis of 400 cases of cardiac arrest at dialysis clinics, staff initiated CPR prior to emergency medical services or first-responder arrival in 81.3 percent of events and initiated automated external defibrillator (AED) application in 52.6 percent of events.

The findings were presented Monday at the American College of Cardiology 67th Annual Scientific Session in Orlando, Florida.

These cases are included in the Cardiac Arrest Registry to Enhance Survival (CARES) comprehensive prospective registry of patients with OHCA, coordinated by Emory University. Data were collected between 2010 and 2016 from 71 participating counties in North Carolina (covering a population of around 8 million) and nine metropolitan Atlanta counties in Georgia (with a population of 5.2 million).

“It’s reassuring that bystander CPR improves outcomes in dialysis clinics just as it does in other settings, but it’s also concerning that the rate of dialysis staff-initiated CPR isn’t closer to 100 percent considering that all staff should be CPR-trained,” said lead author Patrick Pun, MD, MHS, associate professor of medicine and nephrology.

“We found that dialysis staff initiated CPR three times more often when they directly witnessed the cardiac arrest,” he said. “This suggests that improved monitoring of hemodialysis patients during and directly after dialysis could improve outcomes for out-of-hospital cardiac arrest. Further research is needed into understanding what other facilitators and barriers to CPR exist in the unique environment of the dialysis clinic.”

Dialysis staff-initiated AED application was not associated with improvement in outcomes, which could be due to the fact that 66 percent of patients presented with an unshockable heart rhythm.

In addition to Pun, Duke authors of the presentation included Matthew Dupre, PhD; Monique Anderson, MD; Clark Tyson; James Jollis, MD; and Christopher Granger, MD.

ACC 2018: Physician judgment more accurate than traditional risk score in predicting coronary artery disease

March 12, 2018 – Integration of physician judgment and risk estimation may optimize stable chest pain evaluation.

Suspected coronary artery disease (CAD) is one of the most common, potentially life-threatening diagnostic problems encountered by clinicians. Informal physician judgment is often used to estimate risk and guide treatment in these patients. However, the relationship between physician estimates and guideline-recommended scores to predict CAD, such as Diamond-Forrester (D-F), was not known.

A study led by DCRI researchers evaluated 4,533 patients with stable chest pain who underwent computed tomography (CT) coronary or invasive angiography in the PROspective Multicenter Imaging Study for Evaluation of chest pain (PROMISE) trial. This randomized, pragmatic comparative effectiveness trial included stable, symptomatic outpatients without known coronary artery disease referred for noninvasive testing at 193 sites in North America. The median follow-up time was 25 months.

Researchers categorized a priori the pre-test likelihood of obstructive CAD for each patient; D-F estimates were also calculated. Overall, the agreement rate between the physician and D-F estimates was poor.

The findings were presented today at the American College of Cardiology 67th Annual Scientific Session in Orlando, Florida.

Compared to the D-F score, physician judgment more accurately identified obstructive CAD and worse patient outcomes. The highest and lowest rates of obstructive CAD – and the highest rates of death, myocardial infarction and unstable angina – were in patients with physician and D-F agreement.

“We believe this is the first study to show that physician judgment in CAD is more accurate than the use of risk scores, and that this was associated with fewer events,” said lead author Christopher Fordyce, MD, a former cardiology fellow at the DCRI who is now clinical assistant professor in the Division of Cardiology at the University of British Columbia. “From the physician standpoint, this validates the need to take into account all available information for each patient, rather than rely on a risk score alone.

“This analysis confirms that clinical expertise still has a very important role in evaluating patients,” noted senior author Pamela S. Douglas, MD, MACC, FACC, Geller Professor of Research in Cardiovascular Diseases at the DCRI. “As we move increasingly towards algorithmic care, we must leave room for physician expertise to individualize approaches. We also need new risk scores, such as the PROMISE Minimal-Risk Tool, which uses readily available pretest variables to discriminates minimal-risk patients, for whom deferred testing may be considered.”

Other Duke authors of the presentation included C. Larry Hill; Adrian Coles, PhD; Kerry L. Lee, PhD; Daniel B. Mark, MD; and Manesh R. Patel, MD.

ACC 2018: Bleeding rates in PAD patients higher than previously known

March 11, 2018 – An analysis of data from the EUCLID trial showed revascularization patients with peripheral artery disease were more likely to have bleeding.

A recent study of major bleeding in peripheral artery disease (PAD) patients found that overall incidence and rate were low, and similar for patients randomized to two antiplatelet drugs, ticagrelor and clopidogrel.

These findings were based on a substudy analysis by DCRI researchers of the Examining Use of Ticagrelor in Peripheral Artery Disease (EUCLID) trial. EUCLID was a multicenter, randomized controlled trial of 13,885 patients with symptomatic PAD (narrowing of the blood vessels to the extremities) at 811 sites in 28 countries. Factors associated with major bleeding included advanced age, geographic region, and treatment with beta-blockers.

Patients with PAD who underwent revascularization to restore blood flow had a significantly higher rate of major bleeding when compared with patients who did not undergo revascularization, and post-procedure major bleeding rates were similar for coronary/peripheral revascularization and amputation.

The results of this analysis were presented today at the American College of Cardiology 67th Annual Scientific Session in Orlando, Florida.

During EUCLID, the primary safety endpoint of major bleeding was assessed using Thrombolysis in Myocardial Infarction (TIMI) criteria. As part of a comprehensive clinical events classification process at the DCRI, three other bleeding scores were also adjudicated and the results were compared to TIMI criteria.

“Our analysis revealed higher bleeding rates in this population than we were aware of, and these were unrelated to the randomized comparison (ticagrelor versus clopidogrel),” said senior author W. Schuyler Jones, MD, associate professor of medicine.

“We have studied and know a lot about major bleeding in patients with coronary artery disease, but the literature about bleeding in peripheral artery disease is less formed,” he said. “Future studies are needed to determine the impact of major bleeding on antiplatelet discontinuation, major adverse cardiovascular events, and quality of life in patients with peripheral artery disease.”

In addition to Jones, Duke authors on the paper were: Rachael Ward, MPH; Zhen Huang, MS; Frank Rockhold, PhD; Rajendra Mehta, MD; Thomas Povsic, MD; Sreekanth Vemulapalli, MD; and Manesh R. Patel, MD.

ACC 2018: Inhaled inorganic nitrite ineffective in treatment of heart failure

March 11, 2018 – Results from the INDIE-HFpEF trial showed that the treatment did not increase patients’ peak exercise capacity.

Inhaled, nebulized inorganic nitrite does not improve peak exercise capacity or other indicators of clinical status in patients with heart failure with preserved ejection fraction (HFpEF), according to a recent trial by DCRI and other researchers.

Results from the late-breaking Inorganic Nitrite Delivery to Improve Exercise Capacity in Heart Failure With Preserved Ejection Fraction (INDIE-HFpEF) trial were presented today at this year’s annual American College of Cardiology conference in Orlando, Florida.

Adrian Hernandez“Approximately half of the six million people living with heart failure in the United States have HFpEF,” said the DCRI’s Adrian Hernandez, director of Health Services and Outcomes Research. “Despite patients with HFpEF being seen commonly, we do not have a great understanding of what can work.”

HFpEF is characterized by abnormal diastolic function, which manifests as an increase in the stiffness of the heart’s left ventricle and a decrease in left ventricular relaxation when filling with blood before the next beat. There is an increased risk for atrial fibrillation and pulmonary hypertension in patients with HFpEF. To date, no real therapy exists for the condition and no treatment has been shown to dramatically improve outcomes in patients.

INDIE-HFpEF was conducted by the Heart Failure Network, which is funded by a grant from the National Heart, Lung, and Blood Institute, to see whether four weeks of treatment with inhaled, nebulized inorganic nitrite could help improve patients’ exercise capacity and their functional quality of life.

According to Hernandez, small, single-center studies have shown improvements in hemodynamics and exercise capacity with inorganic nitrite, which is a byproduct of the breakdown of nitric oxide in the human body and has been shown to play a significant role in calming blood vessels and decreasing the stiffness of the heart muscle.

The trial enrolled 105 HFpEF patients with a median age of 68 years. Patients were randomly assigned to receive a placebo, or the inorganic nitrite administered with a nebulizer three times a day for four weeks and then switched.

“We used very novel patient-worn accelerometers called Arbitrary Activity Units or AAUs, that are very much like FitBits that are very commonly used these days, to observe changes in a patient’s daily activity levels,” said Hernandez.

According to the researchers, as compared to placebo, inhaled, nebulized inorganic nitrite did not improve peak exercise capacity or other indicators of clinical status in patients with HFpEF such as daily activity levels or quality-of-life scores.

“There could be many factors that contributed to such a result,” said Hernandez, “it could be that we did not have the right dose or duration of the drug or that patients needed physical activity training before the test was administered. Or it could simply mean that the condition is really challenging to treat.”

According to Hernandez, whatever the factors may be that contributed to the neutral result, more research and investigation remain the answer.

“There is still a lot about HFpEF that we do not fully understand, especially the underlying biology and pathophysiology,” said Hernandez. “What we do know is that the data we have collected does not support the use of inhaled nebulized inorganic nitrite for symptom relief in patients with HFpEF and further studies are required to determine the potential efficacy of other such therapies.”

In addition to Hernandez, other researchers included Yogesh N.V. Reddy, Gregory D. Lewis, Sanjiv J. Shah, Martin LeWinter, Marc Semigran, Victor G. Davila-Roman, Kevin Anstrom, Eugene Braunwald, Margaret M. Redfield and Barry A. Borlaug.

ACC 2018: Perceived work-life balance issues deter trainees from choosing cardiology careers

March 11, 2018 – A survey of internal medicine trainees showed residents’ negative perceptions of cardiology are at odds with their professional development needs.

Increasing cardiovascular disease prevalence, technological advances, and increasing patient diversity require continued successful recruitment of internal medicine residents into cardiology fellowships.

In the first ever survey of internal medicine trainees, work-life balance was identified as paramount for professional development, yet the culture of cardiology was perceived negatively in this area. This was especially true for women and non-cardiologists, who placed a higher value on stable hours, family and female friendliness, patient focus, and positive role models, while men and future cardiologists  valued professional challenges and stimulating career.

For all trainees, their professional needs and perceptions of cardiology strongly predicted whether they chose a career in cardiology or other fields. Residents choosing cardiology emphasized positive aspects of cardiology while others were more likely to agree with perceptions describing interference with family life, challenges of having children during cardiology fellowship, and excessive demands of a cardiology career.

The poster was presented today at the American College of Cardiology 67th Annual Scientific Session in Orlando, Florida.

Surveys were e-mailed to 4,850 trainees and circulated by 44 U.S. program directors in 2009-10. A total of 1,123 trainees (494 women and 625 men) in 198 residencies completed surveys, a 23.1 percent response rate. Questions focused on demographics, 38 professional development needs, and 19 perceptions of cardiology, using a five-point scale. Demographics and survey responses were used to model predictors of career choice.

“These unique findings will help inform the content and direction of the American College of Cardiology’s  efforts to ensure a robust workforce and improve provider well-being,” said lead author Pamela S. Douglas, MD, Geller Professor of Research in Cardiovascular Diseases at the DCRI. “Efforts to increase the capacity and diversity of the future cardiology workforce should address the apparent misalignment of cardiology culture with trainees’ professional needs.”

In addition to Douglas, authors of the poster were: Anne K. Rzeszut, MA; C. Noel Bairey Merz, MD; Claire S. Duvernoy, MD; Sandra J. Lewis, MD; Mary Norine Walsh, MD; and Linda Gillam, MD, on behalf of the ACC Task Force on Diversity and Women in Cardiology Section.

This study was funded by the American College of Cardiology and by the Women in Cardiology Section of the ACC.

ACC 2018: Loading doses of atorvastatin do not reduce major adverse cardiac events at 30 days

March 11, 2018 – Favorable results were seen in subgroup that underwent PCI.

Atorvastatin is a widely prescribed drug that lowers cholesterol blood levels. But until recently, it was unclear whether a loading dose of atorvastatin could prevent periprocedural myocardial infarction (MI) and other adverse endpoints in patients with acute coronary syndrome (ACS) and planned invasive management.

The Statins Evaluation in Coronary procedUres and REvascularization (SECURE-PCI) study was designed to answer this question. The DCRI’s Renato D. Lopes, MD, MHS, PhD, study co-chair, was senior author of the study, published simulataneously in the Journal of American Medical Association. Co-chair Otavio Berwanger, MD, PhD, of the Hospital de Coração (HCor) in Brazil, presented the study results at the American College of Cardiology meeting in Orlando, Florida today.

SECURE-PCI was a randomized, double-blind, multicenter trial in which patients with ACS were randomized to loading doses of 80mg of atorvastatin or matching placebo before and 24 hours after planned percutaneous coronary intervention (PCI).

The Brazilian Clinical Research Institute (BCRI) coordinated the five-and-a-half-year trial with HCor. SECURE-PCI was conducted at 60 sites throughout Brazil under a grant from the Brazilian Ministry of Health. The DCRI’s Christopher Granger, MD, and John Alexander, MD, MHS, were part of the trial’s steering committee and co-authors on the manuscript.

The study enrolled 4,197 patients with ACS (with or without ST elevation.) The mean age was 61.8 years, and nearly 26 percent of the patients were women. Follow-up for the primary end point was 30 days.

“At 30 days, there were really no differences between the loading dose and placebo,” said Lopes. “But, very interestingly, we did find a 28 percent reduction in the primary endpoint over placebo in the pre-specified subgroup of PCI patients during that time. These findings were primarily driven by the subgroup of patients with ST elevation myocardial infarction, or STEMI.”

The study also showed a 32 percent reduction in myocardial infarction, according to Lopes. “With loading doses in patients undergoing PCI seeming to show improved outcomes, this can be an attractive and reasonable strategy for physicians, especially when treating patients with STEMI and in hospitals that do not use this statin regimen in the first 24 to 48 hours of an ACS event. Of course, caution should be taken when interpreting these results since they derived from a post-randomization subgroup.”

The timing of the study medication varied according to the type of ACS – for those without ST elevation (NSTEMI), the pre-PCI dose was administered between 2 and 12 hours before the procedure. For those with ST elevation myocardial infarction (STEMI), the loading dose was administered as soon as possible before the primary PCI. In both cases, the second dose of 80mg atorvastatin or placebo was administered 24 hours after the procedure.

Of the study population, 4,191 completed the 30-day follow-up and 2,710 patients underwent PCI. The primary endpoint was a composite of all-cause mortality, MI, stroke, and unplanned coronary revascularization through those 30 days.

Major adverse cardiac event (MACE) occurred in 130 patients in the atorvastatin group and 149 of those receiving a placebo. Of the patients who underwent PCI, MACE at 30 days occurred in 81 of 1,351 patients receiving atorvastatin compared with 112 of 1,359 in the placebo group.

“The bottom line is that loading doses of atorvastatin do no harm and can potentially provide benefit for patients undergoing PCI,” said Lopes. “This drug is well known in cardiology, and the SECURE-PCI results can provide insights to help physicians with decisions on whether to start statins in the very early phase of ACS, particularly in patients with STEMI that are undergoing an invasive strategy.”

ACC 2018: Ticagrelor noninferior to clopidogrel for TIMI major bleeding at 30 days

March 11, 2018 – Thrombolysis in myocardial infarction (TIMI) endpoints were similar between both groups.

Ticagrelor and clopidogrel are platelet aggregation inhibitors that help prevent thrombotic events such as stroke or heart attack in patients with acute coronary syndrome or myocardial infarction with ST elevation. But while ticagrelor is widely considered the superior therapy, until now there has been no large-scale, randomized studies of its risk for major bleeding, both intracranial and fatal.

At the American College of Cardiology meeting in Orlando, Florida today, Otavio Berwanger, MD, PhD, of the Hospital de Coração (HCor) in Brazil, presented results from the TicagRElor in pAtients with ST-elevation myocardial infarction treated with pharmacological Thrombolysis (TREAT) study completed late last year.

“There were really no surprises,” said the DCRI’s Renato D. Lopes, MD, MHS, PhD, who was senior author on the study,  which was published in  JAMA Cardiology. “We found there were no bleeding differences between the two therapies – rates of intracranial and fatal TIMI bleeding, the primary endpoints, were similar between both groups at 30 days. However, patients treated with ticagrelor had higher rates of minor bleeding compared with clopidogrel.”

TREAT was a phase III, randomized, international clinical trial designed to explore the safety and efficacy of ticagrelor compared to clopidogrel in patients with acute coronary syndrome with ST elevation treated with thrombolysis in a clinical setting.

Nearly 3,800 patients from 167 centers in 10 countries were enrolled between November 2015 and November 2017. Patients were eligible for enrollment if they presented within 24 hours after the onset of symptoms, had evidence of acute ST-elevation on their qualifying electrocardiogram, were under 75 years of age, and received fibrinolytic therapy as their initial reperfusion strategy.

Lopes and the DCRI’s Christopher Granger, MD, were on the trial’s steering committee while the DCRI’s John Alexander, MD, and Karen Pieper, MS, were on the Data Safety Monitoring Board. Alexander was also Chair of that board.

“Trial logistics were a challenge,” said Lopes, “as the window of time to enroll patients was short. A patient arrived at the hospital and you may not have time for randomization, so they often received the standard therapy, which is clopidogrel. It’s not always feasible to randomize them earlier, of course, which limited the ability to test ticagrelor around the time of fibrinolytic therapy. It is important to remember that patients were randomized with a median of 11 hours after fibrinolytic therapy and 90 percent were pre-treated with clopidogrel.”

Ticagrelor’s effectiveness was established by the 2009 PLATO (Platelet Inhibition and Patient Outcomes) study, which showed it to provide faster, greater, and more consistent P2Y12 inhibition than clopidogrel. That study showed that ticagrelor significantly reduced the rate of death from vascular causes, myocardial infarction, or stroke without an increase in the rate of overall major bleeding, but patients who received fibrinolytic therapy within 24 hours of their cardiac event had been excluded from PLATO.

In TREAT, at 30 days, TIMI major bleeding had occurred in 14 of 1,913 patients receiving ticagrelor and in 13 of 1,886 patients receiving clopidogrel. Major bleeding as defined by PLATO and BARC (Bleeding Academic Research Consortium) occurred in 23 patients in the ticagrelor group and 26 patients in the clopidogrel group.

In addition, while primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy for patients with ST-segment elevation myocardial coronary infarction (STEMI), it is not always possible for patients with PCI capabilities to be treated at hospitals in a timely manner in many parts of the world where the trial took place. In these cases, many STEMI patients received fibrinolytic therapy as the initial reperfusion strategy instead.

“We wanted to do a non-inferior trial to show that ticagrelor is as safe as clopidogrel, and not inferior,” said Lopes. “Because most patients were pre-treated with clopidogrel, our results reflect the non-inferiority of switching from clopidogrel to ticagrelor in patients already fully loaded with clopidogrel. We also did not find any difference in ischemic events between study groups. Finally, patients will continue to be treated over the following 12 months, and we will report again one year from now. The study is ongoing.”

ACC 2018: Eliminating cost barriers helps heart patients comply with drug regimens

March 11, 2018 – A new study on drug adherence provides insights on prescribing patterns and clinical outcomes.

Doctors often cite the high price of a prescription drug as a reason they don’t prescribe it, while patients similarly say that cost is a main reason they quit taking a drug.

Removing this financial barrier might increase the use of evidence-based therapies, improve patient adherence to those medications, and potentially save lives. That theory was tested in a study of heart attack survivors led by the DCRI; the findings were presented today at the American College of Cardiology annual scientific sessions meeting in Orlando, Florida.

“This study provides some good insights into medication-taking behavior and tackling the adherence problem, a big problem in the U.S,” said study chair, Eric Peterson, MD, MPH, executive director of the DCRI. ”While financial issues are certainly part of the problem, a more complete answer will be needed to further improve adherence and patient outcomes.”

The researchers enrolled 11,001 heart attack patients between June 2015 and June 2016 at hundreds of sites across the country in a study known as ARTEMIS. Doctors at participating hospitals provided usual care, but at roughly half the sites selected randomly, the cost of anti-platelet medications were offset by vouchers over the course of the study’s one-year span.

Payment vouchers eliminated price differences between an older generic therapy called clopidogrel and a newer, more effective version of the therapy, ticagrelor. Doctors had full discretion on which of the two drugs to prescribe.

The study found that clinicians were indeed sensitive to their patient cost concerns. When patient co-pays were covered, doctors were more than 30 percent more likely to prescribe the more effective drug.

When patients were asked about their medication use, 80 to 85 percent reported that they filled all their prescriptions continuously, but the study’s analysis of pharmacy fill data indicated that only 55 percent had been fully compliant.

Regardless of the measure of medication use, the study confirmed that more of the patients who got the pay vouchers stuck to their recommended drug regimens.

But those improvements did not appear to result in a reduced rate of death, heart attacks or strokes compared with patients who got usual care.

“Our study confirms some of our thoughts on how drug prices affect doctors and patients behaviors,” said lead author Tracy Wang, MD, MHS, MSc.

“But we still have a lot of work to do to understand how we can both measure and improve treatment adherence,” Wang said. “We should consider copayment reductions as part of broader initiatives to improve medication use and clinical outcomes.

“Interestingly, only 72 percent of patients took advantage of the provided copayment reduction voucher, which may have been why we didn’t see any clinical improvement, and that bears further study.” Wang said. “We should consider copayment reduction as part of broader initiatives to improve medication use and clinical outcomes”

The study was funded by AstraZeneca, which markets BRILINTA, a brand of ticagrelor.