ACC 2019: 12-month results show ticagrelor safe in STEMI patients treated with thrombolysis

March 18, 2019 – When comparing ischemic endpoints, no significant difference was found between patients who received ticagrelor and patients who received clopidogrel.

According to results presented as a late-breaking clinical trial in New Orleans at the 2019 American College of Cardiology’s Scientific Sessions and published in the Journal of the American College of Cardiology, ticagrelor is as safe as clopidogrel when administered to patients with ST-elevation myocardial infarction (STEMI) who were treated with thrombolysis.

The TicagRElor in pAtients with ST-elevation myocardial infarction treated with pharmacological Thrombolysis (TREAT) trial was led by Otavio Berwanger, MD, PhD, chair of the TREAT Trial Steering Committee. Previous literature had shown that ticagrelor is superior to clopidogrel in both patients with STEMI and non-ST-elevation myocardial infarction, but patients who were treated with thrombolysis were excluded from previous trials. Because thrombolysis is associated with greater bleeding risk, there had been concern about using the more potent option, said the DCRI’s Renato D. Lopes, MD, MHS, PhD, who served on the steering committee and as the clinical events classification (CEC) chair for the trial.

TREAT enrolled 3,799 patients younger than 75 in 10 countries and randomized participants to one of two treatment arms: ticagrelor or clopidogrel. The initial results, which were published in JAMA Cardiology last year, showed no significant difference in major bleeding between the treatment groups after 30 days.

The 12-month results presented at the ACC again examined bleeding, as well as ischemic endpoints, such as death, recurring myocardial infarction (MI), stroke, and vascular death. Again, there was no significant difference between the two groups:

  • Composite outcome of death from vascular causes, MI, or stroke: 6.7 percent of patients who received ticagrelor versus 7.3 percent of patients who received clopidogrel;
  • Composite outcome of death from vascular causes, MI, stroke, severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events: 8.0 percent of ticagrelor patients, as compared to 9.1 percent of patients on clopidogrel.

These results confirm, 12 months after treatment, ticagrelor’s safety as compared to clopidogrel in patients who received thrombolysis.

“Investigators and clinicians can be encouraged by these results, which extend ticagrelor’s safety in patients who received thrombolysis from 30 days to 12 months,” Berwanger said. “We can now be confident in using a more antiplatelet agent without compromising the safety of our patients.”

This trial represents the largest trial of ticagrelor in STEMI patients treated with thrombolysis. This was an investigator-initiated trial funded by AstraZeneca.

ACC 2019: Use of guideline-directed medical therapies for comorbidities may improve outcomes for patients with atrial fibrillation

March 17, 2019 – Although nearly two-thirds of the study population did not receive all the guideline-directed medical therapies for which they were eligible, use of all therapies was linked to better outcomes in specific populations, such as patients with heart failure.

Most atrial fibrillation patients with comorbidities do not receive all the guideline-directed medical therapies (GDMT) they are eligible for, but new evidence from the DCRI suggests use of these therapies is associated with better outcomes in populations with certain comorbidities.

A study led by DCRI Fellow Zak Loring, MD, examined GDMT use for a range of conditions that are often seen in conjunction with atrial fibrillation, including coronary artery disease, diabetes, congestive heart failure, hyperlipidemia, hypertension, peripheral vascular disease, and obstructive sleep apnea. The findings were presented Sunday at the annual Scientific Sessions of American College of Cardiology in New Orleans.

After examining a population of 20,434 patients from the Outcomes for Better Informed Treatment of AF (ORBIT-AF) registry, the study team found that only about 33 percent of patients receive all the therapies for which they are eligible.

GDMT use varied widely by comorbidity type. Hyperlipidemia had a high GDMT ratio, with 75.6 percent of patients on a statin, while only 43.1 percent diabetes patients were treated with all therapies for which they were eligible.

The team was also interested in how patient outcomes were associated with both overall GDMT use and comorbidity-specific GDMT use. While the researchers did see a downward trend in all-cause mortality and major adverse cardiac or neurological events associated with GDMT use, the difference between patients who received all the therapies for which they were eligible and patients who did not was not statistically significant.

However, significant trends did emerge in specific comorbidity types. In patients with congestive heart failure, patients who used all the GDMT they were eligible for saw a 23 percent decrease in all-cause mortality compared to patients who received only some or no GDMT.

“These results are really interesting because it tells us there’s an interaction between the comorbidities and outcomes with atrial fibrillation patients,” Loring said. “For example, previous research has shown that catheter ablation as a treatment for atrial fibrillation can improve outcomes in heart failure patients. It makes us think about the interrelationship among those different conditions because treating one has an effect on the outcomes of the other.”

Not only can treatments for atrial fibrillation have an effect on comorbidities, but the team’s findings show that treatments for comorbidities can also affect the severity of atrial fibrillation. Use of continuous positive airway pressure to treat sleep apnea was associated in a reduction in the progression of atrial fibrillation.

“The associations our team found suggest that if you can get a patient on all the GDMT for which they are eligible, they are likely to experience a better outcome,” Loring said.

Other DCRI contributors to this project include Peter Shrader, MA; Rosalia Blanco, MS; Karen Pieper, MS; Eric Peterson, MD; and Jonathan Piccini, MD, MHS.

ACC 2019: Study confirms diagnostic accuracy of non-invasive technology for heart pain

March 17, 2019 – Patients with negative FFR-CT scans had a low, one-year risk of a heart attack or death.

One-year follow-up results show that a newer, non-invasive technology to evaluate heart pain provided a reliable way to identify which patients had dangerous artery blockages, according to a study co-led by the DCRI.

The findings, reported Sunday at the annual College of Cardiology meeting in New Orleans, suggest that fractional flow reserve CT (FFR-CT) scans are effective in helping doctors determine which patients need more aggressive treatments.

“Our study shows that in clinical practice, when new technology provides a negative result regarding the chance for a physiologically significant stenosis, the patient and physician should be reassured that the chances of major adverse cardiac events are low,” said lead author Manesh Patel, MD, chief of the Division of Cardiology at Duke University School of Medicine.

Patel and colleagues analyzed data from more than 5,000 patients who underwent FFR-CT scans for clinically suspected coronary artery disease. In patients with moderate-to-severe coronary artery disease, a negative FFR-CT was associated with a low, one-year risk of a major cardiac event such as heart attack or death compared to patients with a positive FFR-CT.

Specifically, the researchers found that among those with an FFR-CT reading above 0.80, suggesting blood flow is not dangerously restricted, the cardiovascular death and heart attack risks were significantly lower, and revascularization was significantly lower (5.8 percent vs. 38.4 percent) and was unlikely after 90 days.

“This research, with one-year follow-up, suggests that an FFR-CT test can be trusted when used as it was in this real-world observational registry,” Patel said. “And while we don’t have perfect warranties in medicine, a negative FFR-CT result was seen to have low risk for a major heart event in the following year.”

In addition to Patel, study authors include Bjarne Linde Nørgaard, Timothy A. Fairbairn, Koen Nieman, Takashi Akasaka, Daniel S. Berman, Gilbert L. Raff, Lynne M. Hurwitz Koweek Gianluca Pontone, Tomohiro Kawasaki, Niels Peter Rønnow Sand, Jesper M. Jensen, Tetsuya Amano, Michael Poon, Kristian A. Øvrehus, Jeroen Sonck, Mark G. Rabbat, Sarah Mullen, Bernard De Bruyne, Campbell Rogers, Hitoshi Matsuo, Jeroen J. Bax and Jonathon Leipsic.

The study, called ADVANCE Registry was funded by HeartFlow, Inc., which markets FFR-CT technology. Patel reported receiving research grants from Heartflow.

ACC 2019: Some heart disease, AF patients on combined therapies could skip aspirin

March 17, 2019 – Data show bleeding risk from aspirin could outweigh protection from another heart event.

In a finding that suggests less is more, researchers led by the DCRI found that the drugs apixaban and clopidogrel — without aspirin — comprise the safest treatment regimen for certain patients with atrial fibrillation (AF).

The finding, which applies specifically to patients with AF who have had a heart attack and/or are undergoing percutaneous coronary intervention, should reassure clinicians and patients that dropping aspirin results in no significant increase in ischemic events such as heart attacks, strokes and blood clots.

The researchers presented data from the large study, known as AUGUSTUS, on March 17 at the American College of Cardiology annual meeting. The research was also simultaneously published by The New England Journal of Medicine.

“We have a lot of studies on antithrombotic drugs in patients with coronary artery disease and similarly in patients with AF, but few studies in patients with both conditions,” said cardiologist Renato D. Lopes, MD, PhD, principal investigator for the trial and a member of the DCRI.

“The reality is that doctors and patients have a challenge in treating these patients without causing bleeding,” Lopes said. “The results of this trial give us an opportunity to better understand how to best treat them.”

Atrial fibrillation is the most common heart arrhythmia in clinical practice. Around a third of patients with AF also have coronary artery disease and might be taking as many as three different blood thinners to prevent heart attack and stroke. But taking multiple blood thinners increases the risk of uncontrolled bleeding.

Findings from the 4,600-person trial suggest patients double their bleeding risk by adding aspirin to blood thinners without any obvious reduction in risk for heart attack or stroke.

The trial used a factorial design to determine which combinations of antiplatelet and anticoagulant drugs could reduce bleeding in patients who have both coronary artery disease and AF and were already taking an anti-platelet drug such as clopidogrel.

Patients were randomly assigned to add the newer anticoagulant drug apixaban, or a vitamin-K antagonist (VKA) such as warfarin; patients were additionally randomized to take aspirin or a placebo as part of the regimen.

Comparing patients who used apixaban to those who used a VKA, the researchers found that apixaban reduced bleeding by 31 percent and cut death or hospitalizations by 17 percent. There was no difference between apixaban and a VKA to prevent a subsequent major coronary event such as a heart attack.

In the double-blinded segment of the trial that randomized patients to receive either aspirin or a placebo in addition to their other antiplatelet and anticoagulant regimen, the data suggest adding aspirin might do these patients more harm than good, Lopes said.

People who added aspirin had similar rates of death and hospitalization and heart attack compared to patients who received a placebo, Lopes said, but faced almost double the risk of bleeding.

“Patients who got aspirin actually ended up having about an 89 percent increase in major bleeds or clinically relevant non-major bleeds,” Lopes said. “By not giving aspirin, the reduction in bleeds was about 47 percent.”

The data did suggest that although a placebo reduced bleeding risk, more patients experienced ischemic events such as stent thrombosis, myocardial infarction and urgent revascularization. But these findings were not statistically significant and the study was not designed to fully evaluate each specific risk.

“In AUGUSTUS, we identified two effective independent strategies to substantially reduce bleeding, using apixaban rather than a VKA and stopping aspirin, which adds to a growing body of evidence on how to best treat these high-risk and complicated patients,” said cardiologist John H. Alexander, MD, chair of the trial’s executive committee and a member of the DCRI. “While there might be some increased risk of thrombotic events, these are rare compared to the large reductions we saw in bleeding.”

In addition to Lopes, study collaborators included Gretchen Heizer, Ronald Aronson, Amit N. Vora, Tyler Massaro, Roxana Mehran, Shaun G. Goodman, Stephan Windecker, Harald Darius, Jia Li, Oleg Averkov, María Cecilia Bahit, Otavio Berwanger, Andrzej Budaj, Ziad Hijazi, Alexander Parkhomenko, Peter Sinnaeve, Robert F. Storey, Holger Thiele, Dragos Vinereanu, Christopher B. Granger, John H. Alexander and others.

The trial was funded by Bristol-Myers Squibb and Pfizer, Inc., which market the drugs studied. Authors provided individual statements with financial disclosures and potential conflicts of interest.

ACC 2019: Benefits and drawbacks of high-sensitivity troponin use in low-risk patients with chest pain

March 16, 2019 – High-sensitivity troponin, an assay that is relatively new in the U.S., allows providers to assess low-risk chest pain patients more quickly and determine whether they have had a heart attack or myocardial infarction.

High-sensitivity troponin presents opportunities to rule out myocardial infarction or a heart attack more quickly for chest pain patients, thereby reducing hospital stays and alleviating overcrowded emergency departments or observation units.

DCRI Fellow Jennifer Rymer, MD, MBA, gave an invited talk Saturday at the American College of Cardiology Scientific Sessions on the use of high-sensitivity troponin in low-risk patients who come to the emergency room with chest pain. Both Rymer and DCRI Fellow Angela Lowenstern, MD, assisted with the recent high-sensitivity troponin roll-out at Duke.

Although high-sensitivity troponin has been available in Europe, Australia, and Canada for some time, it had not been approved by the U.S. Food and Drug Administration until recently. Thus far, only a few centers have rolled out use of high-sensitivity troponin, and Duke is in the process of implementing its use.

When patients come into the emergency department with chest pain, they undergo a series of labs to determine the cause of the pain. With conventional troponin, patients often wait up to 12 hours before they are told they have not had a heart attack. Because the algorithms and protocols of high-sensitivity troponin work more quickly, this process can be shortened to a couple of hours.

This accelerated pathway has the potential to have huge impacts, Rymer said. Because length of hospital stay decreases with use of high-sensitivity troponin, so does the cost to the health system. Utilization of other resources could also potentially decrease — for example, fewer patients may need to be observed in observation units, but instead may be safe for close outpatient follow-up or discharge.

Duke was one of the first institutions in the world to successfully integrate high-sensitivity troponin into its electronic medical record. Rymer said she hopes lessons learned will make the process easier for other institutions trying to go through the same process.

Although the use of high-sensitivity troponin is safe, the real challenge lies in knowing which patients to order the test for. In her presentation, Rymer said that it is critical to examine the pre-test probability for myocardial infarction prior to ordering the high-sensitivity troponin test. She also emphasized the importance of knowing that elevations in high sensitivity troponin can be caused by many other causes besides a heart attack, so close clinical history and physical are imperative.

“We know these assays are much more sensitive to pick up any sort of elevation in troponin leak that may be caused by having a myocardial infarction or heart attack,” Rymer said. “It’s quite safe, specific, and sensitive and can pick up heart attacks very quickly.”

ACC 2019: A multidisciplinary approach to improve care for geriatric heart failure patients

March 16, 2019 – Care for older adults with heart failure can be optimized using a four-domain framework including medical, mind, physical function, and social environment.

About 5.7 million adults in the United States and at least 26 million worldwide have heart failure. Heart failure is the number one cause of hospitalization in older adults, accounting for $123 billion per year in Medicare spending. Prevalence rises from 6 percent among individuals aged 60 to 79 years to approximately 14 percent in those aged 80 years or more. Up to 79 percent of patients with heart failure suffer from frailty, a complex syndrome linked to aging and chronic illness that results from multiple organ impairment.

Karen Alexander

Care is fragmented, with visits to the clinic posing a challenge, and despite advances in prevention and treatment, mortality and morbidity remain high. Optimizing the care of this very complex and vulnerable population is a high priority, but remains challenging. Cardiologists are increasingly faced with the need to provide comprehensive care that falls outside of traditional training in cardiovascular medicine.

“A multi-domain approach is needed to provide the best possible treatment to older adults with heart failure,” said the DCRI’s Karen P. Alexander, MD, professor of medicine. “Simply put, heart failure cannot be considered in isolation, without physical functioning, or the social, psychological, and behavioral dimensions of illness. A four-domain framework – involving medical, mind and emotion, physical function, and social environment – should be incorporated in routine clinical work in a tailored, individualized approach.”

Alexander gave a podium lecture Saturday at the American College of Cardiology’s annual Scientific Sessions in New Orleans.

She described a key emerging theme in the science and medicine of heart failure – the need to identify and target specific causes of heart failure, and take into consideration the medical and environmental contributors in selecting an effective intervention.

Multidisciplinary teams can provide a holistic approach, taking into account a broad range of factors, such as cognitive impairment, polypharmacy, physical function, dietary habits and social circumstances. Diverse innovations are being testing in these patients, with personalized care plans increasingly leveraging technology. Advances in digital health and telehealth could potentially change the landscape for these patients in future through mobile health, tele-rehab and tele-visits. Other targeted approaches to heart failure in older patients include community exercise opportunities, provision of meal kits and nutrition support, home diuresis, and social support to address depression and cognitive concerns.

“Multi-domain management of the geriatric heart failure patient is about considering care in the context of the individual,” Alexander said. “This enables the creation of a personalized care plan supported by broad use of community and technology supports to maximize days spent at home.”

ACC 2019: Oral anticoagulants underused, aspirin overused to treat atrial fibrillation in patients with advanced chronic kidney disease

March 16, 2019 — Only approximately half of patients with chronic kidney disease and atrial fibrillation were treated with oral anticoagulants (OACs), and this proportion decreased significantly as kidney disease became more severe.

For patients with kidney disease and atrial fibrillation (AF), the approach to stroke prevention may be affected by how advanced their kidney disease is, according to new findings presented Saturday at the American College of Cardiology Scientific Sessions.

The DCRI’s Sean Pokorney, MD, MBA, who worked on the study team, said that many patients with atrial fibrillation are not treated with oral anticoagulation, which increases risk of stroke. The group was interested in examining how advanced kidney disease affects this under-treatment, as well as how different treatment options affect patient outcomes.

The study included about 300,000 patients with atrial fibrillation and chronic kidney disease from the Premier Healthcare Database, which represents 20 percent of hospital discharges across the U.S. The dataset spanned from 2011 to 2015.

The team examined four patient groups: those treated with warfarin (the conventional OAC), those treated with newer direct oral anticoagulants (DOACs), those treated with aspirin only, and those who received no OAC or aspirin. Results showed that as kidney disease advanced, OAC treatment rates decreased while aspirin treatment rates increased. Likelihood of treatment with a DOAC dropped significantly in the later stages of kidney disease, while warfarin treatment rates remained relatively stable.

“The main way we can intervene here is to address the overuse of aspirin,” Pokorney said. “There is a misconception that aspirin is safer than OACs and still provides some stroke protection, but we believe there is actually minimal protection against atrial fibrillation related strokes provided by aspirin and that it is not any safer than newer OAC options. The trends we found are concerning because by overusing aspirin, we are still exposing patients to risk of bleeding without the benefits of stroke prevention from an OAC.”

The group also examined patient outcomes after one year. Treatment with DOACs resulted in a lower 1-year mortality rate than treatment with warfarin across all stages of kidney disease. In Stages I through III, mortality in the DOAC group was 4.4 percent, as compared to 5 percent in the warfarin group. In patients with stage IV, V, or end-stage renal disease, 6.3 percent of those treated with DOACs experienced mortality versus 8.1 percent of those treated with warfarin.

Pokorney said that providers are appropriately hesitant to prescribe DOACs to patients with end-stage renal disease because of limited data on safety in this patient population. Along with the DCRI’s Christopher Granger, MD, he is working on RENAL-AF, an ongoing DCRI study that is randomizing hemodialysis patients with atrial fibrillation to either apixaban (a DOAC) or warfarin. This study’s results could provide further evidence for DOAC safety in chronic kidney disease patients, he said.

The DCRI’s Kevin Thomas, MD; Kevin Anstrom, PhD; and Christopher Granger, MD, also contributed to the study presented Saturday. Janssen Pharmaceuticals provided funding for the study.

ACC 2019: Disparities persist in treatment of symptomatic aortic valve stenosis

March 16, 2019 — New research shows that although racial disparities have diminished in recent years, gender disparities are still common.

New DCRI research on severe, symptomatic aortic valve stenosis shows that black non-Hispanic patients have historically received treatment less frequently than their white counterparts, while women received treatment less frequently than men.

Because the disease has a mortality rate of up to 80 percent in five years, treatment is especially important. However, said J. Matthew Brennan, MD, MPH, who led the study, more than two-thirds of the patient population studied received no treatment.

The study’s findings were presented Saturday at the annual Scientific Sessions of the American College of Cardiology in New Orleans.

The team used the Optum database, which includes insurance claims from 700 hospitals and 7,000 clinics, as a data source. Using natural language processing of physician notes, they identified 43,822 patients with severe aortic valve stenosis between 2011 and 2016.

Disparities existed within the proportion of patients who received treatment. Through the beginning of the study period, African-Americans were less likely to receive treatment than white patients (about 27 percent versus nearly 35 percent), but the treatment rates have become more level over the past couple years, with no remaining significant difference in the likelihood of treatment.

The team hypothesizes that this is because of the increasing availability of transcatheter aortic valve replacement (TAVR), which arrived on the market in 2011. Now, patients have a less invasive treatment option than the traditional surgical aortic valve replacement (SAVR).

“We saw the greatest increase in treatment in the use of transcatheter therapies,” Brennan said. “It’s been reported widely that African-Americans tend to be less likely to accept invasive procedures, especially as they get older, as compared with whites. With the availability of a less invasive treatment option, we’re starting to see blacks catch up with whites because they’re accepting the treatments more.”

Although treatment ratios eventually leveled between races, disparities persist along gender lines, said DCRI Co-Chief Fellow Angela Lowenstern, MD, who was also a part of the study team. Women were less likely to be treated than men (28.7 percent of women were treated, while 36 percent of men were), but when they were treated, they were more likely to receive TAVR than men were (39.8 percent of women were treated with TAVR versus 32.3 percent of men).

The group also looked outcomes in these populations based on survival rates after one year. There were no significant differences between survival in blacks and whites, regardless of treatment type; even untreated patients from both races fared similarly, although survival was less likely for these groups. Women who received treatment had worse outcomes than men who were treated, which was driven primarily by low survival rates of women who received SAVR.

“The biggest next step is figuring out how we minimize these disparities that still exist,” Lowenstern said. “What can we implement, what are things that we can do to equalize the treatment of both male and female patients?”

ACC 2019: Compound improves heart failure biomarker even after hospitalization

March 16, 2019 – A new study shows sacubitril/valsartan can still improve heart stress if prescribed later.

Starting heart failure patients on the compound sacubitril/valsartan instead of enalapril after they have been discharged from the hospital led to an improvement in biomarkers of heart stress, according to a study led by the DCRI.

The finding, from an additional analysis of a study called PIONEER-HF, described changes in a heart failure biomarker called NT-proBNP when switching from enalapril to sacubitril/valsartan. The results of the study were reported Saturday at the American College of Cardiology meeting in New Orleans.

Adam DeVore“This is very practical information from a clinical standpoint,” said lead author  Adam D. DeVore, MD, an advanced heart failure specialist at Duke and member of the DCRI. “Our earlier analysis showed that patients have improved NT-proBNP values, an important biomarker of heart failure, when starting sacubitril/valsartan versus enalapril in the hospital.

“We’ve demonstrated that there are similar benefits even when receiving the therapy later in a patient’s course of treatment,” DeVore said “However, if you look at the risk of poor early outcomes after the hospitalization, the data support the early initiation of therapy.”

In the original PIONEER-HF study, DeVore and colleagues analyzed outcomes among heart failure patients who were randomized to either receive sacubitril/valsartan or enalapril during hospitalization. That study showed an improvement in NT-proBNP values at eight weeks among patients receiving sacubitril/valsartan.

In the current study, the researchers augmented the original PIONEER-HF study with an additional follow-up. Patients who had been in the enalapril group were then switched to sacubitril/valsartan for four weeks. Among those patients, concentrations of NT-proBNP, declined by 35.8 percent.

Patients who originally received sacubitril/valsartan in the hospital and continued on the therapy upon discharged also saw concentrations of NT-proBNP decline, by 18.5 percent.

“Switching patients from enalapril to sacubitril/valsartan at eight weeks after randomization led to a further reduction in NT-proBNP in heart failure patients and improved serious clinical outcomes,” DeVore said. “Together, these two studies show that outcomes improve with the use of sacubitril/valsartan, and are even better with earlier use.”

In addition to DeVore, study authors include Eugene Braunwald, David A. Morrow, Carol I. Duffy, Andrew P. Ambrosy, Kevin McCague, Ricardo Rocha and Eric J. Velazquez.

The PIONEER-HF study was funded by Novartis Pharmaceuticals, which markets sacubitril/valsartan under the brand name Entresto.

ACC 2019: Heart failure patients not having medication doses increased to recommended targets

March 16, 2019 — Despite guideline recommendations, most heart failure patients eligible for medical therapies never have these therapies titrated to the target dose.

In current U.S. practice, the majority of patients who have heart failure with reduced ejection fraction do not receive medical therapy at guideline-recommended target doses, and their medications are often not titrated to the target dose during follow-up, according to new findings from DCRI researchers.

The study was led by DCRI fellow Stephen Greene, MD, and was presented on Saturday at the 2019 American College of Cardiology Scientific Sessions. In conjunction with the presentation, the study was published simultaneously in the Journal of the American College of Cardiology.

Strong clinical evidence has shown that multiple heart failure medications can substantially improve patient survival and quality of life, and guidelines recommend that these medications are titrated to a target dose so that patients receive the maximal benefit. However, Greene said, the group’s findings show that many patients eligible for these important medications are not receiving them or receiving only low doses, and that most patients never have doses of medication increased to the target dose at any point in time.

The study examined 2,588 U.S. outpatients enrolled in the CHAnge the Management of Patients with Heart Failure (CHAMP-HF) registry between December 2015 and July 2017. All the patients included had heart failure with reduced ejection fraction, complete medication data, and no contraindications to medical therapy.

The study focused on the four main classes of medical therapies proven to improve patient outcomes: angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEI/ARB), angiotensin receptor-neprilysin inhibitors (ARNI), beta-blockers, and mineralocorticoid receptor antagonists (MRA).  The study then compared the use of each these therapies over a 12-month follow-up period.

“Understanding that guidelines recommend that we constantly work toward increasing the dose of these medications to the target dose if at all possible so that we best improve patient outcomes, we wanted to determine to what degree this happens in current U.S. practice, and to better understand the overall patterns of medication changes,” Greene said.

The proportion of patients receiving a target dose of medication at baseline ranged from 1.7 percent for ARNI to 25.4 percent for MRA. After 12 months, the team found the following:

  • For all medical therapies, more than 80 percent of patients had stable dosing over 12 month follow-up, with the vast majority of patients consistently receiving doses below the recommended target;
  • 7 percent of patients had ACEI/ARB therapy started or dose increased, while 11 percent had therapy discontinued or dose decreased;
  • 10 percent of patients had ARNI therapy started or dose increased, while 3 percent had therapy discontinued or dose decreased;
  • 10 percent of patients had beta-blocker therapy started or dose increased, while 7 percent had therapy discontinued or dose decreased;
  • 6 percent of patients had MRA therapy started or dose increased, while 4 percent had therapy discontinued or dose decreased;
  • Several high-risk patient characteristics were associated with higher likelihood of having medications discontinued or doses decreased.

“Clinicians should recognize that there is a strong tendency to not up-titrate or initiate medical therapy as patients continue to receive outpatient follow-up visits. Many of these patients are eligible for these important medications and would benefit from having them started or from having the doses increased,” said Greene.

“Overall, this study identifies major gaps in the quality of heart failure care in the U.S.,” he said. “Given that heart failure remains a leading cause of death, hospitalization, and impaired quality of life, every effort must be made to use all the tools proven to improve patient outcomes. As we care for each patient over time, we need to constantly work on starting each patient on the beneficial medications for which they are eligible, and then titrating each medication to the target or maximally tolerated dose. Every time we see a heart failure patient in practice, we should see this as a possible opportunity to improve the quality of their medical therapy, and in turn, improve their outcomes.”

The DCRI’s Adam DeVore, MD; C. Larry Hill, PhD; Laine Thomas, PhD; and Adrian Hernandez, MD, also contributed to this study. The analysis and the CHAMP-HF registry were funded by Novartis Pharmaceuticals Corporation.