HF Care Gaps May Stem From Patient-Specific Factors, Canadian Study Finds

It’s not a question of “set it and forget it” with drug doses. Some patients may simply be taking as much drug as they can handle.

HF Care Gaps May Stem From Patient-Specific Factors, Canadian Study Finds

Although there are gaps in adherence to optimal medical therapy as recommended by heart failure guidelines, failure to prescribe up to the recommended treatment doses may not be a lapse on the part of physicians, a single-center study suggests. Instead, say authors, physiological factors such as heart rate, blood pressure, and renal function that limit tolerance likely play a key role.

At their center, the proportion of HF patients who received guideline-recommended target doses of beta-blockers and mineralocorticoid receptor antagonists (MRAs) was just 30% and 39%, respectively. But when investigators accounted for patients’ physiological limitations, the proportion receiving the maximally tolerated dose nearly doubled. Additionally, roughly 20% of patients were still in the titration phase, leaving a little less than one in five patients undertreated.

The findings, albeit from a specialized heart failure center, have implications for device therapies or approaches that require patients to first max out on guideline-recommended therapies, particularly in the face of trial results like COAPT that strenuously screened out patients who couldn’t be fully “optimized” on medical therapy.  

To TCTMD, senior investigator Anique Ducharme, MD (Montreal Heart Institute, Canada), said that previous registry data have suggested that only 25% to 35% of patients with HF are optimized on medical therapy, but that many of those registries lack the granularity to account for patient-specific factors preventing dose escalation.

I didn’t like the idea from leaders in the field saying, ‘There is inertia, do a better job.’ We thought we were doing a pretty good job. Anique Ducharme

“Obviously, there are limitations that the large registries don’t account for,” she said. “For example, if you use a beta-blocker to reduce heart rate, if the patient is taking 2.5 mg of vasopril and the target dose is 10 mg, but the patient’s heart rate is 55 [beats per minute], there are physiological limitations that preclude increasing the dose. They’re not at target dose, per se, but that patient is optimized. There is not a one-size-fits-all approach, so we try to look at the limitations to personalize the treatment of patients.”

Gregg Fonarow, MD (University of California, Los Angeles), who wasn’t involved in the study, praised the study investigators, saying the study showed that “clinical inertia can be overcome” in certain settings, but cautioned that such specialized clinics aren’t where most HF patients are treated. In fact, less than 1% of HF patients in the United States are managed in such specialty programs, he said.

In the settings where most HF patients are cared for, including general cardiology, primary care, family medicine, and geriatric clinics, “there is marked underutilization of evidence-based, guideline-directed medical therapies,” Fonarow told TCTMD in an email. “Further, there is marked underutilization of target dosing of guideline-directed medical therapy, in the absence of contraindications, documented intolerance, or limitations by either systolic blood pressure or heart rate.”

Specialized HF Clinic

The new research, which was published online August 12, 2020, ahead of print in JACC: Heart Failure, included all HF patients with reduced EF with at least one visit to a specialized hospital-based clinic in Montreal, Canada. The 511 patients were followed for at least 6 months to allow for the optimization of medical therapy and/or use of implantable cardioverter-defibrillators (ICDs) or cardiac resynchronization therapy (CRT). The researchers developed an algorithm that incorporated clinical data, such as heart rate, systolic blood pressure, NYHA functional class, creatinine, potassium, and QRS width on ECG, all of which may influence drug initiation or titration to higher doses.

For those eligible for beta-blockers, 29.9% were at the target dose, but 67.5% were at the maximally tolerated dose when physiological parameters were considered. Another 20.4% of patients were still in the process of being uptitrated to higher doses while 12.1% received inappropriately low doses without any documented limitations or intolerance. With vasodilators, 24.1% of HF patients were at the recommended ACE inhibitor/ARB target dose, as were 50.6% of patients treated with the angiotensin receptor-neprilysin inhibitor (ARNI), but 63.4% of all patients taking a vasodilator were at the maximally tolerated dose when physiological factors were considered. One in five patients treated with a vasodilator received a low dose without any explanation. For MRAs, 39.1% were treated to the recommend target, but 58.9% were optimized when patient-specific factors were taken into account. Similarly, 18.6% received inappropriately low doses without a justified reason.

Overall, 33.2% of 391 patients eligible for triple therapy with a beta-blocker, vasodilator, and MRA were at the guideline-recommended doses, or at the maximally tolerated doses. Roughly 38% of patients were still in the process of having the dose of at least one drug increased, and 113 patients were considered undertreated without a justifiable explanation.   

With ICDs and CRT, 75.1% and 82.1% of eligible patients received the device, respectively. For those who didn’t receive an ICD despite eligibility, 11% were still in the course of escalating medical therapy and 15 refused the device, leaving 9.9% untreated despite recommendations for the ICD. With CRT, just 1.4% of patients were potentially untreated despite eligibility.

While the study showed that roughly two-thirds of patients treated with guideline-directed medical therapy were on maximally tolerated doses, Ducharme said they were struck by the unexpected finding that roughly 15% to 20% were not optimized despite being followed in clinic for at least 6 months. She added that survey data suggest it takes roughly 6 months for physicians to get patients to the maximally tolerated dose, so their data suggest these patients are either undertreated or it takes longer to ramp up therapy.

In the US, Fonarow painted a bleaker picture, citing data from the CHAMP-HF registry. Of more than 3,500 HF patients (with reduced EF) from 150 primary care and cardiology outpatient clinics, 27% were not prescribed an ACE inhibitor/ARB/ARNI, 33% were not prescribed beta-blockers, and 67% were not prescribed MRA therapy, despite the absence of contraindications documenting intolerance. Even when prescribed, only 14% and 17% of patients receiving an ARNI or ACE inhibitor/ARB, respectively, received the recommended dose. Less than 1% of patients received the target dose of all three major categories of guideline-directed medical therapy, said Fonarow.

In certain settings, clinical inertia can be overcome. Gregg Fonarow

“Other studies have shown similar findings in non-heart failure specialized care settings,” he said. “Together with other colleagues we have demonstrated that use of comprehensive disease-modifying medical therapy can extend median survival by more than 6 years. The efforts needed for optimal implementation are more than justified by the substantial patient-centered, life-enhancing benefits.”

In an editorial, Stephen Greene, MD, and Adam DeVore, MD (Duke Clinical Research Institute, Durham, NC), make a similar argument, praising the Canadian researchers for their excellent work, but stating it’s unlikely to reflect routine US practice. They point out that one of the key messages from clinical trials and guidelines in HF is that a “subtarget dose may in fact be evidence-based if it is the maximally tolerated dose.” They acknowledge that not every patient will reach the guideline target, but still encourage physicians to escalate treatment where possible.

“Stable symptoms should not be misconstrued as ‘low risk’ or a reason to not attempt an indicated escalation of medical therapy,” they write.     

Team Effort

Ducharme said their HF clinic includes a multidisciplinary team of cardiologists, nurses (including one nurse practitioner), pharmacists, and dieticians. “It’s really a team effort,” she said.

The COAPT trial, which evaluated transcatheter mitral valve repair in patients with heart failure and severe functional mitral regurgitation, and which also required that patients be treated with maximally tolerated medical therapy to be eligible for the trial, showed what can be achieved in terms of guideline-directed medical therapy within the setting of a randomized study, noted Ducharme. Overall, though, she believes that most heart failure clinics can achieve the excellent results they observed at their center.

“I don’t think we’re outliers,” she said. “There are 40 heart failure clinics in the province of Quebec and there are heart failure clinics throughout the world. I didn’t like the idea from leaders in the field saying, ‘There is inertia, do a better job.’ We thought we were doing a pretty good job. That’s why we ended up looking at this.”

Nonetheless, there is a need to study the question in other centers to see how well they are performing with respect to treating to the maximally tolerated dose, she said. Additionally, it is important to allow hospitals participating in registries to document that they treated patients to an appropriate dose based on physiological limitations as opposed to simply achieving the target dose in the guidelines.

Michael O’Riordan is the Associate Managing Editor for TCTMD and a Senior Journalist. He completed his undergraduate degrees at Queen’s…

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  • Ducharme reports no relevant conflicts of interest.
  • Greene reports receiving research support from the Heart Failure Society of America/Emergency Medicine Foundation Acute Heart Failure Young Investigator Award (funded by Novartis), Amgen, AstraZeneca, Bristol-Myers Squibb, Merck, and Novartis; serving on advisory boards for Amgen and Cytokinetics; and serving as a consultant for Amgen and Merck.
  • DeVore reports receiving research funding through his institution from the American Heart Association, Amgen, AstraZeneca, Bayer, Intra-Cellular Therapies, American Regent, Inc., the National Heart, Lung, and Blood Institute, Novartis, and the Patient-Centered Outcomes Research Institute; and consulting for Amgen, AstraZeneca, Bayer, Novartis, and scPharmaceuticals.