Scoring System Puts Focus on Medical Therapy Optimization in HFrEF

Patients with heart failure with reduced ejection fraction (HFrEF) who receive guideline-directed medical therapy (GDMT) have lower 2-year rates of all-cause and cardiovascular death than those who receive suboptimal therapy, an analysis of the CHAMP-HF registry shows. Older patients appear apt to reap the most benefit from optimization.

For their study, researchers used a new scoring system developed by the Heart Failure Collaboratory (HFC) to rate patients’ drug regimens as optimal, suboptimal, and acceptable based on prescribing and dosing of HF medications. The score integrates classes and target doses of GDMT while also accounting for known contraindications and intolerances.

Patients scored as optimal had a 23% lower risk of all-cause death and a 21% lower risk of CV death at 2 years than those who had a suboptimal score.

Lead author Vishal N. Rao, MD, MPH (Medical University of South Carolina and the Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston), said the results suggest it may be feasible to apply the new tool in clinical practice as a way of gauging where patients are versus where they should be with regard to GDMT. Until now, it has primarily been used to stratify patients in HF clinical trials.

“Optimal medical therapy scores can be a useful tool to identify potential groups of patients within clinical practice who may require more frequent visits or focused care in order to improve long-term all-cause mortality outcomes,” he said. “However, these scores are not perfect and may certainly require fine-tuning, particularly across heart failure populations in the ambulatory and hospital settings, in order to understand specific heart failure outcomes such as heart failure hospitalizations.”

Generally speaking, younger patients with fewer comorbidities were more likely to be scored as receiving optimal medical therapy (OMT) compared with their older, sicker counterparts—despite the fact that the latter population was poised to derive more benefit. This, Rao noted, is evidence that the score needs to be tested in various groups to ensure the current findings can be replicated.

CHAMP-HF Scoring Results

The most recent guidelines for diagnosis and treatment of acute and chronic HF give class 1 recommendations for prescribing beta-blockers, ACE inhibitors/ARBs/angiotensin receptor-neprilysin inhibitors (ARNIs), mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter 2 (SGLT2) inhibitors at the same time and as soon as possible. Rao and colleagues applied the score to patients from the CHAMP-HF registry, but based their scoring on triple therapy since the study enrolled patients before the introduction of SGLT2 inhibitors.

CHAMP-HF enrolled 4,969 outpatients from 152 sites in the United States. All had chronic HFrEF with LVEF ≤ 40% and were receiving one or more oral medications for HF. The new analysis included 4,582 trial participants (median age 68 years; 29% women) who had available 2-year follow-up.

Participants eligible for triple therapy were categorized by < 50% or ≥ 50% maximal target dosing for each drug class based on prespecified dosing targets. A modified OMT score was generated for each patient based on the sum of points for each medication class, accounting for the combined use and target dosing of GDMT. Maximal points were given for prescribing of all drug class at ≥ 50% maximal target dosing.

Patients were considered suboptimal if they had a score less than 3 and were not on a HF-specific beta-blocker, ACE inhibitor, ARB, or ARNI and had no documented intolerances. A score of 3 was considered acceptable and meant that patients were on an HF-specific beta-blocker and an ACE inhibitor/ARB/ARNI, unless there was a documented intolerance to 1 or both of these agents. Finally, a score of 4 or higher was considered optimal and meant the patient was on an HF-specific beta-blocker and an ACE inhibitor/ARB/ARNI unless there was a documented intolerance to 1 or both of these agents.

The median OMT score across the cohort was 4. Overall, 50% of patients had an optimal score, 35% had a suboptimal score and 14% had an acceptable score.

Patients with optimal baseline OMT scores were more likely to be younger, have college or higher education, and have a greater annual household income. This group also was more likely than the suboptimal and acceptable groups to be enrolled from practices affiliated with teaching universities, transplant centers, and dedicated HF clinics.  

Having suboptimal OMT scores was associated with lower body mass index, greater left ventricular ejection fraction, chronic obstructive lung disease, chronic kidney disease, and depression.

At 2 years, the rate of all-cause death was lowest in those with optimal scores, at 12%, versus 14.1% for those with acceptable scores and 16.2% for those with suboptimal scores (P = 0.010). Similarly, for CV mortality, the rates were 10.2%, 11.2%, and 12.9%, respectively (P = 0.059). No difference was seen by score for the outcomes of HF hospitalization or the composite of CV death or HF hospitalization.

A likely explanation for not seeing a similar pattern in other outcomes is the overall low event rates for non-mortality-related endpoints over the 2-year follow-up, say Rao and colleagues. They further add that use of OMT scores in clinical practice are potentially useful in light of data suggesting that aggregate treatment with contemporary GDMT for HF may result in up to a 41% reduction in all-cause death.

For the endpoint of all-cause death, the most significant difference between the optimal and suboptimal groups in the current study was seen in those age 65 or older (adjusted HR 0.63; 95% CI 0.51-0.79).

Insights and Score Applications

In an editorial accompanying the study in JACC: Heart Failure, Aldo P. Maggioni, MD (Associazione Nazionale Medici Cardiologi Ospedalieri Research Center, Heart Care Foundation, Florence, Italy), points out that a notable characteristic of patients with the highest OMT scores is that they were followed in centers with dedicated HF clinics. This, he says, adds support to prior studies suggesting such clinics offer better outcomes and increased uptake of OMT.

However, the patient population from the CHAMP-HF registry may not fully represent “the entire world of HF, where internists, geriatricians, and intensivists play an important role in managing patients who are generally older, are female, and have more comorbidities,” Maggioni writes.

He also notes that the study doesn’t provide information on the continuity of care or adherence to prescribed therapies.

“It is possible that patients with the highest OMT scores may discontinue treatment or reduce dosages over time, moving from optimal to suboptimal medical treatment. The changes in therapy that are generally common in patients with this serious clinical problem, characterized by possible drug intolerance and/or worsening clinical conditions, should also be considered,” he says.

Now is the best time to really try to understand how we can apply these scores into our electronic health record system. Vishal N. Rao

To TCTMD, Rao said that other analyses of the CHAMP-HF registry of the same population have shown no meaningfully change in dosing or prescribing over the course of 1-2 years.

It’s interesting, too, that despite so many patients in the registry being seen at dedicated HF clinics, “we still see this variation in achievement of optimal medical therapy,” he added. What that may suggest is that while clinical inertia may play some role in the failure to optimize HFrEF patients and keep them optimized, the problem of underprescribing and underdosing may be much more complex and difficult to categorize.

Noncardiovascular comorbidities stood out as clinical characteristics of the patients who didn’t receive OMT, Rao specified.

“I think now is the best time to really try to understand how we can apply these scores into our electronic health record system even though they may not perfectly differentiate the clinical risk for every single patient in front of you,” he said. “It may provide us subgroups within our own clinical practices whom we can draw into more focused care, more frequent visits, and understand their cardiovascular or noncardiovascular conditions that are driving either hospitalization rates or clinical risk [so we can] potentially try to optimize that further with medical therapies and/or consideration for advanced heart failure therapy.”