Potential impact of optimal implementation of evidence-based heart failure therapies on mortality

doi:10.1016/j.ahj.2011.01.027

American Heart Journal

Volume 161, Issue 6, June 2011, Pages 1024-1030.e3

https://doi.org/10.1016/j.ahj.2011.01.027 Get rights and content

Background

Although multiple therapies have been shown to lower mortality in patients with heart failure (HF) and reduced left ventricular ejection fraction, their application in clinical practice has been less than ideal. To date, empiric estimation of the potential benefits that could be gained from eliminating these existing treatment gaps with optimal implementation has not been quantified.

Methods

Eligibility criteria for each evidence-based HF therapy, the estimated frequency of use/nonuse of specific treatments, the case fatality rates, and the risk reductions due to treatment were obtained from published sources. The numbers of deaths prevented or postponed because of each guideline-recommended therapy and overall were determined.

Results

Among patients with HF with reduced left ventricular ejection fraction in the United States (n = 2,644,800), the number eligible but not currently treated ranged from 139,749 for hydralazine/isorbide dinitrate to 852,512 for implantable cardioverter defibrillators. The comparative number of deaths that could potentially be prevented per year with optimal implementation of angiotensin-converting enzyme inhibitor/angiotensin receptor antagonist is 6,516; β-blockers, 12,922; aldosterone antagonists, 21,407; hydralazine/isorbide dinitrate, 6,655; cardiac resynchronization therapy, 8,317; and implantable cardioverter defibrillators, 12,179. If these treatment benefits were additive, optimal implementation of all 6 therapies could potentially prevent 67,996 deaths a year.

Conclusions

A substantial number of HF deaths in this country could potentially be prevented by optimal implementation of evidence-based therapies. These data may underscore the importance of performance improvement efforts to translate evidence-based therapy to routine clinical practice so as to reduce contemporary HF mortality.

Section snippets

Evidence-based, guideline-recommended HF therapies

Six HF therapies have been demonstrated in randomized clinical trials to reduce all-cause mortality and for which the evidence has been judged to be sufficient to warrant a class I guideline recommendation in the most current version of the American College of Cardiology/American Heart Association HF guidelines.3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 The identified mortality-reducing therapies for HF with reduced LVEF are (1) ACEI or ARB, (2) β-blocker, (3)

Results

The prevalence of HF is 5,800,000, and 48% of these patients have LVEF <40%.1, 23, 26, 27, 28 Of the 2,784,000 patients with HF and reduced LVEF, 4% of patients under hospice or comfort care only measures and 1% receiving continuous inotropic agents, requiring ventricular assist devices, or requiring urgent heart transplantation were excluded.1, 23, 25, 26, 27, 28, 29 For the remaining 2,644,800 patients with HF and LVEF <40%, additional eligibility and exclusion criteria for each individual

Discussion

The burden of HF in the United States is enormous.¹ The last 2 decades have seen 4 types of pharmaceutical treatments and 2 device-based therapies become proven in randomized clinical trials to reduce all-cause mortality in patients with HF and reduced LVEF.2, 3 Each of these therapies has received the highest level recommendation (class I) in national guidelines, having proven benefits that outweigh the potential risks and for which it is recommended that each of these therapies should be

Conclusions

We have demonstrated the potential gains that may be achieved with optimal application of current therapeutic approaches for HF. A substantial number of deaths may be prevented by optimal implementation of evidence-based, guideline-recommended HF therapies if the efficacy demonstrated in clinical trials translates to clinical effectiveness in practice. The expected gains would be much smaller if performance improvement efforts are limited to only a few of these therapies. Given the substantial

Disclosures

Gregg C. Fonarow, MD: research grants, National Institutes of Health (significant); consultant, Novartis (significant); honoraria, Medtronic (modest).

Clyde W. Yancy, MD: no relationships to disclose.

Eric D. Peterson, MD: research grants from Bristol-Myers Squibb/Schering Plough (significant).

Adrian F. Hernandez, MD: research support from Johnson & Johnson, Amylin, and Proventys (all significant) and receiving honoraria from AstraZeneca, Corthera, and Medtronic (all modest).

John A. Spertus, MD:

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Cited by (183)

Impact of Visit Volume on the Effectiveness of Electronic Tools to Improve Heart Failure Care
2024, JACC: Heart Failure
Electronic health record (EHR) tools can improve prescribing of guideline-recommended therapies for heart failure with reduced ejection fraction (HFrEF), but their effectiveness may vary by physician workload.
This paper aims to assess whether physician workload modifies the effectiveness of EHR tools for HFrEF.
This was a prespecified subgroup analysis of the BETTER CARE-HF (Building Electronic Tools to Enhance and Reinforce Cardiovascular Recommendations for Heart Failure) cluster-randomized trial, which compared effectiveness of an alert vs message vs usual care on prescribing of mineralocorticoid antagonists (MRAs). The trial included adults with HFrEF seen in cardiology offices who were eligible for and not prescribed MRAs. Visit volume was defined at the cardiologist-level as number of visits per 6-month study period (high = upper tertile vs non-high = remaining). Analysis at the patient-level used likelihood ratio test for interaction with log-binomial models.
Among 2,211 patients seen by 174 cardiologists, 932 (42.2%) were seen by high-volume cardiologists (median: 1,853; Q1-Q3: 1,637-2,225 visits/6 mo; and median: 10; Q1-Q3: 9-12 visits/half-day). MRA was prescribed to 5.5% in the high-volume vs 14.8% in the non–high-volume groups in the usual care arm, 10.3% vs 19.6% in the message arm, and 31.2% vs 28.2% in the alert arm, respectively. Visit volume modified treatment effect (P for interaction = 0.02) such that the alert was more effective in the high-volume group (relative risk: 5.16; 95% CI: 2.57-10.4) than the non–high-volume group (relative risk: 1.93; 95% CI: 1.29-2.90).
An EHR-embedded alert increased prescribing by >5-fold among patients seen by high-volume cardiologists. Our findings support use of EHR alerts, especially in busy practice settings. (Building Electronic Tools to Enhance and Reinforce Cardiovascular Recommendations for Heart Failure [BETTER CARE-HF]; NCT05275920)
Heart Failure Epidemiology and Outcomes Statistics: A Report of the Heart Failure Society of America
2023, Journal of Cardiac Failure
A Computable Algorithm for Medication Optimization in Heart Failure With Reduced Ejection Fraction
2023, JACC: Advances
Guideline-directed medical therapy (GDMT) optimization can improve outcomes in heart failure with reduced ejection fraction.
The objective of this study was to determine if a novel computable algorithm appropriately recommended GDMT.
Clinical trial data from the GUIDE-IT (Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment in Heart Failure) and HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trials were evaluated with a computable medication optimization algorithm that outputs GDMT recommendations and a medication optimization score (MOS). Algorithm-based recommendations were compared to medication changes. A Cox proportional-hazards model was used to estimate the associations between MOS and the composite primary end point for both trials.
The algorithm recommended initiation of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, beta-blockers, and mineralocorticoid receptor antagonists in 52.8%, 34.9%, and 68.1% of GUIDE-IT visits, respectively, when not prescribed the drug. Initiation only occurred in 20.8%, 56.9%, and 15.8% of subsequent visits. The algorithm also identified dose titration in 48.8% of visits for angiotensin-converting enzyme inhibitor/angiotensin receptor blockers and 39.4% of visits for beta-blockers. Those increases only occurred in 24.3% and 36.8% of subsequent visits. A higher baseline MOS was associated with a lower risk of cardiovascular death or heart failure hospitalization (HR: 0.41; 95% CI: 0.21-0.80; P = 0.009) in GUIDE-IT and all-cause death and hospitalization (HR: 0.61; 95% CI: 0.44-0.84; P = 0.003) in HF-ACTION.
The algorithm accurately identified patients for GDMT optimization. Even in a clinical trial with robust protocols, GDMT could have been further optimized in a meaningful number of visits. The algorithm-generated MOS was associated with a lower risk of clinical outcomes. Implementation into clinical care may identify and address suboptimal GDMT in patients with heart failure with reduced ejection fraction.
The EHR Has Exposed an Urgent Moral Imperative to Improve Heart Failure Care
2023, Journal of the American College of Cardiology
Cluster-Randomized Trial Comparing Ambulatory Decision Support Tools to Improve Heart Failure Care
2023, Journal of the American College of Cardiology
Mineralocorticoid receptor antagonists (MRAs) are underprescribed for patients with heart failure with reduced ejection fraction (HFrEF).
This study sought to compare effectiveness of 2 automated, electronic health record–embedded tools vs usual care on MRA prescribing in eligible patients with HFrEF.
BETTER CARE-HF (Building Electronic Tools to Enhance and Reinforce Cardiovascular Recommendations for Heart Failure) was a 3-arm, pragmatic, cluster-randomized trial comparing the effectiveness of an alert during individual patient encounters vs a message about multiple patients between encounters vs usual care on MRA prescribing. This study included adult patients with HFrEF, no active MRA prescription, no contraindication to MRAs, and an outpatient cardiologist in a large health system. Patients were cluster-randomized by cardiologist (60 per arm).
The study included 2,211 patients (alert: 755, message: 812, usual care [control]: 644), with average age 72.2 years, average ejection fraction 33%, who were predominantly male (71.4%) and White (68.9%). New MRA prescribing occurred in 29.6% of patients in the alert arm, 15.6% in the message arm, and 11.7% in the control arm. The alert more than doubled MRA prescribing compared to usual care (relative risk: 2.53; 95% CI: 1.77-3.62; P < 0.0001) and improved MRA prescribing compared to the message (relative risk: 1.67; 95% CI: 1.21-2.29; P = 0.002). The number of patients with alert needed to result in an additional MRA prescription was 5.6.
An automated, patient-specific, electronic health record–embedded alert increased MRA prescribing compared to both a message and usual care. These findings highlight the potential for electronic health record–embedded tools to substantially increase prescription of life-saving therapies for HFrEF. (Building Electronic Tools to Enhance and Reinforce Cardiovascular Recommendations—Heart Failure [BETTER CARE-HF]; NCT05275920)
Design and pilot implementation for the BETTER CARE-HF trial: A pragmatic cluster-randomized controlled trial comparing two targeted approaches to ambulatory clinical decision support for cardiologists
2023, American Heart Journal
Beart failure with reduced ejection fraction (HFrEF) is a leading cause of morbidity and mortality. However, shortfalls in prescribing of proven therapies, particularly mineralocorticoid receptor antagonist (MRA) therapy, account for several thousand preventable deaths per year nationwide. Electronic clinical decision support (CDS) is a potential low-cost and scalable solution to improve prescribing of therapies. However, the optimal timing and format of CDS tools is unknown.
We developed two targeted CDS tools to inform cardiologists of gaps in MRA therapy for patients with HFrEF and without contraindication to MRA therapy: (1) an alert that notifies cardiologists at the time of patient visit, and (2) an automated electronic message that allows for review between visits. We designed these tools using an established CDS framework and findings from semistructured interviews with cardiologists. We then pilot tested both CDS tools (n = 596 patients) and further enhanced them based on additional semistructured interviews (n = 11 cardiologists). The message was modified to reduce the number of patients listed, include future visits, and list date of next visit. The alert was modified to improve noticeability, reduce extraneous information on guidelines, and include key information on contraindications.
The BETTER CARE-HF (Building Electronic Tools to Enhance and Reinforce CArdiovascular REcommendations for Heart Failure) trial aims to compare the effectiveness of the alert vs. the automated message vs. usual care on the primary outcome of MRA prescribing. To our knowledge, no study has directly compared the efficacy of these two different types of electronic CDS interventions. If effective, our findings can be rapidly disseminated to improve morbidity and mortality for patients with HFrEF, and can also inform the development of future CDS interventions for other disease states. (Trial registration: Clinicaltrials.gov NCT05275920).

View all citing articles on Scopus

: Jerome Fleg, MD, served as guest editor for this article.

View full text

Clinical InvestigationCongestive Heart FailurePotential impact of optimal implementation of evidence-based heart failure therapies on mortality

Background

Methods

Results

Conclusions

Section snippets

Evidence-based, guideline-recommended HF therapies

Results

Discussion

Conclusions

Disclosures

Lancet

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Heart Rhythm

Am Heart J

J Am Coll Cardiol

J Card Fail

J Card Fail

J Am Coll Cardiol

Heart disease and stroke statistics—2010 update: a report from the American Heart Association

Circulation

ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult

Circulation

2009 focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults

Circulation

Effect of enalapril in patients with reduced left ventricular ejection fractions and congestive heart failure

N Engl J Med

Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. Collaborative Group on ACE Inhibitor Trials

JAMA

Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF)

Lancet

Effect of carvedilol on survival in severe chronic heart failure

N Engl J Med

Beta-blockers in congestive heart failure: a Bayesian meta-analysis

Ann Intern Med

The effect of spironolactone on morbidity and mortality in patients with severe heart failure: Randomized Aldactone Evaluation Study Investigators

N Engl J Med

Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction

N Engl J Med

Aldosterone blockade and left ventricular dysfunction: a systematic review of randomized clinical trials

Eur Heart J

Combination of isosorbide dinitrate and hydralazine in blacks with heart failure

N Engl J Med

Clinical Investigation
Congestive Heart Failure
Potential impact of optimal implementation of evidence-based heart failure therapies on mortality