Highlights
- •Despite long-standing guideline recommendations, triple therapy remains under-used in clinical practice, with only one-fifth of patients with heart failure (HF) and reduced ejection fraction (HFrEF) receiving all 3 classes within 1 year after the index HF diagnosis.
- •Younger patients with lower LVEF, higher natriuretic peptide levels and better renal function were more likely to be initiated on triple therapy, and even after adjustment for potential confounders, triple therapy was associated with better clinical outcomes.
- •Identifying barriers to the timely initiation of triple therapy could help clinicians and policymakers in devising implementation strategies to improve the initiation of quadruple therapy.
ABSTRACT
Background
Quadruple therapy is recommended for the management of patients with heart failure
(HF) and reduced ejection fraction (HFrEF). In order to provide background and identify
barriers to quadruple therapy, in this study, the aim was to explore the time to initiation
of triple therapy in a population-based cohort of patients with de novo HF.
Methods
Adult patients with de novo hospital or emergency department (ED) diagnosis of HF
between April 1, 2008, and March 31, 2018, in Alberta, Canada, were included and were
linked to echocardiography data to identify patients with HFrEF (EF ≤ 40%). Any treatment
with angiotensin-converting enzyme inhibitors/ angiotensin receptor blockers/ angiotensin
receptor neprilysin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists
was captured if prescribed for ≥ 28 days and filled at least once during the 12 months
after the index episode.
Results
Among 14,092 patients with de novo HF and available echocardiography data, 54.9% had
HFrEF. By 1 year after diagnosis, of those in the HFrEF cohort, 9.5% had received
no therapy, 27.5% monotherapy, 41.6% dual therapy, and 21.4% triple therapy. The median
(interquartile range) of time to mono-, dual- and triple therapy in patients with
HFrEF were 1 (0, 26), 8 (0, 44), and 14 (0, 52) days, respectively. Patients who received
triple therapy were younger, more likely to be male and to have higher frequencies
of coronary artery disease, higher glomerular filtration rates and lower left ventricular
ejection fraction levels compared to their counterparts. Patients with triple therapy
had lower rates of clinical outcomes compared to those on no, mono or dual therapy
(adjusted hazard ratio 0.15, 95% confidence interval 0.13, 0.17 for the composite
outcome of death, hospitalization due to HF, or ED visit due to HF).
Conclusion
Despite guideline recommendations, triple therapy is underused and is slowly deployed
in patients with HFrEF, even after hospitalization and ED presentation.
Graphical Abstract
Graphical Abstract
Key Words
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References
- The current and future financial burden of hospital admissions for heart failure in Canada: a cost analysis.CMAJ Open. 2016; 4: E365-Ee70https://doi.org/10.9778/cmajo.20150130
- 2021 Update to the 2017 ACC Expert Consensus Decision Pathway for Optimization of Heart Failure Treatment: Answers to 10 Pivotal Issues About Heart Failure With Reduced Ejection Fraction: a report of the American College of Cardiology Solution Set Oversight Committee.J Am Coll Cardiol. 2021; 77: 772-810https://doi.org/10.1016/j.jacc.2020.11.022
- 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: developed by the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) with the special contribution of the Heart Failure Association (HFA) of the ESC.Eur Heart J. 2021; 42: 3599-3726https://doi.org/10.1093/eurheartj/ehab368
- CCS/CHFS Heart Failure Guidelines Update: defining a new pharmacologic standard of care for heart failure with reduced ejection fraction.Can J Cardiol. 2021; 37: 531-546https://doi.org/10.1016/j.cjca.2021.01.017
- Use of aldosterone antagonists in heart failure.JAMA. 2009; 302: 1658-1665https://doi.org/10.1001/jama.2009.1493
- Adherence to evidence-based guidelines for heart failure in physicians and their patients: lessons from the Heart Failure Adherence RetentionTrial (HART).Congest Heart Fail. 2012; 18: 73-78https://doi.org/10.1111/j.1751-7133.2011.00263.x
- Improving evidence-based care for heart failure in outpatient cardiology practices: primary results of the Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting (IMPROVE HF).Circulation. 2010; 122: 585-596https://doi.org/10.1161/circulationaha.109.934471
- Characteristics, treatments, and outcomes of patients with preserved systolic function hospitalized for heart failure: a report from the OPTIMIZE-HF Registry.J Am Coll Cardiol. 2007; 50: 768-777https://doi.org/10.1016/j.jacc.2007.04.064
- Outpatient management of heart failure in the United States, 2006–2008.Tex Heart Inst J. 2014; 41: 253-261https://doi.org/10.14503/thij-12-2947
- Triple therapy" of heart failure with angiotensin-converting enzyme inhibitor, beta-blocker, and aldosterone antagonist may triple survival time: shouldn't we tell patients?.JACC Heart Fail. 2014; 2: 545-548https://doi.org/10.1016/j.jchf.2014.04.012
- Lancet. 2020; 396: 121-128https://doi.org/10.1016/s0140-6736(20)30748-0
- Pharmacotherapy choice is associated with 2-year mortality for patients with heart failure and reduced ejection fraction.Adv Ther. 2017; 34: 2345-2359https://doi.org/10.1007/s12325-017-0618-4
- Reasons for lack of improvement in treatment with evidence-based therapies in heart failure.J Am Coll Cardiol. 2019; 73: 2384-2387https://doi.org/10.1016/j.jacc.2019.03.464
- Heart failure re-admission: measuring the ever shortening gap between repeat heart failure hospitalizations.PLoS One. 2014; 9e106494https://doi.org/10.1371/journal.pone.0106494
- Trends in heart failure care: has the incident diagnosis of heart failure shifted from the hospital to the emergency department and outpatient clinics?.Eur J Heart Fail. 2011; 13: 142-147https://doi.org/10.1093/eurjhf/hfq185
- Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data.Med Care. 2005; 43: 1130-1139
- Assessing the use of international classification of diseases-10th revision codes from the emergency department for the identification of acute heart failure.JACC Heart Fail. 2015; 3: 386-391https://doi.org/10.1016/j.jchf.2014.11.010
- Validity of information on comorbidity derived rom ICD-9-CCM administrative data.Med Care. 2002; 40: 675-685https://doi.org/10.1097/01.mlr.0000020927.46398.5d
- Validation of a case definition to define hypertension using administrative data.Hypertension. 2009; 54: 1423-1428https://doi.org/10.1161/hypertensionaha.109.139279
- A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.J Chronic Dis. 1987; 40: 373-383https://doi.org/10.1016/0021-9681(87)90171-8
- Improved comorbidity adjustment for predicting mortality in Medicare populations.Health Serv Res. 2003; 38: 1103-1120
- Do outcomes for patients with heart failure vary by emergency department volume?.Circ Heart Fail. 2013; 6: 1147-1154https://doi.org/10.1161/circheartfailure.113.000415
- Factors associated with natriuretic peptide testing in patients presenting to emergency departments with suspected heart failure.Can J Cardiol. 2016; 32: e1-e8https://doi.org/10.1016/j.cjca.2015.11.019
Peterson AM, Nau DP, Cramer JA, Benner J, Gwadry-Sridhar F, Nichol M. A checklist for medication compliance and persistence studies using retrospective databases. Value Health. 2007;10:3–12. 10.1111/j.1524-4733.2006.00139.x
- Eplerenone in patients with systolic heart failure and mild symptoms.N Engl J Med. 2011; 364: 11-21https://doi.org/10.1056/NEJMoa1009492
- Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions.N Engl J Med. 1992; 327: 685-691https://doi.org/10.1056/nejm199209033271003
- Treatment initiation patterns, modifications, and medication adherence among newly diagnosed heart failure patients: a retrospective claims database analysis.J Manag Care Spec Pharm. 2016; 22: 561-571https://doi.org/10.18553/jmcp.2016.22.5.561
- Association of optimal implementation of sodium-glucose cotransporter 2 inhibitor therapy with outcome for patients with heart failure.JAMA Cardiol. 2020; 5: 948-951https://doi.org/10.1001/jamacardio.2020.0898
- Transitional adherence and persistence in the use of aldosterone antagonist therapy in patients with heart failure.Am Heart J. 2013; 165 (979–86.e1)https://doi.org/10.1016/j.ahj.2013.03.007
- Sacubitril/valsartan initiation and postdischarge adherence among patients hospitalized for heart failure.J Card Fail. 2021; 27: 826-836https://doi.org/10.1016/j.cardfail.2021.03.012
- Changes in heart failure outcomes after a province-wide change in health service provision a natural experiment in Alberta.Canada. Circ Heart Fail. 2013; 6: 76-82https://doi.org/10.1161/circheartfailure.112.971119
- Impact of specialist follow-up in outpatients with congestive heart failure.CMAJ. 2005; 172: 189-194https://doi.org/10.1503/cmaj.1032017
- Is heart failure guideline adherence being underestimated? The impact of therapeutic contraindications.Am Heart J. 2012; 164 (750–5.e1)https://doi.org/10.1016/j.ahj.2012.08.002
- Care gaps in adherence to heart failure guidelines: clinical inertia or physiological limitations?.JACC Heart Fail. 2020; 8: 725-738https://doi.org/10.1016/j.jchf.2020.04.019
- From knowledge to practice in chronic cardiovascular disease: a long and winding road.J Am Coll Cardiol. 2004; 43: 1738-1742https://doi.org/10.1016/j.jacc.2003.12.043
- Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry.Eur J Heart Fail. 2020; 22: 92-102https://doi.org/10.1002/ejhf.1645
- Unravelling the interplay between hyperkalaemia, renin–angiotensin– aldosterone inhibitor use and clinical outcomes: data from 9222 chronic heart failure patients of the ESC-HFA-EORP Heart Failure Long-Term Registry.Eur J Heart Fail. 2020; 22: 1378-1389https://doi.org/10.1002/ejhf.1793
- Use of evidence-based therapy in heart failure with reduced ejection fraction across age strata.Eur J Heart Fail. 2022; 24: 1047-1062https://doi.org/10.1002/ejhf.2483
- Factors associated with underuse of mineralocorticoid receptor antagonists in heart failure with reduced ejection fraction: an analysis of 11 215 patients from the Swedish Heart Failure Registry.Eur J Heart Fail. 2018; 20: 1326-1334https://doi.org/10.1002/ejhf.1182
- Initiation, continuation, switching, and withdrawal of heart failure medical therapies during hospitalization.JACC Heart Fail. 2019; 7: 1-12https://doi.org/10.1016/j.jchf.2018.06.011
- Improving care for heart failure with reduced ejection fraction-a potential polypill-based strategy.JAMA. 2020; 324: 2259-2260https://doi.org/10.1001/jama.2020.21395
- Electronic alerts to improve heart failure therapy in outpatient practice.J Am Coll Cardiol. 2022; 79: 2203-2213https://doi.org/10.1016/j.jacc.2022.03.338
- Disparity in the Setting of incident heart failure diagnosis.Circ Heart Fail. 2021; 14e008538https://doi.org/10.1161/circheartfailure.121.008538
Article info
Publication history
Published online: February 06, 2023
Accepted:
January 17,
2023
Received in revised form:
January 13,
2023
Received:
October 9,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 Elsevier Inc. All rights reserved.
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- Time to Quadruple Guideline-Directed Medical Therapy as a Key Performance Measure for Heart FailureJournal of Cardiac Failure
- PreviewThe prevalence of heart failure (HF) continues to steadily rise and now more than 64 million people globally carry the diagnosis.1 Together with a 5-year survival rate of ∼50% and high rates of hospitalization, there are few other conditions across medicine that have such an unfortunate combination of being exceedingly common, morbid, and deadly.2 Fortunately, for patients with HF with reduced ejection (HFrEF), there are now multiple medications definitively proven to substantially increase survival, reduce hospitalizations, and improve patient quality of life.
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