By Connor Emdin
September 26, 2018
Over the past thirty years, survival after the diagnosis of heart failure has improved, with five-year mortality falling from 57% in 1979 to 1984 to 48% in 1996 to 2000.1 Much of this reduction in mortality has been due to the development of novel therapeutics for treatment of heart failure.2 Large randomized clinical trials have demonstrated that angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), angiotensin receptor neprilysin inhibitors (ARNIs), beta-blockers (BBs) and mineralcorticoid receptor antagonists (MRAs) all reduce the risk of death and re-hospitalization among patients with heart failure with reduced ejection fraction (HFrEF).2 Current guidelines strongly recommend that all eligible patients with HFrEF be treated with a combination of these agents.2
Considering the compelling evidence that guideline-directed therapies improve survival, efforts to assess their application in clinical practice and identify barriers to use are of critical importance. Recently reported in the Journal of American College of Cardiology, CHAMP-HF, was a prospective observational study of adults with HFrEF (defined as those with EF <40%), across 150 cardiology and primary care practices.3 As part of the study protocol, medication dosing along with demographics, data on comorbidities, laboratory findings, and vital signs were recorded. The investigators assessed the proportion of patients with HFrEF who received guideline-directed therapy for HFrEF and also examined the intensity of treatment they received, including the numbers receiving full target doses of each medication.3
Data was recorded between 2015 and 2017 and the study enrolled 3,518 patients with HFrEF. All patients were receiving at least one medication for heart failure, including diuretics, anti-hypertensives, vasoactive/inotropic agents, guideline recommended therapies as above, or other cardiovascular medications. The study population was primarily male (71%), and white (75%) with a mean age of 66 years. These patients had significant HFrEF, with a mean EF 29%.
The data on treatment makes quite striking reading. Around 60.5% of patients were treated with ACEI/ARB, but only 13% received ARNI; despite data from the landmark PARADIGM-HF study which showed a 20% reduction in mortality with treatment with a ARNI/ARB combination therapy (sacubitril-valsartan) versus enalapril, published in 2014 (ref).
Other therapies had similarly low rates of use. Only 67% of eligible patients were prescribed a beta blocker, and only 33% of eligible patients were receiving treatment with MRAs. The investigators found similarly low rates of achieving recommended therapeutic doses of each agent, with more than half of enrolled patients receiving less than 50% of the recommended treatment doses of ACEI/ARB/ARNI, and similar low rates of BB use. Most patients receiving an MRA (77%) received > 100% of the target dose (although only 33% of eligible patients were treated).
|Medication||Eligible Patients (n)||Eligible patients receiving medication (%)||Eligible patients not receiving medication (%)|
|ACEI/ARB/ARNI||3481||2536 (73%)||945 (27%)|
|BB||3510||2351 (67%)||1159 (33%)|
|MRA||3480||1163 (33%)||2317 (67%)|
Overall, only 22% of patients were simultaneously prescribed any dose of the three classes of agents, and only 1% were on target doses of all three therapies. Interestingly, rates of medication use were considerably lower among patients treated at primary care or internal medicine practices, as compared to those treated by cardiologists.
These findings demonstrate that the majority of eligible patients with HFrEF are not receiving the guideline-recommended combination of an ACEI/ARB/ARNI, a BB, and an MRA. As these medications have all been shown to reduce morbidity and mortality in randomized trials, these findings indicate a considerable missed opportunity to reduce the risk of death and hospitalization in this large population of HFrEF patients.
- Roger VL, Weston SA, Redfield MM, et al. Trends in heart failure incidence and survival in a community-based population. JAMA. 2004;292(3):344-350. doi:10.1001/jama.292.3.344.
- Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013;128(16):e240-e327. doi:10.1161/CIR.0b013e31829e8776.
- Greene SJ, Butler J, Albert NM, et al. Medical Therapy for Heart Failure With Reduced Ejection Fraction: The CHAMP-HF Registry. J Am Coll Cardiol. 2018;72(4):351-366. doi:10.1016/j.jacc.2018.04.070.
- McMurray JJ, Packer M, Desai AS, et al. Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure. N Engl J Med 2014; 371:993-1004. DOI: 10.1056/NEJMoa1409077.
- Jefferies JL, Ibrahim NE. Are Guidelines Merely Suggestions? J Am Coll Cardiol. 2018;72(4):367-369. doi:10.1016/j.jacc.2018.05.023.
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Connor Emdin is a post-doctoral research fellow in Sek Kathiresan’s lab at the Broad, specializing in the genetics of cardiovascular disease. He completed his doctorate in cardiovascular epidemiology at the University of Oxford from 2009-2013.
Follow Connor on Twitter: @connoremdin