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Author: Stormi Gale, PharmD, BCCP

Too often, I notice hesitation of inpatient care teams to initiate guideline-directed medical therapy (GDMT) for patients with heart failure prior to discharge, mostly due to safety concerns. Guidelines recommend prompt initiation of GDMT upon diagnosis of heart failure (HF), but don’t specify consideration for patients that are acutely hospitalized.1 Although admitted patients often have acute medical issues that may preclude them from certain therapies (e.g. acute kidney injury, acute decompensation) early on during hospitalization, many patients are appropriate for GDMT once stabilized. As such, I feel that it is important to re-emphasize the need to optimize GDMT prior to discharge, whenever possible.

The importance of initiating GDMT prior to discharge was demonstrated in the Predischarge initiation of carvedilol in patients hospitalized for decompensated heart failure: results of the Initiation Management Predischarge: Process for Assessment of Carvedilol Therapy in Heart Failure (IMPACT-HF) trial.2 This study randomized 363 hospitalized patients with HF to carvedilol initiation pre- and post-hospital discharge. Results demonstrated that although 91.2% of patients randomized to pre-discharge initiation of a beta-blocker (BB) were on a BB at 60 days, this was only true for 73.4% in the post-discharge initiation group. IMPACT-HF revealed that although initiating GDMT as an outpatient theoretically seems appropriate, the reality is that this is not carried out in over 25% of patients. Similar results have also been demonstrated with angiotensin-converting enzyme inhibitors (ACEi), as evidence suggests that patients not discharged on this therapy are unlikely to be started in the outpatient setting.3

IMPACT-HF focused on presence of BB therapy after hospital discharge; however, this study did not assess outcomes associated with post-discharge medication initiation. Recently, a post-hoc analysis of the Registry Focused on Very Early Presentation and Treatment in Emergency Department of Acute Heart Failure (REALITY-AHF) data examined 1,682 patients hospitalized with acute heart failure in Japan.4 Of these, 534 patients with HF with reduced ejection fraction (HFrEF) were assessed for prescription status prior to discharge. Patients were stratified into 3 different groups: 1) those with prescriptions for both a BB and an ACEi or angiotensin receptor blocker (ARB), 2) patients with prescriptions for either a BB or an ACEi/ARB but not both, and 3) patients with neither a prescription for a BB or an ACEi/ARB. This study found that presence of prescriptions for GDMT before discharge was associated with a significant reduction in 1-year mortality (group 2: hazard ratio [HR] 0.44, 95% confidence interval [CI] 0.21 to 0.90, p = 0.025 and group 1: HR 0.29, 95% CI 0.13–0.65, p = 0.002, vs. group 3), but there was no difference in rehospitalization for heart failure. It is well known that certain patient characteristics (e.g. renal dysfunction, hypotension) may preclude the use of GDMT; however, there was no difference in discharge systolic blood pressures and heart rates between groups. Similar to previous studies, not being prescribed GDMT prior to discharge was more common in patients who were 80 years of age or greater.5,6 This real world analysis confirms the importance of pre-discharge initiation of GDMT, including the impact on mortality. Similar outcomes have also been published in the United States, including an analysis of 1,384 Medicare beneficiaries with HFrEF.7 Not only did this study find a mortality benefit in patients discharged with ACEi/ARB therapy, but also a reduction in 30-day all-cause readmission (driven by a reduction in readmissions for HF) in the pre-discharge therapy group. Improved outcomes have also been reported with other GDMT, including a reduction in cardiac death with discharge use of spironolactone.8

Bottom Line
Evidence suggests that pre-discharge initiation of GDMT not only increases the likelihood of therapy long-term, but also translates into improved outcomes. Pre-discharge can be an ideal time to start medications as patients with HF should have close discharge follow-up, and therefore the ability to monitor and possibly uptitrate therapy. In my practice, we emphasize starting even the lowest doses of medications (i.e. lisinopril 2.5 mg) prior to discharge. If nothing else, this can serve as a placeholder for the outpatient physician to uptitrate, although there are known benefits of GDMT even at lower-than-target doses.9 When considering GDMT, as general rule of thumb –something is better than nothing.

 

Stormi Gale, PharmD, BCCP

Dr. Gale is an assistant professor in the Department of Pharmacy Practice and Science at the University of Maryland School of Pharmacy, and practices as a clinical pharmacy specialist at the University of Maryland Medical Center in Baltimore, MD. Follow her on Twitter @stormigale.

References:

  1. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Drazner MH, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure: Executive Summary. Journal of the American College of Cardiology. 2013 Oct;62(16):1495–539.
  2. Gattis WA, O’Connor CM, Gallup DS, Hasselblad V, Gheorghiade M, IMPACT-HF Investigators and Coordinators. Predischarge initiation of carvedilol in patients hospitalized for decompensated heart failure: results of the Initiation Management Predischarge: Process for Assessment of Carvedilol Therapy in Heart Failure (IMPACT-HF) trial. J Am Coll Cardiol. 2004 May 5;43(9):1534–41.
  3. Butler J, Arbogast PG, Daugherty J, Jain MK, Ray WA, Griffin MR. Outpatient utilization of angiotensin-converting enzyme inhibitors among heart failure patients after hospital discharge. Journal of the American College of Cardiology. 2004 Jun 2;43(11):2036–43.
  4. Yamaguchi T, Kitai T, Miyamoto T, Kagiyama N, Okumura T, Kida K, et al. Effect of Optimizing Guideline-Directed Medical Therapy Before Discharge on Mortality and Heart Failure Readmission in Patients Hospitalized With Heart Failure With Reduced Ejection Fraction. The American Journal of Cardiology. 2018 Apr 15;121(8):969–74.
  5. Hamaguchi S, Kinugawa S, Goto D, Tsuchihashi-Makaya M, Yokota T, Yamada S, et al. Predictors of Long-Term Adverse Outcomes in Elderly Patients Over 80 Years Hospitalized With Heart Failure. Circulation Journal. 2011;75(10):2403–10.
  6. Akita K, Kohno T, Kohsaka S, Shiraishi Y, Nagatomo Y, Izumi Y, et al. Current use of guideline-based medical therapy in elderly patients admitted with acute heart failure with reduced ejection fraction and its impact on event-free survival. International Journal of Cardiology. 2017 May 15;235:162–8.
  7. Sanam K, Bhatia V, Bajaj NS, Gaba S, Morgan CJ, Fonarow GC, et al. Renin-Angiotensin System Inhibition and Lower 30-day All-cause Readmission in Medicare Beneficiaries with Heart Failure. Am J Med. 2016 Oct;129(10):1067–73.
  8. Hamaguchi S, Kinugawa S, Tsuchihashi-Makaya M, Goto K, Goto D, Yokota T, et al. Spironolactone use at discharge was associated with improved survival in hospitalized patients with systolic heart failure. American Heart Journal. 2010 Dec 1;160(6):1156–62.
  9. Packer M, Poole-Wilson PA, Armstrong PW, Cleland JG, Horowitz JD, Massie BM, et al. Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. ATLAS Study Group. Circulation. 1999 Dec 7;100(23):2312–8.
Understanding the IMPACT(-HF) of Initiating GDMT Prior to Discharge

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