Guidance on titrating therapy for heart failure with reduced ejection fraction

Recent developments in the management of heart failure (HF) are reviewed in a new article written by Canadian pharmacists. Highlights are summarized below: Systolic dysfunction is now referred to as HF with reduced ejection fraction (HFrEF), defined as a left ventricular ejection fraction (LVEF) of ≤ 40%.(1) A table within the article reviews the classification of HF according to a) NYHA functional classification (I to IV), with severity descriptions and examples of activities that patients can perform without producing symptoms, for each of the four HF categories; and b) ejection fraction, with LVEF for each of the four HF categories.(1) Individuals with HF have a mortality rate of about 50% within five years of diagnosis. They also have a high risk of being hospitalized for HF, which is associated with a subsequent increased risk of death.(1) Underuse and underdosing of HFrEF medications are believed to be key contributors to the continued high rates of mortality and HF hospitalizations.(1) The article includes a table of individual drugs that have evidence for reducing mortality and morbidity in individuals with HFrEF, along with initial doses, target doses and select monitoring parameters.(1) Medications, such as sacubitril-valsartan and sodium-glucose cotransporter-2 (SGLT2) inhibitors (dapagliflozin, empagliflozin), have been added to the list of agents that provide mortality and morbidity benefits in HFrEF.(1) Recommended pharmacotherapy for most patients has expanded to include four types of foundational medications, also referred to as HFrEF quadruple therapy.(1) Quadruple therapy consists of an angiotensin receptor-neprilysin inhibitor (sacubitril-valsartan; as first-line therapy or after angiotensin converting enzyme inhibitor/angiotensin receptor blocker titration); a beta-blocker; a mineralocorticoid receptor antagonist (MRA; eplerenone or spironolactone); and an SGLT2 inhibitor.(2) 2021 Canadian Cardiovascular Society HF guidelines suggest initiating HFrEF quadruple therapy and completing titration to maximally tolerated doses within three to six months of diagnosis.(2) There is no evidence-based sequence for initiating or titrating HFrEF quadruple therapy. The order can be tailored to individuals and additional medications (e.g., ivabradine, digoxin) may be added in select patients as needed.(1) Loop diuretics (e.g., furosemide) are crucial to managing fluid retention, but do not reduce the risk of mortality and may limit the titration of other mortality-reducing HF medications. They should be reassessed at every visit and tapered to the minimum effective dose to maintain euvolemia.(1) The article tabulates medications that can cause or worsen HF, including those that cause fluid retention, decrease cardiac output or have high sodium content, certain oncology drugs, and miscellaneous medications that can cause cardiotoxicity.(1) A patient case is used to illustrate how HFrEF quadruple therapy can be initiated and titrated within a six-month time frame. The patient case also highlights practical approaches to managing some common clinical concerns related to HF medications, including mild hyperkalemia after starting a MRA, asymptomatic hypotension with sacubitril-valsartan, reduced renal function after starting an SGLT2 inhibitor, and reassessing diuretics at every visit to maintain euvolemia.(1) The article provides a link to a more detailed summary of practical tips for managing common clinical concerns that may arise when optimizing HFrEF medications, prepared by RxFiles Academic Detailing, College of Pharmacy and Nutrition, University of Saskatchewan.(3) The authors note that virtual or telephone visits can be used to start medications (e.g., MRAs, SGLT2 inhibitors), titrate medications, and follow up with patients if their HF is stable, provided that patients have demonstrated the ability to self-assess their HF symptoms and have tools at home to do this (e.g., weigh scale, blood pressure monitor). Medication adherence should be assessed regularly and efforts made to address any barriers to implementing therapy.(1) References 1. Barry AR, Kosar L, Koshman SL, et al. Medication management for heart failure with reduced ejection fraction. Clinical pearls for optimizing evidenced-informed therapy. Can Family Physician 2021;67:915-22. https://www.cfp.ca/content/cfp/67/12/915.full.pdf (accessed December 30, 2021). 2. McDonald M, Virani S, Chan M, et al. 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(4):531-46. https://www.onlinecjc.ca/action/showPdf?pii=S0828-282X%2821%2900055-6 (accessed December 30, 2021). 3. Kosar L; RxFiles. The art of optimizing HF-rEF medications: practical tips for common clinical concerns. https://www.cfp.ca/content/cfp/suppl/2021/12/07/67.12.915.DC1/Heart-Failure-Art-of-Optimizing-HF-rEF-Medications.pdf (accessed December 30, 2021).

Guidance on titrating therapy for heart failure with reduced ejection fraction

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