Guideline-Directed Care in Heart Failure Must Target Optimal Dosing
Robert J. DiDomenico, PharmD, FCCP, FHFSA, FACC, who is Associate Professor, Cardiovascular Clinical Pharmacist at the University of Illinois at Chicago College of Pharmacy, brought the 2019 Directions in Pharmacy conference to a close. He discussed improving transitions of care for patients who have heart failure, with an emphasis on the pharmacist’s role. This topic is timely because 6.2 million adults in the United States are currently diagnosed with heart failure. Experts estimate that by 2030, heart failure’s prevalence will increase by 46%. Among adults aged 45 to 95 years, the lifetime risk is 20% to 45%.
In the United States, heart failure and its associated transitions of care are significant problems. Most importantly, 30% of patients who are diagnosed with heart failure will die within 1 year and approximately 50% will die within 5 years. This condition accounts for approximately 900,000 hospitalizations annually. Among Medicare beneficiaries, the 30-day hospital readmission rate approaches 23%, which places heart failure on Medicare’s radar.
Dr. DiDomenico highlighted the pathophysiology of heart failure with reduced ejection fraction (HFrEF), focusing on the neurohormonal models of the disease. He moved on to drug therapy options, which include neurohormonal mediators as well as non-neurohormonal therapies. He advocated for evidencebased, guideline-directed medical therapy (GDMT). After covering the various heart failure stages and functional class definitions, Dr. DiDomenico discussed drug classes commonly used to treat HFrEF. Using an interactive graphic, he started with beta-blockers, indicating that by blocking catecholamine-related vasoconstrictive pathways, beta-blockers decrease heart rate and counteract cardiac remodeling. Beta-blockers are associated with an almost 30% reduction in risk of all-cause mortality.
Next, Dr. DiDomenico discussed the anti–renin-angiotensinaldosterone (RAAS) medications. These include angiotensinconverting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists (MRAs), and angiotensin receptor-neprilysin inhibitors (ARNIs). These drugs lower all-cause mortality by about 20%, although the reduction in mortality varies by specific class. They also reduce risk of heart failure or cardiovascular hospitalizations by up to 35%, and the guidelines strongly recommend use of these drugs. Dr. DiDomenico called the audience’s attention to 1 medication issue: adding an MRA to an ACEI or an ARB increases the incidence of hyperkalemia as high as 10% in some settings. This requires diligent, persistent monitoring because this adverse effect may be delayed.
Many prescribers use nitrates and hydralazine to address oxidative stress. Hydralazine seems to prevent or minimize oxidative stress, while isosorbide dinitrate is metabolized to nitric oxide, resulting in vasodilation. The guidelines strongly recommend adding isosorbide dinitrate and hydralazine to other drugs in African American patients with New York Heart Association (NYHA) class III HFrEF. This combination can also be administered if any patient cannot tolerate ACEIs or ARBs.
Sacubitril/valsartan is an ARNI medication combination that provides “additive effects” compared with valsartan alone. The valsartan component works as the anti-RAAS drugs do. The sacubitril component is a prodrug that is rapidly converted to the active neprilysin inhibitor, preventing the breakdown of the natriuretic peptides, enhancing the vasodilatory effects of these vasoactive substances. When compared with enalapril, sacubitril/ valsartan was associated with a 20% lower risk of cardiovascular death or heart failure hospitalization. Clinicians who transition patients from an ACEI to sacubitril/valsartan should allow at least 36 hours between administration of the 2 drugs to allow the ACEI to clear the body.
Next, Dr. DiDomenico discussed ivabradine. It is the newest of the non-neurohormonal therapies (the other 2 being digoxin and diuretics) and the only non-neurohormonal drug he discussed. Ivabradine significantly reduced the risk of hospitalization for worsening heart failure or cardiovascular death by 18% compared with placebo when added to optimal GDMT, predominantly by lowering the risk of hospitalization for heart failure by 26%. It also reduced the risk of death from heart failure by 26%.
Dr. DiDomenico stressed that clinicians must follow heart failure treatment guidelines and utilize transitions of care as an opportunity to improve the GDMT regimens of their patients. GDMT is often underutilized in patients with HFrEF, particularly at the time of hospital discharge. Unless contraindicated, all patients with HFrEF should be treated with a beta-blocker and either an ACEI or ARB. Clinicians need to make decisions based on patients’ renal status, potassium levels, and blood pressures. They also need to look at heart rates when patients are taking betablockers and consider ACEI or ARB intolerance. Ancestry should also be considered as African American patients with NYHA class III heart failure should be considered for the combination of isosorbide dinitrate and hydralazine, if possible.
While prescribing appropriate GDMT is important, he emphasized that these drugs should be titrated to the target dose rather than an arbitrary physiologic response (eg, blood pressure). He demonstrated that half of patients treated with beta-blockers and anti-RAAS drugs in the United States are prescribed doses less than 50% of the target dose, potentially increasing the risk of death. Dr. DiDomenico’s final message: Pharmacists must focus on the dose. Pharmacists are well poised to work with other clinicians and encourage dose titration in appropriate patients.
Dr. DiDomenico discussed treatment goals (symptomatic control, prevention of hospitalization, reduced mortality, excellent patient education, and use of guideline-based pharmacotherapies at target doses) as well as how pharmacists help ensure good outcomes during transitions of care. Key elements include medication reconciliation, participation in the multidisciplinary team, patient and caregiver education, and active involvement at the time of discharge and during post-discharge follow-up. Pharmacists need to clarify any discrepancies they identify and ensure that automated refills are appropriately continued or discontinued. Pharmacists also need to understand the unique needs of individuals who are medically underserved or homeless.
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