Long-Term Care Updates

Transcription

1 Long-Term Care Updates July 2015 By Amy Friedman Wilson, PharmD Heart failure (HF) is a clinical condition in which ventricular filling or ejection of blood is structurally or functionally impaired. 1 Primary symptoms of HF include dyspnea, fatigue and fluid retention. The incidence of HF increases with age. Estimates indicate that in the United States, persons aged 65 to 69 years old have a 2% rate of HF. 2 This incidence increases to more than 8% in the population 85 years of age. Heart failure has been identified as a leading cause of hospitalization and re-hospitalization in the Medicare population. 2 Data suggest those patients discharged to a skilled nursing facility (SNF) are at very high risk for re-hospitalization and death. The prevalence of HF in the SNF population is estimated to approach 30%. Diagnosis of HF is clinical in nature, based upon physical examination and a history of symptoms. Two classification systems, the American College of Cardiology Foundation (ACCF)/American Heart Association (AHA) Stages of Heart Failure and the New York Heart Association (NYHA) Functional Classification, are currently in used in practice to assist in guiding management of HF patients. The systems are complementary to each other. The ACCF/AHA stages (A through D) focus on disease development and progression, whereas the NYHA classes (I through IV) address symptomatic status and exercise capacity. See Table 1 for a comparison of these classification systems.

2 Table 1: Comparison of Heart Failure Classification Schemes A: At high risk for HF without structural heart disease or symptoms of HF None B: Structural heart disease without signs or symptoms of HF I: No limitation of physical activity. Ordinary physical activity does not cause HF symptoms. C: Structural heart disease with prior or current symptoms of HF I: No limitation of physical activity. Ordinary physical activity does not cause HF symptoms. II: Slight limitation of physical activity. Comfortable at rest, but less than ordinary activity causes HF symptoms. III: Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes HF symptoms. IV: Unable to carry on any physical activity without HF symptoms, or HF symptoms at rest. D. Refractory HR requiring specialized interventions IV: Unable to carry on any physical activity without HF symptoms, or HF symptoms at rest. Heart failure treatment includes both non-pharmacologic and pharmacologic interventions. Management of contributing co-morbidities (e.g., hypertension or hyperlipidemia) and/or other conditions that may impact HF (e.g., obesity, diabetes, tobacco use) is critical. This article will address the pharmacologic management of HF, based on current guidance from the American College of Cardiology Foundation and American Heart Association (ACCF/AHA); American Heart Association and Heart Failure Society of America (AHA/HFSA) and AMDA: The Society for Post-Acute and Long-Term Care Medicine (AMDA). Although these guidance documents are developed based on the most recently available evidence at the time of publication, clinician judgment should be used when assessing and managing individual patient situations.

3 The American College of Cardiology Foundation and American Heart Association (ACCF/AHA) jointly issued practice guidelines for the management of HF in These guidelines are intended for use in the general adult population. Pharmacologic treatment recommendations are organized by ACCF/AHA Stage, and further characterized by Class of Recommendation and Level of Evidence assignment. General recommendations related to pharmacotherapy in each stage are included below. For more specific information on the total approach to management of each Stage of disease, please refer to the full guidelines. Stage A patients are at high risk for the development of HF, but are not yet exhibiting symptoms or structural changes associated with disease. Persons in this category have risk factors that predispose them to HF, including coronary artery disease, hypertension and diabetes. This population has no specific pharmacologic therapy recommendations beyond appropriate management of hypertension and hyperlipidemia. The majority of meaningful pharmacologic therapy is focused on patients classified as having Stage B or C failure, which is outlined below. In addition, Table 2 provides a brief summary of the class of drugs and role in therapy. Patients categorized as Stage D are experiencing refractory HF. This stage requires specialized intervention, such as mechanical circulatory support and/or cardiac transplantation. This population should receive intravenous inotropic support as adjunctive therapy in their management. It should be noted that individual patient characteristics must be considered when choosing a drug regimen. Table 2: Drug Therapy by ACCF/AHA Stage Medication/Class Stage B Stage C ACE-Inhibitors X X ARBs X X Beta-Blockers* X X Statins X X Diuretics X X Aldosterone Receptor Antagonists X X (caution) Hydralazine/ISDN X Digoxin X ACE: Angiotensin-converting enzyme; ARB: Angiotensin receptor blocker; CCB: Calcium channel blocker; ISDN: Isosorbide dinitrate; *mortality-reducing agents (bisoprolol, carvedilol, metoprolol succinate SR)

4 T Symptom prevention and mortality reduction All patients with a history of myocardial infarction (MI) or acute coronary syndrome (ACS) and reduced ejection fraction (HFrEF). Patients with reduced ejection fraction without a history of MI should still receive for symptomatic benefit. Consider ARBs in patients intolerant to ACE inhibitors (if not contraindicated) Mortality reduction All patients with a history of myocardial infarction (MI) or acute coronary syndrome (ACS) and reduced ejection fraction (EF). Patients with reduced ejection fraction without a history of MI should still receive for symptomatic benefit. Evidence-based agents should be selected: bisoprolol, carvedilol, metoprolol succinate SR Symptom and cardiovascular event prevention All patients with a history of MI Symptom control Patients with fluid retention and reduced symptom ejection fraction Morbidity and mortality reduction Patients intolerant to ACE Inhibitors o o o May be considered first line alternative to ACE Inhibitor May be given in addition to ACE Inhibitor in HFrEF patients with persistent symptoms when aldosterone antagonists are not indicated or tolerated Routine use of an ACE Inhibitor, ARB and Aldosterone Antagonist may be harmful Morbidity and mortality reduction Patients with - NYHA Class II-IV HF and LVEF 35% - NYHA Class II with prior cardiac hospitalization or elected plasma natriuretic peptide levels o o Harm if increased creatinine or potassium: Creatinine 2.5 mg/dl (men); 2.0 mg/dl (women); K <5 meq/l May be used following acute MI with LVEF 40% with HF symptoms or history of DM Morbidity and mortality reduction African American patients with Class III-IV HFrEF receiving optimal ACE Inhibitor & beta blocker therapy May be useful in patients with current or prior HFeEF who cannot take ACE I/ARB Decreased hospitalization

5 The American Heart Association and Heart Failure Society of America (AHA/HFSA) jointly issued a scientific statement on Heart Failure Management in Skilled Nursing Facilities (SNF), which was published in This statement addresses comprehensive care of HF in the SNF population, with a goal of improving patient outcomes and decreasing hospitalizations. The guidelines categorize patients into 3 groups, based on clinical scenarios and goals: Recently discharged from hospital with the goal of recovering independent function and returning to prior residence Discharged from hospital with complications, frailty or multiple comorbidities; recovery is uncertain Residents with frailty and dependency who are expected to remain in SNF care until death This scientific statement provides an overview of the medical management of HF patients, in relation to their admission goals. With regard to pharmacotherapy for HF patients, the guidance reflects recommendations from the ACCF/AHA Practice Guidelines (see above). However, the statement indicates that treatment should be individualized within the context of the patient-specific goal. In addition, adverse effects, costs and personal preferences should be considered. Pharmacologic management of HFrEF for SNF residents should generally reflect that of community-dwelling patients with similar disease status; however the increased age and co-morbidity burden place SNF patients at an increased risk for adverse effects, drug drug and drug-disease interactions. Pharmacotherapy has not been shown to improve survival for patients experiencing failure with preserved ejection fraction. Therefore, treatment for this population should focus on minimizing symptoms, improving quality of life and reducing hospitalizations.

6 AMDA clinical practice guidelines for the management of heart failure in the post-acute and long-term care setting were updated in The goal of the document is to guide recognition, assessment, treatment and monitoring of heart failure patients in these settings. This population of patients is more likely to be older (greater than 80 years of age), female and have multiple co-morbidities and medications. In addition, data show that patients discharged to a LTC facility with heart failure have an increased risk of death or re-hospitalization as compared to those discharged home. Overall, the guidelines address improving quality of life, minimizing hospitalizations or readmissions and providing symptoms relief. However, because of the circumstances of patients in this population, the goals of management are broad in scope and may address additional issues including prolonging life to the extent possible or desired and providing palliative and hospice care. The need for interprofessional collaboration to address the needs of the entire patient is stressed throughout the document. Clinically, the AMDA guidelines rely heavily on the pharmacologic treatment recommendations put forth by the ACCF/AHA, which are described above. In addition, the guidelines strongly recommend loop diuretic therapy for patients with evidence of fluid retention and avoidance of non-steroidal anti-inflammatory drugs (NSAIDs). Considerations related to adjustments or modifications of medication choice and/or dosing in the elderly population are addressed. Entresto is a new agent indicated to reduce the risk of cardiovascular death and hospitalization for heart failure patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction. 4 The product was approved in July 2015 and is a combination of sacubitril (a neprilysin inhibitor) and valsartan (an ARB). The combination product is generally administered as an alternative to an ACE-Inhibitor or ARB, in conjunction with other heart failure therapies.

7 Neprilysin is responsible for the degradation of atrial and brain natriuretic peptide; inhibition from sacubitril results in increased levels of peptide which affect cardiovascular and renal activity. Valsartan inhibits angiotensin II effects through selective blocking of this receptor. Angiotensin II-dependent aldosterone release is also inhibited. In combination, these actions result in decreases in vasoconstriction, sodium retention, maladaptive modeling and blood pressure. Sacubitril/valsartan exhibits linear pharmacokinetics. The combination product is minimally metabolized by CYP450, so co-administration with other drugs that impact CYP450 enzymes is not expected to have an effect on the pharmacokinetic parameters. Sacubitril/valsartan was approved based on the results of PARADIGM-HF, a large, multinational, randomized doubleblind trial that compared the combination product to enalapril in more than 8,000 adult patients with symptomatic chronic heart failure and systolic dysfunction. 5 The majority of patients were categorized as NYHA class II (approximately 70%) and class III (approximately 24%). The average age of patients enrolled was 63, with 80% of the population male and 66% reporting their race as white. Approximately 5% of patients reported to be black. The majority of patients were taking beta-blockers, diuretics and aldosterone (mineralocorticoid) antagonists. Patients enrolled participated in a run-in period of enalapril 10mg orally twice daily, followed by sacubitril/valsartan 100mg twice daily, which was increased to 200mg twice daily. Patients successfully completing the run-in period were randomized to receive either sacubitril/valsartan 200mg twice daily (n=4209) or enalapril 10mg twice daily (n=4223). The primary outcome of the study was a composite of cardiovascular death or first hospitalization due to heart failure. The study was stopped prematurely due to positive results with the sacubitril/valsartan group; the composite end point was identified in 21.8% of patients

8 of patients in the sacubitril/valsartan group and 26.5% in the enalapril group. [(HR=0.80; 95% CI 0.73 to 0.87); p<0.001; NNT 21]. Based on these results, for every 21 patients treated with sacubitril/valsartan 200mg twice daily as compared to enalapril 10mg as in the study, one additional person would avoid experiencing cardiovascular death or first hospitalization due to heart failure. Death from any cause, cardiovascular death and HR-related hospitalization were also significantly lower in the sacubitril/valsartan population. Significantly more patients in the sacubitril/valsartan group experienced symptomatic hypotension compared to those receiving valsartan (14% vs 9.2%; p<0.001; NNH 21). Mean systolic blood pressure 8 months after initiating therapy was 3.2±0.4 mm Hg lower in the sacubitril/valsartan group (p<0.001). The clinical significance of this difference is unclear. Sacubitril/valsartan is contraindicated in patients with a history of angioedema to ACE-Inhibitors or ARBs, and should be avoided within 36 hours of switching to or from an ACE-Inhibitor. It should also not be used with combination with aliskiren in diabetic patients, due to the risk of renal impairment, hypotension and hyperkalemia. 7 Sacubitril/valsartan holds a Boxed Warning related to fetal toxicity, and as previously described, has been associated with lowered blood pressure, kidney impairment and increased potassium levels. There is potential concern related to the development of dementia due to the inhibition of Beta-amyloid peptide, which could result in amyloid deposition in the brain. 6 Cognition issues were not identified in the clinical data, however, the trial length of 2.5 years may not have supported such long-term findings. Significantly more patients in the sacubitril/valsartan group experienced symptomatic hypotension compared to those receiving valsara findings. Any correlation between the drug and dementia is not clear at this time. Although drug interactions related to metabolism are not likely, sacubitril/valsartan should be avoided or used with caution with other agents that block the renin-angiotensin-aldosterone system, potassium-sparing diuretics, NSAIDs and lithium.

9 Sacubitril/valsartan is available in 24/26 mg, 49/51 mg and 97/103 mg strengths. The recommended starting dose is 49/51 mg twice daily, with an increase to the maintenance dose of 97/103 mg within 2 to 4 weeks. Patients not previously taking an ACE-Inhibitor or ARB, or those previously taking low doses of these medications should be started at 24/26 mg twice daily and titrated to 97/103 mg twice daily as tolerated by the patient. Dosage adjustments are recommended for severe renal impairment (egfr < 30mL/min/1.73m 2 ) and moderate hepatic (Child-Pugh B) impairment. The most recent heart failure guidelines do not recommend sacubitril/valsartan due to the ACCF/AHA AHA/HFSA AMDA: The Society of Post-Acute and Long- Term Care Medicine timing of product approval in relation to the most recent guideline updates. However, it appears that sacubitril/valsartan may offer an alternative therapy to ACE-Inhibitors or ARBs for management of HF patients. Although positive results have been shown, there are factors to consider before a place in therapy can be established. Attention should be given to the comparison doses of valsartan to enalparil in the trial. Valsartan was given at a high dose, compared to a low to moderate dose of enalapril. It is unclear if results would have been similar with an optimized dose of enalapril. In addition, the study population of relatively young, male, white patients may not be reflective of the typical HF patient. The impact of the hypotension experienced is not clear, and may be of concern. Finally, the absolute difference in death rate was 2.8% over 2.5 years. These factors suggest that more data may help to identify the role that sacubitril/valsartan will play in the management of chronic heart failure.

10 Summary: Heart failure is a common chronic condition among the elderly population. Published evidence-based guidelines are available to assist in managing care. Multiple established therapeutic agents have shown positive outcomes in the treatment of heart failure. Furthermore, agents with unique mechanisms of action may provide additional methods of treating this condition. Additional data will help to clarify the role newer agents may play in the management of chronic heart failure. References: 1. Yancy CW, Jessup M, Bozkurt B et al 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 ; 128:e240-e Jurgens CY, Goodlin S, Dolasky M et al. Heart failure management: A scientific statement from the American Heart Association and the Heart Failure Society of America. 2015;8(3): American Medical Directors Association. Heart failure in the post-acute and long-term care setting clinical practice guideline. Columbia, MD: AMDA Entresto [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; July McMurray JJV, Packer MP, Desai AS et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. 2014;371(11): Vodovar N, Paquet C, Mebazaa A et al. Neprilysin, cardiovascular and Alzheimer s diseases: The therapeutic split? 2015;36(15): U.S. Food and Drug Administration. FDA Drug Safety Communication: New warning and contraindication for blood pressure medicines containing aliskiren (Tekturna). Accessed July 25,