Acute Diuretic-Sparing Effects of Sacubitril-Valsartan: Staying in the Loop.

BACKGROUND: Previous literature has suggested a potential diuretic sparing effect as early as 6 months following sacubitril-valsartan initiation in patients with heart failure with reduced ejection fraction (HFrEF); however, whether this effect manifests earlier after initiation is unclear. Objective: To evaluate the acute diuretic-sparing effects of sacubitril-valsartan. METHODS: This was a single-center, retrospective analysis of outpatients with HFrEF initiated on sacubitril-valsartan with follow up within 90 ± 30 days and a concomitant loop diuretic prescription. The primary outcome was the percent of patients with an increase, decrease or no change in loop diuretic total daily dose (TDD). Key secondary outcomes included change in loop diuretic TDD (mg furosemide equivalents) and hospital admissions or emergency department (ED) visits. RESULTS: A total of 145 patients were included (overall cohort) with 120 continuing sacubitril-valsartan at follow up (on-treatment cohort). In the on-treatment cohort, 20% (n = 24) had a reduction in loop diuretic TDD and 10% had an increase (n = 12). Median change in loop diuretic TDD was unchanged from baseline to follow up (p 0.13). In patients on >80 mg TDD of furosemide at baseline (n = 9), mean change was-53 ± 44 mg (p 0.006). Hospitalizations (6.2%) and ED visits (0.7%) for heart failure were infrequent. CONCLUSION: Patients may require a loop diuretic dose reduction within 2-3 months following sacubitril-valsartan initiation. This diuretic-sparing effect appears larger in those on higher baseline loop diuretic doses, and closer follow up may be warranted for these patients.

Risk Factors for Intolerance of Inpatient Sacubitril/Valsartan Initiation.

BACKGROUND: Sacubitril/valsartan has been shown to improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF). However, initiation of sacubitril/valsartan has primarily been studied in stable, ambulatory patients with HFrEF. OBJECTIVE: The objective of this study was to determine risk factors for intolerance to inpatient sacubitril/valsartan initiation. METHODS: This was a retrospective, single-center study from August 1, 2015 through April 30, 2018. Patients were at least 18 years old and were newly initiated on sacubitril/valsartan during their hospitalization. RESULTS: A total of 143 patients met inclusion criteria. Of these patients, 20.3% (n = 29) were intolerant to inpatient initiation of sacubitril/valsartan. The primary reason for intolerance was hypotension (n = 19, 65.5%). Patients with newly diagnosed heart failure were more likely to tolerate the initiation of sacubitril/valsartan (32.5% vs 10.3%; P = 0.03). No differences between groups were identified among other potential predictors for intolerance to sacubitril/valsartan, including systolic blood pressure, acutely decompensated heart failure, or serum creatinine. The most common adverse event was hypotension, which occurred in 26.6% (n = 38) of all patients. CONCLUSION: The majority of inpatients tolerated sacubitril/valsartan initiation. Larger, prospective, randomized controlled trials would be helpful in further determining ideal candidates for inpatient sacubitril/valsartan initiation.

Evaluation of a Pharmacist-Driven Aldosterone Antagonist Stewardship Program in Patients With Heart Failure.

OBJECTIVE: To evaluate the impact of a pharmacist-driven initiative to optimize aldosterone antagonist use in patients with heart failure with reduced ejection fraction (HFrEF) at a large community hospital. METHODS: This single-center, retrospective cohort study compared patients with heart failure before and after the implementation of the initiative. Data for pre- and postinitiative patients were retrospectively collected to assess patient characteristics and aldosterone antagonist use. The primary outcome was a composite of eligible patients with heart failure discharged on aldosterone antagonist therapy or with a documented reason for ineligibility before and after commencement of pharmacist-driven aldosterone antagonist initiative. RESULTS: The preinitiative cohort included 96 patients and the postinitiative cohort contained 92 patients. When the 3 month pre- and postinitiative groups were assessed, the primary outcome was noted in 60 (63%) of 96 patients in the preinitiative group and 87 (95%) of 92 patients in the postinitiative group ( P < .0001). CONCLUSION: In patients with HFrEF, a pharmacist-driven aldosterone antagonist optimization initiative significantly increased appropriate prescribing and documentation for aldosterone antagonist therapy.

Elevated Creatine Kinase due to Potential Drug Interaction With Ticagrelor and Atorvastatin.

PURPOSE:: Ticagrelor and atorvastatin are commonly used medications in the management of acute coronary syndrome and percutaneous intervention. This is a report of a patient case of a potential drug interaction leading to the use of alternative therapy. CASE REPORT:: A 58-year-old male presented for cardiac catheterization following an abnormal stress test. He underwent placement of a drug-eluting stent and was started on ticagrelor. Three months later, he was noted to have elevated creatine kinase (CK), thought to be related to a potential drug-drug interaction between ticagrelor and atorvastatin. Ticagrelor was discontinued and he was successfully transitioned to clopidogrel. CK returned to normal within weeks of this change. DISCUSSION:: Pharmacokinetic studies have demonstrated a potential interaction between ticagrelor and atorvastatin but have not been deemed clinically significant. To date, only one other case report has been published discussing this interaction and consideration of alternative therapy. This case report is unique, with ticagrelor being the only new medication added prior to the abnormal CK finding. CONCLUSIONS:: A probable drug-drug interaction occurred with concomitant ticagrelor and atorvastatin. While this interaction may not always be clinically significant, it is reasonable to consider in patients who present with signs and symptoms of adverse effects.

Heparin Versus Bivalirudin Monotherapy in the Setting of Primary Percutaneous Coronary Intervention for Patients With ST-Segment Elevation Myocardial Infarction.

OBJECTIVE: To evaluate direct comparisons of bivalirudin versus unfractionated heparin (UFH) as anticoagulants during ST-segment elevation myocardial infarction (STEMI) in patients undergoing primary percutaneous coronary intervention (PPCI). DATA SOURCES: Relevant information was identified through a search of MEDLINE (1966-September 2015), International Pharmaceutical Abstracts (1960-September 2015), and Cochrane Databases (publications archived until September 2015) using the terms bivalirudin, unfractionated heparin, ST-segment elevation myocardial infarction, and primary percutaneous coronary intervention. STUDY SELECTION AND DATA EXTRACTION: English-language randomized controlled trials and meta-analyses were eligible for inclusion for data review of STEMI where PPCI was performed. DATA SYNTHESIS: Either bivalirudin or UFH is recommended in the setting of STEMI where PPCI is to be performed. Bivalirudin is touted for its predictable pharmacokinetics, effects on thrombin-mediated platelet inhibition, and favorable outcomes with regard to adverse bleeding profiles, whereas UFH, the gold standard anticoagulant during PPCI, remains a viable treatment strategy. Only recently have direct comparisons of UFH and bivalirudin during PPCI become available. The evidence available is complicated by variances in use of glycoprotein IIb/IIIa inhibitors (GPIs), P2Y12 inhibitors, access sites, and anticoagulant dosing strategies. We provide a review of contemporary trials and advancements in this area. CONCLUSIONS: When compared to UFH with limited use of GPI, available evidence demonstrates that bivalirudin reduces bleeding at the expense of increasing risk for acute stent thrombosis. Further randomized studies are needed to determine the potential benefits of a post-PCI infusion of bivalirudin to reduce the risk for acute stent thrombosis, long-term follow-up beyond 30 days, and mortality.