Pharmacotherapy Considerations in Heart Failure with Mildly-Reduced Ejection Fraction.

Heart failure with mildly reduced ejection fraction (HFmrEF) has been classified using various definitions since its first mention in the literature in 2014. This group was most recently defined in the Universal Definition and Classification of Heart Failure (HF) as HF with a left ventricular ejection fraction of 41% to 49%. An increasing emphasis has been placed on HFmrEF over the past several years, with many recent publications suggesting that common therapies used in HF with reduced ejection fraction provide benefit in this population as well. Patients with HFmrEF comprise approximately one-quarter of all patients with HF. The lack of authoritative guidance concerning pharmacotherapeutic approaches in these patients leaves a significant portion of HF patients without an evidence-based approach. Although it remains unclear if HFmrEF is simply a transitional state from preserved to reduced ejection fraction, or a distinct phenotype requiring medical optimization, there are clear cardiovascular benefits to managing this subset appropriately. This publication was created to help serve as a resource for clinicians on this evolving subset of HF and aid in preventing the progression of this disease state through improved therapy optimization. The objective of this article is to briefly discuss the epidemiology and pathophysiology of HFmrEF and review the pharmacology and clinical application of therapies for the management of HFmrEF.

Reduced-Dose Apixaban in the Treatment of Left Ventricular Thrombus: A Report of 2 Cases.

According to the American College of Cardiology and the American Heart Association, warfarin has historically been the standard of care anticoagulant for the treatment of left ventricular thrombus. The use of direct oral anticoagulants (DOACs) has become more prevalent, as they require less frequent laboratory monitoring, offer fixed-dose regimens, are associated with fewer drug-drug and drug-food interactions, and provide more favorable safety profiles when compared to warfarin. However, DOACs are not currently FDA-indicated in the treatment of left ventricular (LV) thrombus. Numerous recent studies have reported and evaluated the use of DOACs for treatment of LV thrombus. Recently, a prospective, open-label, multicenter study evaluated warfarin compared to DOACs for LV thrombus treatment. The AHA recently published a scientific statement regarding the management of patients at risk for and with left ventricular thrombus, which included DOACs as a reasonable alternative to warfarin. This report describes two patients treated with DOACs following LV thrombus diagnosis. The first case is a 71-year-old male admitted for cerebrovascular accident and non-ST-elevation myocardial infarction complicated by a LV thrombus. The second case is an 83-year-old female admitted for acute myocardial infarction complicated with an LV thrombus. Both patients were prescribed apixaban 2.5 mg twice daily. Neither patient has experienced LV thrombus or DOAC treatment related complications. This case series serves as evidence for reduced-dose DOACs as an alternative to warfarin in the treatment of LV thrombus.

Metformin-Induced Fixed-Drug Eruption Confirmed by Multiple Exposures.

BACKGROUND: A fixed-drug eruption (FDE) is a reaction characterized by cutaneous lesions that appear due to exposure to a particular drug. Barbiturates, carbamazepine, sulfamethoxazole, and tetracyclines have all been associated with causation of FDEs. Although these drugs are more commonly associated with FDEs, any introduction of a medication has the potential to result in a FDE. Metformin, a commonly used medication to improve glycemic control, has been reported to cause dermatologic reactions in some case reports, but only a single previously documented case report discusses the potential of metformin-associated FDE. CASE REPORT: We describe a 56-year-old woman who developed a FDE with multiple exposures to metformin. Upon each exposure, small, round, erythematic lesions developed on the palms of the hands and soles of the feet; these lesions resolved each time after discontinuation of metformin. According to the Naranjo scale, there is a definite association between metformin and FDE in this case (score of 8). CONCLUSIONS: This report contributes to the limited documented literature on metformin-induced FDE. Clinicians should be made aware of possible FDEs associated with this commonly used medication.

Ziv-aflibercept (Zaltrap) for the treatment of metastatic colorectal cancer.

OBJECTIVE: Review pharmacology, pharmacokinetics, efficacy, and safety of ziv-aflibercept in combination with FOLFIRI for treatment of metastatic colorectal cancer (mCRC) resistant to or progressed following oxaliplatin-containing regimens. DATA SOURCES: Articles indexed in PubMed (1948-August 2013), TOXLINE (2001-August 2013), and Google Scholar as well as meeting abstracts were identified using the search terms ziv-aflibercept and colorectal cancer. STUDY SELECTION AND DATA EXTRACTION: Available English-language articles DATA SYNTHESIS: Ziv-aflibercept, a selective vascular endothelial growth factor antagonist, was evaluated as monotherapy for treatment of mCRC in a phase 2 study and added to FOLFIRI in a phase 3 trial. Patient response to ziv-aflibercept as monotherapy did not reach statistical significance. Results suggest that response to ziv-aflibercept treatment is not influenced by prior bevacizumab therapy. A phase 3 trial compared the safety and efficacy of ziv-aflibercept plus FOLFIRI with placebo plus FOLFIRI in patients with mCRC who experienced disease progression on an oxaliplatin-containing regimen. Patients in the ziv-aflibercept arm had a median overall survival of 13.5 months, versus 12.06 months for those receiving placebo (hazard ratio [HR] = 0.817, 95% CI = 0.713 to 0.937). Progression-free survival for patients receiving ziv-aflibercept was higher compared with placebo (HR = 0.758; 95% CI = 0.661 to 0.869). The most common adverse effects observed were anemia, diarrhea, and neutropenia. CONCLUSIONS: Ziv-aflibercept is a safe and effective option in combination with FOLFIRI for the treatment of mCRC in patients who progress on oxaliplatin-containing therapy. Superiority over other antiangiogenic treatment has not been established.