Medicine and Health Sciences Commons^™

Enhanced Interleukin-1 Activity Contributes To Exercise Intolerance In Patients With Systolic Heart Failure, Benjamin W. Van Tassell, Ross A. Arena, Stefano Toldo, Eleonora Mezzaroma, Tania Azam, Ignacio M. Seropian, Keyur Shah, Justin Canada, Norbert F. Voelkel, Charles A. Dinarello, Antonio Abbate

Pharmacotherapy and Outcomes Science Publications

Background

Heart failure (HF) is a complex clinical syndrome characterized by impaired cardiac function and poor exercise tolerance. Enhanced inflammation is associated with worsening outcomes in HF patients and may play a direct role in disease progression. Interleukin-1β (IL-1β) is a pro-inflammatory cytokine that becomes chronically elevated in HF and exerts putative negative inotropic effects.

Methods and Results

We developed a model of IL-1β-induced left ventricular (LV) dysfunction in healthy mice that exhibited a 32% reduction in LV fractional shortening (P

Conclusions

These findings suggest that IL-1β activity contributes to poor exercise tolerance in patients with systolic HF and identifies …

Atorvastatin With Or Without An Antibody To Pcsk9 In Primary Hypercholesterolemia, Eli M. Roth, James M. Mckenny, Corinne Hanotin, Gaelle Asset, Evan A. Stein

Pharmacotherapy and Outcomes Science Publications

Background

Serum proprotein convertase subtilisin/kexin 9 (PCSK9) binds to low-density lipoprotein (LDL) receptors, increasing the degradation of LDL receptors and reducing the rate at which LDL cholesterol is removed from the circulation. REGN727/SAR236553 (designated here as SAR236553), a fully human PCSK9 monoclonal antibody, increases the recycling of LDL receptors and reduces LDL cholesterol levels.

Methods

We performed a phase 2, multicenter, double-blind, placebo-controlled trial involving 92 patients who had LDL cholesterol levels of 100 mg per deciliter (2.6 mmol per liter) or higher after treatment with 10 mg of atorvastatin for at least 7 weeks. Patients were randomly assigned to …