Drug Discovery for Kinetoplastid Diseases: Future Directions.

Kinetoplastid parasites have caused human disease for millennia. Significant achievements have been made toward developing new treatments for leishmaniasis (particularly on the Indian subcontinent) and for human African trypanosomiasis (HAT). Moreover, the sustained decrease in the incidence of HAT has made the prospect of elimination a tantalizing reality.

Contemporary Characteristics and Outcomes in Chagasic Heart Failure Compared With Other Nonischemic and Ischemic Cardiomyopathy.

Background: Chagas' disease is an important cause of cardiomyopathy in Latin America. We aimed to compare clinical characteristics and outcomes in patients with heart failure (HF) with reduced ejection fraction caused by Chagas' disease, with other etiologies, in the era of modern HF therapies.

Methods And Results: This study included 2552 Latin American patients randomized in the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) and ATMOSPHERE (Aliskiren Trial to Minimize Outcomes in Patients With Heart Failure) trials.

Aliskiren alone or in combination with enalapril vs. enalapril among patients with chronic heart failure with and without diabetes: a subgroup analysis from the ATMOSPHERE trial.

Aims: Because of concerns about the safety of aliskiren in patients with diabetes, study treatment was stopped prematurely in the Aliskiren Trial of Minimizing OutcomeS for Patients with HEart failuRE (ATMOSPHERE). We examined outcomes and treatment effect in these patients compared with those without diabetes.

Methods And Results: ATMOSPHERE included 7016 patients with heart failure and a reduced ejection fraction (HFrEF) randomly assigned to enalapril plus aliskiren, aliskiren alone, or enalapril.

Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial.

Aims: The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM).

Methods And Results: ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators).

Effect of aliskiren on postdischarge mortality and heart failure readmissions among patients hospitalized for heart failure: the ASTRONAUT randomized trial.

Importance: Hospitalizations for heart failure (HHF) represent a major health burden, with high rates of early postdischarge rehospitalization and mortality.

Objective: To investigate whether aliskiren, a direct renin inhibitor, when added to standard therapy, would reduce the rate of cardiovascular (CV) death or HF rehospitalization among HHF patients.

Design, Setting, And Participants: International, double-blind, placebo-controlled study that randomized hemodynamically stable HHF patients a median 5 days after admission.

Effect of aliskiren in patients with heart failure according to background dose of ACE inhibitor: a retrospective analysis of the Aliskiren Observation of Heart Failure Treatment (ALOFT) trial.

Aims: To compare the effect of the direct renin inhibitor aliskiren on neurohumoral activity in heart failure patients treated with low-dose and high-dose ACE inhibitor.

Methods: A retrospective analysis of the ALOFT trial. Comparison of the effects of 6 months treatment with aliskiren (versus placebo) in patients receiving View Article and Find Full Text PDF

Efficacy and tolerability of fluvastatin XL 80 mg alone, ezetimibe alone, and the combination of fluvastatin XL 80 mg with ezetimibe in patients with a history of muscle-related side effects with other statins.

Although statin treatment is generally well tolerated, it is estimated that 5% to 10% of patients develop muscle-related side effects (MRSEs), resulting in less effective nonstatin alternatives or cessation of lipid-lowering therapy completely. This study was designed to assess the efficacy and tolerability of extended-release fluvastatin (fluvastatin XL) and ezetimibe alone or in combination in patients with previous MRSEs with other statins. This was a double-blinded, double-dummy trial of 199 mostly moderate- or high-risk dyslipidemic patients randomized to fluvastatin XL 80 mg/day (n = 69), ezetimibe 10 mg/day (n = 66), or fluvastatin XL 80 mg/day plus ezetimibe 10 mg/day (n = 64) for 12 weeks.