Pearl Index study with levonorgestrel-releasing intravaginal rings: using pharmacokinetic results to investigate treatment compliance as a potential contributor for contraceptive failure.

Study Question: What is the reason for insufficient contraceptive efficacy of levonorgestrel (LNG) delivered by intravaginal ring (IVR) releasing comparable amounts of LNG as approved progestogen-only pills (POPs)?

Summary Answer: The pharmacokinetic (PK) evaluation in a subpopulation indicated that the steady-state concentration of plasma LNG was markedly lower in the participants in the USA compared to those in Japan suggesting non-compliance in the US participants which may explain a clearly higher Pearl Index (PI) in USA (8.2, unadjusted PI) compared to Japan (1.4, unadjusted PI).

Ranolazine Prevents Levosimendan-Induced Atrial Fibrillation.

Objectives: Levosimendan is a calcium sensitizer that is used as positive inotropic drug in acute decompensated heart failure. An increased incidence of atrial fibrillation after levosimendan-treatment was observed in clinical and experimental studies. Due to the limited range of antiarrhythmic drugs, the aim of the present study was to assess potential antiarrhythmic effects of ranolazine in levosimendan-pretreated isolated rabbit hearts.

Acute infusion of levosimendan enhances atrial fibrillation in an experimental whole-heart model.

Background: The calcium sensitizer levosimendan is clinically employed in decompensated heart failure. The aim of the present study was to assess effects of levosimendan on atrial electrophysiology in an experimental whole-heart model.

Methods And Results: 13 rabbit hearts were isolated and Langendorff-perfused.

Experimental evidence for a severe proarrhythmic potential of levosimendan.

Background: The calcium sensitizer levosimendan is established for therapy of acutely decompensated congestive heart failure. Clinical experience suggests a possible proarrhythmic potential. The aim of the present study was to assess possible proarrhythmic effects and underlying electrophysiological mechanisms.