Patient-Reported Improvements in Patients with PNH Treated with Iptacopan from Two Phase 3 Studies.

Iptacopan, a first-in-class, oral, selective complement factor B inhibitor, demonstrated efficacy and safety as monotherapy in C5 inhibitor (C5i)-experienced (APPLY-PNH [NCT04558918]) and C5i-naive (APPOINT-PNH [NCT04820530]) patients with paroxysmal nocturnal hemoglobinuria (PNH). In APPLY-PNH and APPOINT-PNH, changes in fatigue (FACIT-Fatigue) and health-related quality of life (HRQOL; EORTC QLQ-C30) from baseline to Day 168 were evaluated. The proportion of patients achieving meaningful within-patient change (MWPC) on the FACIT-Fatigue and 4 EORTC QLQ-C30 subscales (physical functioning, role functioning, fatigue, dyspnea) was evaluated using anchor-based thresholds.

Choice of estimand and analysis methods in diabetes trials with rescue medication.

The analysis of clinical trials aiming to show symptomatic benefits is often complicated by the ethical requirement for rescue medication when the disease state of patients worsens. In type 2 diabetes trials, patients receive glucose-lowering rescue medications continuously for the remaining trial duration, if one of several markers of glycemic control exceeds pre-specified thresholds. This may mask differences in glycemic values between treatment groups, because it will occur more frequently in less effective treatment groups.

International REgistry to assess medical Practice with lOngitudinal obseRvation for Treatment of Heart Failure (REPORT-HF): rationale for and design of a global registry.

Aims: The clinical characteristics, initial presentation, management, and outcomes of patients hospitalized with new-onset (first diagnosis) heart failure (HF) or decompensation of chronic HF are poorly understood worldwide. REPORT-HF (International REgistry to assess medical Practice with lOngitudinal obseRvation for Treatment of Heart Failure) is a global, prospective, and observational study designed to characterize patient trajectories longitudinally during and following an index hospitalization for HF.

Methods: Data collection for the registry will be conducted at ∼300 sites located in ∼40 countries.

Effects of a novel aldosterone synthase inhibitor for treatment of primary hypertension: results of a randomized, double-blind, placebo- and active-controlled phase 2 trial.

Background: LCI699, a novel inhibitor of aldosterone synthase, reduces serum aldosterone, and may have benefit in the treatment of hypertension.

Methods And Results: We performed the first double-blind, randomized trial with LCI699 in patients with primary hypertension. We randomized 524 patients to LCI699 0.

Genetic analysis of fluvastatin response and dyslipidemia in renal transplant recipients.

The Assessment of Lescol in Renal Transplantation clinical trial demonstrated the efficacy of fluvastatin in reducing cardiovascular (CV) disease in renal transplant recipients. The study included a voluntary pharmacogenetic component, enrolling 1,404 patients, which allowed association testing of baseline measures and longitudinal analysis of the 707 fluvastatin-treated and 697 placebo-treated individuals. A candidate gene approach, examining 42 polymorphisms in 18 genes, was used to test for association between selected polymorphisms and major adverse cardiac events, graft failure, change in LDL and HDL cholesterol, and baseline LDL and HDL cholesterol.

What resting heart rate should one aim for when treating patients with heart failure with a beta-blocker? Experiences from the Metoprolol Controlled Release/Extended Release Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF).

Objectives: The goal of this study was to explore the question: what resting heart rate (HR) should one aim for when treating patients with heart failure with a beta-blocker?

Background: The interaction of pretreatment and achieved resting HR with the risk-reducing effect of beta-blocker treatment needs further evaluation.

Methods: Cardiovascular risk and risk reduction were analyzed in five subgroups defined by quintiles (Q) of pretreatment resting HR in the Metoprolol Controlled Release/Extended Release Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF).

Results: Mean baseline HR in the 5 Qs were 71, 76, 81, 87, and 98 beats/min; achieved HR 63, 66, 68, 72, and 75 beats/min; and net change -8, -10, -11, -13, and -14 beats/min, respectively.

Effects of angiotensin type-1 receptor antagonism on small artery function in patients with type 2 diabetes mellitus.

Endothelial dysfunction has been demonstrated to occur in small arteries from patients with type 2 diabetes and hypertension. The effects of angiotensin II receptor blockade on vessel function were examined using pressure myography in a randomized 12-week double-blind placebo-controlled parallel group study using candesartan cilexitil. The maximal vascular response to acetylcholine (Ach) was impaired at baseline and improved with candesartan.