Reduced cardiovascular morbidity in patients with hemophilia: results of a 5-year multinational prospective study

Hemophilia is a congenital bleeding disorder caused by low clotting factor VIII or IX levels. Life expectancy of people with hemophilia (PWH) has increased with the availability of clotting factor concentrates. At the same time, the incidence of cardiovascular disease (CVD) has increased. In retrospective studies there are conflicting data if, despite this increase, the incidence is still lower than in the general population. We prospectively compared the incidence of CVD in PWH with the predicted incidence. This prospective, multicenter, observational study included adult PWH (>30y) from the Netherlands and United Kingdom (UK). They were followed for a 5-year period and CVD incidence was compared with a predicted event rate based on the QRISK2-2011 CVD risk model. The primary endpoint was the observed fatal and nonfatal CVD incidence after 5 years compared to the estimated events and in relation to severity of hemophilia. The study included 709 patients, of whom 687 (96.9%) completed 5 years follow up or reached an endpoint. For 108 patients the QRISK score could not be calculated at inclusion. For the remaining 579 fewer CVD events were observed than predicted: 9 versus 24 (RR 0.38; 95% CI: 0.18 - 0.80 p=0.01), corresponding with an absolute risk reduction of 2.4%. Severe hemophilia treated on demand had the highest risk reduction. There was no statistical significant relation between severity of hemophilia and incidence of CVD. In hemophilia a lower than predicted CVD incidence was found, supporting the theory that hemophilia protects against CVD. The study is registered at www.clinicaltrials.gov (identification number NCT01303900).

The Pattern of Use, Effectiveness, and Safety of Gadoteric Acid (Clariscan) in Patients Undergoing Contrast-Enhanced Magnetic Resonance Imaging: A Prospective, Multicenter, Observational Study

Objective. Contrast-enhanced MR (CE-MR) imaging is often required to improve lesion detection and characterization and to increase diagnostic confidence. This study aimed to evaluate the safety and effectiveness, as well as the use pattern, of the macrocyclic gadolinium-based contrast agent Clariscan in real-world clinical practice in Korea. Materials and Methods. This was a prospective, multicenter, observational study of patients undergoing CE-MR as part of routine clinical care at 6 university hospitals in Korea. Effectiveness was evaluated by determining diagnostic confidence and image quality; safety evaluation included the adverse event (AE) expression rate. Subgroup analyses were conducted by body regions of diagnosis (musculoskeletal, nervous system, others) and in pediatric patients (aged ≤7 years). Results. From October 2019 to September 2020, 1,376 subjects were included in the study. The mean volume of Clariscan used was 0.26 mL/kg (0.13 mmol/kg). In the overall study population and in each subgroup, diagnostic confidence increased after contrast enhancement with Clariscan. Overall, image quality was excellent in 72.5% of subjects and good-to-adequate in 27.2%. Clariscan was well tolerated (14 AEs occurred in 10 subjects); all AEs were of mild severity. Subgroup analyses showed that the mean dose of Clariscan used was ≥0.1 mmol/kg for nervous system-related diagnoses (e.g., brain) and ≤0.1 mmol/kg for musculoskeletal and pediatric-related diagnoses. All musculoskeletal and pediatric examinations were provided with a smaller package of 5 mL Clariscan. By body region of MR examination, the most common region was the nervous system in 69.0%, musculoskeletal system in 13.6%, and reproductive system in 4.9%. Conclusions. This study confirmed the use pattern of Clariscan and its excellent effectiveness and safety in the real-world clinical environment in Korea. The small-dose package indicated the possibility of increasing the convenience and efficiency of drug use.