In randomized clinical trials (RCTs) proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors showed a favorable safety profile, however, "real-world" data on adverse events (AEs) is scarce. Three datasets, a hospital registry (n = 164), and two Pharmacovigilance databases, Lareb (n = 149) and VigiLyze (n = 15,554), reporting AEs attributed to PCSK9 inhibitors (alirocumab or evolocumab) prescribed in clinical practice were analyzed. In the hospital registry, 41.5% of the patients reported any AE, most often injection-site reactions (33.8%) and influenza-like illness (27.9%). Twelve patients (7%) discontinued PCSK9 inhibitor treatment. Most common AE reported in the Lareb and VigiLyze database was myalgia (12.8% and 8.3%, respectively). No clinically relevant differences in gender or between drugs were observed. No specific subgroup of patients could be identified at risk of developing AEs. During follow-up, AEs resolved in most patients (71.1%). In a real-world setting, PCSK9 inhibitors are well tolerated with an overall safety profile comparable to RCTs.

Aims Health insurance claims (HIC) databases in the Netherlands capture unselected patient populations, which makes them suitable for epidemiological research on sex differences. Based on a HIC database, we aimed to reveal sex differences in heart failure (HF) outcomes, with particular focus on co‐morbidities and medication. Methods and results The Achmea HIC database included 14 517 men and 11 259 (45%) women with a diagnosis treatment code for chronic HF by January 2015. We related their sex, co‐morbidities, and medication adherence (medication possession rate >0.8) with the primary endpoint (PE) of all‐cause mortality or HF admission during a median follow‐up of 3.3 years, using Cox regression. Median age of men and women was 72 and 76 years, respectively. Prevalence of co‐morbidities and use of disease‐modifying drugs was higher in men; however, medication adherence was similar. At the end of follow‐up, 35.1% men and 31.8% women had reached the PE. The adjusted hazard ratio for men was 1.25 (95% confidence interval: 1.19–1.30). A broad range of co‐morbidities was associated with the PE. Overall, these associations were stronger in women than in men, particularly for renal insufficiency, chronic obstructive pulmonary disease/asthma, and diabetes. Non‐adherence to disease‐modifying drugs was related with a higher incidence of the PE, with similar effects between sexes. Conclusions In a representative sample of the Dutch population, as captured in a HIC database, men with chronic HF had a 25% higher incidence of death or HF admission than women. The impact of co‐morbidities on the outcome was sex dependent, while medication adherence was not.

BACKGROUND: Studies on serially measured GDF-15 (growth differentiation factor 15) in acute heart failure (HF) are limited. Moreover, several pathophysiological pathways contribute to HF. Therefore, we aimed to explore the (additional) prognostic value of serially measured GDF-15 using a multi-marker approach to more accurately predict HF risk. METHODS: TRIUMPH (Translational Initiative on Unique and Novel Strategies for Management of Patients With Heart Failure) is a prospective cohort of 496 patients with acute HF who were enrolled in 14 hospitals in the Netherlands between 2009 and 2014. Blood sampling was scheduled at 7 moments during 1-year follow-up. GDF-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), ST2 (suppression of tumorigenicity 2), galectin-3, troponin I, and creatinine were measured in a central laboratory. We associated repeated measurements of these biomarkers with the composite primary end point of all-cause mortality and HF rehospitalization, using multivariable joint modeling. RESULTS: Median age was 74 years, and 37% were women. Median baseline GDF-15 was 4632 pg/mL. The primary end point was reached in 188 (40%) patients. The average estimated GDF-15 level increased weeks before the primary end point was reached. The hazard ratio per 1 SD difference in log-GDF-15 was 2.14 (95% CI, 1.78–2.57) unadjusted, 1.96 (1.49–2.53) after adjustment for clinical confounders and 1.44 (1.05–1.91) when jointly modeled with all biomarkers. The adjusted HRs for NT-proBNP were 2.38 (1.78–3.33) and 1.52 (1.15–2.08), respectively. The multimarker model combining GDF-15, NT-proBNP, and troponin I provided a favorable risk discrimination (area under the curve=0.785). CONCLUSIONS: Sequentially measured GDF-15 independently and dynamically predicts risk of adverse outcomes during 1-year follow-up after index admission for acute HF. NT-proBNP remains a robust predictor among potential candidates. Multiple biomarkers should be considered for stratification in clinical practice. REGISTRATION: URL: https://www.trialregister.nl/trial/1783 ; Unique Identifier: NTR1893. (The trial can be found temporarily at https://trialsearch.who.int/Trial2.aspx?TrialID=NTR1893 .)

Aims Telemonitoring modalities in heart failure (HF) have been proposed as being essential for future organization and transition of HF care, however, efficacy has not been proven. A comprehensive meta-analysis of studies on home telemonitoring systems (hTMS) in HF and the effect on clinical outcomes are provided. Methods and results A systematic literature search was performed in four bibliographic databases, including randomized trials and observational studies that were published during January 1996–July 2022. A random-effects meta-analysis was carried out comparing hTMS with standard of care. All-cause mortality, first HF hospitalization, and total HF hospitalizations were evaluated as study endpoints. Sixty-five non-invasive hTMS studies and 27 invasive hTMS studies enrolled 36 549 HF patients, with a mean follow-up of 11.5 months. In patients using hTMS compared with standard of care, a significant 16% reduction in all-cause mortality was observed [pooled odds ratio (OR): 0.84, 95% confidence interval (CI): 0.77–0.93, I2: 24%], as well as a significant 19% reduction in first HF hospitalization (OR: 0.81, 95% CI 0.74–0.88, I2: 22%) and a 15% reduction in total HF hospitalizations (pooled incidence rate ratio: 0.85, 95% CI 0.76–0.96, I2: 70%). Conclusion These results are an advocacy for the use of hTMS in HF patients to reduce all-cause mortality and HF-related hospitalizations. Still, the methods of hTMS remain diverse, so future research should strive to standardize modes of effective hTMS.