In recent clinical trials some cardiac arrhythmias were reported with use of remdesivir for COVID-19. To address this safety concern, we investigated whether use of remdesivir for COVID-19 is ...associated with an increased risk of bradycardia.
Using VigiBase®, the World Health Organization Global Individual Case Safety Reports database, we compared the cases of bradycardia reported in COVID-19 patients exposed to remdesivir with those reported in COVID-19 patients exposed to hydroxychloroquine, lopinavir/ritonavir, tocilizumab or glucocorticoids. All reports of patients with COVID-19 registered up to the 23 September 2020 were included. We conducted disproportionality analyses allowing the estimation of reporting odds ratios (RORs) with 95% CI.
We found 302 cardiac effects including 94 bradycardia (31%) among the 2603 reports with remdesivir prescribed in COVID-19 patients. Most of the 94 reports were serious (75, 80%), and in 16 reports (17%) evolution was fatal. Compared with hydroxychloroquine, lopinavir/ritonavir, tocilizumab or glucocorticoids, the use of remdesivir was associated with an increased risk of reporting bradycardia (ROR 1.65; 95% CI 1.23–2.22). Consistent results were observed in other sensitivity analyses.
This post-marketing study in a real-world setting suggests that the use of remdesivir is significantly associated with an increased risk of reporting bradycardia and serious bradycardia when compared with the use of with hydroxychloroquine, lopinavir/ritonavir, tocilizumab or glucocorticoids. This result is in line with the pharmacodynamic properties of remdesivir.
Rationale
While meta-analyses of clinical trials found that lurasidone and partial dopamine agonists (brexpiprazole and aripiprazole) were the antipsychotics less likely to cause QTc prolongation, ...and sertindole, amisulpride, and ziprasidone were the most frequently associated with this adverse drug reaction; no real-world studies have investigated this risk between the different antipsychotics.
Objectives and methods
Using data recorded from 1967 to 2019 in VigiBase®, the World Health Organization’s Global Individual Case Safety Reports database, we performed disproportionality analysis to investigate the risk of reporting QT prolongation between 20 antipsychotics.
Results
Sertindole had the highest risk of reporting QT prolongation, followed by ziprasidone and amisulpride. Lurasidone was associated with the lowest risk. First-generation antipsychotics were associated with a greater QT prolongation reporting risk (ROR, 1.21; 95%CI, 1.10–1.33) than second-generation antipsychotics. A positive correlation was found between the risk of reporting QT prolongation and affinity for hERG channel (
R
2
= 0.14, slope = Pearson coefficient = 0.41,
p
value = 0.1945).
Conclusions
This large study in a real-world setting suggests that sertindole and ziprasidone were the antipsychotics drugs associated with the highest risk of QT prolongation reporting. Our results suggest that lurasidone is less associated with QT interval prolongation reports. Our study also suggests that antipsychotics with the higher hERG affinity are more associated with to QT prolongations reports.
Antipsychotic drugs possess side atropinic (anticholinergic) properties that may induce several adverse drug reactions (ADRs), such as memory loss or cognitive impairment. The aim of this study was ...to investigate anticholinergic burden in patients treated with antipsychotic drugs. All ADR reports including at least one antipsychotic and registered between 2000 and 2015 in the Midi‐Pyrénées PharmacoVigilance Database were extracted and analyzed using the Anticholinergic Duran's list. The primary objective of this cross‐sectional study was to calculate anticholinergic burden in antipsychotic‐treated patients; the secondary one was to investigate associated factors. Among the 1948 reports, the average number of atropinic drugs per report was 2.4 ± 1.4. At least one atropinic drug was found in 59.4% of reports (1158), in addition to antipsychotic drugs. The mean anticholinergic burden per report was 3.9 ± 2.9. A value ≥3 was found in 61.7% of the reports. A significant association between anticholinergic burden, age, and male gender of patients was found. The mean value of anticholinergic burden remained stable during the study period. This study showed high values of anticholinergic burden in patients receiving antipsychotics. Thus, considering the potential noxious clinical impact of atropinic properties on cognitive functions, an appropriate approach should be used to reduce prescription of antipsychotics with a high anticholinergic burden but also coprescription of other frequently associated atropinic drugs, such as antiparkinsonians, H1 antihistamines, or imipraminic antidepressants in these patients.
BACKGROUNDData on cardiogenic shock in adults with congenital heart disease (ACHD) are scarce.AIMWe sought to describe cardiogenic shock in ACHD patients in a nationwide cardiogenic shock ...registry.METHODSFrom the multicentric FRENSHOCK registry (772 patients with cardiogenic shock from 49 French centres between April and October 2016), ACHD patients were compared with adults without congenital heart disease (non-ACHD). The primary outcome was defined by all-cause mortality, chronic ventricular assist device or heart transplantation at 1year.RESULTSOut of the 772 patients, seven (0.9%) were ACHD, who were younger (median age: 56 vs. 67years), had fewer cardiovascular risk factors, such as hypertension (14.3% vs. 47.5%) and diabetes (14.3% vs. 28.3%), and no previous ischaemic cardiopathy (0 vs. 61.5%). Right heart catheterization (57.1% vs. 15.4%), pacemakers (28.6% vs. 4.6%) and implantable cardioverter-defibrillators (28.6% vs. 4.8%) were indicated more frequently in the management of ACHD patients compared with non-ACHD patients, whereas temporary mechanical circulatory support (0 vs. 18.7%) and invasive mechanical ventilation (14.3% vs. 38.1%) were less likely to be used in ACHD patients. At 1year, the primary outcome occurred in 85.7% (95% confidence interval: 42.1-99.6) ACHD patients and 52.3% (95% confidence interval: 48.7-55.9) non-ACHD patients. Although 1-year mortality was not significantly different between ACHD patients (42.9%) and non-ACHD patients (45.4%), ventricular assist devices and heart transplantation tended to be more frequent in the ACHD group.CONCLUSIONSCardiogenic shock in ACHD patients is rare, accounting for only 0.9% of an unselected cardiogenic shock population. Despite being younger and having fewer co-morbidities, the prognosis of ACHD patients with cardiogenic shock remains severe, and is similar to that of other patients.
Data on cardiogenic shock (CS) in adults with congenital heart disease (ACHD) are scarce.
We sought to describe CS in ACHD in a nationwide CS registry.
From the multicentric FRENSHOCK registry (n=772 ...CS from 49 French centers between April and October 2016), ACHD CS were compared with non-ACHD ones. The primary outcome was defined by all-cause mortality, chronic ventricular assist device (VAD) or heart transplantation at 1-year.
Out of the 772 patients, 7 (1%) were ACHD. ACHD patients were younger (54 vs. 66years old), with less cardiovascular risk factors, such as hypertension (14.2 vs. 47.5%) and diabetes (14.3 vs. 36.1%), and no ischemic cardiopathy (0 vs. 61.5%). Right heart catheterization (57.1 vs. 15.4%), pacemaker (28.6 vs. 4.6%) and ICD (28.6 vs. 4.8%) were more frequently indicated in the ACHD CS management compared to non-ACHD CS, whereas temporary MCS (0 vs. 7.2%) and invasive mechanical ventilation (14.3 vs. 38.1%) were less likely used in ACHD. At 1-year, primary outcome occurred in 85.7% ACHD and 52.2% non-ACHD (P=0.127) (Fig. 1). Although 1-year mortality was similar (45.4 vs. 42.9% respectively for ACHD and non-ACHD patients, P=1), VAD (14.3 vs. 5.4%, P=0.325), and heart transplantation (28.6 vs. 5.2%, P=0.05) seemed more frequent in ACHD group.
CS in ACHD is rare accounting for only 1% of an unselected CS population. Despite a younger age and less comorbidities its prognosis remains severe and similar to others patients.
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