Objectives The goal of the study was to assess the effects of angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) on the composite of cardiovascular (CV) death, ...myocardial infarction (MI), and stroke, and on all-cause death, new-onset heart failure (HF), and new-onset diabetes mellitus (DM) in high-risk patients without HF. Background ACE-Is reduce CV events in high-risk patients without HF whereas the effects of ARBs are less certain. Methods Twenty-six randomized trials comparing ARBs or ACE-Is versus placebo in 108,212 patients without HF were collected in a meta-analysis and analyzed for the risk of the composite outcome, all-cause death, new-onset HF, and new-onset DM. Results ACE-Is significantly reduced the risk of the composite outcome (odds ratio OR: 0.830 95% confidence interval (CI): 0.744 to 0.927; p = 0.001), MI (OR: 0.811 95% CI: 0.748 to 0.879; p < 0.001), stroke (OR: 0.796 95% CI: 0.682 to 0.928; p < 0.004), all-cause death (OR: 0.908 95% CI: 0.845 to 0.975; p = 0.008), new-onset HF (OR: 0.789 95% CI: 0.686 to 0.908; p = 0.001), and new-onset DM (OR: 0.851 95% CI: 0.749 to 0.965; p < 0.012). ARBs significantly reduced the risk of the composite outcome (OR: 0.920 95% CI: 0.869 to 0.975, p = 0.005), stroke (OR: 0.900 95% CI: 0.830 to 0.977, p = 0.011), and new-onset DM (OR: 0.855 95% CI: 0.798 to 0.915; p < 0.001). Conclusions In patients at high CV risk without HF, ACE-Is and ARBs reduced the risk of the composite outcome of CV death, MI, and stroke. ACE-Is also reduced the risk of all-cause death, new-onset HF, and new-onset DM. Thus, ARBs represent a valuable option to reduce CV mortality and morbidity in patients in whom ACE-Is cannot be used.
Despite the available evidence showing an association between cardiac arrhythmia and Immune Checkpoint Inhibitors (ICIs), few studies have compared this risk between ICIs.
We aim to evaluate ...Individual Case Safety Reports (ICSRs) of ICIs-induced cardiac arrhythmias and compare the reporting frequency of cardiac arrhythmias among ICIs.
ICSRs were retrieved from the European Pharmacovigilance database (Eudravigilance). ICSRs were classified based on the ICI reported (pembrolizumab, nivolumab, atezolizumab, ipilimumab, durvalumab, avelumab, cemiplimab, and dostarlimab). If more than one ICI was reported, the ICSR was classified as a combination of ICIs. ICSRs of ICI-related arrhythmias were described and the reporting frequency of cardiac arrhythmias was assessed by applying the reporting odds ratio (ROR) and its 95 % confidence interval (95 %CI).
A total of 1262 ICSRs were retrieved, of which 147 (11.65 %) were related to combinations of ICIs. A total of 1426 events of cardiac arrhythmias were identified. The three most reported events were atrial fibrillation, tachycardia, and cardiac arrest. Ipilimumab was associated with a reduced reporting frequency of cardiac arrhythmias compared to all other ICIs (ROR 0.71, 95 %CI 0.55–0.92; p = 0.009). Anti-PD1 was associated with a higher reporting frequency of cardiac arrhythmias than anti-CTLA4 (ROR 1.47, 95 %CI 1.14–1.90; p = 0.003).
This study is the first comparing ICIs for the risk of cardiac arrhythmias. We found that ipilimumab was the only ICI associated with a reduced reporting frequency. Further high-quality studies are needed to confirm our results.
Display omitted
•Most events of cardiac arrhythmias were severe and fatal.•Ipilimumab had a lower reporting frequency of arrhythmia than all other ICIs.•ICIs may share different pharmacological feature in terms of cardiac arrhythmias•The CTLA4 pathway may be less critical in the heart.
Background:
The risk of falls and bone fractures with sodium-glucose co-transporter-2 (SGLT2) inhibitors has been characterized by conflicting evidence. Therefore, we decided to investigate the ...reporting probability of falls and fractures by comparing SGLT2 inhibitors with DPP4 inhibitors.
Methods
A retrospective, pharmacovigilance study of the European database of Individual Case Safety Reports (ICSRs) was conducted. Disproportionality analyses (Reporting Odds Ratio, ROR) were conducted to compare the reporting probability of falls or fracture between treatments.
Results
A total of 507 ICSRs reporting at least one fall or fracture with SGLT2 inhibitors were identified. The most reported SGLT2 inhibitor was canagliflozin (
N
= 188; 36.9%), followed by empagliflozin (
N
= 176; 34.5%), and dapagliflozin (
N
= 143; 28.0%). A total of 653 events related to fall or bone fracture were reported. Fall was the most reported event (
N
= 333; 51.0%). Among fractures (
N
= 320; 49.0%), the most reported were foot fractures (
N
= 40; 6.1%) and hip fractures (
N
= 32; 4.9%). SGLT2 inhibitors were associated with a lower reporting probability of fall than DPP4 inhibitors (ROR, 0.66; 95%CI, 0.57-0.78). The lower reporting probability of fall was also observed when the single SGLT2 inhibitor was compared to DPP4 inhibitors: dapagliflozin (ROR, 0.67; 95%CI, 0.53-0.83), canagliflozin (ROR, 0.56; 95%CI, 0.45-0.70), and empagliflozin (ROR, 0.77; 95%CI, 0.63-0.94). For fractures, canagliflozin showed a slightly significant increased reporting when compared with DPP4 inhibitors (not confirmed in the sensitivity analysis), whereas all other comparison showed no statistically significant difference.
Conclusion
SGLT2 inhibitors were associated with a lower reporting probability of fall than DPP4 inhibitors, in accordance with the reassuring evidence about the safety profile of these drugs. Future researches will help to confirm their long-term safety profile.
Atrial fibrillation (AF) has been described in COVID-19 patients. Recently, some case reports and US pharmacovigilance analyses described AF onset as a rare adverse event following COVID-19 ...vaccination. The possible correlation is unclear. We systematically analyzed the reports of AF related to COVID-19 vaccines collected in the European pharmacovigilance database, EudraVigilance (EV), from 2020 to November 2022. We carried out descriptive and disproportionality analyses. Moreover, we performed a sensitivity analysis, excluding the reports describing other possible alternative AF causes (pericarditis, myocarditis, COVID-19, or other drugs that may cause/exacerbate AF). Overall, we retrieved 6226 reports, which represented only 0.3% of all those related to COVID-19 vaccines collected in EV during our study period. AF reports mainly referred to adults (in particular, >65 years old), with an equal distribution in sex. Reports were mainly related to tozinameran (54.04%), elasomeran (28.3%), and ChAdOx1-S (14.32%). The reported AF required patient hospitalization in 35% of cases and resulted in a life-threatening condition in 10% of cases. The AF duration (when reported) was highly variable, but the majority of the events had a short duration (moda = 24 h). Although an increased frequency of AF reporting with mRNA vaccines emerges from our study, other investigations are required to investigate the possible correlation between COVID-19 vaccination and the rare AF occurrence.
Background. Although biosimilars have been increasingly used over recent years, some concerns about a potential loss of efficacy and altered safety profile when switching from an originator to a ...biosimilar still exist. Interchangeability can be a challenge for dermatologists too. An extensive systematic review of published switching studies among originators and biosimilars was carried out in order to provide evidence regarding the effects derived from the switch in terms of efficacy and safety outcomes in real-life contexts. Results. Thirty-seven articles were included in this systematic review (14 studies related to adalimumab, 10 to etanercept, 12 to infliximab, and 1 each to adalimumab, etanercept, and infliximab). Studies were mainly carried out among European countries. Most of them were observational studies or register-based studies. The majority of studies enrolled patients diagnosed with psoriasis or psoriatic arthritis who underwent a single switch from the originator to the biosimilar. Overall, the studies’ results demonstrated that switching between adalimumab, etanercept, and infliximab originators and biosimilars is safe and effective in a real-life setting of patients with dermatological conditions. Only a few studies highlighted an increase in the risk of loss of efficacy as well as an increased rate of AEs, both of which were identified as the main causes of biosimilar discontinuation, probably associated with the well-known phenomenon of the nocebo effect. Conclusion. Switching from a biologic originator to its biosimilar is safe and effective. Only a few studies have evaluated the switch among biosimilars; thus, no firm conclusion can be drawn for this type of switch in terms of the efficacy and safety outcomes. Based on our results, we believe that biosimilars can be considered interchangeable with their reference products and that no additional switch studies are necessary to support switching among originators and biosimilars in clinical practice. However, the continuous monitoring of all biologics (both originators and biosimilars) in routine clinical practice is strongly needed given their peculiar safety profile.
Background
Immune checkpoint inhibitors (ICIs) can be commonly associated with the occurrence of immune-related adverse drug reactions (irADRs), which can involve any tissue and organ. ICI-induced ...skin toxicities are common irADRs and they can be a consequence of a rheumatologic ADR, such as in the case of scleroderma. A recent literature review reported that scleroderma and scleroderma mimics represent a group of disorders with significant morbidity that have been described during ICIs’ use.
Objective and Methods
Considering the clinical significance of scleroderma cases, the present study aimed to analyze the occurrence of these events in patients receiving ICIs by describing data from individual case safety reports (ICSRs) retrieved from the European spontaneous reporting system, EudraVigilance (EV).
Results
Until February 2023, 70 ICSRs with at least one ICI as the suspected drug and at least one preferred term (PT) related to scleroderma cases were retrieved from the EV. Pembrolizumab was reported as suspected in 41 ICSRs, nivolumab in 25 ICSRs, ipilimumab in 8 ICSRs and atezolizumab in 3 ICSRs. Patients who experienced scleroderma cases were adults, and no differences were found in terms of sex distribution. Scleroderma cases were mainly classified as serious, while the outcome was mainly reported as favorable. The most reported PTs were scleroderma and morphea.
Conclusions
Considering the seriousness of ICI-induced scleroderma cases and the recent marketing authorization of some ICIs, we believe that further high-quality clinical studies should be conducted on this topic to better estimate the impact of these events in patients with cancer.
Objectives The purpose of this paper was to assess whether statins reduce all-cause mortality and cardiovascular (CV) events in elderly people without established CV disease. Background Because of ...population aging, prevention of CV disease in the elderly is relevant. In elderly patients with previous CV events, the use of statins is recommended by guidelines, whereas the benefits of these drugs in elderly subjects without previous CV events are still debated. Methods Randomized trials comparing statins versus placebo and reporting all-cause and CV mortality, myocardial infarction (MI), stroke, and new cancer onset in elderly subjects (age ≥65 years) without established CV disease were included. Results Eight trials enrolling 24,674 subjects (42.7% females; mean age 73.0 ± 2.9 years; mean follow up 3.5 ± 1.5 years) were included in analyses. Statins, compared with placebo, significantly reduced the risk of MI by 39.4% (relative risk RR: 0.606 95% confidence interval (CI): 0.434 to 0.847; p = 0.003) and the risk of stroke by 23.8% (RR: 0.762 95% CI: 0.626 to 0.926; p = 0.006). In contrast, the risk of all-cause death (RR: 0.941 95% CI: 0.856 to 1.035; p = 0.210) and of CV death (RR: 0.907 95% CI: 0.686 to 1.199; p = 0.493) were not significantly reduced. New cancer onset did not differ between statin- and placebo-treated subjects (RR: 0.989 95% CI: 0.851 to 1.151; p = 0.890). Conclusions In elderly subjects at high CV risk without established CV disease, statins significantly reduce the incidence of MI and stroke, but do not significantly prolong survival in the short-term.
Functional characterization of atherosclerosis is a promising application of molecular imaging. Radionuclide-based techniques for molecular imaging in the large arteries (e.g. aorta and carotids), ...along with ultrasound and magnetic resonance imaging (MRI), have been studied both experimentally and in clinical studies. Technical factors including cardiac and respiratory motion, low spatial resolution and partial volume effects mean that noninvasive molecular imaging of atherosclerosis in the coronary arteries is not ready for prime time. Positron emission tomography imaging with fluorodeoxyglucose can measure vascular inflammation in the large arteries with high reproducibility, and signal change in response to anti-inflammatory therapy has been described. MRI has proven of value for quantifying carotid artery inflammation when iron oxide nanoparticles are used as a contrast agent. Macrophage accumulation of the iron particles allows regression of inflammation to be measured with drug therapy. Similarly, contrast-enhanced ultrasound imaging is also being evaluated for functional characterization of atherosclerotic plaques. For all of these techniques, however, large-scale clinical trials are mandatory to define the prognostic importance of the imaging signals in terms of risk of future vascular events.
PDF
