Cardiovascular toxicities associated with bispecific T-cell engager therapy.

BACKGROUND: Bispecific T-cell engagers (BTEs) are novel agents used to treat hematological malignancies. Early trials were underpowered to define cardiovascular adverse events (CVAE) and no large-scale studies systematically examined the CVAEs associated with BTEs. METHODS: Leveraging the US Food and Drug Administration's Adverse Event Reporting System-(FAERS), we identified the relative frequency of CVAEs after initiation of five BTE products approved by the Food and Drug Administration between 2014 and 2023 for the treatment of hematological malignancies. Adjusted reporting ORs (aROR) were used to identify disproportionate reporting of CVAEs with BTEs compared with background rates in the database. Fatality rates and risk ratios (RRs) for each adverse event (AE) were calculated. RESULTS: From 3668 BTE-related cases reported to FAERS, 747 (20.4%) involved CVAEs. BTEs as a class were associated with fatal CVAEs (aROR 1.29 (95% CI 1.12 to 1.50)), an association mainly driven by teclistamab (aROR 2.44 (95% CI 1.65 to 3.60)). Teclistamab was also associated with a disproportionate risk of myocarditis (aROR 25.70 (95% CI 9.54 to 69.23)) and shock (aROR 3.63 (95% CI 2.30 to 5.74)), whereas blinatumomab was associated with a disproportionate risk of disseminated intravascular coagulation (aROR 3.02 (95% CI 1.98 to 4.60)) and hypotension (aROR 1.59 (95% CI 1.25 to 2.03)). CVAEs were more fatal compared with non-CVAEs (31.1% vs 17.4%; RR 1.76 (95% CI 1.54 to 2.03)). Most CVAEs (83.3%) did not overlap with cytokine release syndrome. CONCLUSION: In the first postmarketing surveillance study of BTEs, CVAEs were involved in approximately one in five AE reports and carried a significant mortality risk.

The underutilization of preventive cardiovascular measures in patients with cancer: an analysis of the Behavioural Risk Factor Surveillance System, 2011-22.

AIMS: This study aimed to characterize the influence of a cancer diagnosis on the use of preventive cardiovascular measures in patients with and without cardiovascular disease (CVD). METHODS AND RESULTS: Data from the Behavioural Risk Factor Surveillance System Survey (spanning 2011-22) were used. Multivariable logistic regression models adjusted for potential confounders were applied to calculate average marginal effects (AME), the average difference in the probability of using a given therapy between patients with and without cancer. Outcomes of interest included the use of pharmacological therapies, physical activity, smoking cessation, and post-CVD rehabilitation. Among 5 012 721 respondents, 579 114 reported a history of CVD (coronary disease or stroke), and 842 221 reported a diagnosis of cancer. The association between cancer and the use of pharmacological therapies varied between those with vs. without CVD (P-value for interaction: <0.001). Among patients with CVD, a cancer diagnosis was associated with a lower use of blood pressure-lowering medications {AME: -1.46% [95% confidence interval (CI): -2.19% to -0.73%]}, lipid-lowering medications [AME: -2.34% (95% CI: -4.03% to -0.66%)], and aspirin [AME: -6.05% (95% CI: -8.88% to -3.23%)]. Among patients without CVD, there were no statistically significant differences between patients with and without cancer regarding pharmacological therapies. Additionally, cancer was associated with a significantly lower likelihood of engaging in physical activity in the overall cohort and in using post-CVD rehabilitation regimens, particularly post-stroke rehabilitation. CONCLUSION: Preventive pharmacological agents are underutilized in those with cancer and concomitant CVD, and physical activity is underutilized in patients with cancer in those with or without CVD. LAY SUMMARY: •This paper compared the use of preventive cardiovascular measures, both pharmaceutical and non-pharmaceutical, in patients with and without cancer.•In patients with cardiovascular disease and cancer, there is a lower use of preventive cardiovascular medications compared with those with cardiovascular disease but without cancer. This includes a lower utilization of blood pressure-lowering medications, cholesterol-lowering medications, and aspirin.•Patients with cancer reported lower levels of exercise but higher levels of smoking cessation compared with those without cancer.

Fixed-Dose Combination (Polypill) for Cardiovascular Disease Prevention: A Meta-Analysis.

INTRODUCTION: This meta-analysis was performed to assess the efficacy of fixed-dose combination (polypill) in reducing the risk of mortality and cardiovascular events. METHODS: Medline, Scopus, Web of Science, and Cochrane Central were searched during May 2021. All randomized trials investigating the efficacy of antihypertensive and lipid-lowering ± antiplatelet drug combinations in patients at cardiovascular risk were included. Outcomes were presented as risk ratios or standardized mean differences with 95% CIs. RESULTS: A total of 16 trials (N = 26,567 participants) were included. The risk reduction for all-cause mortality (risk ratio = 0.90; 95% CI = 0.79, 1.01; I2 = 0%; moderate certainty) and major adverse cardiac events (risk ratio=0.84; 95% CI=0.68, 1.04; I2=51%; very low certainty) did not reach statistical significance in comparison with those of the control group. Subgroup analysis of studies that used an active control yielded similar results. However, significant reductions in major adverse cardiac event risk were observed in studies that exclusively targeted primary prevention, followed patients for ≥4 years, and had a low risk of bias. The polypill group had significantly higher adherence (risk ratio=1.18; 95% CI=1.06, 1.32; I2=96%; very low certainty) and comprable rates of adverse side effects (risk ratio=1.10; 95% CI=0.98, 1.23; I2=58%; moderate certainty) with those of the control group. Patients randomized to the polypill had significant reductions in systolic and diastolic blood pressure as well as in total and low-density lipoprotein cholesterol. DISCUSSION: Despite reductions in cardiovascular risk factors, the observed mortality benefit for the polypill did not reach statistical significance. Further studies are needed to validate its clinical benefits and determine the patient populations likely to achieve such benefits.

Long-term effectiveness of empiric cardio-protection in patients receiving cardiotoxic chemotherapies: A systematic review & bayesian network meta-analysis.

BACKGROUND: Cardioprotective therapies represent an important avenue to reduce treatment-limiting cardiotoxicities in patients receiving chemotherapy. However, the optimal duration, strategy and long-term efficacy of empiric cardio-protection remains unknown. METHODS: Leveraging the MEDLINE/Pubmed, CENTRAL and clinicaltrials.gov databases, we identified all randomised controlled trials investigating cardioprotective therapies from inception to November 2021 (PROSPERO-ID:CRD42021265006). Cardioprotective classes included ACEIs, ARBs, Beta-blockers, dexrazoxane (DEX), statins and mineralocorticoid receptor antagonists. The primary end-point was new-onset heart failure (HF). Secondary outcomes were the mean difference in left ventricular ejection fraction (LVEF) change, hypotension and all-cause mortality. Network meta-analyses were used to assess the cardioprotective effects of each therapy to deduce the most effective therapies. Both analyses were performed using a Bayesian random effects model to estimate risk ratios (RR) and 95% credible intervals (95% CrI). RESULTS: Overall, from 726 articles, 39 trials evaluating 5931 participants (38.0 ± 19.1 years, 72.0% females) were identified. The use of any cardioprotective strategy associated with reduction in new-onset HF (RR:0.32; 95% CrI:0.19-0.55), improved LVEF (mean difference: 3.92%; 95% CrI:2.81-5.07), increased hypotension (RR:3.27; 95% CrI:1.38-9.87) and no difference in mortality. Based on control arms, the number-needed-to-treat for 'any' cardioprotective therapy to prevent one incident HF event was 45, including a number-needed-to-treat of 21 with ≥1 year of therapy. Dexrazoxane was most effective at HF prevention (Surface Under the Cumulative Ranking curve: 81.47%), and mineralocorticoid receptor antagonists were most effective at preserving LVEF (Surface Under the Cumulative Ranking curve: 99.22%). CONCLUSION: Cardiotoxicity remains a challenge for patients requiring anticancer therapies. The initiation of extended duration cardioprotection reduces incident HF. Additional head-to-head trials are needed.

Neural Stem Cell-Based Therapies and Glioblastoma Management: Current Evidence and Clinical Challenges.

Gliomas, which account for nearly a quarter of all primary CNS tumors, present significant contemporary therapeutic challenges, particularly the highest-grade variant (glioblastoma multiforme), which has an especially poor prognosis. These difficulties are due to the tumor's aggressiveness and the adverse effects of radio/chemotherapy on the brain. Stem cell therapy is an exciting area of research being explored for several medical issues. Neural stem cells, normally present in the subventricular zone and the hippocampus, preferentially migrate to tumor masses. Thus, they have two main advantages: They can minimize the side effects associated with systemic radio/chemotherapy while simultaneously maximizing drug delivery to the tumor site. Another feature of stem cell therapy is the variety of treatment approaches it allows. Stem cells can be genetically engineered into expressing a wide variety of immunomodulatory substances that can inhibit tumor growth. They can also be used as delivery vehicles for oncolytic viral vectors, which can then be used to combat the tumorous mass. An alternative approach would be to combine stem cells with prodrugs, which can subsequently convert them into the active form upon migration to the tumor mass. As with any therapeutic modality still in its infancy, much of the research regarding their use is primarily based upon knowledge gained from animal studies, and a number of ongoing clinical trials are currently investigating their effectiveness in humans. The aim of this review is to highlight the current state of stem cell therapy in the treatment of gliomas, exploring the different mechanistic approaches, clinical applicability, and the existing limitations.

Minimally invasive surgery versus transcatheter aortic valve replacement: a systematic review and meta-analysis.

Transcatheter aortic valve replacement (TAVR) has recently been approved for use in patients who are at intermediate and low surgical risk. Moreover, recent years have witnessed a renewed interest in minimally invasive aortic valve replacement (miAVR). The present meta-analysis compared the outcomes of TAVR and miAVR in the management of aortic stenosis (AS). We conducted an electronic search across six databases from 2002 (TAVR inception) to December 2019. Data from relevant studies regarding the clinical and length of hospitalisation outcomes were extracted and analysed using R software. We identified a total of 11 cohort studies, of which seven were matched/propensity matched. Our analysis demonstrated higher rates of midterm mortality (≥1 year) with TAVR (risk ratio (RR): 1.93, 95% CI: 1.16 to 3.22), but no significant differences with respect to 1 month mortality (RR: 1.00, 95% CI: 0.55 to 1.81), stroke (RR: 1.08, 95% CI: 0.40 to 2.87) and bleeding (RR: 1.45, 95% CI: 0.56 to 3.75) rates. Patients undergoing TAVR were more likely to experience paravalvular leakage (RR: 14.89, 95% CI: 6.89 to 32.16), yet less likely to suffer acute kidney injury (RR: 0.38, 95% CI: 0.21 to 0.69) compared with miAVR. The duration of hospitalisation was significantly longer in the miAVR group (mean difference: 1.92 (0.61 to 3.24)). Grading of Recommendations Assessment, Development and Evaluation assessment revealed ≤moderate quality of evidence in all outcomes. TAVR was associated with lower acute kidney injury rate and shorter length of hospitalisation, yet higher risks of midterm mortality and paravalvular leakage. Given the increasing adoption of both techniques, there is an urgent need for head-to-head randomised trials with adequate follow-up periods.

Aortic Dissection: A Review of the Pathophysiology, Management and Prospective Advances.

Aortic dissection is an emergent medical condition, generally affecting the elderly, characterized by a separation of the aortic wall layers and subsequent creation of a pseudolumen that may compress the true aortic lumen. Predisposing factors mediate their risk by either increasing tension on the wall or by causing structural degeneration. They include hypertension, atherosclerosis, and a number of connective tissue diseases. If it goes undetected, aortic dissection carries a significant mortality risk; therefore, a high degree of clinical suspicion and a prompt diagnosis are required to maximize survival chances. Imaging methods, most commonly a CT scan, are essential for diagnosis; however, several studies have also investigated the effect of several biomarkers to aid in the detection of the condition. The choice of intervention varies depending on the type of dissection, with open surgical repair remaining of choice in those with type. In dissections, however, the role of conventional open surgery has considerably diminished in complicated type B dissections, with endovascular repair, a much less invasive technique, proving to be more effective. In uncomplicated type B dissections, where medical choice reigned supreme as the optimal intervention, endovascular repair is being explored as a viable option which may reduce long- term mortality outcomes, although the ideal intervention in this situation is far from settled.