Antagonists In Patients Research Articles

Prognosis Comparison of Use of Oral Anticoagulants and Vitamin K Antagonists in Patients with Intracerebral Hemorrhage

This study reviewed the literature on the incidence of Intracerebral Hemorrhage (ICH) associated with the use of oral anticoagulant drugs (OAC) and vitamin K antagonists (VKA), then compared the outcomes of using these drugs in terms of mortality, morbidity or prognosis in patients. We did a search on online databases including Pubmed, Google Scholar and Science Direct according to the specified keywords. The results obtained amounted to 935 articles. From these articles, the types of research that met the inclusion and exclusion criteria were then re-screened and the final search results were obtained as many as 10 articles. The results of this study found that of the 10 articles reviewed, 8 of them showed p value > 0.05 so that there was no significant difference between the outcomes of ICH related to OAC or VKA, where outcomes were viewed from the factors of bleeding widening, ICH volume, mortality, and functional impact. Meanwhile, from 2 articles that showed significant results, it was stated that the prognosis of the incidence of ICH related to the use of OAC was better than the use of VKA. Research on ICH, research on original article types, according to predetermined keywords, is a publication in the period 2012-2022, human studies and articles can be accessed.

Finerenone in Mild to Severe Chronic Kidney Disease and Type 2 Diabetes: A Fidelity Subgroup Analysis in Patients with Heart Failure

Patients with chronic kidney disease (CKD), type 2 diabetes (T2D), and heart failure (HF) have a very high risk of adverse cardiorenal events. FIDELITY (prespecified pooled analysis of FIDELIO-DKD [NCT02540993] and FIGARO-DKD [NCT02545049]) evaluated finerenone, a selective, nonsteroidal mineralocorticoid receptor antagonist in patients with CKD and T2D. This FIDELITY substudy analyzed the effects of finerenone in patients with and without a history of HF at baseline. Eligible patients had T2D and either a urine albumin-to-creatinine ratio (UACR [mg/g])≥30–<300 and estimated glomerular filtration rate (eGFR [mL/min/1.73m2])≥25–≤90, or UACR≥300–≤5000 and eGFR≥25, and received optimized renin–angiotensin system blockade. Key exclusion criteria included symptomatic chronic HF with reduced ejection fraction or recent HF hospitalization (HHF). Patients were randomized to finerenone or placebo. Outcomes included a cardiovascular outcome (time to cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or HHF) and a kidney outcome (kidney failure, sustained eGFR decrease≥57%, or kidney death). Investigator-reported adverse events were assessed. 1007/13,026 eligible patients had a history of HF at baseline. Primary results of the FIDELITY analysis were presented at the European Cardiology Society Congress 2021. This abstract will present detailed HF outcomes, including new onset and recurrent HF events in the total population and cardiovascular and kidney efficacy and safety results by history of HF at baseline. In FIDELITY, finerenone improved CV and kidney outcomes in patients with CKD and T2D versus placebo. The proposed analysis will provide further insights into the effects of finerenone on HF outcomes across a broad spectrum of CKD severity.

Incremental value of mineralocorticoid receptor antagonists in patients with heart failure with reduced ejection fraction treated with sacubitril/valsartan

AimsWe investigated the incremental advantage in terms of N-terminal pro-B-type natriuretic peptide (NT-proBNP) reduction in patients affected by heart failure with reduced ejection fraction (HFrEF) treated with sacubitril/valsartan (S/V) and...

Cardiovascular and kidney outcomes of combination therapy with sodium-glucose cotransporter-2 inhibitors and mineralocorticoid receptor antagonists in patients with type 2 diabetes and chronic kidney disease: A systematic review and network meta-analysis

AimsBoth sodium-glucose cotransporter-2 (SGLT-2) inhibitors and mineralocorticoid receptor antagonists (MRAs) have been shown to reduce cardiovascular (CV) event in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). However, little evidence pertains to the benefits of their combined use. MethodsWe systematically searched the PubMed, MEDLINE, EMBASE, and Cochrane Library databases through July 2022. We selected randomized controlled trials comparing SGLT-2 inhibitors, MRAs, or SGLT-2 inhibitor + MRA combination therapy, with placebo in patients with T2D and CKD. We performed a network meta-analysis to indirectly compare the treatments. The primary outcome was a composite of CV events. ResultsEight studies were selected with 36,186 patients. The primary outcome was significantly improved in the combination therapy group compared with the other groups (RR [95% CI]; vs SGLT-2 inhibitors, 0.76 [0.60; 0.96]; vs MRAs, 0.66 [0.53; 0.82]; vs placebo, 0.58 [0.47; 0.73]). Additionally, the combination therapy was associated with a considerable reduction in the risk of hyperkalemia (RR vs MRA, 0.43 [0.23; 0.79]). ConclusionCombination of SGLT-2 inhibitors and MRAs potentially reduced CV events compared with SGLT-2 inhibitors or MRAs alone. This combination may be a candidate treatment strategy for patients with T2D and CKD.

Abstract 12596: Comparison of the Efficacy and Safety of Direct Oral Anticoagulants With Vitamin K Antagonists in Patients With Thrombotic Antiphospholipid Syndrome: Systematic Review and Meta-analysis of Randomized Clinical Trials

Introduction: The efficacy and safety of direct oral anticoagulants (DOACs) as treatment alternatives for patients with thrombotic antiphospholipid syndrome (APS) remain controversial. Methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) that compared the efficacy and safety of DOACs with vitamin-K antagonists (VKAs) in patients with thrombotic APS. We searched PubMed, EMBASE and Cochrane Central Register of Controlled Trials through April 9, 2022. Main efficacy outcomes were a composite of arterial thrombotic events, and a composite of venous thromboembolic events (VTE). The main safety outcome was major bleeding according to the International Society on Thrombosis and Hemostasis (ISTH) criteria. A random effects model with inverse variance was used for the primary analysis. Risk of bias was assessed using the Cochrane Collaboration criteria. Results: Our search retrieved 253 studies. Four RCTs involving 474 patients were included (Figure). All four RCTs were open-label but had proper random sequence generation and adequate allocation concealment. The DOACs used were rivaroxaban (3 trials) and apixaban (1 trial). The mean percent time in therapeutic range in the warfarin arm among the four studies was 60%. Overall, use of DOACs compared with VKAs was associated with increased odds of composite of arterial thrombotic events (OR 5.64, 95% confidence interval [CI] 1.96-16.27, p =0.001, I 2 = 0%). The odds of subsequent VTE events (OR 1.19, 95% CI 0.31-4.53, p =0.80, I 2 = 0%), or major bleeding (OR 1.02, 95% CI 0.42-2.47, p =0.97, I 2 = 0%) were not significantly different between the two groups. Conclusions: Patients with thrombotic APS randomized to DOACs compared to VKAs appear to have increased risk for arterial thrombosis. No significant differences were observed between patients randomized to DOACs vs VKAs in the risk of subsequent VTE or major bleeding.

Comparative Combinatorial Implications and Theranostics of Immunotherapy in the Impediment of Alveolar Soft Part Sarcoma.

Immune checkpoint inhibitors (ICIs), specifically programmed cell death receptor- 1/ligand 1 (PD-1/L1) inhibitors, have shown potential pharmacological efficacy in several cancers. Nonetheless, data pertinent to their therapeutic efficacy in alveolar soft-part sarcoma (ASPS) are limited. The retrospective aspects of ICIs (anti-PD1/PD-L1 blockers) to target ASPS are comparatively analyzed for clinical outcomes with other targeted immunotherapy modalities. We have conducted a systematic review without statistical analysis or comprehensive meta-analysis by collecting the articles published between 1952 and Sep 10th, 2020, by searching the following words: alveolar soft part sarcoma and immunotherapy including immune checkpoint, immune checkpoint inhibitors, and PD-1, PD-L1. We performed a pooled analysis of case reports, conferences, clinical trials, and other research reports pertinent to the efficacy of a PD-1 or PD-L1 antagonist in patients diagnosed with metastatic ASPS. The effective studies include 10 case reports, 2 conference reports, 5 clinical trials, and 2 additional research reports. A total of 110 patients were reported to be enrolled in the pooled analysis; among them, 87 (78.38%) received a PD-1/PD-L1 antagonist. For patients who received anti-PD-1/PD-L1as monotherapy, their clinical response rates (CRR) were 63.22% whereas those who received targeted therapy and immunotherapy had a CRR of 78.95% (15/19). In the patients treated with double immunotherapy, their CRR was 100% (4/4). Tumor mutational burden and mismatch repair status have significant implications for predicting the ASPS prognosis. Alveolar soft-part sarcoma patients with distant metastases can exhibit better clinical outcomes with immunotherapy, particularly toripalimab, atezolizumab, and axitinib combinatorial regimen with pembrolizumab. In addition, this review describes the therapeutic implications to guide personalized medicine depending on the expression patterns of PD-1/PD-L1 during the immunotherapy with ASPS.

Mechanisms of mineralocorticoid receptor-associated hypertension in diabetes mellitus: the role of O-GlcNAc modification.

This study investigated the mechanism underlying the beneficial effects of mineralocorticoid receptor (MR) antagonists in patients with resistant hypertension and diabetic nephropathy by examining post-translational modification of the MR by O-linked-N-acetylglucosamine (O-GlcNAc), which is strongly associated with type 2 diabetes. Coimmunoprecipitation assays in HEK293T cells showed that MR is a target of O-GlcNAc modification (O-GlcNAcylation). The expression levels and transcriptional activities of the receptor increased in parallel with its O-GlcNAcylation under high-glucose conditions. Liquid chromatography-tandem mass spectrometry revealed O-GlcNAcylation of the MR at amino acids 295-307. Point mutations in those residues decreased O-GlcNAcylation, and both the protein levels and transcriptional activities of MR. In db/db mouse kidneys, MR protein levels increased in parallel with overall O-GlcNAc levels of the tissue, accompanied by increased SGK1 mRNA levels. The administration of 6-diazo-5-oxo-L-norleucin, an inhibitor of O-GlcNAcylation, reduced tissue O-GlcNAc levels and MR protein levels in db/db mice. Thus, our study showed that O-GlcNAcylation of the MR directly increases protein levels and transcriptional activities of the receptor under high-glucose conditions in vitro and in vivo. These findings provide a novel mechanism of MR as a target for prevention of complications associated with diabetes mellitus.

Comparing direct oral anticoagulants versus vitamin K antagonist in patients with atrial fibrillation after transcatheter aortic valve replacement: an updated meta-analysis

Abstract Background Oral anticoagulation therapy is indicated for patients undergoing transcatheter aortic valve replacement (TAVR) with concomitant or new onset atrial fibrillation (AF). However the data on optimal anticoagulation regimen in this population remains unclear. Purpose To compare efficacy and safety outcomes of direct oral anticoagulants (DOACs) versus Vitamin K antagonists (VKA) in patients with AF post TAVR. Methods We searched electronic databases (PubMed, Embase, Scopus, Cochrane) from inception to February28th, 2022 using MeSH terms and keywords for DOACs, AF or TAVR. Primary outcome of interest was all-cause stroke or systemic embolic event. Secondary safety outcomes were major bleeding and all-cause mortality. Pooled risk ratio (RR) and 95% confidence interval (CI) were calculated using a random-effects model. Interstudy heterogeneity was assessed using the Higgins I 2 value. All statistical analysis were performed using RevMan 5.4.1 software. Results We identified five eligible studies (1RCT, 4 observational) including 3694 patients (DOAC n=1581, VKA n=2113). The mean age was 81.4±0.9 years. The mean follow-up was 12.4±14.3 months. Type of DOACs included apixaban (n=394, 24.9%), rivaroxaban (n=354, 22.4%), dabigatran (n=119, 7.5%) and edoxaban (n=714, 45.2%).There was no significant difference in primary outcome of stroke or systemic embolic event (RR: 0.93; CI: 0.65–1.33; p&amp;gt;0.05; I2=5%), or in secondary outcomes of major bleeding (RR: 1.02; CI: 0.78–1.34; p&amp;gt;0.05; I2=44%) and all-cause mortality (RR: 0.87; CI: 0.59–1.27; p&amp;gt;0.05; I2=56%) between DOACs and VKA groups. Conclusion This meta-analysis shows anticoagulation therapy with DOACs has similar safety and efficacy outcomes compared to VKA in patients with AF undergoing TAVR. Funding Acknowledgement Type of funding sources: None.

Persistence with macitentan versus other endothelin receptor antagonists in patients with pulmonary arterial hypertension: experience from a real-world data repository in the USA

Abstract Background Pulmonary arterial hypertension (PAH) is a progressive and fatal disease and as such, it is imperative that patients remain on therapy to delay progression and maintain functional status. Previous research has demonstrated differences in overall survival in the real-world by endothelin receptor antagonists (ERA) treatments with a lower risk of death with macitentan than ambrisentan and bosentan. However, real-world data on persistence to ERAs are limited. Purpose To compare persistence to macitentan versus ambrisentan and bosentan) in patients with PAH. Methods This retrospective, non-interventional, observational study identified patients between 10/21/2013–3/31/2021 (study period) from the Decision Resources Group (DRG) Real World Data Repository. The repository links medical and prescription claims from commercial, Medicaid, and Medicare plans with electronic health records (EHRs) to provide longitudinal patient-level data representative of over 300 million patients in the US. Patients selected must have been dispensed an ERA prescription from 4/14/14–3/31/20 AND 1) either an inpatient diagnosis of pulmonary hypertension (PH), or 2) a right heart catheterization with any PH diagnosis, or 3) were taking a phosphodiesterase 5 inhibitor (PDE5i). The primary outcome was persistence defined by time from index to drug discontinuation (90-day gap after the end of the last prescription's days of supply). Descriptive analysis comprised means, standard deviations, medians, and interquartile ranges for continuous variables and frequencies and percentages for categorical variables. Three-sample proportion tests were conducted at baseline to detect differences between the three cohorts and identify potentially confounding variables. Hazard ratios (HR) for pairwise comparisons (macitentan vs ambrisentan; macitentan vs bosentan) were calculated using an inverse probability of treatment weighting (IPTW)-adjusted Cox proportional regression model, to adjust for potential confounders (see Table 1) of the probability of receiving a specific ERA. Data were analyzed by Kaplan-Meier method. Results A total of 4,526 patients were included, of whom 1,205 received macitentan, 2,592 received ambrisentan and 729 received bosentan. Study population characteristics were representative of a general PAH population (Table 1). Unadjusted Kaplan-Meier analysis showed that median persistence was shortest for ambrisentan (12.6 months) followed by bosentan (13.6 months) and greatest for macitentan (15.8 months; overall log-rank p-value: 0.061). Compared to macitentan, patients on other ERAs had a greater risk of discontinuation: ambrisentan (10%) and bosentan (18%) (Table 2). Conclusions Persistence to therapy was significantly greater for macitentan-treated patients than in those receiving ambrisentan or bosentan. Further research examining variability in key sub-groups as well as the impact of improved persistence on long-term outcomes is warranted. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Janssen Scientific Affairs, LLC

Effects of interleukin-1 antagonists on de novo and pre-existing damage in patients with familial Mediterranean fever.

Colchicine is the mainstay of familial Mediterranean fever treatment and interleukin (IL-1) antagonists are the treatment of choice in resistant patients. We aimed to investigate efficacy of IL-1 antagonists in the prevention of damage, as well as the causes of treatment failure. A total of 111 patients fulfilling Euro fever and Tel-Hashomer criteria and treated with IL-1 antagonists were included in the study. Patients were grouped according to their recent damage status; no damage, pre-existing damage and de novo damage that developed under IL-1 antagonist treatment. The degree of damage was determined using Auto Inflammatory Disease Damage Index (ADDI). Total damage score was calculated separately as its original definition and with excluding chronic musculoskeletal pain, creating modified ADDI (mADDI). Forty-six patients (43,2 %) had damage according to mADDI. Damage was commonly observed at musculoskeletal, renal and reproductive domains. Median duration of treatment was forty-five months. Two patients developed de novo damage; one musculoskeletal and one reproductive in this time-period. Five patients had worsening of their damage while using IL-1 antagonists. De novo damage with IL-1 antagonist treatment was associated with acute phase protein levels. We evaluated change in damage accrual while using IL-1 antagonists in patients with FMF. Physicians should pay attention to controlling inflammation to prevent further damage, especially in those with pre-existing damage.

Starting Neurohormonal Antagonists in Patients With Acute Heart Failure With Mid-Range and Preserved Ejection Fraction.

The clinical benefits of neurohormonal antagonists for patients with heart failure (HF) with mid-range and preserved ejection fraction (HFmrEF and HFpEF) are uncertain. This study analyzed 858 consecutive patients with HFmrEF (EF: 40-49%) or HFpEF (EF ≥50%), who were hospitalized for acute HF, and who were discharged alive, and were not taking angiotensin-converting enzyme inhibitors (ACE)-I/ angiotensin II receptor blockers (ARB) or β-blockers at admission. The study population was classified into 4 groups according to the status of prescription of ACE-I/ARB and β-blocker at discharge: no neurohormonal antagonist (n=342, 39.9%), ACE-I/ARB only (n=128, 14.9%), β-blocker only (n=189, 22.0%), and both ACE-I/ARB and β-blocker (n=199, 23.2%) groups. The primary outcome measure was a composite of all-cause death or HF hospitalization. The cumulative 1-year incidence of the primary outcome measure was 41.2% in the no neurohormonal antagonist group, 34.0% in the ACE-I/ARB only group, 28.6% in the β-blocker only group, and 16.4% in the both ACE-I/ARB and β-blocker group (P<0.001). Compared with the no neurohormonal antagonist group, both the ACE-I/ARB and β-blocker groups were associated with a significantly lower risk for a composite of all-cause death or HF hospitalization (HR: 0.46, 95% CI: 0.28-0.76, P=0.002). In hospitalized patients with HFmrEF and HFpEF, starting both ACE-I/ARB and a β-blocker was associated with a reduced risk of the composite of all-cause death or HF hospitalization compared with patients not starting on an ACE-I/ARB or β-blocker.

742P First-in-human phase I study of INCAGN02385, a LAG-3 monoclonal antibody antagonist in patients with advanced malignancies

Lymphocyte activation gene 3 (LAG-3) is a cell-surface immune checkpoint receptor that negatively regulates cell activation and proliferation. INCAGN02385 is a humanized Fc-engineered IgG1κ monoclonal antibody with selective and potent LAG-3 antagonist action against LAG-3 binding to MHC class II, leading to enhanced TCR signaling and cytokine secretion of activated T cells. This study primarily aims to determine safety and tolerability and define the MTD or PAD of INCAGN02385 monotherapy.

730MO First-in-human phase I study of INCAGN02390, a TIM-3 monoclonal antibody antagonist in patients with advanced malignancies

TIM-3 is a transmembrane checkpoint receptor expressed on multiple immune cells that promotes an inhibitory tumor microenvironment. INCAGN02390 is a fully human Fc-engineered IgG1κ monoclonal antibody that selectively inhibits TIM-3 ligand interactions. This study is primarily aimed to determine the safety and tolerability and define the MTD or PAD of INCAGN02390 monotherapy. This is a phase 1, multicenter, open-label, dose-escalation study that enrolled pts with locally advanced or metastatic solid tumors that failed available therapies, were intolerant to treatment, or refused noncurative standard treatment. A 3+3 dose-escalation design was used; pts received intravenous INCAGN02390 Q2W in 7 dose levels (DLs): 10 mg, 30 mg, 100 mg, 200 mg, 400 mg, 800 mg, or 1600 mg. The primary endpoint was safety and tolerability. Other endpoints were PK, PD and preliminary efficacy per RECIST v1.1. Forty pts (median age, 63 y) were enrolled; 53% were male and 83% had ECOG PS 1. Lead cancer types were breast (15%), lung (13%), and colorectal (10%). 98% received prior systemic therapy (58% had prior immunotherapy). No DLT was observed and MTD was not reached. Most frequent treatment-emergent adverse events (TEAEs) were anemia (35%), back pain (30%), and fatigue (28%). Drug-related grade ≥3 TEAEs were observed in 7.5% of pts (anemia, adrenal insufficiency, and amylase increased [n=1 each]; all Gr3). One drug-related serious TEAE (adrenal insufficiency) occurred at the 1600 mg DL. One drug-unrelated fatal TEAE (multi-organ failure) occurred in the 800-mg DL. INCAGN02390 trough serum concentrations achieved steady state around Cycles 4 to 6. Maximum concentration and area under the serum concentration-time curve were linear across most DLs. Doses ≥400 mg led to trough TIM-3 receptor occupancy levels of ≥90% in peripheral blood. Disease control rate was 17.5%, with 1 confirmed partial response in a pt with an adenoid cystic carcinoma in lung. INCAGN02390 monotherapy was generally well tolerated, with linear PK. The 400 mg Q2W dose is selected for further investigation in phase 1b/2 studies in combinations with other immunotherapies (NCT04370704, NCT05287113).

Primary versus secondary antiemetic prophylaxis with NK1 receptor antagonists in patients affected by gastrointestinal malignancies and treated with a doublet or triplet combination regimen including oxaliplatin and/or irinotecan plus fluoropyrimidines: A propensity score matched analysis.

AimThe aim of the current study is to investigate the impact of primary compared to secondary chemotherapy-induced nausea and vomiting (CINV) prophylaxis with NK1 receptor antagonists (NK1-RA) in patients affected by gastrointestinal malignancies and treated with oxaliplatin- and/or irinotecan-based doublet or triplet regimens.Study design and methodsClinical data of patients affected by gastrointestinal malignancies, treated with an oxaliplatin and/or irinotecan-based doublet or triplet regimen as neo/adjuvant or advanced-line treatment, and who received NK1-RA as primary (from the first cycle of treatment) or secondary (after the onset of CINV with a previous regimen with 5HT3-RA and dexamethasone) prophylaxis for CINV, were retrospectively collected in an observational study involving 16 Italian centers. A propensity score matching was performed by taking into account the following stratification factors: sex (male vs. female), age (< vs. ≥70 years old), overweight (body mass index, BMI < vs. ≥25), underweight (BMI < vs. ≥19), disease spread (early vs. advanced/metastatic), tumor type (esophagogastric cancer vs. the rest, hepatobiliary tumor vs. the rest, colorectal cancer vs. the rest), type of NK1-RA used as primary/secondary prophylaxis (netupitant-palonosetron vs. fosaprepitant/aprepitant), concomitant use of opioids (yes vs. no), concomitant use of antidepressant/antipsychotic drugs (yes vs. no), Eastern Cooperative Oncology Group (ECOG) performance status at the start of NK1-RA treatment (0 vs. 1–2), and intensity of chemotherapy regimen (doublet vs. triplet).ResultsAmong 409 patients included from January 2015 to January 2022 and eligible for analysis, 284 (69%) and 125 (31%) were treated with NK1-RA as primary and secondary antiemetic prophylaxis, respectively. After matching, primary NK1-RA use was not associated with higher rates of protection from emesis regardless the emesis phase (acute phase, p = 0.34; delayed phase, p = 0.14; overall phase, p = 0.80). On the other hand, a lower rate of relevant nausea (p = 0.02) and need for rescue antiemetic therapy (p = 0.000007) in the overall phase was found in primary NK1-RA users. Furthermore, a higher rate of both complete antiemetic response (p = 0.00001) and complete antiemetic protection (p = 0.00007) in the overall phase was more frequently observed in primary NK1-RA users. Finally, chemotherapy delays (p = 0.000009) and chemotherapy dose reductions (p = 0.0000006) were less frequently observed in primary NK1-RA users.ConclusionIn patients affected by gastrointestinal malignancies, a primary CINV prophylaxis with NK1-RA, 5HT3-RA, and dexamethasone might be appropriate, particularly in those situations at higher risk of emesis and in which it is important to avoid dose delays and/or dose reductions, keeping a proper dose intensity of chemotherapy drugs.

Direct Oral Anticoagulants Versus Vitamin K Antagonists in Cerebral Venous Thrombosis: A Systematic Review and Meta-Analysis.

High level evidence for direct oral anticoagulants (DOACs) in patients with cerebral venous thrombosis is lacking. We performed a systematic review and meta-analysis to assess the efficacy and safety of DOACs versus vitamin K antagonists in patients with cerebral venous thrombosis. This systematic review was registered in PROSPERO (CRD42021228800). We searched MEDLINE (via Ovid), EMBASE, CINAHL, and the Web of Science Core Collection between January 1, 2007 and Feb 22, 2022. Search terms included a combination of keywords and controlled vocabulary terms for cerebral venous thrombosis, vitamin K antagonists/warfarin, and DOACs. We included both randomized and nonrandomized studies that compared vitamin K antagonists and DOACs in 5 or more patients with cerebral venous thrombosis. Where studies were sufficiently similar, we performed meta-analyses for efficacy (recurrent venous thromboembolism and complete recanalization) and safety (major hemorrhage) outcomes, using relative risks (RRs). Out of 10 665 records identified, we screened 254 as potentially eligible. Nineteen studies (16 observational studies [n=1735] and 3 randomized controlled trials [n=215]) met the inclusion criteria. All 3 randomized controlled trials had some concerns, and all 16 observational studies had at least moderate risk of bias. When compared with vitamin K antagonist treatment, DOAC had comparable risks of recurrent venous thromboembolism (relative risk [RR], 0.85 [95% CI, 0.52-1.37], I2=0%), major hemorrhage (RR, 0.70 [95% CI, 0.40-1.21], I2=0%), intracranial hemorrhage (RR, 0.58 [95% CI, 0.30-1.12]; I2=0%), death (RR, 1.14 [95% CI, 0.54-2.43], I2=1%), and complete venous recanalization (RR, 0.98 [95% CI, 0.87-1.11]; I2=0%). This systematic review and meta-analysis suggest that in patients with cerebral venous thrombosis, DOACs, and warfarin may have comparable efficacy and safety. Given the limitations of the studies included (low number of randomized controlled trials, modest total sample size, rare outcome events), our findings should be interpreted with caution pending confirmation by ongoing randomized controlled trials and large, prospective, observational studies.

Experiense of treatment with a growth hormone receptor antagonist in patients with hereditary form of acromegaly: clinical cases

Acromegaly is a severe neuroendocrine disease caused by chronic excessive production of somatotropic hormone (STH), characterized by specific changes in appearance, metabolic disorders. In 95% of cases, the cause of pathology is STH-producing pituitary adenomas. The priority method of treatment for acromegaly is transnasal transsphenoidal adenomectomy. If it is impossible to carry out neurosurgical intervention, in order to prevent the progression of the disease and the development of complications, patients are recommended drug therapy with long-acting somatostatin analogues, and if their effectiveness is low, additional radiation therapy may be applied to the neoplasm area. The usage of a relatively new group of drugs, antagonists of STH receptors, namely Pegvisomant for the purpose of drug treatment of acromegaly demonstrates high efficacy even in cases of aggressive forms resistant to other types of treatment. In this article we present two clinical cases of hereditary acromegaly, when the initiation of Pegvisomant therapy led to the achievement of clinical and laboratory remission of acromegaly in patients with an aggressive form of the disease, accompanied by continued growth of residual neoplasm tissue and preservation of its secreting ability even after surgical interventions, radiatiotherapy and long-term drug treatment with somatostatin analogues. The results of the above clinical cases confirm the success of mono- or combined (in cases with continued growth of the neoplasm) therapy with a growth hormone receptor antagonist, Pegvisomant, especially in the case of aggressive acromegaly.

Uninterrupted vitamin K antagonists in patients undergoing transcatheter aortic valve implantation: A promising strategy still looking for the right patient.

Uninterrupted vitamin K antagonists in patients undergoing transcatheter aortic valve implantation: A promising strategy still looking for the right patient.

Comparing the efficacy and safety of direct oral anticoagulants versus Vitamin K antagonists in patients with antiphospholipid syndrome: a systematic review and meta-analysis.

Thromboprophylaxis is the cornerstone strategy for thrombotic antiphospholipid syndrome (APS). Data comparing direct oral anticoagulants (DOACs) to Vitamin K antagonists (VKAs) in the secondary prevention of thrombosis in APS patients remain contentious.We aim to review and analyse literature on the efficacy and safety of DOACs compared with VKAs in treating patients with APS. A literature search was performed from inception to 31 December 2021. Subgroups were analysed based on the risk stratification of APS profiles and different DOAC types.A total of nine studies with 1131 patients were included in the meta-analysis. High-risk APS patients (triple positive APS) who used DOACs displayed an increased risk of recurrent thrombosis [risk ratio = 3.65, 95% confidence interval (95% CI): 1.49–8.93; I2 = 29%, P = 0.005] compared with those taking VKAs. Similar risk of recurrent thrombosis or major bleeding was noted in low-risk APS patients (single or double antibody-positive) upon administering DOACs or VKAs. The utilization of Rivaroxaban was associated with a high risk of recurrent thromboses (RR = 2.63; 95% CI: 1.56–4.42; I2 = 0, P = 0.0003), particularly recurrent arterial thromboses (RR = 4.52; 95% CI: 1.99–10.29; I2 = 0, P = 0.18) in overall APS patients. Comparisons of the rate of recurrent thrombosis events and major bleeding events when using dabigatran or apixaban versus VKAs yielded no statistical differences.In the absence of contraindications, this meta-analysis suggests that VKAs remain the first-choice treatment for high-risk APS patients, with DOACs a more appropriate option for low-risk APS patients. Different DOACs may exhibit different levels of efficacy and safety for thromboprophylaxis in APS patients and require further exploration.

Early Experience With Interleukin-6 Receptor Antagonists in Patients With COVID-19 Admitted to a Community Hospital.

Background/objective: The efficacy of interleukin-6 (IL-6) inhibitors in hospitalized patients with severe coronavirus disease 2019 (COVID-19) pneumonitis is unclear. Method: This retrospective, observational cohort study included patients hospitalized at a community hospital with COVID-19 pneumonia from March 2020 to May 2020. All patients were treated with standard of care (SOC), and a nonrandomly selected subset of patients also received an IL-6 inhibitor. The primary outcome was clinical response, defined as an improvement of at least 2 categories relative to baseline on a 7-category ordinal scale up to hospital discharge or 30 days. In adjusted analyses, logistic and linear regression models were conducted, controlling for covariates of hospital length of stay (LOS), intensive care unit (ICU) care, ICU LOS, gender, age, race, and Charlson Comorbidity Index. Results: A total of 133 patients met inclusion criteria. In all, 30 patients received an IL-6 inhibitor plus SOC. There was no statistical difference in clinical outcome between groups as 76.7% in the SOC alone group and 70.0% in the IL-6 inhibitor group met the defined endpoints for clinical response (P = 0.477). In the adjusted analysis, patients treated with IL-6 inhibitors were approximately 4 times more likely to meet the primary endpoint compared with patients with SOC alone (adj. odds ratio = 4.325; P = 0.038, 95% confidence interval = [1.09-17.18]). Conclusions: Compared with SOC alone, IL-6 inhibitors were not associated with a significant clinical response. However, after adjusting for covariates, this study suggests that the initiation of IL-6 inhibitors in patients with early COVID-19 pneumonitis before progression to the ICU may be associated with improved clinical status.

Association of cardiovascular disease risk and changes in renin levels by mineralocorticoid receptor antagonists in patients with primary aldosteronism.

A recent report stated that patients with primary aldosteronism who remain renin suppressed during mineralocorticoid receptor antagonist treatment might have a higher risk of developing cardiovascular disease than those with unsuppressed renin activity. We retrospectively investigated the incidence of composite cardiovascular disease and risk factors for cardiovascular disease in 1115 Japanese patients with primary aldosteronism treated with mineralocorticoid receptor antagonists. The median follow-up period was 3.0 years, and the incidence of cardiovascular events was very low (2.1%) throughout 5 years of follow-up. Changes in plasma renin activity from before to after mineralocorticoid receptor antagonist treatment were divided into three groups based on tertile, low, intermediate, and high plasma renin activity change groups, with incidences of cardiovascular disease events of 2.1%, 0.5%, and 3.7%, respectively. Multivariate Cox regression analysis revealed age (adjusted hazard ratio, 1.07; 95% confidence interval, [1.02-1.12]) and body mass index (adjusted hazard ratio, 1.13 [1.04-1.23]) as independent risk factors for cardiovascular disease. The high plasma renin activity change group had significantly higher cardiovascular disease risk with mineralocorticoid receptor antagonist treatment than the intermediate plasma renin activity change group (adjusted hazard ratio, 5.71 [1.28-25.5]). These data suggest that a high change in renin level after mineralocorticoid receptor antagonist treatment may not necessarily predict a better prognosis of cardiovascular disease in patients with primary aldosteronism.