scholarly journals Efficacy and Safety of Rivaroxaban in Patients with CAT: A Pooled Meta-Analysis of 3 Randomized Controlled Trials

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1068-1068
Author(s):  
Silvy Laporte ◽  
Andrea Marshall ◽  
Annie Young ◽  
Hanno Riess ◽  
Marianne Sinn ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Financial Support ◽  
Research Funding ◽  
Treatment Effects ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Patient Characteristics ◽  
Efficacy And Safety ◽  
Hazard Ratios ◽  
Bayer Healthcare

Abstract Introduction: CALLISTO, a comprehensive programme of research on cancer-associated thrombosis (CAT) , included 3 randomized trials of rivaroxaban versus low molecular weight heparin (LMWH) for the treatment of venous thrombosis in patients with solid and haematological cancers (SELECT-D, CASTA-DIVA and CONKO-11). A meta-analysis of these studies was conducted to improve the precision of current estimates of the efficacy and safety of rivaroxaban in this patient group and investigate how patient characteristics impact the treatment effects. Methods: The primary endpoint was the cumulative incidence of venous thromboembolism (VTE) recurrence at the end of the treatment period (≥3 months). Other endpoints included major bleeding (MB), a composite of MB or clinically relevant non-major bleeding (clinically relevant bleeding [CRB]) and deaths from any cause. All endpoints were assessed by 8 pre-defined subgroup analyses: age, gender, creatinine clearance, type of index VTE, index VTE localization, cancer localization, performance status and presence of metastases (Prospero submission 266227). Patient-level data were used in this analysis. The cumulative incidences of VTE recurrence, CRB were estimated using the Kalbfleisch and Prentice model, while the Kaplan-Meier model was used to estimate the incidence of death. Comparisons between rivaroxaban and LMWH for VTE recurrence, MB and CRB were assessed by sub-distribution hazard ratios (SubHR) and 95% confidence intervals (CI), whereas hazard ratios and 95% CIs were used for the all-cause death endpoint. The pooled treatment effect size of each study was estimated using fixed-effect and random-effects models. Results: When considering the prevention of VTE recurrence in the 3 randomized trials (N=804), an overall reduction of 48% was observed with rivaroxaban compared with LMWH (SubHR = 0.52, 95% CI 0.28─0.98). The estimation appeared to be homogeneous across subgroups of patients. In comparison with LMWH, rivaroxaban was associated with an increased risk of CRB (SubHR = 2.03, 95% CI 1.34─3.09), without significant difference in MB (SubHR = 1.24, 95% CI 0.60─2.57), and no difference was observed for death. Conclusions: This pooled analysis suggests that rivaroxaban may be an alternative treatment option for the prevention of VTE recurrence in cancer patients with VTE. The gain in statistical power has shown significant benefit, as well as some risk associated with rivaroxaban treatment in this complex patient population. The impact of patient characteristics on these treatment effects will be presented at the meeting. Disclosures Laporte: Bayer Healthcare: Other: personal fees and non-financial support; Pfizer: Other: non-financial support; LEO Pharma: Other: non-financial support. Marshall: Bayer: Research Funding. Young: BMS/Pfizer Alliance: Honoraria; Leo Pharma: Honoraria; Chugai: Honoraria; Bayer: Honoraria, Research Funding. Riess: Bristel Myers Squibb: Honoraria; Bayer: Honoraria, Research Funding; Daiichi Sankyo: Honoraria; ASPEN: Honoraria; Leo Pharma: Honoraria; Pfizer: Honoraria. Sinn: BMS: Honoraria, Research Funding; Incyte: Honoraria, Research Funding; Pfizer: Honoraria; Servier: Consultancy, Honoraria, Research Funding; Astra Zenica: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; MSD: Consultancy, Research Funding; Sanofi: Consultancy; Bayer: Research Funding. Girard: Bayer Healthcare: Other: Personal fees, Research Funding; LEO Pharma: Other: Perconal fees, Research Funding. Sanchez: BAYER: Other: reports grants, personal fees and non-financial suppor; BMS: Other: grants, personal fees and non-financial support; PFIZER: Other: personal fees and non-financial support; BOEHRINGER INGELHEIM: Other: personal fees and non-financial support; CHIESI: Other: personal fees; BOSTON SCIENTIFICS: Other: grants and personal fees.

Efficacy and safety of aspirin for cardiovascular risk prevention in younger and older age: an updated systematic review and meta-analysis

2021 ◽  
Author(s):  
Dario Calderone ◽  
Antonio Greco ◽  
Salvatore Ingala ◽  
Federica Agnello ◽  
Antonio Gabriele Franchina ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Major Bleeding ◽  
Cardiovascular Events ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Major Adverse Cardiovascular Events ◽  
Older Individuals ◽  
Efficacy And Safety ◽  
Safety Outcome ◽  
Increased Risk

Aims - The efficacy and safety of aspirin for primary cardiovascular disease (CVD) prevention is controversial. The aim of this study was to investigate the merits of aspirin in subjects with no overt CVD, with a focus on age as a treatment modifier. Methods and results - Randomized trials comparing aspirin use versus no aspirin use or placebo were included. The primary efficacy outcome was all-cause death. The primary safety outcome was major bleeding. Subgroups analyses were conducted to investigate the consistency of the effect sizes in studies including younger and older individuals, using a cut-off of 65 years. A total of 21 randomized trials including 173,810 individuals at a mean follow-up of 5.3 years were included. Compared with control, aspirin did not reduce significantly the risk of all-cause death (risk ratio 0.96, 95% CI 0.92-1.00, p=0.057). Major adverse cardiovascular events were significantly reduced by 11%, paralleled by significant reductions in myocardial infarction and transient ischemic attack. Major bleeding, intracranial hemorrhage, and gastrointestinal bleeding were significantly increased by aspirin. There was a significant age interaction for death (p for interaction=0.007), with aspirin showing a statistically significant 7% relative benefit on all-cause death in studies including younger patients. Conclusions - The use of aspirin in subjects with no overt cardiovascular disease was associated with a neutral effect on all-cause death and a modest lower risk of major cardiovascular events at the price of an increased risk in major bleeding. The benefit of aspirin might be more pronounced in younger individuals.

scholarly journals Patterns of VTE Treatment with Noac in Cancer Patients - Results of the Prospective Dresden Noac Registry (NCT01588119)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3667-3667
Author(s):  
Sandra Marten ◽  
Luise Tittl ◽  
Christiane Naue ◽  
Jan Beyer-Westendorf
Keyword(s):  
Cancer Patients ◽  
Incidence Rate ◽  
Major Bleeding ◽  
Research Funding ◽  
Randomized Trials ◽  
Gi Cancer ◽  
Bayer Healthcare ◽  
Term Data ◽  
Active Cancer

Background: Until recently, patients with cancer associated thrombosis (CAT) were predominantly treated with low-molecular weight heparin (LMWH) but trial data and updated guidelines suggest that direct oral anticoagulants (DOAC) may represent feasible and convenient oral alternatives. However, most data supporting this relate to 6-12 months outcomes only and long-term data in this setting are scarce Aims: To evaluate the effectiveness and safety of CAT treatment with DOAC in daily care. Patients and methods: From the multicentric Dresden NOAC Registry, long-term outcomes of a subgroup of CAT patients (active or recent cancer, defined as cancer therapy within 5 years prior to thrombosis) receiving CAT therapy with DOAC were evaluated, based on prospectively collected data and centrally adjudicated outcome events. Results: Of the 1667 VTE patients enrolled in the registry until 30th June 2019, 186 patients (11.2%) were identified to have CAT (mean age 67.3 years; 61.3% male). At enrolment, cancer was reported as active in 97 (52.2) cases and recent in 89 (47.8) cases. Solid malignancies were diagnosed in 163 (87.6%) cases were, the remaining 23 (12.4%) cases were hematologic malignancies; table 1; figure 1). Of the 97 cases with active malignancies, 43.3% had metastatic disease. CAT treatment consisted of rivaroxaban in 80 (43.0%) patients, 66 (35.5%) received edoxaban and 40 (21.5%) apixaban. During follow-up (mean 27.8 months, range 0.5 - 88.6), 14 patients experienced recurrent VTE events (7.5 %; incidence rate 3.5/100 pt. years) of which 4 occurred during DOAC treatment and 10 after discontinuation or during prolonged (>3d) DOAC interruption (figure 2a). During DOAC exposure (within 3 days of last intake), major bleeding occurred in 15 patients (8.1%; incidence rate 5.9/100 pt. years; figure 2b) and presented as gastrointestinal (GI) bleeding in 7, intracranial bleeding in 3 and in other bleeding manifestations in 5 cases. For 34 patients with GI cancer, the incidence rate for major bleeding was 13.3/100 pt. years and all four major bleedings in this group presented as upper GI bleed. 40 patients died during FU (21.5%; incidence rate 9.4/100 pt. years). Causes of death included terminal malignant disease (n=22), infection (n=6), fatal bleeding (n=4), age related death (n=3), fatal cardiovascular event (n=3), and other reasons (n=2). Conclusions: Our results now contribute long-term data of DOAC treatment for CAT. Incidence rates of recurrent VTE and major bleeding were consistent with the results from recent randomized trials in CAT. Most VTE recurrences occurred after interruption or discontinuation of DOAC, which indicates the importance of continued therapy especially for patients with active cancer. On-treatment rates of major bleeding were comparable for patients with recent or active cancer, indicating a need for an individualized risk-benefit assessment, especially since patients with recent cancer were at lower risk for VTE recurrence. Our findings of higher major bleeding rates in patients with GI cancer (both active and recent) is in line with the observations in randomized trials and supports guidelines recommendations, cautioning against DOAC use in CAT patients at high risk for bleeding, such as GI cancer patients. Disclosures Marten: Daiichi Sankyo: Honoraria; Bayer HealthCare: Honoraria. Tittl:Daiichi Sankyo: Honoraria. Beyer-Westendorf:Pfizer: Honoraria, Research Funding; Bayer HealthCare: Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding; Boehringer Ingelheim: Honoraria, Research Funding.

Safety and efficacy of direct acting oral anticoagulants and vitamin K antagonists in nonvalvular atrial fibrillation – a network meta-analysis of real-world data

VASA ◽  
2019 ◽  
Vol 48 (2) ◽  
pp. 134-147 ◽  
Author(s):  
Mirko Hirschl ◽  
Michael Kundi
Keyword(s):  
Real World ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Efficacy And Safety ◽  
Nonvalvular Atrial Fibrillation ◽  
Real World Data ◽  
Hazard Ratios ◽  
Direct Acting ◽  
Event Rates

Abstract. Background: In randomized controlled trials (RCTs) direct acting oral anticoagulants (DOACs) showed a superior risk-benefit profile in comparison to vitamin K antagonists (VKAs) for patients with nonvalvular atrial fibrillation. Patients enrolled in such studies do not necessarily reflect the whole target population treated in real-world practice. Materials and methods: By a systematic literature search, 88 studies including 3,351,628 patients providing over 2.9 million patient-years of follow-up were identified. Hazard ratios and event-rates for the main efficacy and safety outcomes were extracted and the results for DOACs and VKAs combined by network meta-analysis. In addition, meta-regression was performed to identify factors responsible for heterogeneity across studies. Results: For stroke and systemic embolism as well as for major bleeding and intracranial bleeding real-world studies gave virtually the same result as RCTs with higher efficacy and lower major bleeding risk (for dabigatran and apixaban) and lower risk of intracranial bleeding (all DOACs) compared to VKAs. Results for gastrointestinal bleeding were consistently better for DOACs and hazard ratios of myocardial infarction were significantly lower in real-world for dabigatran and apixaban compared to RCTs. By a ranking analysis we found that apixaban is the safest anticoagulant drug, while rivaroxaban closely followed by dabigatran are the most efficacious. Risk of bias and heterogeneity was assessed and had little impact on the overall results. Analysis of effect modification could guide the clinical decision as no single DOAC was superior/inferior to the others under all conditions. Conclusions: DOACs were at least as efficacious as VKAs. In terms of safety endpoints, DOACs performed better under real-world conditions than in RCTs. The current real-world data showed that differences in efficacy and safety, despite generally low event rates, exist between DOACs. Knowledge about these differences in performance can contribute to a more personalized medicine.

Comparative Efficacy and Safety of Duration of Dual Antiplatelet Therapy in Patients with CAD Undergoing Drug-eluting Stent Implantation: A Systematic Review and Network Meta-analysis

2020 ◽  
Vol 26 (44) ◽  
pp. 5739-5745
Author(s):  
Jieqiong Guan ◽  
Wenjing Song ◽  
Pan He ◽  
Siyu Fan ◽  
Hong Zhi ◽  
...  
Keyword(s):  
Antiplatelet Therapy ◽  
Major Bleeding ◽  
Dual Antiplatelet Therapy ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Drug Eluting Stent ◽  
Efficacy And Safety ◽  
Risk Of Bleeding ◽  
Increased Risk ◽  
Drug Eluting

Objective: The aim was to evaluate the efficacy and safety of duration of dual antiplatelet therapy (DAPT) for patients who received percutaneous coronary intervention (PCI) with a drug-eluting stent. Background: The optimal duration of DAPT to balance the risk of ischemia and bleeding in CAD patients undergoing drug-eluting stent (DES) implantation remains controversial. Methods: PubMed, Cochrane Library, Web of Science, Clinicaltrials.gov, CNKI and Wanfang Databases were searched for randomized controlled trials of comparing different durations of DAPT after DES implantation. Primary outcomes were major adverse cardiac and cerebrovascular events (MACCE), and major bleeding, and were pooled by Bayes network meta-analysis. Net adverse clinical and cerebral events were used to estimate the surface under the cumulative ranking (SUCRA) curves. The subgroup analysis based on clinical status, follow-up and area was conducted using traditional pairwise meta-analysis. Results: A total of nineteen trials (n=51,035) were included, involving six duration strategies. The network metaanalysis showed that T2 (<6-month DAPT followed by aspirin, HR:1.51, 95%CI:1.02-2.22), T3 (standard 6-month DAPT, HR:1.47, 95%CI:1.14-1.91), T4 (standard 12-month DAPT, HR:1.41, 95%CI:1.15-1.75) and T5 (18-24 months DAPT, HR:1.47, 95%CI:1.09-1.97) was associated with significantly increased risk of MACCE compared to T6 (>24-month DAPT). However, no significant difference was found in MACCE risk between T1 (<6-month DAPT followed by P2Y12 monotherapy) and T6. Moreover, T5 was associated with significantly increased risk of bleeding compared to T1(RR:3.94, 95%CI:1.66-10.60), T2(RR:3.65, 95%CI:1.32-9.97), T3(RR:1.93, 95%CI:1.21-3.50) and T4(RR:1.89, 95%CI:1.15-3.30). The cumulative probabilities showed that T6(85.0%), T1(78.3%) and T4(44.5%) were the most efficacious treatment compared to the other durations. In the ACS (<50%) subgroup, T1 was observed to significantly reduce the risk of major bleeding compared to T4, but not in the ACS (≥50%) subgroup. Conclusions: Compared with other durations, short DAPT followed by P2Y12 inhibitor monotherapy showed non-inferiority, with a lower risk of bleeding and not associated with an increased MACCE. In addition, the risk of major bleeding increased significantly, starting with DAPT for 18-month. Compared with the short-term treatment, patients with ACS with the standard 12-month treatment have a better prognosis, including lower bleeding rate and the decreased risk of MACCE. Due to study's limitations, the results should be verified in different risk populations.

scholarly journals Intravenous dexmedetomidine during spinal anaesthesia for caesarean section: A meta-analysis of randomized trials

2017 ◽  
Vol 45 (3) ◽  
pp. 924-932 ◽  
Author(s):  
Zeqing Bao ◽  
Chengmao Zhou ◽  
Xianxue Wang ◽  
Yu Zhu
Keyword(s):  
Caesarean Section ◽  
Spinal Anaesthesia ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Relevant Literature ◽  
Nausea And Vomiting ◽  
Cochrane Library ◽  
Control Group ◽  
Efficacy And Safety ◽  
The Cochrane Library

Objective To evaluate the efficacy and safety of spinal anaesthesia using dexmedetomidine for caesarean section. Methods PubMed, The Cochrane Library, and CNKI were searched for relevant literature. Results The incidence of nausea and vomiting in the dexmedetomidine group was significantly lower than that in the control group (OR = 0.21, 95% CI: 0.12–0.35, P < 0.00001). No difference was found in the incidence of pruritus between the two groups (OR = 1.21, 95% CI: 0.36–4.09, P = 0.76).The dexmedetomidine group had a higher incidence of bradycardia than did the control group (OR = 2.20, 95% CI: 1.02–4.77, P = 0.05). The incidence of shivering in the dexmedetomidine group was significantly lower than that in the control group (OR = 0.20, 95% CI: 0.13–0.32, P < 0.00001). The incidence of hypotension was not different between the two groups (OR = 0.88, 95% CI: 0.49–1.56, P = 0.65). Conclusion Dexmedetomidine can decrease the incidence of nausea, vomiting, bradycardia, and shivering with spinal anaesthesia during caesarean section.

Efficacy and safety of drug-eluting stents in ST-segment elevation myocardial infarction: A meta-analysis of randomized trials

2009 ◽  
Vol 133 (2) ◽  
pp. 213-222 ◽  
Author(s):  
Giuseppe De Luca ◽  
Gregg W. Stone ◽  
Harry Suryapranata ◽  
Gerrit Jan Laarman ◽  
Maurizio Menichelli ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Drug Eluting Stents ◽  
Efficacy And Safety ◽  
St Segment Elevation ◽  
Segment Elevation Myocardial Infarction ◽  
St Segment ◽  
Drug Eluting
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