Anticoagulants for the treatment of venous thromboembolism in patients with cancer: An updated pairwise and network meta-analysis of randomized trials.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14692-e14692
Author(s):  
Shima Sidahmed ◽  
Ahmed Abdalla ◽  
Babikir Kheiri ◽  
Areeg Bala ◽  
Mohammed Salih ◽  
...  

e14692 Background: Cancer-associated venous thromboembolism (VTE) is common. Although low molecular weight heparin (LMWH) is the standard therapy in this setting, little is known with regard to non-vitamin K antagonist oral anticoagulants (NOACs). Therefore, we thought about evaluating the safety and efficacy of various anticoagulants in this vulnerable population. Methods: Electronic database search was conducted to identify randomized clinical trials (RCTs) that compared LMWH, NOACs, and/or vitamin-K-antagonists (VKA) in cancer patients. We performed frequentist direct and Bayesian network meta-analysis using random-effects model to calculate odds ratios (ORs), 95% confidence intervals (CIs), and 95% credible intervals (CrIs). The primary outcome was VTE (pulmonary embolism and deep-vein thrombosis) recurrence. Secondary outcomes were major bleeding and all-cause mortality. Results: We identified 13 RCTs with 6,595 total patients (mean age 62.4 ± 12.2; 50.4% female; 17.7% hematological malignancies; and 6 months median follow-up). The most common cancer type was colorectal and 48% of the population had metastatic cancer at baseline. NOACs were associated with significantly reduced VTE recurrence compared with VKA (OR = 0.58; 95% CI = 0.40-0.83; P < 0.01; number needed to treat [NNT] = 40) and LMWH (OR = 0.46; 95% CI = 0.25-0.85; P = 0.01; NNT = 20). LMHW was associated with significantly reduced VTE recurrence compared with VKA (OR = 0.52; 95% CI = 0.39-0.71; P < 0.01; NNT = 18). NOACs were associated with significantly reduced major bleeding compared with VKA (OR = 0.56; 95% CI = 0.35-0.91; P = 0.02; NNT = 64). There was no significant difference identified between the anticoagulant groups in regard to all-cause mortality. Conclusions: Among cancer patients with VTE, NOACs were associated with significantly reduced VTE recurrence compared to LMWH and VKA, and significantly reduced major bleeding compared with VKA. LMWH was associated with significantly reduced VTE recurrence compared with VKA.

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Sunil Upadhaya ◽  
Seetharamprasad Madala ◽  
Sunil Badami

Introduction: Patients with cancer are at high risk for recurrent thromboembolic phenomenon. Use of novel oral anticoagulants (NOAC) for treatment of venous thromboembolism (VTE) in such patients is controversial. We conducted this updated meta-analysis to evaluate the pooled efficacy and safety of NOAC in patients with cancer. Methods: We did systematic search of PubMed and Cochrane library databases for randomized controlled trials comparing NOAC with low molecular weight heparin (LMWH) for VTE treatment in cancer patients till April 2020. The efficacy outcomes were recurrent VTE and all-cause mortality rates, and the primary safety outcome was incidence of major bleeding rate. Results: Four randomized controlled studies comparing NOAC with LMWH (1446 patients in NOAC group and 1448 patients in LMWH group) were included in our study. Use of NOAC lead to significant reduction in recurrent VTE rate (odds ratio (OR): 0.55 [0.36-0.84], I 2 = 45 %, p value = 0.006) (Figure 1). However, we did not find any significant difference in rate of major bleeding (OR: 1.30 [0.76-2.23], I 2 = 35%, p value = 0.34) (Figure 2) and all-cause mortality (OR: 1 [0.80 - 1.26], I 2 = 33%, p value = 0.98). Conclusions: This updated meta-analysis showed comparatively lower pooled recurrent VTE rate in patient being treated with NOAC, whereas similar rates of major bleeding and all-cause death. NOAC are more efficacious and has similar safety profile compared with LMWH.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Mahmoud El Iskandarani ◽  
Islam Shatla ◽  
Muhammad Khalid ◽  
Bara El Kurdi ◽  
Timir Paul ◽  
...  

Background: Current guidelines recommend against the use of direct oral anticoagulation (DOAC) therapy in patients with atrial fibrillation (AF) in the setting of significant liver disease (LD) due to lack of evidence in safety and efficacy studies. However, recently studies have investigated the role of DOAC in comparison to Vitamin K antagonist (VKA) in this category of patients. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of this approach. Hypothesis: DOAC is safe and effective compared to VKA in AF with LD patients. Method: Unrestricted search of the PubMed, EMBASE, and Cochrane databases performed from inception until June 1, 2020 for studies comparing DOAC with VKA including more than 100 AF patients with LD. Relevant data were extracted and analyzed using Revman 5.3 software. Hazard ratio (HR) and 95% Confidence interval (CI) were calculated using the random-effects model. Result: A total of 5 studies (3 retrospective and 2 post hoc analysis) were included examining 39,064 patients with AF and LD (25,398 DOAC vs 13,669 VKA). DOAC is associated with lower risk of major bleeding compared to VKA with a HR of 0.68 (95% CI 0.47-0.98; I 2 =53%), all-cause mortality (HR 0.74;95% CI 0.59-0.94; I 2 =61%), and intracranial bleeding (HR 0.48; 95% CI 0.40-0.58; I 2 =0). There was no significant difference in ischemic stroke risk (HR 0.73; 95% CI 0.47-1.14; I 2 =72%) and gastrointestinal bleeding risk (0.96; 95% CI 0.61-1.51; I 2 =41%) between DOAC and VKA. Conclusion: DOAC is non-inferior to VKA regarding ischemic stroke prevention in AF patients with LD. Moreover, DOAC is associated with a lower risk of major bleeding, intracranial bleeding and all-cause mortality. Further randomized trials are needed to validate our findings.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
I Cavallari ◽  
G Verolino ◽  
G Patti

Abstract Background Anticoagulation in patients with cancer and atrial fibrillation (AF) is particularly challenging given the higher risk of both thrombotic and bleeding complications in this setting. Data regarding the efficacy and safety of non-vitamin K oral anticoagulants (NOACs) in AF patients with malignancy remain unclear. Purpose In the present meta-analysis we further investigate the efficacy and safety of NOACs compared to warfarin in patients with AF and cancer assuming that available studies may be individually underpowered for endpoints at low incidence, i.e. stroke, major and intracranial bleeding. Methods We performed a systematic review and meta-analysis of studies comparing the use of NOACs vs. warfarin in AF patients with cancer. Efficacy outcome measures included stroke or systemic embolism, venous thromboembolism and mortality. Safety outcome measures were major bleeding and intracranial hemorrhage. Results We pooled data from 6 identified studies enrolling a total of 31,756 AF patients with cancer. Mean follow-up was 1.7 years. Patients with cancer had significantly increased annualized rates of venous thromboembolism (1.38% vs. 0.74%), major bleeding (9.01% vs. 5.13%), in particular major gastrointestinal bleeding (2.38% vs. 1.60%), and all-cause mortality (17.73% vs. 8.50%) vs. those without (all P values <0.001), whereas the incidence of stroke or systemic embolism and intracranial hemorrhage did not differ. Compared with warfarin, treatment with NOACs nominally decreased the risk of stroke or systemic embolism (5.41% vs. 2.70%; odds ratio, OR; 95% confidence intervals, CI 0.51, 0.26–1.01; P=0.05; Figure), mainly of ischemic stroke (OR 0.56; 95% CI 0.35–0.89; P=0.01), and the risk of venous thromboembolism (OR 0.51; 95% CI 0.42–0.61; P<0.001). In cancer patients receiving NOACs there was a significant reduction of major bleeding (3.95% vs. 4.66%; OR 0.66, 95% CI 0.46–0.94; P=0.02; Figure) and intracranial hemorrhage (0.26% vs. 0.66%; OR 0.25, 95% CI 0.08–0.82; P=0.02) vs. warfarin, with no difference in gastrointestinal major bleeding rates. Conclusion AF patients on oral anticoagulation and concomitant cancer are at higher risk of venous thromboembolism, major bleeding and all-cause mortality. NOACs may represent a safer and more effective alternative to warfarin also in this setting of patients.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Bangsheng Hu ◽  
Lianxiang Jiang ◽  
Haixia Tang ◽  
Meizhu Hu ◽  
Jun Yu ◽  
...  

Abstract Objective To evaluates the efficacy and safety of rivaroxaban versus aspirin in prevention of venous thromboembolism (VTE) following total hip (THA) or knee arthroplasty (TKA) or hip fracture surgery. Methods Major databases were systematically searched for all relevant studies published in English up to October 2020. The meta-analysis was conducted using RevMan 5.3 software. Results In total, 7 studies were retrieved which contained 5133 patients. Among these patients, 2605 patients (50.8%) received rivaroxaban, whereas 2528 patients (49.2%) received aspirin. There were no statistical difference between aspirin and rivaroxaban for reducing VTE (RR = 0.75, 95% CI 0.50–1.11, I2 = 36%, p = 0.15), major bleeding (RR = 0.94, 95% CI 0.45–2.37, I2 = 21%, p = 0.95), and all-cause mortality (RR = 0.88, 95% CI 0.12–6.44, I2 = 0%, p = 0.90) between the two groups. Compared with aspirin, rivaroxaban significantly increased nonmajor bleeding (RR = 1.29, 95% CI 1.05–1.58, I2 = 0%, p = 0.02). Conclusion There was no significant difference between aspirin and rivaroxaban in prevention of venous thromboembolism following total joint arthroplasty or hip fracture surgery. Aspirin may be an effective, safe, convenient, and cheap alternative for prevention of VTE. Further large randomized studies are required to confirm these findings.


Vascular ◽  
2021 ◽  
pp. 170853812110027
Author(s):  
Gustavo Muçouçah Sampaio Brandão ◽  
Rafael D Malgor ◽  
Tarsila Vieceli ◽  
Raissa Carolina Fonseca Cândido ◽  
José Francisco Secorun Inácio ◽  
...  

Introduction Treatment of cancer-associated venous thromboembolism (CAVTE) remains challenging. The aim of this study was to assess the outcomes of direct acting oral anticoagulants (DOAs) for the treatment of CAVTE. Materials and methods A network meta-analysis of randomized clinical trials comparing DOAs (Apixaban, Rivaroxaban, and Edoxaban) versus Dalteparin for the treatment of CAVTE was performed. Outcomes of interest included, VTE recurrence, all-cause mortality, event-free survival, major bleeding, and clinically relevant non-major bleeding (CRNMB). Analysis was based on a random effects model and Bayesian Markov-chain Monte Carlo method was used for indirect comparisons. Results Four RCTs involving 2894 patients were included. Overall certainty of evidence was moderate regarding all outcomes. DOAs exhibited lower risk of VTE (RR 0.62; 95% CI 0.44, 0.87; P = 0.007), similar risk of major bleeding (RR 1.33; 95% CI 0.84, 2.11; P = 0.23), and higher risk of CRNMB (RR 1.66, 95% CI 1.08, 2.56; P = 0.02), compared with Dalteparin. Risk of all-cause mortality and event-free survival were similar between groups with RR 0.99 (95% CI 0.84, 1.16) and RR 1.03 (95% CI 0.94, 1.13), respectively. Apixaban ranked first for recurrent VTE (42.4%) and major bleeding (62.3%) and Dalteparin ranked first for CRNMB (54.7%). Rivaroxaban ranked best considering all-cause mortality (58.7%); Apixaban ranked best for event-free survival (83.6%). Conclusions DOAs presented a reduced risk of recurrent VTE with similar risk of major bleeding compared to Dalteparin. However, a higher risk of CRNMB is expected when this cohort of patients are treated with DOAs instead of Dalteparin.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yi Xu ◽  
Yimin Shen ◽  
Delong Chen ◽  
Pengfei Zhao ◽  
Jun Jiang

Introduction. This network meta-analysis aimed to evaluate the efficacy and safety of different dual antiplatelet therapies (DAPTs) after percutaneous coronary intervention (PCI) with drug-eluting stents (DESs). Methods. Randomized controlled trials (RCTs) comparing longer-term (>12 months) DAPT (L-DAPT), 12-month DAPT (DAPT 12Mo), 6-month DAPT (DAPT 6Mo), 3-month DAPT followed by aspirin monotherapy (DAPT 3Mo + ASA), 3-month DAPT followed by a P2Y12 receptor inhibitor monotherapy (DAPT 3Mo + P2Y12), or 1-month DAPT with a P2Y12 receptor inhibitor monotherapy (DAPT 1Mo + P2Y12) were searched. Primary endpoints were all-cause mortality, cardiac death, myocardial infarction (MI), major bleeding, any bleeding, definite or probable stent thrombosis (ST), and net adverse clinical events (NACE). This Bayesian network meta-analysis was performed with the random-effects model. Results. Twenty-four RCTs (n = 81339) were included. In comparison with L-DAPT, DAPT 6Mo (OR: 0.50, 95% CI: 0.29–0.83), DAPT 3Mo + P2Y12 (OR: 0.38, 95% CI: 0.18–0.82), DAPT 3Mo + ASA (OR: 0.44, 95% CI: 0.17–0.98), and DAPT 1Mo + P2Y12 (OR: 0.45, 95% CI: 0.14–0.93) were associated with a lower risk of major bleeding. DAPT 3Mo + P2Y12 (OR: 0.58, 95% CI: 0.38–0.88) reduced the risk of any bleeding when compared with DAPT 12Mo. L-DAPT decreased the risk of MI and definite or probable stent ST when compared with DAPT 6Mo. DAPT 3Mo + P2Y12 decreased the risk of NACE in comparison with DAPT 6Mo and DAPT 12Mo. No significant difference in all-cause mortality and cardiac death was observed. In patients with acute coronary syndrome, DAPT 6Mo was comparable to DAPT 12Mo. Conclusion. Short-term (1–3 months) DAPT is noninferior to DAPT 6Mo after DESs implantation, while L-DAPT reduces MI and definite or probable ST rates. DAPT 3Mo + P2Y12 might be a reasonable trade-off in patients with high risk of bleeding accompanied by ischemia.


2015 ◽  
Vol 114 (10) ◽  
pp. 768-777 ◽  
Author(s):  
Emilie Belley-Cote ◽  
Hasib Hanif ◽  
Frederick D’Aragon ◽  
John Eikelboom ◽  
Jeffrey Anderson ◽  
...  

SummaryVariability in vitamin K antagonist (VKA) dosing is partially explained by genetic polymorphisms. We performed a meta-analysis to determine whether genotype-guided VKA dosing algorithms decrease a composite of death, thromboembolic events and major bleeding (pri-mary outcome) and improve time in therapeutic range (TTR). We searched MEDLINE, EMBASE, CENTRAL, trial registries and conference proceedings for randomised trials comparing genotype-guided and standard (non genotype-guided) VKA dosing algorithms in adults initiating anticoagulation. Data were pooled using a random effects model. Of the 12 included studies (3,217 patients), six reported all components of the primary outcome of mortality, thromboembolic events and major bleeding (2,223 patients, 87 events). Our meta-analysis found no significant difference between groups for the primary outcome (relative risk 0.85, 95 % confidence interval [CI] 0.54–1.34; heterogeneity X2=4.46, p=0.35, I2=10 %). Based on 10 studies (2,767 patients), TTR was significantly higher in the genotype-guided group (mean difference (MD) 4.31 %; 95 % CI 0.35, 8.26; heterogeneity X2=43.31, p< 0.001, I2=79 %). Pre-specified exploratory analyses demonstrated that TTR was significantly higher when geno-type-guided dosing was compared with fixed VKA dosing (6 trials, 997 patients: MD 8.41 %; 95 % CI 3.50,13.31; heterogeneity X2=15.18, p=0.01, I2=67 %) but not when compared with clinical algorithm-guided dosing (4 trials, 1,770 patients: MD –0.29 %; 95 % CI –2.48,1.90; heterogeneity X2=1.53, p=0.68, I2=0 %; p for interaction=0.002). In conclusion, genotype-guided compared with standard VKA dosing algorithms were not found to decrease a composite of death, thromboembolism and major bleeding, but did result in improved TTR. An improvement in TTR was observed in comparison with fixed VKA dosing algorithms, but not with clinical algorithms.


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