scholarly journals Updated Meta-Analysis of Randomized Controlled Trials on Primary Ambulatory Thromboprophylaxis (PATP) in Patients with Advanced Pancreatic Cancer (APC) Receiving Chemotherapy

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3469-3469 ◽  
Author(s):  
Kyaw Zin Thein ◽  
Donald P. Quick ◽  
Thein H. Oo
Keyword(s):  
Relative Risk ◽  
High Risk ◽  
Cancer Patients ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Advanced Pancreatic Cancer ◽  
Control Group ◽  
Number Needed To Treat ◽  
Solid Cancer

Introduction: Thrombosis is the second leading cause of death in cancer patients and patients with APC are categorized as high-risk of developing venous thromboembolism (VTE). Many trials had failed to demonstrate improvement in survival with PATP. Despite decreasing VTE events, PATP in solid cancer patients is not routinely recommended. We conducted an updated meta- analysis of RCTs to determine the benefit and risk of PATP with low-molecular weight heparins (LMWH) and direct oral anticoagulants (DOAC) in patients with APC receiving chemotherapy. Methods: We performed a comprehensive literature search using MEDLINE and EMBASE databases through June 30, 2019. The references of all potential studies were also reviewed for any additional relevant studies. The RCTs with reduction in VTE as a primary or secondary endpoint and the major bleeding (MB) as a safety outcome were incorporated in the analysis. The primary meta- analytic approach was a random effects model using the Mantel-Haenszel (MH) method. It was used to calculate the estimated pooled risk ratio (RR), and risk difference (RD) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran's Q- statistic. Results: A total of 1,013 patients with APC from two RCTs and a subgroup of another three RCTs were included in our meta-analysis. The prophylactic, intermediate and therapeutic doses of LMWH and prophylactic dose of DOAC (rivaroxaban) were used in the studies. The duration of LMWH and DOAC ranged from 3 to 6 months. The randomization ratio was 2 to 1 in PROTECHT study and 1 to 1 in all other studies. The I2statistic for heterogeneity was 60, suggesting some heterogeneity among RCTs. The VTE incidence was 28 (5.43%) in PATP group and 60 (12.07%) in control group with a RR of 0.44 (95% CI: 0.20 to 0.99, P = 0.05) and RD of -0.06 (95% CI: -0.11 to -0.01, P = 0.01). In fixed effects model, the pooled RR was 0.45 (95% CI: 0.29 to 0.70, P = 0.0003) and the absolute RD in VTE was -0.07 (95% CI: -0.10 to -0.03, P = 0.0002) with an estimate of the number needed to treat (NNT) of 15 to prevent one VTE event. MB events were reported in 9 (4.11%) patients in PATP group compared to 7 (3.27%) in control group according to an analysis of 2 RCTs. The pooled relative risk for MB was statistically non-significant at 1.25 (95% CI: 0.47 to 3.31, P = 0.65). Conclusions: In our study, PATP in APC may statistically significantly decrease VTE events, approximately with relative risk reduction of 55% and a NNT of 15, without increasing MB events. Proper selection of patients who are high risk for VTE in outpatient setting is important. More RCTs are required to further define high risk subsets of APC patients receiving chemotherapy who may benefit from PATP. Disclosures Oo: Medical Education Speakers Network: Honoraria; Janssen and Janssen: Other: Research: site co-investigator .

scholarly journals A Systematic Review and Meta- Analysis of Randomized Controlled Trials on Primary Ambulatory Thromboprophylaxis (PATP) in Patients with Gastrointestinal Cancers Receiving Chemotherapy

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3679-3679
Author(s):  
Kyaw Zin Thein ◽  
Donald P. Quick ◽  
Thein Hlaing Oo
Keyword(s):  
Systematic Review ◽  
High Risk ◽  
Cancer Patients ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Control Group ◽  
Number Needed To Treat ◽  
Solid Cancer ◽  
Gastrointestinal Cancers

Introduction: PATP in solid cancer patients remains uncertain and is not routinely recommended although thrombosis is shown to be the second leading cause of death in cancer patients. Many studies failed to demonstrate in solid cancer outpatients improvement in overall survival despite decreasing venous thromboembolism (VTE) rates by PATP. We conducted a systematic review and meta-analysis of RCTs to determine the benefit and risk of PATP with low-molecular weight heparins (LMWHs) and direct oral anticoagulants (DOACs) in patients with gastrointestinal cancers receiving chemotherapy. Methods: We performed a comprehensive literature search using MEDLINE and EMBASE databases through June 30, 2019. The references of all potential studies were also reviewed for any additional relevant studies. The RCTs with reduction in VTE as a primary or secondary endpoint and the major bleeding (MB) as a safety outcome were incorporated in the analysis. The primary meta- analytic approach was a fixed effects model using the Mantel-Haenszel (MH) method. It was used to calculate the estimated pooled risk ratio (RR), and risk difference (RD) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran's Q- statistic. Results: A total of 1,932 patients with gastric, gastroesophageal junctional (GEJ) and colorectal cancers from a subgroup of three RCTs were included in our meta-analysis. The prophylactic doses of LMWHs and DOAC (rivaroxaban) were used in the studies. The duration of LMWH and DOAC ranged from 3 to 6 months. The randomization ratio was 2 to 1 in PROTECHT study and 1 to 1 in all other studies. The I2 statistic for heterogeneity was 0, suggesting homogeneity among RCTs. The VTE incidence was 13 (1.26%) in PATP group and 23 (2.55%) in control group with a RR of 0.49 (95% CI: 0.25 to 0.96, P = 0.04). The absolute RD in VTE was -0.01 (95% CI: -0.03 to -0.00, P 0.04) with an estimate of the number needed to treat (NNT) of 78 to prevent one VTE event. In a subset of patients with gastric and GEJ cancers (n=587), the VTE incidence was 4 (1.37%) in PATP group and 10 (3.40%) in control group with a RR of 0.40 (95% CI: 0.13 to 1.24, P = 0.11). Conclusions: In our study, the relative risk reduction is 48% with a NNT of 78 to prevent one VTE in ambulatory patients with gastrointestinal cancers. Nevertheless, there is no statistically significant reduction in VTE events in a subset of gastric and GEJ cancers which are considered high risk in Khorana score. Based on the findings, PATP is not recommended in patients with gastrointestinal cancers on chemotherapy at this time. Further studies are necessary to define high risk subsets of gastrointestinal cancer patients receiving chemotherapy who may benefit from PATP. Disclosures Oo: Medical Education Speakers Network: Honoraria; Janssen and Janssen: Other: site co-investigator.

scholarly journals Updated Meta-Analysis of Randomized Controlled Trials on Primary Ambulatory Thromboprophylaxis (PATP) in Patients with Locally Advanced or Metastatic Lung Cancer Receiving Chemotherapy

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2435-2435
Author(s):  
Kyaw Zin Thein ◽  
Lukman Tijani ◽  
Thein H. Oo
Keyword(s):  
Lung Cancer ◽  
Relative Risk ◽  
High Risk ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Locally Advanced ◽  
The United States ◽  
Control Group ◽  
Number Needed To Treat ◽  
Solid Cancer

Introduction: Lung cancer (LC) is the second most common cancer in both sexes and is the leading cause of cancer mortality in the United States. Thrombosis is the second leading cause of death in cancer patients and PATP in solid cancer patients were performed in research trials to decrease venous thromboembolism (VTE) rates with ultimate aim to improve survival. We undertook an updated meta- analysis of RCTs to determine the benefit and risk of PATP with low-molecular weight heparins (LMWHs) and direct oral anticoagulants (DOAC) in patients with locally advanced or metastatic LC receiving chemotherapy. Methods: We performed a comprehensive literature search using MEDLINE and EMBASE databases through June 30, 2019. The references of all potential studies were also reviewed for any additional relevant studies. The RCTs with reduction in VTE as a primary or secondary endpoint and the major bleeding (MB) as a safety outcome were incorporated in the analysis. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR), and risk difference (RD) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran's Q- statistic. Fixed effects model was applied. Results: A total of 5,375 patients with LC from five RCTs and a subgroup of another four RCTs were included in our meta-analysis. The prophylactic doses of bemiparin, certoparin, dalteparin, nadroparin, semuloparin and tinzaparin, intermediate dose of enoxaparin and prophylactic dose of rivaroxaban were used in the studies. The duration of LMWH and DOAC ranged from 3 to 6 months. The randomization ratio was 2 to 1 in PROTECHT study and 1 to 1 in all other studies. The I2statistic for heterogeneity was 0, suggesting homogeneity among RCTs. The VTE incidence was 114 (4.16%) in PATP group and 207 (7.85%) in control group with a RR of 0.53 (95% CI: 0.43 to 0.67, P < 0.001). The absolute RD in VTE was -0.04 (95% CI: -0.05 to -0.02, P < 0.001) with an estimate of the number needed to treat (NNT) of 28 to prevent one VTE event. MB events were reported in 26 (1.37%) patients in PATP group compared to 15 (0.84%) in control group according to an analysis of 6 RCTs. The pooled relative risk for MB was statistically non-significant at 1.57 (95% CI: 0.85 to 2.88, P = 0.15). Conclusions: Our analysis showed that the relative risk reduction is 46% with a NNT of 28 to prevent one VTE without increasing MB events in ambulatory patients with locally advanced or metastatic LC. Selection of appropriate patients who are high risk for VTE is crucial and further studies are required to define high risk subsets of LC patients receiving chemotherapy who may benefit from PATP. Disclosures Oo: Janssen and Janssen: Other: Research: site co-investigator ; Medical Education Speakers Network: Honoraria.

A Systematic Review and Meta-Analysis of Randomized Controlled Trials (RCT) in Ambulatory Thromboprophylaxis (ATP) in Patients with Lung Cancer Receiving Chemotherapy

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3825-3825
Author(s):  
Kyaw Zin Thein ◽  
Sai-Ching J Yeung ◽  
Thein H. Oo
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Cancer Patients ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Control Group ◽  
Number Needed To Treat ◽  
Solid Cancer ◽  
Fixed Effects Model ◽  
Bleeding Events

Abstract Introduction: Lung cancer (LC) is the commonest cause of cancer mortality in USA. Thromboembolism (TE) is the second leading cause of death in cancer patients. The ambulatory thromboprophylaxis (ATP) in solid cancer patients remains uncertain. However, LC is at least an intermediate risk for TE according to Khorana scoring system. We conducted a systematic review and meta-analysis of RCTs to determine the benefit and risk of ATP with low-molecular weight heparins (LMWH) in LC patients receiving chemotherapy. Methods: We performed a comprehensive literature search using MEDLINE and EMBASE databases through June 30, 2016. The RCTs with reduction in TE as a primary or secondary endpoint and the major bleeding (MB) as a safety outcome were included in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio (RR), and risk difference (RD) with 95% confidence interval (CI). Fixed effects model was applied. Results: A total of 4315 patients with LC from 4 RCTs and a subgroup of another 2 RCTs were included in our analysis. The prophylactic doses of dalteparin, nadroparin, certoparin, semuloparin and bemiparin were used in the studies. The ATP duration ranged from 3 to 6 months. The randomization ratio was 2 to 1 in PROTECHT study and 1 to 1 in other studies. The TE incidence was 89 (4.007%) in ATP group and 166 (7.927%) in control group with a RR of 0.510 (95% CI: 0.397 to 0.654, P < 0.001). The absolute RD was -0.039 (95% CI: -0.053 to -0.025, P < 0.001) with an estimated number needed to treat (NNT) of 25 to prevent one TE event. MB events were 24 (1.506%) in ATP group compared to 15 (1.019%) in control group according to an analysis of 4 RCTs. The pooled RR for MB was statistically nonsignificant at 1.468 (95% CI: 0.785 to 2.746, P = 0.229). Clinically relevant nonmajor (CRNM) bleeding events were 80 (5.571%) in ATP group and in 24 (1.674%) in control group on an analysis of 4 RCTs. The RR for CRNM bleeding was statistically significant at 3.253 (95% CI: 2.092 to 5.059, P < 0.001). Conclusions: In our study, the relative risk reduction for TE is 49% with a NNT of 25 to prevent one TE without increasing MB. Nevertheless, CRNM bleeding episodes were significant at a ratio of 3.253. Based on the findings, selection of LC patients who are at high TE risk is important. Further studies are necessary to define a subset of LC patients who may benefit from ATP. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Oo: Daiichi Sankyo: Research Funding.

scholarly journals Direct Anticoagulants and Risk of Myocardial Infarction, a Multiple Treatment Network Meta-Analysis

Angiology ◽  
2019 ◽  
Vol 71 (1) ◽  
pp. 27-37 ◽  
Author(s):  
Péter Kupó ◽  
Zsolt Szakács ◽  
Margit Solymár ◽  
Tamás Habon ◽  
László Czopf ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Relative Risk ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Credible Interval ◽  
Control Group ◽  
Cardiovascular Safety ◽  
Coronary Syndrome

We assessed the cardiovascular safety of long-term direct-acting oral anticoagulant (DOAC) treatment. A search of the medical literature was performed from inception until May 31, 2019. Inclusion criteria were (1) randomized trial that assessed the clinical efficacy and/or safety of 1 or more DOAC, (2) control group including oral anticoagulation and/or antiplatelet and/or placebo treatment, and (3) the incidence of acute coronary syndrome during follow-up was reported. Fixed-effect and random-effects models were applied. The analyzed outcomes were myocardial infarction (MI), major bleeding, and mortality. Twenty-eight randomized clinical trials (196 761 patients) were included. Rivaroxaban was associated with a 21% reduction in the relative risk of MI when compared to placebo (relative risk [RR]: 0.79 [95% credible interval, CrI: 0.65-0.94]) and a 31% reduction (RR: 0.70 [95% CrI: 0.53-0.89]) when compared to dabigatran. Apixaban resulted in 24% (RR: 0.76 [95% CrI: 0.58-0.99]) and vitamin K antagonists anticoagulation resulted in 19% (RR: 0.81 [95% CrI: 0.65-0.98]) risk reduction compared to dabigatran. The computed probability of being the first best choice of treatment was 61.8% for rivaroxaban. Cardiovascular safety shows considerable heterogeneity among oral anticoagulants. Treatment with rivaroxaban is associated with reduced rate of MI.

A meta-analysis of spinal surgical site infection and vancomycin powder

2014 ◽  
Vol 21 (6) ◽  
pp. 974-983 ◽  
Author(s):  
Nickalus R. Khan ◽  
Clinton J. Thompson ◽  
Michael DeCuypere ◽  
Jonathan M. Angotti ◽  
Erick Kalobwe ◽  
...  
Keyword(s):  
Relative Risk ◽  
Surgical Site Infection ◽  
Risk Reduction ◽  
Spine Surgery ◽  
Spinal Surgery ◽  
Meta Analysis ◽  
Control Group ◽  
Number Needed To Treat ◽  
Site Infection ◽  
Vancomycin Powder

Object Surgical site infection (SSI) is a serious and costly complication of spinal surgery. There have been several conflicting reports on the use of intrawound vancomycin powder in decreasing SSI in spine surgery. The purpose of this study is to answer the question: “Does intrawound vancomycin powder reduce the rate of SSIs in spine surgery?” Methods A comprehensive search of multiple electronic databases and bibliographies was conducted to identify clinical studies that evaluated the rates of SSI with and without the use of intrawound vancomycin powder in spine surgery. Independent reviewers extracted data and graded the quality of each paper that met inclusion criteria. A random effects meta-analysis was then performed. Results The search identified 9 retrospective cohort studies (Level III evidence) and 1 randomized controlled trial (Level II evidence). There were 2574 cases and 106 infections in the control group (4.1%) and 2518 cases and 33 infections (1.3%) in the treatment group, yielding a pooled absolute risk reduction and relative risk reduction of 2.8% and 68%, respectively. The meta-analysis revealed the use of vancomycin powder to be protective in preventing SSI (relative risk = 0.34, 95% confidence interval 0.17–0.66, p = 0.021). The number needed to treat to prevent 1 SSI was 36. A subgroup analysis found that patients who had implants had a reduced risk of SSI with vancomycin powder (p = 0.023), compared with those who had noninstrumented spinal operations (p = 0.226). Conclusions This meta-analysis suggests that the use of vancomycin powder may be protective against SSI in open spinal surgery; however, the exact population in which it should be used is not clear. This benefit may be most appreciated in higher-risk populations or in facilities with a high baseline rate of infection.

Hemorrhagic and thrombotic events in oncology patients treated with antiangiogenic therapy: Impact of study design on the results assessed by meta-analysis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14058-e14058
Author(s):  
Jane-Chloe Trone ◽  
Céline Chapelle ◽  
Edouard Ollier ◽  
Laurent Bertoletti ◽  
Michel Cucherat ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cancer Patients ◽  
Study Design ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Antiangiogenic Therapy ◽  
Solid Cancer ◽  
Increasing Risk ◽  
Meta Analyses ◽  
The Impact

e14058 Background: Antiangiogenic (AA) therapies emerge as a new cornerstone for cancer treatment, but carry their own particular risk profile. Several previous meta-analyses have showed increasing risk of bleeding and paradoxically thrombosis in cancer patients receiving antiangiogenic. The aim of the meta-analysis is to investigate the impact of studies design (open or double blind (DB)), on the incidence and the occurrence of bleeding, venous thrombotic events (VTE) and arterial thrombotic events (ATE) in cancer patients treated by AA therapies. Methods: We searched Medline, Cochrane, ClinicalTrial databases, meeting abstracts of the American Society of Clinical Oncology and the European Society of Medical Oncology for relevant clinical trials. We included prospective phase II and III clinical trials that randomly assigned patients with solid cancer to AA therapy or control. Statistical analyses were conducted to calculate the summary incidence, ORs, and 95% CIs, using random-effects or fixed-effects models based on the heterogeneity of included studies. Results: A total of 166 trials (72,024 patients) were included. For bleeding events, comparison on AA treatment versus control yielded an OR of 2.41 (95% CI 2.07 to 2.71; p < 0.001) with an exaggeration of treatment effects by 68% (95% CI, 33 to 113) in open-label studies compared with DB trials. Concerning VTE, an OR of 1.18 (95% CI 1.04 to 1.35; p = 0.0115) was noted, with a significant enhancement of 53% (95% CI, 19 to 96) of treatment side effects with open trials compared with DB trials. AA don’t increase significantly the frequency of VTE when considering only DB trials. For ATE, an OR of 1.59 (95% CI 1.30 to 1.94; p < 0.001) was observed, associated with a significant exaggeration of 65% (95% CI, 13 to 143) with open trials compared with DB trials. Conclusions: The present meta-analysis showed a significant interaction of study design for the tolerance assessment in the AA therapies in cancers. The increasing risk of hemorrhagic events, VTE and ATE appear to have been overestimated in the previous meta-analyses. In the future, meta-analyses should be restricted to DB trials for analysis of toxicity profile.

Nonvitamin-K-antagonist oral anticoagulants versus warfarin in patients with atrial fibrillation and previous stroke or transient ischemic attack: An updated systematic review and meta-analysis of randomized controlled trials

2017 ◽  
Vol 12 (6) ◽  
pp. 589-596 ◽  
Author(s):  
George Ntaios ◽  
Vasileios Papavasileiou ◽  
Hans-Chris Diener ◽  
Konstantinos Makaritsis ◽  
Patrik Michel
Keyword(s):  
Atrial Fibrillation ◽  
Relative Risk ◽  
Risk Reduction ◽  
Relative Risk Reduction ◽  
Absolute Risk ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Absolute Risk Reduction ◽  
Number Needed To Treat ◽  
Ischemic Attack

Background In a previous systematic review and meta-analysis, we assessed the efficacy and safety of nonvitamin-K antagonist oral anticoagulants versus warfarin in patients with atrial fibrillation and stroke or transient ischemic attack. Since then, new information became available. Aim The aim of the present work was to update the results of the previous systematic review and meta-analysis. Methods We searched PubMed until 24 August 2016 for randomized controlled trials using the following search items: “atrial fibrillation” and “anticoagulation” and “warfarin” and “previous stroke or transient ischemic attack.” Eligible studies had to be phase III trials in patients with atrial fibrillation comparing warfarin with nonvitamin-K antagonist oral anticoagulants currently on the market or with the intention to be brought to the market in North America or Europe. The outcomes assessed in the efficacy analysis included stroke or systemic embolism, stroke, ischemic or unknown stroke, disabling or fatal stroke, hemorrhagic stroke, cardiovascular death, death from any cause, and myocardial infarction. The outcomes assessed in the safety analysis included major bleeding, intracranial bleeding, and major gastrointestinal bleeding. We performed fixed effects analyses on intention-to-treat basis. Results Among 183 potentially eligible articles, four were included in the meta-analysis. In 20,500 patients, compared to warfarin, nonvitamin-K antagonist oral anticoagulants were associated with a significant reduction of stroke/systemic embolism (relative risk reduction: 13.7%, absolute risk reduction: 0.78%, number needed to treat to prevent one event: 127), hemorrhagic stroke (relative risk reduction: 50.0%, absolute risk reduction: 0.63%, number needed to treat: 157), any stroke (relative risk reduction: 13.1%, absolute risk reduction: 0.7%, number needed to treat: 142), and intracranial hemorrhage (relative risk reduction: 46.1%, absolute risk reduction: 0.88%, number needed to treat: 113) over 1.8–2.8 years. Conclusions This updated meta-analysis in 20,500 atrial fibrillation patients with previous stroke or transient ischemic attack shows that compared to warfarin non-vitamin-K antagonist oral anticoagulants are associated with a significant reduction of stroke, stroke or systemic embolism, hemorrhagic stroke, and intracranial bleeding.

scholarly journals Review of Subcutaneous Wound Drainage in Reducing Surgical Site Infections after Laparotomy

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
B. Manzoor ◽  
N. Heywood ◽  
A. Sharma
Keyword(s):  
High Risk ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Surgical Site Infections ◽  
Control Group ◽  
Fixed Effects Model ◽  
Wound Drainage ◽  
Risk Patients ◽  
Contaminated Wound ◽  
Clean Contaminated

Purpose.Surgical site infections (SSIs) remain a significant problem after laparotomies. The aim of this review was to assess the evidence on the efficacy of subcutaneous wound drainage in reducing SSI.Methods. MEDLINE database was searched. Studies were identified and screened according to criteria to determine their eligibility for meta-analysis. Meta-analysis was performed using the Mantel-Haenszel method and a fixed effects model.Results. Eleven studies were included with two thousand eight hundred and sixty-four patients. One thousand four hundred and fifty patients were in the control group and one thousand four hundred and fourteen patients were in the drain group. Wound drainage in all patients shows no statistically significant benefit in reducing SSI incidence. Use of drainage in high risk patients, contaminated wound types, and obese patients appears beneficial.Conclusion. Using subcutaneous wound drainage after laparotomy in all patients is unnecessary as it does not reduce SSI risk. Similarly, there seems to be no benefit in using it in clean and clean contaminated wounds. However, there may be benefit in using drains in patients who are at high risk, including patients who are obese and/or have contaminated wound types. A well designed trial is needed which examines these factors.

Risk of Bleeding from Primary Thromboprophylaxis (PTP) in Patients with Solid Cancer Receiving Chemotherapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (RCT)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3820-3820
Author(s):  
Kyaw Zin Thein ◽  
Aung M Tun ◽  
Sai-Ching J Yeung ◽  
Thein H. Oo
Keyword(s):  
Systematic Review ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Bleeding Event ◽  
Bleeding Risk ◽  
Risk Difference ◽  
Control Group ◽  
Solid Cancer ◽  
Bleeding Events ◽  
Risk Of Bleeding

Abstract Introduction: Thrombosis is the second leading cause of death in cancer patients. Hypothetically, prognosis might be improved by preventing thrombotic events by PTP. PTP has to be outweighed with the bleeding risk from PTP benefit. Moreover, PTP in ambulatory cancer patients remains uncertain. We performed a systematic review and meta-analysis of RCTs to determine the risk of major bleeding (MB) and clinically relevant non-major (CRNM) bleeding from PTP with low-molecular weight heparins (LMWH) in solid cancer patients receiving chemotherapy. Methods: We systematically conducted a comprehensive literature search using MEDLINE and EMBASE databases through May 31, 2016. The RCTs with MB and CRNM bleeding as safety outcomes were included in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio (RR), and risk difference (RD) with 95% confidence interval (CI). Random effects model was applied. Results: 12 RCTs with a total of 8643 patients were eligible for analysis. Dalteparin, nadroparin, certoparin, semuloparin and bemiparin were used in the studies. 9 studies utilized prophylactic doses, while one used intermediate doses and 2 employed therapeutic dose. The PTP duration was from 6 weeks to 6 months. MB events were reported in 67 (1.486%) patients on PTP compared to 46 (1.112%) in control group. The pooled RR for MB was statistically nonsignificant at 1.341 (95% CI: 0.917 to 1.960, P = 0.130). CRNM bleeding events were noted in 209 (4.637%) in PTP group and 106 (2.563%) in control group. The RR for CRNM bleeding was statistically significant at 1.729 (95% CI: 1.017 to 2.938, P = 0.043). The absolute RD in CRNM bleeding was 0.020 (95% CI: 0.004 to 0.035, P = 0.012) with an estimated number needed to harm (NNH) of 48 to cause one CRNM bleeding event. Conclusions: Approximately 60 patients are needed to be treated with PTP to prevent one symptomatic venous thrombosis among all ambulatory unselected cancer patients on chemotherapy in a previous meta-analysis. Our meta-analysis revealed that PTP contributed an increase in CRNM bleeding events with NNH of 48. The risk of bleeding should not be underestimated and more RCTs are required before making any recommendations. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Oo: Daiichi Sankyo: Research Funding.

A Systematic Review and Meta-Analysis about the Effect of Bisphosphonates on the Risk of Skeletal-Related Event in Men with Prostate Cancer

2020 ◽  
Vol 20 (13) ◽  
pp. 1604-1612
Author(s):  
Congcong Wu ◽  
Hua Jiang ◽  
Jianghua Chen
Keyword(s):  
Prostate Cancer ◽  
Fixed Effects ◽  
Data Extraction ◽  
Controlled Trial ◽  
Meta Analysis ◽  
Control Group ◽  
Fixed Effects Model ◽  
Related Event ◽  
Mineral Density ◽  
Skeletal Related Event

Background: Although the adjuvant therapy of bisphosphonates in prostate cancer is effective in improving bone mineral density, it is still uncertain whether bisphosphonates could decrease the risk of Skeletal- Related Event (SRE) in patients with prostate cancer. We reviewed and analyzed the effect of different types of bisphosphonates on the risk of SRE, defined as pathological fracture, spinal cord compression, radiation therapy to the bone, surgery to bone, hypercalcemia, bone pain, or death as a result of prostate cancer. Methods: A systemic literature search was conducted on PubMed and related bibliographies. The emphasis during data extraction was laid on the Hazard Ratio (HR) and the corresponding 95% Confidence Interval (CI) from every eligible Randomized Controlled Trial (RCT). HR was pooled with the fixed effects model, and preplanned subgroup analyses were performed. Results: 5 RCTs (n = 4651) were included and analyzed finally after screening 51 articles. The meta-analysis of all participants showed no significant decrease in the risk of SRE when adding bisphosphonates to control group (HR = 0.968, 95% CI = 0.874 - 1.072, p = 0.536) with low heterogeneity (I2 = 0.0% (d.f. = 4) p = 0.679). There was no significant improvement on SRE neither in the subgroups with Metastases (M1) or Castration-Sensitive Prostate Cancer (CSPC) (respectively HR = 0.968, 95% CI = 0.874 - 1.072, p = 0.536, I2 = 0.0% (d.f. = 4) p = 0.679; HR = 0.954, 95% CI = 0.837 - 1.088, p = 0.484, I2 = 0.0% (d.f. = 3) p = 0.534). Conclusion: Our study demonstrated that bisphosphonates could not statistically significantly reduce the risk of SRE in patients with prostate cancer, neither in the subgroups with M1 or CSPC.

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