Abstract 3114: Antiplatelet Therapy Use and the Risk of Venous Thromboembolic Events in the Double-Blind Raloxifene Use in The Heart (RUTH) Trial

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Claire S Duvernoy ◽  
Adeline A Yeo ◽  
Mayme Wong ◽  
David A Cox ◽  
Hyungin M Kim

Background: Raloxifene (RLX) use in postmenopausal women (PMW) with osteoporosis increases risk of venous thromboembolic events (VTE) 2-fold, compared to placebo (PL). Platelet activation is involved in the pathophysiology of arterial thromboses more than venous thromboses, but some data suggest that aspirin may reduce VTE risk associated with estrogen use. This analysis examines the effects of concomitant antiplatelet (AP) therapy on VTE risk in RLX-treated women. Methods: In RUTH, 10,101 PMW with coronary heart disease (CHD) or increased risk of CHD were randomized to either PL or RLX 60 mg/d and followed for a median 5.6 yr. Reports of clinical symptoms of VTE were supported by relevant diagnostic data and adjudicated. Concomitant use of AP agents (aspirin, clopidogrel, ticlopidine, dipyridamole) was allowed. Cox proportional hazard models, with use of warfarin, presence of fracture, and/or hospitalization as covariates, were used to estimate hazard ratios (HR) with 95% confidence intervals (CI). Results: Overall, RLX 60 mg/d use was associated with an increased VTE risk [HR 1.44 (95% CI 1.06 –1.95)] from PL. Most women (71%) reported using aspirin, and 14.2% reported using non-aspirin AP agents. VTE risk was similar (HR = 1.04, Table ) for women who used RLX alone versus those who used RLX with AP agents. The increase in VTE risk with RLX compared to PL was similar between women who used any AP prior to VTE and those who did not (interaction P=0.29). Women who used aspirin prior to VTE had a similar increased VTE risk with RLX from PL [HR 1.57(95% CI 1.00 –2.47)], compared to women who did not use aspirin [HR 1.34 (95% CI 0.89 –2.01)] (interaction P=0.62). Conclusion: In RUTH, PMW with CHD or at high risk of CHD treated with RLX had an increased risk of VTE compared to PL. Concomitant use of aspirin or non-aspirin AP agents with RLX therapy did not lower VTE risk from RLX alone.

2021 ◽  
Vol 5 (8) ◽  
pp. 2055-2062
Author(s):  
Soravis Osataphan ◽  
Rushad Patell ◽  
Thita Chiasakul ◽  
Alok A. Khorana ◽  
Jeffrey I. Zwicker

Abstract Hospitalized medically ill patients with cancer are at increased risk of both venous thromboembolism and bleeding. The safety and efficacy of extended thromboprophylaxis in patients with cancer are unclear. We conducted a systematic review and meta-analysis of the literature using of MEDLINE, EMBASE, and the Cochrane CENTRAL databases to identify cancer subgroups enrolled in randomized controlled trials evaluating extended thromboprophylaxis following hospitalization. The primary outcomes were symptomatic and incidental venous thromboembolic events and hemorrhage (major hemorrhage and clinically relevant nonmajor bleeding). Four randomized controlled trials reported the outcomes of extended thromboprophylaxis in 3655 medically ill patients with active or history of cancer. The rates of venous thromboembolic events were similar between the extended-duration and standard-duration groups (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.61-1.18; I2 = 0%). However, major and clinically relevant nonmajor bleeding occurred significantly more frequently in the extended-duration thromboprophylaxis group (OR, 2.10; 95% CI, 1.33-3.35; I2 = 8%). Extended thromboprophylaxis in hospitalized medically ill patients with cancer was not associated with a reduced rate of venous thromboembolic events but was associated with increased risk of hemorrhage. This study protocol was registered on PROSPERO as #CRD42020209333.


2019 ◽  
pp. oemed-2018-105361 ◽  
Author(s):  
Christine G Parks ◽  
Armando Meyer ◽  
Laura E Beane Freeman ◽  
Jonathan Hofmann ◽  
Dale P Sandler

ObjectivesFarming has been associated with rheumatoid arthritis (RA). Some studies have evaluated the effects of pesticides, but other agricultural exposures may also affect immune response.MethodsWe investigated non-pesticide agricultural exposures in relation to RA in licensed pesticide applicators (n=27 175, mostly male farmers) and their spouses (n=22 231) in the Agricultural Health Study (AHS) cohort (1993–1997) who completed at least one follow-up survey through 2015. Incident RA cases (n=229 applicators and 249 spouses) were identified based on self-report confirmed by use of disease-modifying antirheumatic drugs or medical records. Hazard Ratios (HRs) and 95% Confidence Intervals (CIs) were estimated by Cox proportional hazard models adjusting for applicator status, state, smoking, education and specific pesticide use, allowing estimates to vary by median age when hazards assumptions were not met.ResultsOverall, RA was associated with regularly applying chemical fertilisers (HR=1.50; 95% CI 1.11 to 2.02), using non-gasoline solvents (HR=1.40; 95% CI 1.09 to 1.80), and painting (HR=1.26; 95% CI 1.00 to 1.59). In older applicators (>62 years), RA was associated with driving combines (HR=2.46; 95% CI 1.05 to 5.78) and milking cows (HR=2.56; 95% CI 1.01 to 6.53). In younger participants (≤62 years), RA was inversely associated with raising animals as well as crops (HR=0.68; 95% CI 0.51 to 0.89 vs crops only). Associations with specific crops varied by age: some (eg, hay) were inversely associated with RA in younger participants, while others (eg, alfalfa) were associated with RA in older participants.ConclusionThese findings suggest several agricultural tasks and exposures may contribute to development of RA.


2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S682-S682
Author(s):  
Joanna M Blodgett ◽  
Kenneth Rockwood ◽  
Olga Theou

Abstract Positive advances in life expectancy, healthcare access and medical technology have been accompanied by an increased prevalence of chronic diseases and substantial population ageing. How this impacts changes in both frailty level and subsequent mortality in recent decades are not well understood. We aimed to investigate how these factors changed over an 18-year period. Nine waves of the National Health and Nutrition Examination Survey (1999-2016) were harmonized to create a 46-item frailty index (FI) using self-reported and laboratory-based health deficits. Individuals aged 20+ were included in analyses (n=44086). Mortality was ascertained in December 2015. Weighted multilevel models estimated the effect of cohort on FI score in 10-year age-stratified groups. Cox proportional hazard models estimated if two or four-year mortality risk of frailty changed across the 1999-2012 cohorts. Mean FI score was 0.11±0.10. In the five older age groups (>40 years), later cohorts had higher frailty levels than did earlier cohorts. For example, in people aged 80+, each subsequent cohort had an estimated 0.007 (95%CI: 0.005, 0.009) higher FI score. However, in those aged 20-29, later cohorts had lower frailty [β=-0.0009 (-0.0013, -0.0005)]. Hazard ratios and cohort-frailty interactions indicated that there was no change in two or four-year lethality of FI score over time (i.e. two-year mortality: HR of 1.069 (1.055, 1.084) in 1999-2000 vs 1.061 (1.044, 1.077) in 2011-2012). Higher frailty levels in the most recent years in middle and older aged adults combined with unchanged frailty lethality suggests that the degree of frailty may continue to increase.


2018 ◽  
Vol 118 (03) ◽  
pp. 526-538 ◽  
Author(s):  
Stefan Hohnloser ◽  
Edin Basic ◽  
Christopher Hohmann ◽  
Michael Nabauer

AbstractAll pivotal trials have evaluated non–vitamin K oral antagonists (NOACs) against warfarin. However, in some regions of the world, phenprocoumon is the most widely used vitamin K antagonist (VKA). There is little evidence documenting effectiveness and safety of NOACs compared with phenprocoumon in atrial fibrillation (AF). A retrospective cohort study using a German claims database was conducted to assess effectiveness (stroke, systemic embolism [SE]) and safety (bleeding leading to hospitalization) during therapy with NOACs and phenprocoumon in 61,205 AF patients. Hazard ratios (HRs) for effectiveness and safety outcomes were derived from Cox proportional hazard models, adjusting for baseline characteristics. Propensity score matching was performed as a sensitivity analysis. As a prespecified subgroup analysis, the effects of reduced NOAC dosing were compared with phenprocoumon. A total of 61,205 patients were identified in whom phenprocoumon (n = 23,823, 38.9%), apixaban (n = 10,117, 16.5%), dabigatran (n = 5,122, 8.4%), or rivaroxaban (n = 22,143, 36.2%) was initiated. After adjusting for baseline confounders, all three NOACs tested had significantly lower risks of stroke/SE compared with phenprocoumon (apixaban—HR: 0.77, 95% CI: 0.66–0.90; dabigatran—HR: 0.74, 95% CI: 0.60–0.91; rivaroxaban—HR: 0.86, 95% CI: 0.76–0.97). Apixaban (HR: 0.58, 95% CI: 0.49–0.69) and dabigatran (HR: 0.64, 95% CI: 0.50–0.80) were associated with lower bleeding risks than phenprocoumon, whereas the risk was similar for rivaroxaban and phenprocoumon. All three NOACs showed reduced risk of intracranial bleeding compared with phenprocoumon. Reduced doses of NOACs were predominantly used in patients with advanced age and comorbidities with generally similar effectiveness and safety benefits compared with phenprocumon as standard-dose NOACs.


2004 ◽  
Vol 91 (03) ◽  
pp. 538-543 ◽  
Author(s):  
Ora Paltiel ◽  
Michael Bursztyn ◽  
Moshe Gatt

SummaryProlonged immobilization and advanced age are considered to be important risk factors for venous thromboembolism (VTE). Nevertheless, the need for VTE prophylaxis in long-term bedridden patients is not known. To assess whether very prolonged immobilization (i.e. over three months) carries an increased risk for clinically apparent VTE, we performed a historical-cohort study of nursing home residents during a ten-year period. Data concerning patient’s mobility and incidence of overt deep vein thrombosis or pulmonary embolism were registered. The mean resident age was 85 ± 8.4 years. Eighteen mobile and eight immobile patients were diagnosed with clinically significant thromboembolic events, during 1137 and 573 patient-years of follow up, respectively. The incidence of venous thromboembolic events was similar in both chronically immobilized and mobile patient groups, 13.9 and 15.8 per thousand patient years, respectively (p = 0.77). The rate ratio for having a VTE event in the immobilized patient group as compared with the mobile group was 0.88 (95% Confidence Interval (CI) 0.33 to 2.13). When taking into account baseline characteristics, risk factors and death rates by various causes, no differences were found between the two groups. In conclusion, chronically immobile bedridden patients are no more prone to clinically overt venous thromboembolic events than institutionalized mobile patients. Until further studies are performed concerning the impact of very prolonged immobilization on the risk of VTE, there is no evidence to support primary prevention after the first three months of immobilization. Evidence for efficacy or cost effectiveness beyond this early period is not available.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21016-e21016
Author(s):  
Sonia Maria Seng ◽  
Ziyue Liu ◽  
Sophia Chiu ◽  
Tracey Proverbs-Singh ◽  
Guru Sonpavde ◽  
...  

e21016 Background: Several reports suggest that cisplatin is associated with an increased risk of thromboembolism (TE). However, patients with solid tumors have multiple risk factors for TE and the excess risk of venous thromboembolic events (VTEs) with cisplatin-based chemotherapy as compared with non-cisplatin-based chemotherapy has not been well described. We performed a systemic review and meta-analysis of randomized controlled trials (RCTs) evaluating the incidence and risk of VTE associated with cisplatin-based chemotherapy. Methods: PubMed was searched for articles published from January 1, 1990 until December 31, 2010.The primary aim was to evaluate the association between treatment with cisplatin and VTEs in patients with cancer. Clinical trials that met the following criteria were included in the meta-analysis: (1) prospective randomized phase 2 and 3 trials of patients with cancer; (2) randomization to treatment with cisplatin versus a non-cisplatin containing chemotherapy regimen (3) available data on venous thromboembolic events. Data on all grade venous thromboembolic events was extracted. Study quality was calculated utilizing Jadad scores. Incidence rates, relative risks, and 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup analyses included the impact of publication year, tumor type, and cisplatin dose. Results: A total of 8216 patients with a variety of advanced solid tumors from 38 RCTs were included for analysis. Among patients treated with cisplatin-based chemotherapy, the summary incidence of VTE was 1.64% (95% CI, 1.06–2.25). Patients treated with cisplatin-based chemotherapy had a significantly increased risk of VTE with a relative risk of 1.65 (95% CI, 1.25–2.18; P = .01) compared with controls. Exploratory subgroup analysis revealed the highest relative risk of VTE in patients receiving a weekly equivalent cisplatin dose >30 mg/m2 (2.64; 95% CI, 1.18–5.77; P = .02) and in studies reported during 2000-2010 (1.70; 95% CI, 1.27–2.28; P = .01). Conclusions: Cisplatin chemotherapy is associated with a significant increase in the risk of VTE in patients with advanced solid tumors compared with non-cisplatin chemotherapy.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20610-e20610
Author(s):  
Wolfgang H Heller ◽  
Alhossain A Khalafallah ◽  
Rebecca Yuan Li ◽  
Anurag Arora ◽  
Maimoona Latif ◽  
...  

e20610 Background: Venous thromboembolic events (VTEs) are a common complication in cancer. The Khorana Score (KS) is widely used for the prediction of VTEs in malignancy. The KS is composed of 5 items: cancer entity, platelet count >350/nL, white cell count (WCC) >11/nL, Hb <100 g/L and body mass index ≥35 (BMI). Scores are grouped into 3 categories indicating the VTE-risk (0=low, 1-2= intermediate, 3 or more points= high-risk). Methods: All ambulatory cancer patients at our institution starting chemotherapy from January 2010 to December 2011 were included. We applied the KS and then modified by adding further cancer subtypes and metastatic status. Results: In 658 of 766 chemotherapy patients, all the data were available for calculating the KS, of whom 52 had a VTE. In multivariate analysis, associations between KS and VTE were found (P≤0.05) in pancreas (p<0.001), lung (p=0.002), stomach (p=0.008), gynaecological cancers (p=0.037), and BMI ≥35 (p=0.004), but not found in lymphoma (p=0.14), high platelet count (p=0.6) and high WCC (p=0.8), or low Hb (p=0.53). There was an increased risk for VTE in some cancers not included in the KS: breast (p=0.01), colorectal (CRC)(p<0.001), prostate (p=0.003) and oesophageal cancer (p= 0.041). The original KS score did not significantly predict VTEs. When adding cases of neoadjuvant/adjuvant (n/a) and/or metastatic (met) CRC, breast, and prostate cancer, significant associations were found, as shown in the Table. Conclusions: The original KS showed only a weak association with VTE occurrence. However, the association was improved by including other cancer entities and / or metastatic status. Major differences between our and other cohorts, such as different proportions of cancer entities and general referral patterns, could explain the discrepancies with other studies. [Table: see text]


2012 ◽  
Vol 39 (7) ◽  
pp. 1433-1440 ◽  
Author(s):  
ANNE GRETE SEMB ◽  
TORE K. KVIEN ◽  
DAVID A. DeMICCO ◽  
RANA FAYYAD ◽  
CHUAN-CHUAN WUN ◽  
...  

Objective.To evaluate lipids and apolipoproteins as predictors of cardiovascular mortality and morbidity (CVD) in patients with spondyloarthritis (SpA).Methods.In the pooled cohort of participants in the IDEAL, TNT, and CARDS trials, 50 had ankylosing spondylitis (AS), 36 had psoriatic arthritis (PsA), and 21,641 did not have AS or PsA (non-SpA). We compared lipid levels at baseline between AS or PsA and non-SpA, and hazard ratios (HR) for CVD were calculated in a Cox proportional hazard model.Results.Atherogenic lipids were lower in samples from AS, but not in PsA, compared to non-SpA. The HR for 1 SD increase in baseline lipids for future CVD was for total cholesterol 1.39 (95% CI 0.82, 2.36) in AS, 1.01 (95% CI 0.44, 2.31) in PsA, and 1.10 (95% CI 1.07, 1.14) in non-SpA. Both high-density lipoprotein (HDL) and apolipoprotein (ApoA-1) were significantly associated with CVD in AS (HR 3.67, 95% CI 1.47, 9.06, and HR 1.89, 95% CI 1.02, 3.54, respectively), in contrast to PsA (HDL: HR 1.03, 95% CI 0.49, 2.15; ApoA-1: HR 0.79, 95% CI 0.34, 1.89) and non-SpA (HDL: HR 0.86, 95% CI 0.84, 0.89; ApoA-1: HR 0.88, 95% CI 0.85, 0.91).Conclusion.HDL and ApoA-1 were surprisingly associated with increased risk of future CVD in patients with AS, whereas these lipids were protective in non-SpA.


Author(s):  
Sharmila Rana ◽  
Gabriel N. Valbuena ◽  
Ed Curry ◽  
Charlotte L. Bevan ◽  
Hector C. Keun

Abstract Background Reliable prognostic biomarkers to distinguish indolent from aggressive prostate cancer (PCa) are lacking. Many studies investigated microRNAs (miRs) as PCa prognostic biomarkers, often reporting inconsistent findings. We present a systematic review of these; also systematic reanalysis of public miR-profile datasets to identify tissue-derived miRs prognostic of biochemical recurrence (BCR) in patients undergoing radical prostatectomy. Methods Independent PubMed searches were performed for relevant articles from January 2007 to December 2019. For the review, 128 studies were included. Pooled-hazard-ratios (HRs) for miRs in multiple studies were calculated using a random-effects model (REM). For the reanalysis, five studies were included and Cox proportional-hazard models, testing miR association with BCR, performed for miRs profiled in all. Results Systematic review identified 120 miRs as prognostic. Five (let-7b-5p, miR-145-5p, miR152-3p, miR-195-5p, miR-224-5p) were consistently associated with progression in multiple cohorts/studies. In the reanalysis, ten (let-7a-5p, miR-148a-3p, miR-203a-3p, miR-26b-5p, miR30a-3p, miR-30c-5p, miR-30e-3p, miR-374a-5p, miR-425-3p, miR-582-5p) were significantly prognostic of BCR. Of these, miR-148a-3p (HR = 0.80/95% CI = 0.68-0.94) and miR-582-5p (HR = 0.73/95% CI = 0.61-0.87) were also reported in prior publication(s) in the review. Conclusions Fifteen miRs were consistently associated with disease progression in multiple publications or datasets. Further research into their biological roles is warranted to support investigations into their performance as prognostic PCa biomarkers.


Author(s):  
Sadia Ilyas ◽  
Stanislav Henkin ◽  
Pablo Martinez‐Camblor ◽  
Bjoern D. Suckow ◽  
Jocelyn M. Beach ◽  
...  

Background Patients hospitalized with COVID‐19 have an increased risk of thromboembolic events. Whether sex, race or ethnicity impacts these events is unknown. We studied the association between sex, race, and ethnicity and venous and arterial thromboembolic events among adults hospitalized with COVID‐19. Methods and Results We used the American Heart Association Cardiovascular Disease COVID‐19 registry. Primary exposures were sex and race and ethnicity, as defined by the registry. Primary outcomes were venous thromboembolic events and arterial thromboembolic events. We used logistic regression for risk adjustment. We studied 21 528 adults hospitalized with COVID‐19 across 107 centers (54.1% men; 38.1% non‐Hispanic White, 25.4% Hispanic, 25.7% non‐Hispanic Black, 0.5% Native American, 4.0% Asian, 0.4% Pacific Islander, and 5.9% other race and ethnicity). The rate of venous thromboembolic events was 3.7% and was more common in men (4.2%) than women (3.2%; P <0.001), and in non‐Hispanic Black patients (4.9%) than other races and ethnicities (range, 1.3%–3.8%; P <0.001). The rate of arterial thromboembolic events was 3.9% and was more common in men (4.3%) than women (3.5%; P =0.002), and in non‐Hispanic Black patients (5.0%) than other races and ethnicities (range, 2.3%–4.7%; P <0.001). Compared with men, women were less likely to experience venous thromboembolic events (adjusted odds ratio [OR], 0.71; 95% CI, 0.61–0.83) and arterial thromboembolic events (adjusted OR, 0.76; 95% CI, 0.66–0.89). Compared with non‐Hispanic White patients, non‐Hispanic Black patients had the highest likelihood of venous thromboembolic events (adjusted OR, 1.27; 95% CI, 1.04–1.54) and arterial thromboembolic events (adjusted OR, 1.35; 95% CI, 1.11–1.65). Conclusions Men and non‐Hispanic Black adults hospitalized with COVID‐19 are more likely to have venous and arterial thromboembolic events. These subgroups may represent at‐risk patients more susceptible to thromboembolic COVID‐19 complications.


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