Incidence Rates Of Thromboembolism Research Articles

Effectiveness and Safety of Edoxaban Compared With Apixaban in Elderly Patients With Nonvalvular Atrial Fibrillation: A Real-World Population-Based Cohort Study.

The very elderly (≥80 years) are at high risk of nonvalvular atrial fibrillation and thromboembolism. Given its recent approval, the comparative effectiveness and safety of edoxaban in this population, relative to the commonly used apixaban, remain unknown. Using the United Kingdom Clinical Practice Research Datalink, we identified a cohort of patients aged ≥80 with incident nonvalvular atrial fibrillation and newly treated with edoxaban or apixaban between 2015 and 2021. Cohort entry was defined as the first prescription for one of the 2 drugs. We used propensity score fine stratification and weighting for confounding adjustment. A weighted Cox proportional hazards model was used to estimate the hazard ratios (HR) with 95% CI of ischemic stroke/transient ischemic attack/systemic embolism (primary effectiveness outcome) and of major bleeding (primary safety outcome) associated with edoxaban compared with apixaban. We also assessed the risk of all-cause mortality and a composite outcome of ischemic stroke/transient ischemic attack, systemic embolism, gastrointestinal bleeding, and intracranial hemorrhage as secondary outcomes. The cohort included 7251 new-users of edoxaban and 39 991 of apixaban. Edoxaban and apixaban had similar incidence rates of thromboembolism (adjusted rates, 20.38 versus 19.22 per 1000 person-years; adjusted HR, 1.06 [95% CI, 0.89-1.26]), although the rates of major bleeding were higher with edoxaban (adjusted rates, 45.57 versus 31.21 per 1000 person-years; adjusted HR, 1.42 [95% CI, 1.26-1.61]). The risk of the composite outcome was 21% higher with edoxaban (adjusted HR, 1.21 [95% CI, 1.07-1.38]). All-cause mortality was similar between edoxaban and apixaban (adjusted HR, 1.04 [95% CI, 0.96-1.12]). In very elderly patients with nonvalvular atrial fibrillation, edoxaban resulted in similar thromboembolism prevention as apixaban, although it was associated with a higher risk of major bleeding. These findings may improve the management of nonvalvular atrial fibrillation by informing physicians on the choice of anticoagulant for this vulnerable population.

Risk of Postoperative Venous Thromboembolism After Benign Colorectal Surgery: Systematic Review and Meta-analysis.

Venous thromboembolism is a well-established preventable complication after colectomy. Specific guidance on venous thromboembolism prevention after colectomy for benign disease is limited. This meta-analysis aimed to quantify the venous thromboembolism risk after benign colorectal resection and determine its variability. Following Preferred Reporting Items for Systematic Review and Meta-Analysis and Meta-analysis of Observational Studies in Epidemiology Guidelines (PROSPERO: CRD42021265438), Embase, MEDLINE, and 4 other registered medical literature databases were searched from the database inception to June 21, 2021. Inclusion criteria: randomized controlled trials and large population-based database cohort studies reporting 30-day and 90-day venous thromboembolism rates after benign colorectal resection in patients aged ≥18 years. Exclusion criteria: patients undergoing colorectal cancer or completely endoscopic surgery. Thirty- and 90-day venous thromboembolism incidence rates per 1000 person-years after benign colorectal surgery. Seventeen studies were eligible for meta-analysis reporting on 250,170 patients. Pooled 30-day and 90-day venous thromboembolism incidence rates after benign colorectal resection were 284 (95% CI, 224-360) and 84 (95% CI, 33-218) per 1000 person-years. Stratified by admission type, 30-day venous thromboembolism incidence rates per 1000 person-years were 532 (95% CI, 447-664) for emergency resections and 213 (95% CI, 100-453) for elective colorectal resections. Thirty-day venous thromboembolism incidence rates per 1000 person-years after colectomy were 485 (95% CI, 411-573) for patients with ulcerative colitis, 228 (95% CI, 181-288) for patients with Crohn's disease, and 208 (95% CI, 152-288) for patients with diverticulitis. High degree of heterogeneity was observed within most meta-analyses attributable to large cohorts minimizing within-study variance. Venous thromboembolism rates remain high up to 90 days after colectomy and vary by indication for surgery. Emergency resections compared to elective benign resections have higher rates of postoperative venous thromboembolism. Further studies reporting venous thromboembolism rates by type of benign disease need to stratify rates by admission type to more accurately define venous thromboembolism risk after colectomy. CRD42021265438.

Hormonal Contraceptive Use and Association with Thromboembolism in Women with Sickle Cell Disease

Introduction Women with sickle cell disease (SCD) require broad access to highly effective contraceptive methods due to high rates of unplanned pregnancy and adverse maternal and fetal outcomes. Combined (estrogen-containing) hormonal contraception carries a known risk of thromboembolism (TE) in the general population, and women with SCD have higher baseline risk of TE, thus use of these agents in women with SCD may further increase that risk. The paucity of safety data on hormonal contraceptive use in women with SCD limits the ability of providers and patients to make informed decisions. Objectives This study aims to use population-level administrative claims data of publicly insured women with SCD in the United States (US) to assess patterns of hormonal contraception use and evaluate risk of TE during the first year of use. We hypothesized that TE rates are higher in women prescribed combined hormonal contraceptives (CHC) as compared to women prescribed progestin-only contraceptives (POC). Methods We obtained data using the Centers for Medicare and Medicaid Services Analytic eXtract (CMS MAX) from 2006-2018. Study population included females of reproductive age (12-44 years) with >3 ICD-9 or ICD-10 codes consistent with SCD. Women had to have ≥12 months of continuous enrollment with at least 6 months of data as 'washout period' prior to enrollment period. A new prescription for hormonal contraception was identified using national drug codes in pharmaceutical claims or ICD-9 or 10 procedure codes. CHC included the combined oral contraceptive pill (OCP), transdermal patch, and vaginal ring. POC included the progestin-only pill, depot medroxyprogesterone acetate (DMPA) injection, intrauterine device (IUD) and subdermal implant. TE was defined as the presence of ≥2 ICD-9 or ICD-10 codes for venous TE (deep vein thrombosis (DVT) or pulmonary embolism (PE)) or arterial TE (stroke or myocardial infarction (MI)). Arterial TE was also required to have an associated inpatient admission. Women were included in the analysis for 12 months after contraception initiation, or censored in the event of either contraceptive switch, pregnancy or abortion, or TE occurrence. Data were summarized descriptively and TE incidence rates were calculated as events per 1,000 person-years. Results We identified a total of 41,012 reproductive-aged women with SCD enrolled in CMS MAX, of whom 22.6% (n=9,261) had received ≥1 new prescription for hormonal contraception. Among women with new contraceptive use, 58.5% (n=5,420) initiated CHC and 41.5% (n=3,841) initiated POC. Median age at the start of contraception was 22.3 years (range: 12.0-43.9) and median age at the start of CHC and POC were 22.1 and 22.7 years respectively. Among CHC users, 84.6% (n=4,584) of women were prescribed the combined OCP, 7.7% (n=419) the transdermal patch, and 7.7% (n=417) the vaginal ring. For POC users, DMPA was prescribed to 72.3% (n=2,777), progestin-only pills to 21.2% (n=816), IUD to 4.2% (n=163) and subdermal implant to 2.2% (n=85) of women. A total of 141 (1.5%) new contraceptive users with SCD were identified to have a TE during the follow-up period. The median time from contraception initiation to TE diagnosis was 183 days (IQR: 82-244). The most common TE event was PE (46.1%) followed by DVT (41.8%), stroke (6.4%), and MI (2.1%); 3.5% of women had multiple TE events. TE rate was 16.4 events per 1,000 person-years in CHC users, and the TE event rate was 17.0 events per 1,000 person-years in POC users (p=0.84). Rates of TE did not differ between the two most commonly used methods in each group, the combined OCP (15.5 events per 1,000 person-years ) and DMPA (17.7 events per 1,000 person-years) (p=0.48). Conclusion Our work provides population-level data regarding contraceptive practices for women with SCD in the US. We found that CHC was more frequently prescribed than POC, and identified low rates of long-acting reversible contraception use. The most frequently prescribed agents were the combined OCP and the DMPA injection. TE rates after initiation of the combined OCP and DMPA did not differ. Although limited by the retrospective study design and use of administrative claims data, this study suggests a similar safety profile for CHC and POC in women with SCD with respect to risk of TE.

Risk and benefit trade-off of thromboprophylaxis in patients with Fontan circulation: insights from the National Database of Health Insurance Claims of Japan

Abstract Background Patients with Fontan circulation are at an increased risk of developing thromboembolic events in the first 3–12 months after surgery [1,2]. Thromboembolic events can lead to significant mortality [3]. The current guidelines recommend the use of antithrombotic therapy, either aspirin or warfarin, as a primary thromboprophylaxis [4,5]. On the other hand, the main adverse effect of thromboprophylaxis is bleeding, which may increase the risk of death. However, there are limited data to assess the outcomes of the thromboembolic and bleeding complications of thromboprophylaxis. Therefore, this retrospective cohort study aimed to evaluate the safety and efficacy of thromboprophylaxis after Fontan surgery. Methods We identified 1903 patients who underwent Fontan surgery between June 2011 and September 2019 from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. The patients were followed-up from 2 months to 1 year after Fontan surgery to assess the primary outcomes of thromboembolic and bleeding events. Moreover, we identified the factors associated with primary outcomes in this population using multivariate logistic regression analysis. Results A total of 1903 patients (56.1% male) underwent Fontan surgery at a median age of 3 years (1–22); 1815 patients (95.4%) had an extracardiac conduit. No thromboprophylaxis was prescribed to 65 patients (3.4%), whereas 228 patients (12.0%) received aspirin alone, 346 patients (18.2%) received warfarin alone, and 1264 patients (66.4%) received a combination therapy of aspirin and warfarin. In the first post-operative year, thromboembolic events occurred in 234 patients (12.3%) and bleeding events occurred in 202 patients (10.6%). Older age (odds ratio, 1.08; 95% confidence interval, 1.06–1.11) and aspirin use (odds ratio, 0.34; 95% confidence interval, 0.15–0.78) were independently associated with thromboembolic events. In particular, up to 5 months after surgery, the incidence rate of thromboembolism was significantly lower in patients who received aspirin alone (0.9%) than in those who received other thromboprophylaxis regimens (no thromboprophylaxis, 13.8%; warfarin, 7.5%; combination therapy, 7.4%; p<0.05). No significant difference in incidence of bleeding events was observed among the four thromboprophylaxis regimens. A history of postoperative hemorrhage (odds ratio, 1.49; 95% confidence interval, 1.01–2.21) and the use of a potassium channel blocker (odds ratio, 2.12; 95% confidence interval, 1.10–4.05) was associated with a higher risk of bleeding events. Conclusions In this study, patients who received aspirin alone showed a significantly lower incidence of thromboembolic events. Aspirin may be useful for preventing thromboembolism a year after Fontan surgery. After Fontan surgery, it is important to select a safe and effective thromboprophylaxis regimen and evaluate the risk factors for thromboembolic and bleeding events in a timely manner. Funding Acknowledgement Type of funding sources: None.

Effect of congestive heart failure on safety and efficacy of left atrial appendage closure in patients with non-valvular atrial fibrillation

ABSTRACT Objectives To evaluate the influence of congestive heart failure (CHF) on safety and efficacy of left atrial appendage closure (LAAC) in non-valvular atrial fibrillation (NVAF) patients. Methods A total of 401 patients who consecutively underwent LAAC with Watchman and LAmbre devices were divided into CHF (85 cases) and non-CHF (316 cases) groups. Comparisons between groups were performed against data. Results No significant differences were found in implantation success and periprocedural complication rates between the two groups. During a mean 2.2 years of follow-up, the incidence rate of thromboembolism, major bleeding, device-related thrombus, and non-cardiovascular death was comparable. However, patients with CHF had significantly increased risk of all-cause death (P = 0.015), cardiovascular death (P = 0.014), and combined efficacy endpoints (P = 0.02). After performing propensity score matching, the risk of all-cause death (P = 0.01), cardiovascular death (P = 0.01), and combined efficacy endpoints (P = 0.006) was still higher. The logistic regression analyses identified CHF (OR: 3.642, 95% CI: 1.296–10.232, P = 0.014) as an independent predictor of cardiovascular death. Conclusions Implantation of atrial appendage occluder is effective and safe in NVAF patients with CHF. The increased risk of mortality and combined efficacy endpoints in patients with CHF versus non-CHF after LAAC may be associated with the high risk of CHF itself.

Thromboembolism and bleeding in patients with atrial fibrillation and liver disease – A nationwide register-based cohort study: Thromboembolism and bleeding in liver disease

BackgroundBalancing the risk of thromboembolism and bleeding in patients with liver disease and atrial fibrillation/flutter is particularly challenging. PurposeTo examine the risks of thromboembolism and bleeding with use/non-use of oral anticoagulation (including vitamin K-antagonists and direct oral anticoagulants) in patients with liver disease and AF. MethodsDanish nationwide register-based cohort study of anticoagulant naive individuals with liver disease, incident atrial fibrillation/flutter, and a CHA2DS2-VASc-score≥1 (men) or ≥2 (women), alive 30 days after atrial fibrillation/flutter diagnosis. Thromboembolism was a composite of ischaemic stroke, transient ischaemic attack, or venous thromboembolism. Bleeding was a composite of gastrointestinal, intracerebral, or urogenital bleeding requiring hospitalisation, or epistaxis requiring emergency department visit or hospital admission. Cause-specific Cox-regression was used to estimate absolute risks and average risk ratios standardised to covariate distributions. Because of significant interactions with anticoagulants, results for thromboembolism were stratified for CHA2DS2-VASc-score, and results for bleeding were stratified for cirrhotic/non-cirrhotic liver disease. ResultsFour hundred and nine of 1,238 patients with liver disease and new atrial fibrillation/flutter initiated anticoagulants. Amongst patients with a CHA2DS2-VASc-score of 1–2 (2–3 for women), five-year thromboembolism incidence rates were low and similar in the anticoagulant (6.5%) versus no anticoagulant (5.5%) groups (average risk ratio 1.19 [95%CI, 0.22–2.16]). In patients with a CHA2DS2-VASc-score>2 (>3 for women), incidence rates were 16% versus 24% (average risk ratio 0.66 [95%CI, 0.45–0.87]). Bleeding risks appeared higher amongst patients with cirrhotic versus non-cirrhotic disease but were not significantly affected by anticoagulant status. ConclusionOral anticoagulant initiation in patients with liver disease, incident new atrial fibrillation/flutter, and a high CHA2DS2-VASc-score was associated with a reduced thromboembolism risk. Bleeding risk was not increased with anticoagulation, irrespective of the type of liver disease.

Incidence Rates of Myomectomy-Related Mortality and Venous Thromboembolism in South Korea: A Population-Based Study.

BackgroundUterine leiomyomas are the most commonly observed pathologies, with an estimated prevalence of 4. 5–68.6%. We aimed to calculate myomectomy-related mortality and venous thromboembolism incidence rates in the Republic of Korea.MethodsThe data of patients who underwent myomectomy (2009–2018) were obtained from the Health Insurance Review and Assessment Service-National Inpatient Sample. The mortality rate after myomectomy was calculated using the leiomyoma diagnostic codes and myomectomy procedure codes. The incidence rates of venous thromboembolism, deep vein thrombosis, and pulmonary embolism were calculated using their diagnostic codes, with concomitant use of an antithrombotic agent during the same period or within 90 days after myomectomy.ResultsThe data of 23,549 women aged 15–55 years who underwent myomectomy were extracted. The myomectomy rate was 14.6 ± 0.1 per 10,000 patients. The average age was 39.39 ± 0.04 years. One patient who underwent myomectomy died; this patient did not have concomitant venous thromboembolism. The post-myomectomy mortality rate was 1.3 ± 0.8 per 10,000 patients. The incidence rates of venous thromboembolism, deep vein thrombosis, and pulmonary embolism after myomectomy were 5.7 ± 1.6 per 10,000 patients, 4.4 ± 1.4 per 10,000 patients, and 2.5 ± 1 per 10,000 patients, respectively. The conversion rate to hysterectomy was 2.9 ± 1.1 per 10,000 patients.ConclusionThe current mortality rate after myomectomy (0.013%) is substantially lower than that described in previous studies at the turn of the 20th century. The incidence of venous thromboembolism is also considerably lower than that in the general population worldwide.

Efficacy and safety of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation and hypertrophic cardiomyopathy

Objective: To evaluate the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOAC) in patients with atrial fibrillation (AF) and hypertrophic cardiomyopathy (HCM). Methods: This study was a prospective cohort study. The data of this study were based on the Chinese Atrial Fibrillation Registry (CAFR) Study, which was a prospective, multicenter registry study. The CAFR Study enrolled inpatients and outpatients with AF from 31 hospitals. Patients with AF and HCM were selected from August 2011 to December 2018. The patients were divided into NOAC-treated group and warfarin-treated group. General clinical data, echocardiographic results and treatment options were collected and compared between the two groups. Patients were followed up every 6 months; outcome events included effective endpoint events(thromboembolism)and safety endpoint events(major bleeding). The incidence of endpoint events in both groups was calculated and compared. Cox proportional hazards regression models and Kaplan-Meier survival analysis were performed to determine the association between NOAC use and endpoint events. Results: A total of 393 patients were included (average age: (60.5±11.8) years, 252 men (64.1%)). There were 133 (34.0%) patients in the NOAC-treated group and 260 (66.0%) patients in the warfarin-treated group. Compared with the warfarin-treated group, the patients in the NOAC-treated group had a higher proportion of paroxysmal AF, catheter ablation of AF, a lower proportion of hypertension, ischemic stroke/transient ischemic attack (TIA), lower heart rate, lower usage rate of angiotensin-converting enzyme inhibitors(ACEI)/angiotensin receptor blockers(ARB), β-blockers, non-dihydropyridine calcium channel blockers(NDH-CCB)(P<0.05). There were no significant differences on the echocardiographic results, including interventricular septal thickness, left ventricular posterior wall thickness, left ventricular end-diastolic diameter, left atrial diameter, left ventricular ejection fraction(P>0.05). After a follow-up of 42 (24, 60)months, the incidence rates of thromboembolism were 1.63 and 2.10 events per 100 person-years for NOAC-and warfarin-treated group, and those of major bleeding were 0.66 and 1.03 events per 100 person-years. Kaplan-Meier survival analysis showed survival rates free from endpoint events were similar between NOAC-treated group and warfarin-treated group(thromboembolism-free survival comparison, P=0.476; major bleeding-free survival comparison, P=0.855). Cox multivariate regression analysis revealed that there was no significant difference on risk of thromboembolism(HR=1.21, 95%CI: 0.42-3.50, P=0.720) and major bleeding(HR=1.50, 95%CI: 0.27-8.41, P=0.642) between NOAC-treated and warfarin-treated group. Conclusion: Patients with AF and HCM can be safely and effectively treated with NOAC.

Left Atrial Appendage Closure Yields Favorable Cardio- and Cerebrovascular Outcomes in Patients With Non-valvular Atrial Fibrillation and Prior Stroke.

Introduction: Patients with non-valvular atrial fibrillation (NVAF) and previous stroke are at significantly higher risk of stroke recurrence. Data on the efficacy of left atrial appendage closure (LAAC) on these patients is limited. The aim of this study was to investigate the differences of LAAC efficacy on long-term cardio- and cerebrovascular outcomes in NVAF patients with vs. without prior stroke.Methods: Three hundred and seventy consecutive NVAF patients who underwent LAAC were enrolled and divided into stroke and non-stroke groups based on history of previous stroke. Endpoints, such as thromboembolism, major bleeding, and mortality post-LAAC, were followed up among groups.Results: Patients in the stroke group had higher mean CHA2DS2-VASc and HAS-BLED scores compared to the non-stroke group (5.1 vs. 3.6 and 4.1 vs. 3.4, both P < 0.001, respectively). Over a median follow-up of 2.2 years, there were no significant differences in incidence rates of thromboembolism, device-related thrombus (DRT), major bleeding, and combined efficacy endpoints between the two groups. In both stroke and non-stroke groups, LAAC decreased the risk of thromboembolism [relative risk reduction (RRR) 87.5%, P = 0.034, and 74.6%, P = 0.004, respectively] and major bleeding (RRR 68.8%, P = 0.034, and 68.6%, P = 0.007, respectively) compared with predicted risk. The RRR in thromboembolism was greater in patients with vs. without prior stroke (OR 2.45, 95% CI: 1.20–5.12, P = 0.016). The incidence rates of all-cause mortality and non-cardiovascular death were similar between the two groups, but the risks of cardiovascular death post-LAAC both before (1.4% vs. 8.1%, respectively, P = 0.038) and after adjustment for confounding factors (P = 0.048) were significantly decreased in the stroke group.Conclusions: Patients with vs. without prior stroke did not exhibit a worse clinical prognosis after LAAC. LAAC may provide an increased benefit in cardio-cerebrovascular outcomes in patients with previous stroke compared to those without previous stroke. Further research is necessary to evaluate the efficacy of LAAC in this field.

Efficacy of R2CHA2DS2-VA score for predicting thromboembolism in Thai patients with non-valvular atrial fibrillation

BackgroundThere is no data specific to the addition of renal dysfunction and age 50–64 years as risk parameters to the CHA2DS2-VA score, which is known as the R2CHA2DS2-VA score, among NVAF patients. Accordingly, the aim of this study was to validate the R2CHA2DS2-VA score for predicting thromboembolism in Thai NVAF patients.MethodsThai NVAF patients were prospectively enrolled in a nationwide multicenter registry from 27 hospitals during 2014–2020. Each component of the CHA2DS2-VA and R2CHA2DS2-VA scores was scored and recorded. The main outcomes were thromboembolism, including ischemic stroke, transient ischemic attack (TIA), and/or systemic embolism. The annual incidence rate of thromboembolism among patients in each R2CHA2DS2-VA and CHA2DS2-VA risk score category is shown as hazard ratio (HR) and 95% confidence interval (95% CI). The performance of the R2CHA2DS2-VA and CHA2DS2-VA scores was demonstrated using c-statistics. Net reclassification index was calculated. Calibration plat was used to assess agreement between observed probabilities and predicted probabilities of both scoring system.ResultsA total of 3402 patients were enrolled during 2014–2020. The average age of patients was 67.38 ± 11.27 years. Of those, 46.9% had renal disease, 30.7% had a history of heart failure, and 17.1% had previous stroke or TIA. The average R2CHA2DS2-VA and CHA2DS2-VA scores were 3.92 ± 1.92 and 2.98 ± 1.43, respectively. Annual thromboembolic risk increased with incremental increase in R2CHA2DS2-VA and CHA2DS2-VA scores. Oral anticoagulants had benefit in stroke prevention in NVAF patients with an R2CHA2DS2-VA score of 2 or more (adjusted HR: 0.630, 95% CI 0.413–0.962, p = 0.032). The c-statistics were 0.630 (95% CI 0.61–0.65) and 0.627 (95% CI 0.61–0.64), for R2CHA2DS2-VA and CHA2DS2-VA scores respectively. NRI was 2.2%. The slope and R2 of the calibration plot were 0.73 and 0.905 for R2CHA2DS2-VA and 0.70 and 0.846 for CHA2DS2-VA score respectively.ConclusionsR2CHA2DS2-VA score was found to be at least as good as CHA2DS2-VA score for predicting thromboembolism in Thai patients with NVAF. Similar to CHA2DS2-VA score, thromboembolism increased with incremental increase in R2CHA2DS2-VA score.

No prospective association of a polygenic risk score for coronary artery disease with venous thromboembolism incidence

BackgroundPrevious studies are inconsistent about whether chronic coronary artery disease or generalized atherosclerosis is a causal risk factor for venous thromboembolism. No study seems to have taken a genomic approach to this question. ObjectiveTo test in a prospective study whether a polygenic risk score for coronary artery disease is associated with risk of venous thromboembolism. Participants/MethodsWithin the Atherosclerosis Risk in Communities Study cohort, we computed a previously validated polygenic risk score for coronary artery disease among 9144 White participants at baseline in 1987–1989. We followed the participants through 2015 for incident hospitalized venous thromboembolism events, validated by physician review. We used Cox proportional hazards regression to associate quintiles of the polygenic risk score to venous thromboembolism incidence rates. ResultsOver the median of 26 years of follow‐up, 476 participants had a venous thromboembolism event. There was no apparent association between the coronary artery disease polygenic risk score and incident venous thromboembolism, with age, sex, body mass index adjusted hazard ratios across quintiles being 1 (reference), 0.87 (0.65, 1.15), 1.08 (0.82, 1.42), 0.96 (0.72, 1.27), and 1.03 (0.78, 1.37). ConclusionsA genetic disposition to coronary artery disease did not confer an increased risk of venous thromboembolism in this prospective study.

Trends in the use of hormonal contraception in Estonia 2005–2019 and the risk of arterial and venous thromboembolism: a population-based study

Purpose To describe trends in hormonal contraceptive use, incidence of thromboembolism and presence of risk factors for thromboembolism among the users in Estonia. Material and methods Data of 223 312 female patients aged 15–49 years in 2005–2019 from national health insurance databases was derived. Annual prevalence rates of hormonal contraceptive users, incidence rates of thromboembolism and prevalence rates of risk factors were calculated. Results Between 2005–2019 usage of progestogen-only contraceptives (POCs) increased steadily (from 24 to 135 users per 1000 population), whereas combined hormonal contraceptive (CHC) use declined (from 209 in 2012 to 161 users per 1000 population in 2019). During the study period, 390 cases of venous thromboembolism and 108 arterial thromboembolism coincided with hormonal contraceptive use. Incidence rate for venous thromboembolism was 5.0 (95% CI 4.5–5.5) and for arterial thromboembolism 1.4 per 10 000 person-years (95% CI 1.1–1.7) among hormonal contraceptive users. Age adjusted incidence of venous thromboembolism among CHC users was 5.8 (95% CI 4.1–8.2) times higher than in POC users. Among CHC users, 10.3% had more than one risk factor for thrombosis. Conclusions In regards to the risk of thromboembolism, wider use of POCs and declining prevalence of CHCs in Estonia is positive trend. Still, women with history of thrombosis receiving CHC is a serious concern.

Incidence of Venous Thromboembolism in Acute Leukemia: A Systematic Review and Meta-Analysis

Background:Venous thromboembolism (VTE) incidence in hematological cancer patients greatly influences their morbidity and mortality. However, VTE complications in acute leukemia (AL) received little attention in comparison to other more frequently occurring complications, such as thrombocytopenia-associated bleeding and granulocytopenia related severe infection.Methods:We conducted a systematic review to systematically assess the incidence rate of VTE in the setting of AL, including acute myeloid leukemia (AML), acute promyelocytic leukemia (APL), and acute lymphoid leukemia (ALL), using the information from available observational studies and randomized trials. A meta-analysis of proportions using fixed and random effects models was performed. Herein, we report all the outcomes in random model estimates.Results:Thirty studies were included (29 observational and 1 case control) with a total of 15,491 AL participants in (age range: 15-91). Of the total participants, the number of evaluable patients was 10,788 in AML, 3,242 in ALL, and 1,031 in APL. The VTE rate was found to be 8.8% (95%CI: 8.78-8.81) in all AL patients, 8.2% (95%CI: 8.21-8.23) in AML, 9.7% (95%CI: 9.68-9.75) in ALL, and 10.8% (95%CI: 10.79-10.85) in APL. The recurrence rate was 12% (95%CI: 9.03-15.08) in AL patients (n=435); 17% (95%CI: 11.02-24.26) with AML (n=135); 12% (95%CI: 7.61-18.33) with ALL (n=142) (AML vs. ALL: p=0.233). A subgroup analysis of catheter related thrombosis (CRT) demonstrated a rate of 4.95% in all AL participants (95%CI: 4.94-4.96), 4.7% (95%CI: 4.68-4.77) in AML, 4.3% (95%CI: 4.27-4.32) in ALL, and 7% (95%CI: 6.99-7.10) in APL. The rate of cerebral vein thrombosis in ALL patients treated with l-asparaginase was 2.8% (95%CI: 2.78-2.90).Conclusion:Our data demonstrates a significant incidence of venous thrombosis in AL patients, with a high recurrence rate among those patients. L-asparaginase seems to be particularly associated with a considerably high rate of cerebral thrombosis in ALL. However, there was a lack in randomized trials addressing thrombosis incidence in AL as a primary outcome. Given these significant incidence rates of thromboembolism, future studies are warranted to address the efficacy and safety of thromboprophylaxis in AL patients. [Display omitted] DisclosuresLazo-Langner:Bayer: Honoraria; Daiichi Sankyo: Research Funding; Alexion: Research Funding; Pfizer: Honoraria.

Thrombosis in Covid-19 Patients and Dilemma of Antithrombotic Choice: A Systematic Review

Background: Coronavirus Disease 2019 (COVID-19) potentially deteriorates the immune system and triggers prothrombotic states in many patient scenarios. Clinical studies so far do not stratify the risk of thromboembolism in COVID-19 cases. Objective: This systematic review investigates the risks of thromboembolism and outcomes of anticoagulation therapy in COVID-19 patients. Methods: We searched PubMed, Cochrane Library, Embase, Web of Science, and Google Scholar to identify relevant studies assessing thromboembolism and anticoagulant therapy in COVID-19 patients. Study Selection, Data Extraction, and Synthesis: Two reviewers screened the titles and abstracts of the included studies in the context of COVID-19, thrombosis, and anticoagulant therapy. The reviewers also ascertained the elimination of duplicate articles. Results: We included eight studies based on the thromboembolism predisposition of COVID-19 (adult/elderly) patients with the status/history of cardiovascular disease, diabetes, hypertension, obesity, and hospital admission. Conclusion: Prospective studies need to explore the risks of thromboembolism in patients with COVID-19. The current body of evidence does not substantiate antithrombotic treatment for managing thromboembolism in the setting of COVID-19. The physicians must take preventive measures for reducing the incidence rate of thromboembolism in COVID-19 scenarios until the availability of definitive treatment.

Mild Renal Dysfunction and Risk of Thromboembolism and Bleeding in Patients with Atrial Fibrillation: The Chinese Atrial Fibrillation Registry Study

Abstract Objective: Previous studies indicated that patients with atrial fibrillation (AF) and moderate-to-severe chronic kidney disease (CKD) are at a higher risk of thromboembolism and bleeding during anticoagulation. Whether mild CKD is associated with an increased risk of thromboembolism and bleeding in AF patients remains unknown. This study aimed to evaluate the impact of mild CKD on thromboembolism and major bleeding among patients with AF. Methods: Baseline serum creatinine was available in 17,559 of 25,512 patients enrolled in the China-AF study between August 2011 and December 2018. After excluding those who underwent AF ablation or with moderate-to-severe CKD, 7191 non-valvular AF patients (2059 with mild CKD and 5132 with normal renal function) with regular follow-up for at least 6 months were included. Primary outcomes were the time to the first occurrence of thromboembolic and major bleeding events. Results: Over a mean follow-up of (44.4 ± 23.4) months, 639 thromboembolism and 231 major bleeding events occurred. The crude incidence rates of thromboembolism were higher in the mild CKD group than that of the normal renal function group (3.0/100 person-years vs. 2.2/100 person-years, P &lt; 0.0001), while the crude incidence rates of major bleeding were comparable between the two groups (1.0/100 person-years vs. 0.8/100 person-years, P = 0.076). After multivariate analyses, mild CKD was not associated with an increased risk of thromboembolism (HR = 1.05, 95% CI: 0.89–1.25, P = 0.547) or major bleeding (HR = 1.11, 95% CI: 0.84–1.47, P = 0.476). Conclusions: Mild CKD was not an independent risk factor of thromboembolism or major bleeding in patients with AF.

Thromboembolic Risk of Cessation of Oral Anticoagulation Post Catheter Ablation in Patients With and Without Atrial Fibrillation Recurrence

Cessation of oral anticoagulation (OAC) is common after the first 3 months of catheter ablation of atrial fibrillation (AF); however, thromboembolic risk has not been defined in patients with and without AF recurrence (RAF vs NRAF) post ablation. We identified 796 patients who discontinued OAC at 3 months post AF ablation from January 2015 to May 2018 in our center. Regular follow-up was performed to detect RAF, collect medication management and thromboembolic and major bleeding events. CHA2DS2-VASc score was 1.79 ± 1.50; 547 (68.7%) patients were at intermediate and high risk (i.e., CHA2DS2-VASc score ≥1 in male patients, or ≥2 in female patients); 169 (21.2%) were RAF. During 29.2±12.2 months follow-up, the incidence rate of thromboembolism was 1.62 per 100 patient-year (7 in 431 years) in RAF, 0.33 per 100 patient-year (5 in 1,503 years) in NRAF. After adjusting for potential confounding factors, RAF was associated with more 3.5-fold higher rate of thromboembolism compared with NRAF (adjusting HR, 4.488; 95% CI, 1.381 to 14.586). Rate of thromboembolism was even higher in patients with intermediate and high risk (2.16 per 100 patient-year [7 in 323 years] vs 0.38 per 100 patient-year [4 in 1,043 years], aHR, 5.807; 95% CI, 1.631 to 20.671). In multivariate logistic regression analysis, RAF was the only independent predictor of thromboembolism (4.837 [1.498 to 15.621], p = 0.008). In conclusion, cessation of OAC in NRAF may be reasonable, especially for patients with the contraindications for continuing OAC; however, cessation of OAC appeared unsafe in RAF with a high-risk stroke profile because of high incidence rate of thromboembolism.

Impact of history of hypertension and blood pressure levels on the risk of thromboembolism in nonvalvular atrial fibrillation patients

Objective: To investigate the impact of history of hypertension and blood pressure levels on the thromboembolism risk in the setting of nonvalvular atrial fibrillation (NVAF). Methods: China Atrial Fibrillation Registry Study prospectively enrolled 25 512 atrial fibrillation (AF) patients between August 2011 and December 2018. After exclusion of patients with valvular AF, hypertrophic cardiomyopathy, receiving anticoagulation or ablation therapy at the enrollment, 7 757 patients were included in analysis. The primary endpoint was the time to the first occurrence of ischemic stroke or systemic embolism. Cox proportional hazards models were performed to evaluate whether a history of hypertension or blood pressure levels were independently associated with thromboembolism. Results: During a mean follow up of (35±25) months, 455 （5.9%）thromboembolic events occurred. The crude incidence rate of thromboembolism in patients with a history of hypertension was higher than that in patients without hypertension (2.38 vs. 1.35 per 100 patient-years, χ²=16.8，Log-rank P<0.001). Patients were further divided into 4 groups according to systolic blood pressure (SBP) levels at baseline, the crude incidence rate of thromboembolism significantly increased in proportion to the elevation of SBP levels (χ²=17.9，Log-rank P<0.001). However, there was no significant difference in thromboembolism risk among 4 groups stratified by diastolic blood pressure (DBP) levels (χ²=0.6，Log-rank P=0.907). Multivariable regression analysis showed that history of hypertension was independently associated with a 27% higher risk of thromboembolism (HR=1.27, 95%CI 1.01-1.61, P=0.045). Patients with SBP≥140 mmHg (1 mmHg=0.133 kPa) was associated with 36% higher risk of thromboembolism than patients with SBP<120 mmHg (HR=1.36, 95%CI 1.02-1.82, P=0.036). However, patients with SBP 120-129 mmHg or 130-139 mmHg were not at a higher risk of thromboembolism as compared to the patients with SBP<120 mmHg (SBP 120-129 mmHg: HR=1.23, 95%CI 0.90-1.67, P=0.193; SBP 130-139 mmHg: HR=1.30, 95%CI 0.95-1.77, P=0.098). In addition, DBP levels were not independently associated with the increased thromboembolism risk. Conclusion: A history of hypertension and SBP≥140 mmHg are independent predictors of thromboembolism risk in patients with NVAF. These results indicate that intensive efforts to lower SBP below 140 mmHg might be an important strategy to reduce the risk of stroke in patients with NVAF.

The Tasmanian Atrial Fibrillation Study (TAFS): Differences in Stroke Prevention According to Sex.

Background: There are limited Australian data on sex differences in oral anticoagulant (OAC) prescribing in atrial fibrillation (AF) and ongoing debate regarding the optimal approach to stroke risk assessment and OAC prescribing in female patients with AF. Objective: The purpose of this study was to investigate sex differences in the prescribing of OACs in patients with AF stratified by stroke risk and in the rate of adverse outcomes. Methods: A retrospective analysis of patients admitted to the Royal Hobart Hospital (Tasmania, Australia) with nonvalvular AF between January 2011 and July 2015 was conducted. Rates of antithrombotic prescribing according to sex and stroke risk were assessed along with a multivariate analysis for predictors of OAC prescribing. Rates of thromboembolism, bleeding, and all-cause mortality were assessed according to sex. Results: A total of 2090 patients were included (44.7% female). Women with a CHA2DS2-VA score ≥2 were less likely to receive an OAC compared with men (56.7% vs 62.2%, P = 0.023). Female sex was an independent negative predictor of OAC prescribing (adjusted odds ratio = 0.83; 95% CI = 0.69-0.99; P = 0.041). There were no sex differences in the incidence rates of thromboembolism, bleeding, or all-cause mortality in patients newly commenced on antithrombotic therapy. Conclusion and Relevance: Female patients with a high stroke risk were less likely to receive guideline-recommended treatment. This study provides new information on prescribing trends within the Australian setting and highlights the opportunity to improve the management of female patients with AF and 1 or more additional stroke risk factors.

The impact of atrial fibrillation type on the risks of thromboembolic recurrence, mortality and major haemorrhage in patients with previous stroke: A systematic review and meta-analysis of observational studies.

There is conflicting evidence on the impact of atrial fibrillation (AF) type, i.e. non-paroxysmal AF or paroxysmal AF, on thromboembolic recurrence. The consensus of risk equivalence is greatly based on historical evidence, focussing on initial stroke risks. We conducted a systematic review and meta-analysis to describe the impact of AF type on the risk of thromboembolic recurrence, mortality and major haemorrhage in patients with previous stroke. We systematically searched four multidisciplinary databases from inception to December 2018. We selected observational studies investigating clinical outcomes in patients with ischaemic stroke and AF, stratified by AF type. We assessed all included studies for risk of bias using the 'Risk of Bias In Non-randomised Studies - of Exposures' tool. The Comprehensive Meta-Analysis Software was used to calculate odds ratios from crude event rates. After reviewing 14,127 citations, we selected 108 studies for full-text screening. We extracted data from a total of 26 studies, reporting outcomes on 23,054 patients. Overall, risk of bias was moderate. The annual incidence rates of thromboembolism in patients with non-paroxysmal AF and paroxysmal AF were 7.1% (95% confidence interval: 4.2-11.7) and 5.2% (95% confidence interval: 3.2-8.2), respectively. The odds ratio for thromboembolism in patients with non-paroxysmal AF versus paroxysmal AF was 1.47 (95% confidence interval: 1.08-1.99, p = 0.013). The annual mortality rates in patients with non-paroxysmal AF and paroxysmal AF were 20.0% (95% confidence interval: 13.2-28.0) and 10.1% (95% confidence interval: 5.4-17.3), respectively, and odds ratio was 1.90 (95% confidence interval: 1.43-2.52, p < 0.001). There was no difference in rates of major haemorrhage, odds ratio = 1.01 (95% confidence interval: 0.61-1.69, p = 0.966). In patients with prior stroke, non-paroxysmal AF is associated with significantly higher risk of thromboembolic recurrence and mortality than paroxysmal AF. Although current guidelines make no distinction between non-paroxysmal AF and paroxysmal AF for secondary stroke prevention, future guidance and risk stratification tools may need to consider this differential risk (PROSPERO ID: CRD42019118531).

Long-term Thromboembolic Risk in Patients With Postoperative Atrial Fibrillation After Left-Sided Heart Valve Surgery

New-onset postoperative atrial fibrillation (POAF) is a common complication of cardiac surgery. However, data on the long-term risk of thromboembolism in patients who develop POAF after heart valve surgery are conflicting. In addition, data on stroke prophylaxis in this setting are lacking. To assess the long-term risk of thromboembolism in patients developing new-onset POAF after isolated left-sided heart valve surgery relative to patients with nonsurgical, nonvalvular atrial fibrillation (NVAF). This observational cohort study was conducted from January 1, 2000, through December 31, 2015, using Danish nationwide registries and the Eastern Danish Heart Surgery Database. Patients who developed POAF after isolated left-sided heart valve surgery (bioprosthetic aortic or mitral valve replacement and/or aortic or mitral valve repair) from 2000 through 2015 were included. These patients were matched with patients with nonsurgical NVAF in a 1:3 ratio by age, sex, heart failure, hypertension, diabetes, a history of thromboembolism, ischemic heart disease, and year of diagnosis. Data analyses took place from January to March 2019. Rates of thromboembolism. Of the 1587 patients who underwent isolated left-sided heart valve surgery, 741 patients (46.7%) developed POAF during admission. Of the 712 patients with POAF who were eligible for matching, 675 patients were matched with 2025 patients with NVAF and made up the study population. In the matched study population, the median age was 71 (interquartile range, 65-77) years, and 1600 (59.3%) were men. Oral anticoagulation therapy was initiated within 30 days postdischarge in 420 patients with POAF (62.9%) and in 1030 patients with NVAF (51.4%). The crude incidence rates of thromboembolism were 21.9 (95% CI, 17.4-27.6) and 17.7 (95% CI, 15.2-20.6) events per 1000 person-years for patients with POAF and patients with NVAF, respectively. In the adjusted analysis, the long-term risk of thromboembolism was similar in patients with POAF and NVAF (hazard ratio, 1.22 [95% CI, 0.88-1.68]). Oral anticoagulation therapy during follow-up was associated with a lower risk of thromboembolic events in patients with POAF (hazard ratio, 0.45 [95% CI, 0.22-0.90]) as well as patients with NVAF (hazard ratio, 0.63 [95% CI, 0.45-0.87]) compared with no anticoagulation therapy. New-onset POAF after isolated left-sided heart valve surgery was associated with a similar long-term risk of thromboembolism as NVAF. These data warrant studies addressing the role of anticoagulation therapy in POAF after left-sided heart valve surgery.