The Economic Burden of Thromboembolic Events Among Patients with Immune-Mediated Diseases.

INTRODUCTION: Thromboembolic events (TEs) are associated with considerable costs. However, there is a paucity of evidence quantifying the economic burden associated with TEs among patients with immune-mediated diseases (IMDs). METHODS: This retrospective cohort study used the IBM MarketScan® Commercial and Medicare Supplemental Claims databases (2014-2018). Commercially insured adults with IMDs were classified into two cohorts based on diagnosis of TEs (deep vein thrombosis, pulmonary embolism, ischemic stroke, myocardial infarction). Patients in the TE cohort were matched on type of IMD, age, sex, and year of diagnosis to patients in the no TE cohort. In the TE cohort, the index date was the date of first TE following first IMD diagnosis. In the no TE cohort, the index date was assigned so the duration from first IMD diagnosis to index date matched the duration for the corresponding patient in the TE cohort. All-cause total healthcare costs were compared between cohorts in the 30-day and 1-year periods following the index date (inclusive). Unadjusted comparisons were conducted using Wilcoxon signed-rank tests. Adjusted results were estimated using generalized estimating equations with robust sandwich estimator. RESULTS: Overall, 9681 matched patients were included in each cohort (mean age 61.1 years; 63.7% female). The TE cohort had higher proportions of comorbidities than the no TE cohort (Charlson Comorbidity Index [1.5 vs. 0.9]; p < 0.0001). Adjusted all-cause total healthcare costs were significantly greater in the TE cohort versus no TE cohort in the 30-day and 1-year periods following the index date (cost difference: 30-day, $17,574; 1-year, $36,459; both p < 0.0001) and were driven by inpatient costs (cost difference: 30-day, $14,864; 1-year, $23,360; both p < 0.0001). TE-related healthcare costs were $15,955 and $20,239 in the 30-day and 1-year periods, respectively. CONCLUSION: Among patients with IMDs, TEs are associated with substantial economic burden within 30-days and 1-year following the event.

Risk of Thromboembolic Events and Associated Healthcare Costs in Patients with Inflammatory Bowel Disease.

INTRODUCTION: Inflammatory bowel disease (IBD) is associated with greater risk of thromboembolic events (TEs) due to the link between systemic inflammation and hypercoagulability. This study assessed the rates of TEs among patients with IBD versus patients without immune-mediated disease (IMD) and the cost of TEs among patients with IBD in the United States. METHODS: This study used the IBM MarketScan® Commercial and Medicare Supplemental Databases (2014-2018). To assess the incremental rates of TEs (deep vein thrombosis [DVT], pulmonary embolism [PE], ischemic stroke [IS], myocardial infarction [MI]), patients with IBD were matched to patients without IMD. Unadjusted and adjusted incidence rate ratios (IRRs) of TEs were used to compare cohorts. To assess the cost of TEs, patients with IBD with TEs were matched to patients with IBD without TEs. Costs were assessed 30 days and 1 year post index date. RESULTS: There were 34,687 matched pairs included in the rates of TE analyses. Compared to patients without IMD, patients with IBD had greater rates of DVT (adjusted IRR [95% confidence interval] 2.44 [2.00, 2.99]; p < 0.01) and PE (1.90 [1.42, 2.54]; p < 0.01). Increased rates were not observed for IS and MI. There were 1885 matched pairs included in the cost of TE analyses. Patients with IBD with TEs incurred greater healthcare costs over 30 days and 1 year versus patients without TEs (adjusted total cost difference: 30 days $20,784; 1 year $44,630; p < 0.01 for both). CONCLUSIONS: Patients with IBD experienced greater rates of DVT and PE compared to patients without IMD; this elevated risk was associated with a substantial economic burden.

Risk of Thromboembolic Events and Associated Risk Factors, Including Treatments, in Patients with Immune-mediated Diseases.

PURPOSE: This study assessed the association between thromboembolic events (TEs) and immune-mediated diseases (IMDs) and characterized the risk profile of TEs among patients with IMDs. METHODS: An administrative claims database (2014-2018) was used to identify adults with ≥2 diagnoses on different dates for ≥1 IMD (IMD cohort; ankylosing spondylitis, atopic dermatitis, inflammatory bowel disease, multiple sclerosis, psoriasis, psoriatic arthritis, rheumatoid arthritis, and systemic lupus erythematosus); patients without an IMD diagnosis were assigned to the non-IMD cohort. Patients in the IMD cohort were matched 1:1 to patients in the non-IMD cohort on age, sex, and index date. Incremental risk of TE (ie, deep vein thrombosis [DVT], pulmonary embolism [PE], myocardial infarction [MI], and ischemic stroke [IS]) was assessed using adjusted incidence rate ratios (aIRRs) to control for covariates in both cohorts. Risk factors for TEs were assessed in the IMD cohort and included age, female sex, comorbidities, baseline TEs, non-IMD treatments, and IMD treatments. FINDINGS: A total of 182,431 patients were included in each cohort (mean age, [51.3] years; 64.3% female). A higher proportion of patients in the IMD cohort versus the non-IMD cohort had ≥1 baseline TE (4.1% vs 2.7%; P < 0.0001). The IMD cohort had a 1.80 (95% CI, 1.68-1.92; P < 0.0001) times higher rate of TEs versus patients in the non-IMD cohort. After adjustments, patients in the IMD cohort had a 1.49 (95% CI, 1.40-1.59; P < 0.0001) times higher rate of TEs versus patients in the non-IMD cohort. Similar results were observed across individual TEs (DVT: aIRR = 1.78; PE: aIRR = 1.66; MI: aIRR = 1.17; IS: aIRR = 1.35; all P < 0.05). Risk factor profiles varied by TE. The greatest risk factor was respective TE during baseline (eg, patients with baseline DVT had 41.1 times the rate of DVT during the study period vs patients without baseline DVT; P < 0.001). Comorbidities, such as cardiovascular diseases, type 2 diabetes, and peripheral vascular disease, were associated with increased rates of MI (IRR = 2.60, 1.30, and 1.54, respectively; all P < 0.05) and IS (IRR = 1.53, 1.54, and 1.24, respectively; all P < 0.05). Janus kinase inhibitors were associated with an increased rate of PE (IRR = 2.52; P < 0.05) and nonsignificant, numerically higher rates of DVT (IRR = 1.23; P = NS) and IS (IRR = 1.82; P = NS). Sphingosine 1-phosphate receptor modulators were associated with decreased rates of TEs (DVT: IRR = 0.61, P = NS; PE: IRR = 0.30, P = NS; MI: IRR = 0.54, P = NS; IS: IRR = 0.33, P < 0.05). IMPLICATIONS: The risk of TEs was higher among patients with IMD versus patients without IMD; several factors may affect this risk.

Reporting of Thromboembolic Events with JAK Inhibitors: Analysis of the FAERS Database 2010-2019.

INTRODUCTION: A potentially elevated risk for pulmonary thrombosis with Janus kinase inhibitors (JAKinibs) was identified, as well as an increased risk for portal vein thrombosis, in ruxolitinib patients. Consequently, the objective of this investigation was to repeat a comprehensive analysis of the US FDA's Adverse Event Reporting System (FAERS) database to assess postmarketing reporting rates of thromboembolic events (TEs) in patients treated with JAKinibs. METHODS: FAERS data (1 January 2010 to 30 September 2019) were searched for reports of all FDA-approved JAKinibs across all indications. For each drug-adverse drug reaction (ADR) pair, the reporting odds ratio (ROR) [two-sided 95% confidence interval (CI)] and empirical Bayesian geometric mean (EBGM) [one-sided 95% lower bound] were calculated to detect drug-ADR pairs with higher-than-expected reporting rates within the FAERS. Significance was declared when both lower 95% CI bounds were > 1. RESULTS: Significantly elevated reporting rates of pulmonary thrombosis were evident with tofacitinib (ROR 2.36 [1.69-3.31]; EBGM 2.01 [1.53]), as was pulmonary embolism with baricitinib (ROR 12.23 [8.35-17.89]; EBGM 7.72 [3.82]) and portal vein thrombosis with ruxolitinib (ROR 4.16 [2.70-6.40]; EBGM 4.52 [3.11]). Deep vein thrombosis reports were increased with baricitinib (ROR 14.84 [9.64-22.84]; EBGM 9.49 [5.91]), as was thrombosis with ruxolitinib (ROR 1.40 [1.20-1.63]; EBGM 1.72 [1.52]). The relationship between the time of treatment initiation and event occurrence indicated that time to events occurred randomly. CONCLUSIONS: This study found significant reporting rates for TEs in patients treated with JAKinibs across brands and indications, providing additional evidence that JAKinibs may be contraindicated in patients at risk of TEs.

Immune-mediated diseases and thromboembolic events: a modified Delphi panel.

INTRODUCTION: A multidisciplinary panel of physicians was convened to gain understanding of the relationship between thromboembolic events (TEs) and immune-mediated diseases (IMDs). The primary objective of the panel was to assess areas of consensus on the IMD most prone to TE as well as modifiable and unmodifiable factors that might exacerbate or mitigate the risk of TEs. METHODS: Thirteen nationally recognized physicians were selected based on their contributions to guidelines, publications and patient care. The modified Delphi panel consisted of four rounds of engagement: (1) a semi-structured interview, (2) an expert panel questionnaire, (3) an in-person panel discussion, and (4) a consensus statement survey. RESULTS: Ulcerative colitis and Crohn's disease were identified as two of four IMDs with the highest TE risk. Consensus was reached on several non-modifiable and modifiable characteristics of high-risk. Approaches to reduce TE incidence were identified such as altering treatment, requiring the monitoring of patients for TEs and modifying patient behaviors. Janus kinase inhibitors and corticosteroids were identified as therapies that required further evaluation given their potential TE risk. DISCUSSION: The panel reached a consensus that several IMDs are at an elevated risk of TEs. Physicians are unable to control most patient level risk factors but can control the therapies being used. Consequently, physicians should consider the specific IMD, be aware of TE risk factors, and take into account risk factors in selecting the therapies to optimally manage their conditions and to reduce the risk of TEs in this population.

Delayed Management of Partial Aortic Valve Avulsion After Transcatheter Aortic Valve Replacement.

We report a case of delayed treatment of a partial aortic valve leaflet avulsion during transcatheter aortic valve replacement (TAVR) and its successful management by a percutaneous snare retrieval technique. Post-TAVR transesophogeal echocardiography showed an avulsed native valve leaflet. We deferred retrieval of the mass with anticoagulant agents. One month later, a 30-mm EN-Snare was used to snare the mass. This case report demonstrates that the management of an avulsed aortic valve leaflet can be safely deferred with the use of an anticoagulant agent. Snare retrieval of the avulsed valve can be achieved under local anesthesia with close neurological monitoring.

New oral anticoagulants for patients with nonvalvular atrial fibrillation.

Four new oral anticoagulants have been approved for reducing stroke risk in patients with nonvalvular atrial fibrillation. Compared with warfarin, these agents offer a more predictable dose response with fewer food and drug interactions and no regular blood monitoring, although some of the drugs have an increased risk of major gastrointestinal bleeding. This article reviews the new drugs.

Angiosarcoma in a pregnant woman presenting with pericardial tamponade--a case report and review of the literature.

Although asymptomatic pericardial effusions are relatively common in pregnancy, their true incidence is not known. Symptomatic effusions are, however, rare in pregnancy. The authors present a rare case of pericardial tamponade complicating pregnancy with resulting diagnosis of angiosarcoma. They review the literature involving pericardial disease in pregnancy and discuss important issues in management and include a discussion of angiosarcoma.

Relation of clinical success in coronary brachytherapy to dose.

Intravascular brachytherapy is the primary treatment for coronary in-stent restenosis. Variations in dose in the treated artery may represent a potential cause of treatment failure. We compared dose distributions in patients who had developed recurrent restenosis (treatment failure) with those in patients who remained event free at 9 months (treatment success). We followed 140 patients who were receiving brachytherapy for in-stent restenosis with 4 radiation delivery devices to identify treatment failures and successes. Through a nested case-control construct, treatment failures (n = 14) were compared 1:2 with treatment successes (n = 28) matched by radiation delivery system and in-stent restenosis lesion pattern. The dose absorbed by 90% of the artery encompassed by the external elastic membrane (D(90)EEM) was calculated by applying intravascular ultrasound at 2-mm intervals along the treated lesion. Dose calculations were performed using dose kernel integration techniques generated from Monte Carlo simulations. The mean minimum D(90)EEM in treatment failures was 7.46 +/- 1.98 Gy, and that in treatment successes was 8.87 +/- 1.13 Gy (p = 0.007). Using a minimum dose threshold of 8.4 Gy, a minimum D(90)EEM

Brachytherapy for in-stent restenosis in general interventional practice: a single institution's experience using four radiation devices.

BACKGROUND: The effectiveness of brachytherapy for the treatment of in-stent restenosis (ISR) has been established in a number of large randomized controlled trials. Efficacy of this therapy in general population is less well established. METHODS AND MATERIALS: We report our experience of 207 patients, 236 coronary lesions, treated with brachytherapy between November 2000 and November 2002. All commercially available brachytherapy devices, as well as one investigational device, were utilized. This cohort was followed over 9 months and clinical outcomes were obtained with subsequent analysis of patient and lesion-specific characteristics. RESULTS: Average treatment age was 62.5 years; 73% were male and the most frequent presentation was unstable angina (74%). All patients had successful delivery of radiation, with no in-hospital deaths. Novoste BetaCath device was used for 163 (65%) lesions, Cordis Checkmate for 56 (24%) lesions, Interventional Therapies device in 13 (8%) lesions, and Guidant Galileo in 4 lesions (3%). At a mean follow-up of 9.1 months, 78.7% were free of major adverse cardiac event (MACE). Twenty-one patients required repeat PTCA (10.1%), 19 had CABG (9.2%), 3 had MI (1.4%), and there was 1 death (0.5%). Unadjusted MACE rates for each device were 21% for Novoste, 28% for Checkmate, 8% for Interventional Therapies, and 50% for Galileo. Lesion length, minimal lumen diameter, renal failure, diabetes, and smoking did not predict treatment failure; only age was inversely correlated with MACE (P=.002). CONCLUSION: When applied across a spectrum of patients, lesions, and devices, brachytherapy retains its effectiveness with outcomes similar to those reported in randomized clinical trials.