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. 2020 Oct 1;3(10):e2022886.
doi: 10.1001/jamanetworkopen.2020.22886.

Assessment of Outcomes Among Patients With Venous Thromboembolism With and Without Chronic Kidney Disease

Shinya Goto  1 , Sylvia Haas  2 , Walter Ageno  3 , Samuel Z Goldhaber  4 , Alexander G G Turpie  5 , Jeffrey I Weitz  6 , Pantep Angchaisuksiri  7 , Joern Dalsgaard Nielsen  8 , Gloria Kayani  9 , Alfredo Farjat  9 , Sebastian Schellong  10 , Henri Bounameaux  11 , Lorenzo G Mantovani  12   13 , Paolo Prandoni  14 , Ajay K Kakkar  15 ; GARFIELD-VTE Investigators
Affiliations

Assessment of Outcomes Among Patients With Venous Thromboembolism With and Without Chronic Kidney Disease

Shinya Goto et al. JAMA Netw Open. .

Abstract

Importance: Patients with venous thromboembolism (VTE) and concomitant chronic kidney disease (CKD) have been reported to have a higher risk of thrombosis and major bleeding complications compared with patients without concomitant CKD. The use of anticoagulation therapy is challenging, as many anticoagulant medications are excreted by the kidney. Large-scale data are needed to clarify the impact of CKD for anticoagulant treatment strategies and clinical outcomes of patients with VTE.

Objective: To compare clinical characteristics, treatment patterns, and 12-month outcomes among patients with VTE and concomitant moderate to severe CKD (stages 3-5) vs patients with VTE and mild to no CKD (stages 1-2) in a contemporary international registry.

Design, setting, and participants: The Global Anticoagulant Registry in the Field-Venous Thromboembolism (GARFIELD-VTE) study is a prospective noninterventional investigation of real-world treatment practices. A total of 10 684 patients from 415 sites in 28 countries were enrolled in the GARFIELD-VTE between May 2014 and January 2017. This cohort study included 8979 patients (6924 patients with mild to no CKD and 2055 patients with moderate to severe CKD) who had objectively confirmed VTE within 30 days before entry in the registry. Chronic kidney disease stages were defined by estimated glomerular filtration rates. Data were extracted from the study database on December 8, 2018, and analyzed between May 1, 2019, and July 30, 2020.

Exposure: Moderate to severe CKD vs mild to no CKD.

Main outcomes and measures: The primary outcomes were all-cause mortality, recurrent VTE, and major bleeding. Event rates and 95% CIs were calculated and expressed per 100 person-years. Hazard ratios (HRs) were estimated with Cox proportional hazards regression models and adjusted for relevant confounding variables. All-cause mortality was considered a competing risk for other clinical outcomes in the estimation of cumulative incidences.

Results: Of the 10 684 patients with objectively confirmed VTE, serum creatinine data were available for 8979 patients (84.0%). Of those, 4432 patients (49.4%) were female and 5912 patients (65.8%) were White; 6924 patients (77.1%; median age, 57 years; interquartile range [IQR], 44-69 years) were classified as having mild to no CKD, and 2055 patients (22.9%; median age, 70 years; IQR, 59-78 years) were classified as having moderate to severe CKD. Calculations using the equation from the Modification of Diet in Renal Disease study indicated that, among the 6924 patients with mild to no CKD, 2991 patients had stage 1 CKD, and 3933 patients had stage 2 CKD; among the 2055 patients with moderate to severe CKD, 1650 patients had stage 3 CKD, 190 patients had stage 4 CKD, and 215 patients had stage 5 CKD. The distribution of VTE presentation was comparable between groups. In total, 1171 patients (57.0%) with moderate to severe CKD and 4079 patients (58.9%) with mild to no CKD presented with deep vein thrombosis alone, 547 patients (26.6%) with moderate to severe CKD and 1723 patients (24.9%) with mild to no CKD presented with pulmonary embolism alone, and 337 patients (16.4%) with moderate to severe CKD and 1122 patients (16.2%) with mild to no CKD presented with both pulmonary embolism and deep vein thrombosis. Compared with patients with mild to no CKD, patients with moderate to severe CKD were more likely to be female (3259 women [47.1%] vs 1173 women [57.1%]) and older than 65 years (2313 patients [33.4%] vs 1278 patients [62.2%]). At baseline, the receipt of parenteral therapy alone was comparable between the 2 groups (355 patients [17.3%] with moderate to severe CKD vs 1253 patients [18.1%] with mild to no CKD). Patients with moderate to severe CKD compared with those with mild to no CKD were less likely to be receiving direct oral anticoagulant therapy, either alone (557 patients [27.1%] vs 2139 patients [30.9%]) or in combination with parenteral therapy (319 patients [15.5%] vs 1239 patients [17.9%]). Patients with moderate to severe CKD had a higher risk of all-cause mortality (adjusted hazard ratio [aHR], 1.44; 95% CI, 1.21-1.73), major bleeding (aHR, 1.40; 95% CI, 1.03-1.90), and recurrent VTE (aHR, 1.40; 95% CI, 1.10-1.77) than patients with mild to no CKD.

Conclusions and relevance: In this study of patients with VTE, the presence of moderate to severe CKD was associated with increases in the risk of death, VTE recurrence, and major bleeding compared with the presence of mild to no CKD.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Goto reported receiving personal fees from the Thrombosis Research Institute during the conduct of the study; grants from Bristol Myers Squibb, Ono Pharmaceutical, Pfizer, and Sanofi outside the submitted work; and personal fees from the American Heart Association outside the submitted work. Dr Haas reported receiving personal fees from Aspen Pharmacare, Bayer Pharma AG, Bristol Myers Squibb, Daiichi Sankyo, Pfizer, Portola Pharmaceuticals, and Sanofi outside the submitted work. Dr Ageno reported receiving personal fees from the Thrombosis Research Institute during the conduct of the study; grants from Bayer Pharma AG and Boehringer Ingelheim outside the submitted work; and personal fees from Aspen Pharmacare, Bayer Pharma AG, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Janssen Pharmaceutica, Pfizer, Portola Pharmaceuticals, and Sanofi outside the submitted work. Dr Goldhaber reported receiving grants from Bayer Pharma AG, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Daiichi Sankyo, Janssen Pharmaceutica, the National Heart, Lung, and Blood Institute, and the Thrombosis Research Institute and personal fees from Bayer Pharma AG and Boehringer Ingelheim outside the submitted work. Dr Turpie reported receiving personal fees from Bayer Pharma AG and Janssen Pharmaceutica outside the submitted work. Dr Weitz reported receiving research support from the Canadian Fund for Innovation, the Canadian Institutes of Health Research, the Heart and Stroke Foundation and personal fees from Anthos Therapeutics, Bayer Pharma AG, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Ionis Pharmaceuticals, Janssen Pharmaceutica, Merck, Novartis, Pfizer, Portola Pharmaceuticals, Servier Pharmaceuticals, and Tetherex Pharmaceuticals outside the submitted work. Dr Nielsen reported receiving personal fees from Bayer Pharma AG, Boehringer Ingelheim, Bristol Myers Squibb, Leo Pharma, Merck Sharp & Dohme, Pfizer, and Roche Diagnostics outside the submitted work. Dr Kayani reported receiving grants from Bayer Pharma AG during the conduct of the study. Dr Schellong reported receiving grants from Bristol Myers Squibb and personal fees from Aspen Pharmacare, Bayer Pharma AG, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Pfizer, and Sanofi-Aventis outside the submitted work. Dr Bounameaux reported receiving grants from the Thrombosis Research Institute during the conduct of the study and personal fees from Bayer Pharma AG outside the submitted work. Dr Mantovani reported receiving grants from the Italian Ministry of Health Ricerca Corrente–IRCCS MultiMedica during the conduct of the study and grants and personal fees from Bayer Pharma AG, Boehringer Ingelheim, Daiichi Sankyo, and Pfizer outside the submitted work. Dr Prandoni reported receiving personal fees from Bayer Pharma AG, Daiichi Sankyo, Pfizer, and Sanofi outside the submitted work. Dr Kakkar reported receiving personal fees from Bayer Pharma AG and Sanofi during the conduct of the study; grants from Bayer Pharma AG outside the submitted work; and personal fees from Anthos Therapeutics, Bayer Pharma AG, Janssen Pharmaceutica, Pfizer, Sanofi, and Verseon outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Study Population Flowchart
CKD indicates chronic kidney disease and VTE, venous thromboembolism.
Figure 2.
Figure 2.. Anticoagulant Treatment in Patients Over 12-Month Follow-Up
Data unavailable for 13 patients with moderate to severe chronic kidney disease and 47 patients with mild to no chronic kidney disease. AC indicates anticoagulant medication; DOAC, direct oral anticoagulant medication; mild/no CKD, mild to no chronic kidney disease; mod/sev CKD, moderate to severe chronic kidney disease; and VKA, vitamin K antagonist medication.
Figure 3.
Figure 3.. Cumulative Incidence Stratified by Stage of Chronic Kidney Disease
Data are shown as percentages of patients experiencing event and 95% CIs. CKD indicates chronic kidney disease and VTE, venous thromboembolism. A, All-cause mortality. B, Recurrent VTE. C, Major bleeding.
Figure 4.
Figure 4.. Adjusted Hazard Ratios for 12-Month Outcomes
Reference group was patients with mild to no chronic kidney disease. eTable 1 in the Supplement lists variables used in the adjustment. HR indicates hazard ratio; TIA, transient ischemic attack; and VTE, venous thromboembolism.
See this image and copyright information in PMC

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