Sequential Expansion of Comparative Effectiveness of Anticoagulants

Atrial Fibrillation Clinical Trial

Official title:

Sequential Expansion of Comparative Effectiveness of Oral Anticoagulants: A Cohort Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02081807
• Other study ID #: 1160.207
• Status: Completed
• Start date: March 7, 2014
• Est. completion date: November 1, 2017

Study information

• Verified date: September 2019
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This cohort study is the sequential expansion of the comparative effectiveness study of oral anticoagulants and plans to identify initiators of oral anticoagulants using electronic claims data from a commercial insurance database to quantify associations between anticoagulant choice (warfarin and dabigatran) and the occurrence of selected outcomes in patients with non-valvular atrial fibrillation at risk for stroke.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 221228
• Est. completion date: November 1, 2017
• Est. primary completion date: November 1, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• A recorded diagnosis of atrial fibrillation.

• Initiation of anticoagulant medication (dabigatran (or other new oral anticoagulants as they become available) or warfarin).

• At least 18 years of age on the date of anticoagulant initiation.

• Congestive Heart Failure, Hypertension, Age > 75, Diabetes Mellitus, Prior Stroke or Transient Ischemic Attack, Vascular Disease, Age 65-74, Sex Category (CHA2DS2-VASc) score at least 1

Exclusion criteria:

• Patients with missing or ambiguous age or sex information.

• Patients with evidence of valvular disease.

• Patients with less than 12 months enrolment preceding the date of anticoagulant initiation

• Patients with a dispensing of any oral anticoagulant during the 12 months preceding the date of anticoagulant initiation

• Patients with a nursing home stay during the 12 months preceding the date of anticoagulant initiation

Related Conditions & MeSH terms

• Atrial Fibrillation

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Stroke (Hemorrhagic, Ischemic, or Stroke of Uncertain Classification)	The rate of overall stroke (hemorrhagic, ischemic or stroke of uncertain classification ) in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: As primary International Classification of Diseases, Ninth Revision (ICD-9) discharge diagnosis (Dx): 431.x Intracerebral hemorrhage (ICH), 433.x1 Occlusion and stenosis of precerebral arteries with cerebral infarction, 434.x1 Occlusion and stenosis of cerebral arteries with cerebral infarction, 436.x Acute, but ill-defined cerebrovascular events.	From October 2010 to September 2015 (the study period)
Primary	Major Bleeding	The rate of major bleeding (Major intracranial bleeding and major extracranial bleed ) in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. For outcome definitions please refer the descriptions section of outcome 8 (major intracranial bleeding) and outcome 9 (major extracranial bleeding).	From October 2010 to September 2015 (the study period)
Secondary	Stroke or Systemic Embolism	The rate of stroke (hemorrhagic, ischemic or stroke of uncertain classification ) or systemic embolism in patients matched on propensity scores and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. For outcome definitions please refer the descriptions section of outcome 4 (Systemic embolism), outcome 5 (Ischemic stroke), outcome 6 (Hemorrhagic stroke) and outcome 7 (Stroke uncertain classification).	From October 2010 to September 2015 (the study period)
Secondary	Systemic Embolism	The rate of systemic embolism in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: ICD-9 Diagnoses: 444.x Arterial embolism.	From October 2010 to September 2015 (the study period)
Secondary	Ischemic Stroke	The rate of ischemic stroke in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: As primary ICD-9 discharge diagnosis (Dx): 433.x1 Occlusion and stenosis of precerebral arteries with cerebral infarction, ICD-9 Dx 434.x1 Occlusion and stenosis of cerebral arteries with cerebral infarction	From October 2010 to September 2015 (the study period)
Secondary	Hemorrhagic Stroke	The rate of hemorrhagic in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: As primary ICD-9 discharge diagnosis (Dx): 431.x Intracerebral hemorrhage (ICH)	From October 2010 to September 2015 (the study period)
Secondary	Stroke Uncertain Classification	The rate of stroke uncertain classification in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: As primary ICD-9 discharge diagnosis (Dx): ICD-9 Dx code 436.x (acute, but ill-defined cerebrovascular disease).	From October 2010 to September 2015 (the study period)
Secondary	Major Intracranial Bleeding	The rate of major intracranial bleeding in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: ICD-9 diagnosis: 430.x Subarachnoid hemorrhage (SAH), 431.x Intracerebral hemorrhage (ICH), 432.x other and unspecified intracranial hemorrhage including 432.1x - subdural hemorrhage	From October 2010 to September 2015 (the study period)
Secondary	Major Extra-cranial Bleeding	The rate of major extracranial bleeding (Major upper GI bleed, major lower and unspecified GI bleed, major urogenital bleed, major other bleed) in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. For outcome definitions please refer the descriptions section of outcome 11 (Major upper gastrointestinal bleeding), outcome 12 (Major lower gastrointestinal bleeding), outcome 13 (Major urogenital bleeding) and outcome 14 (Other major bleeding).	From October 2010 to September 2015 (the study period)
Secondary	Major Gastrointestinal (GI) Bleeding	The rate of major gastrointestinal (GI) bleeding (Major upper GI bleeding, major lower/unspecified GI bleeding) in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. For outcome definitions please refer the descriptions section of outcome 11 (Major upper gastrointestinal bleeding) and outcome 12 (Major lower gastrointestinal bleeding).	From October 2010 to September 2015 (the study period)
Secondary	Major Upper Gastrointestinal Bleeding	The rate of Major upper gastrointestinal bleeding in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: ICD-9 diagnoses: 531.0x, 531.2x, 531.4x, 531.6x, 532.0x, 532.2x, 532.4x, 532.6x, 533.0x, 533.2x, 533.4x, 533.6x, 534.0x, 534.2x, 534.4x, 534.6x, 578.0 OR ICD-9 procedure code 44.43 (endoscopic control of gastric or duodenal bleeding) OR Current Procedural Terminology (CPT) code 43255 (upper gastrointestinal endoscopy including esophagus, stomach, and either the duodenum and/or jejunum as appropriate with control of bleeding, any method).	From October 2010 to September 2015 (the study period)
Secondary	Major Lower Gastrointestinal Bleeding	The rate of lower gastrointestinal bleeding in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: Lower GI/unspecified GI site bleeds :Diverticulosis of small intestine with hemorrhage: 562.02, Diverticulitis of small intestine with hemorrhage: 562.03, Diverticulosis of colon with hemorrhage: 562.12, Diverticulitis of colon with hemorrhage: 562.13, Hemorrhage of rectum and anus: 569.3x, Angiodysplasia of intestine with hemorrhage: 569.85, Blood in stool: 578.1x, Hemorrhage of GI tract, unspecified: 578.9	From October 2010 to September 2015 (the study period)
Secondary	Major Urogenital Bleeding	The rate of major urogenital bleeding in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: ICD-9 diagnoses: Hematuria: ICD-9 Dx: 599.7, Excessive/frequent menstruation: ICD-9 Dx 626.2x and secondary diagnosis indicating acute bleeding: anemia (280.0, 285.1, 285.9). Across databases, only one event for dabigatran versus no event among warfarin initiators observed. Across database, four events for rivaroxaban versus no event among warfarin initiators observed. Across database, no events for apixaban and warfarin observed. Therefore HR estimate is not possible.	From October 2010 to September 2015 (the study period)
Secondary	Other Major Bleeding	The rate of Other major bleeding in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: Other major bleeds: Hemathrosis: 719.1x, Hemopericardium: 423.0x, Hemoptysis: 786.3x, Epistaxis: 784.7x, Hemorrhage not specified 459.0x, Acute posthemorrhagic anemia 285.1x	From October 2010 to September 2015 (the study period)
Secondary	Transient Ischemic Attack (TIA)	The rate of Transient Ischemic Attack (TIA) in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: ICD-9 Dx code 435.xx (transient cerebral ischemia) as the principal (primary) discharge diagnosis	From October 2010 to September 2015 (the study period)
Secondary	Myocardial Infarction (MI)	The rate of Myocardial infarction (MI) in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: ICD-9 Dx 410.X (acute myocardial infarction) excluding 410.x2 (subsequent episode of care), as the principal (primary) or the next (secondary) diagnosis AND a length of stay (LOS) between 3-180 days, or death if LOS is < 3 days	From October 2010 to September 2015 (the study period)
Secondary	Venous Thromboembolism (VTE)	The rate of Venous Thromboembolism (VTE) in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. For outcome definitions please refer the descriptions section of outcome 18 (Deep vein thrombosis (DVT)) and outcome 19 (Pulmonary Embolism (PE)).	From October 2010 to September 2015 (the study period)
Secondary	Deep Vein Thrombosis (DVT)	The rate of DVT in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: Validated algorithm: ICD-9 451.1x, ICD-9 451.2x,ICD-9 451.81, ICD-9 451.9x, ICD-9 453.1x, ICD-9 453.2x, ICD-9 453.8x, ICD-9 453.9x ; Not in the validated algorithm but will be included following Mini-Sentinel recommendation for VTE outcome: ICD-9 453.40 (Venous embolism and thrombosis of unspecified deep vessels of lower extremity (includes DVT), ICD-9 453.41 (Venous embolism and thrombosis of deep vessels of proximal lower extremity (includes femoral, iliac, popliteal, thigh, and upper leg), ICD-9 453.42 (Venous embolism and thrombosis of deep vessels of distal lower extremity (includes calf, lower leg, peroneal, and tibia), ICD-9 453.0 (Hepatic vein thrombosis)	From October 2010 to September 2015 (the study period)
Secondary	Pulmonary Embolism (PE)	The rate of Pulmonary Embolism (PE) in patients who are matched on propensity score and calendar quarter of initiation. Event rates were calculated as the total number of patients in each treatment group who had the outcome during follow-up divided by the total person-years at risk in the cohort. The outcome definition includes following: ICD-9 415.1x (pulmonary embolism and infarction)	From October 2010 to September 2015 (the study period)

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