Sequential Expansion of Comparative Effectiveness of Anticoagulants

Dabigatran

Warfarin

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.

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).

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).

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.

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

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)

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).

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

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).

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).

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).

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

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.

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

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

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

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)).

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)

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)