American Journal of Cardiovascular Drugs

All-cause, Stroke-, and Bleed-Specific Healthcare Costs: Comparison among Patients with Non-Valvular Atrial Fibrillation (NVAF) Newly Treated with Dabigatran or Warfarin

Adrienne M. Gilligan 1, Pranav Gandhi2, Xue Song1,Cheng Wang2, Caroline Henriques1, Stephen Sander2,David M. Smith 1

1Truven Health Analytics, an IBM Company, Cambridge, MA, USA

2Boehringer-Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA

Address for Correspondence

Adrienne M. Gilligan, PhD

Truven Health Analytics, an IBM Company

150 Cambridge Park Dr

Cambridge, MA 02140.

Tel: 832-759-6080

E-mail:

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Supplemental Tables:

Table S1.ICD-9 Codes used to Identify Stroke and Bleeds

Disease / Hemorrhagic / ICD9 Code / Description
Ischemic Stroke / No / 433.xx / Occlusion and stenosis of precerebral arteries
Ischemic Stroke / No / 434.xx / Occlusion of cerebral arteries
Intracranial Bleed / Yes / 430 / Subarachnoid hemorrhage
Intracranial Bleed / Yes / 431 / Intracerebral hemorrhage
Intracranial Bleed / Yes / 432.x / Other and unspecified intracranial hemorrhage
Intracranial Bleed / No / 852.xx / Subarachnoid subdural and extradural hemorrhage following injury
Intracranial Bleed / No / 853.xx / Other and unspecified intracranial hemorrhage following injury
Intracranial Bleed / No / 854.xx / Intracranial injury of other and unspecified nature
GI Bleed / No / 455.x / Hemorrhoids
GI Bleed / No / 456.0 / Esophageal varices with bleeding
GI Bleed / No / 456.20 / Esophageal varices in diseases classified elsewhere, with bleeding
GI Bleed / No / 530.7 / Gastroesophageal laceration-hemorrhage syndrome
GI Bleed / No / 530.21 / Ulcer of esophagus with bleeding
GI Bleed / No / 530.82 / Esophageal hemorrhage
GI Bleed / No / 531.xx / Gastric ulcer
GI Bleed / No / 532.xx / Duodenal ulcer
GI Bleed / No / 533.xx / Peptic ulcer site unspecified
GI Bleed / No / 534.xx / Gastrojejunal ulcer
GI Bleed / No / 535.xx / Gastritis and duodenitis
GI Bleed / No / 537.83 / Angiodysplasia of stomach and duodenum with hemorrhage
GI Bleed / No / 537.84 / Dieulafoy lesion (hemorrhagic) of stomach and duodenum
GI Bleed / No / 562.0x / Diverticula of intestine
GI Bleed / No / 562.1x / Diverticula of colon
GI Bleed / No / 569.3 / Hemorrhage of rectum and anus
GI Bleed / No / 569.83 / Perforation of intestine
GI Bleed / No / 569.85 / Angiodysplasia of intestine with hemorrhage
GI Bleed / No / 569.86 / Dieulafoy lesion (hemorrhagic) of intestine
GI Bleed / No / 578.x / Gastrointestinal hemorrhage
GI Bleed / No / 784.8 / Hemorrhage from throat
GI Bleed / No / 772.4 / Gastrointestinal hemorrhage of fetus or newborn
Extracranial Bleed / No / 336.1 / Vascular myelopathies
Extracranial Bleed / No / 360.43 / Hemophthalmos, except current injury
Extracranial Bleed / No / 362.43 / Hemorrhagic detachment of retinal pigment epithelium
Extracranial Bleed / No / 362.81 / Retinal hemorrhage
Extracranial Bleed / No / 363.61 / Choroidal hemorrhage, unspecified
Extracranial Bleed / No / 363.62 / Expulsive choroidal hemorrhage
Extracranial Bleed / No / 363.72 / Hemorrhagic choroidal detachment
Extracranial Bleed / No / 364.41 / Hyphema of iris and ciliary body
Extracranial Bleed / No / 376.32 / Orbital hemorrhage
Extracranial Bleed / No / 377.42 / Hemorrhage in optic nerve sheaths
Extracranial Bleed / No / 379.23 / Vitreous hemorrhage
Extracranial Bleed / No / 423.0 / Hemopericardium
Extracranial Bleed / No / 455.x / Hemorrhoids
Extracranial Bleed / No / 456.0 / Esophageal varices with bleeding
Extracranial Bleed / No / 456.20 / Esophageal varices in diseases classified elsewhere, with bleeding
Extracranial Bleed / No / 459.0 / Hemorrhage, unspecified
Extracranial Bleed / No / 530.21 / Ulcer of esophagus with bleeding
Extracranial Bleed / No / 530.7 / Gastroesophageal laceration-hemorrhage syndrome
Extracranial Bleed / No / 530.82 / Esophageal hemorrhage
Extracranial Bleed / No / 531.xx / Gastric ulcer
Extracranial Bleed / No / 532.xx / Duodenal ulcer
Extracranial Bleed / No / 533.xx / Peptic ulcer site unspecified
Extracranial Bleed / No / 534.xx / Gastrojejunal ulcer
Extracranial Bleed / No / 535.xx / Gastritis and duodenitis
Extracranial Bleed / No / 537.83 / Angiodysplasia of stomach and duodenum with hemorrhage
Extracranial Bleed / No / 537.84 / Dieulafoy lesion (hemorrhagic) of stomach and duodenum
Extracranial Bleed / No / 562.0x / Diverticula of intestine
Extracranial Bleed / No / 562.1x / Diverticula of colon
Extracranial Bleed / No / 568.81 / Hemoperitoneum (nontraumatic)
Extracranial Bleed / No / 569.3 / Hemorrhage of rectum and anus
Extracranial Bleed / No / 569.83 / Perforation of intestine
Extracranial Bleed / No / 569.85 / Angiodysplasia of intestine with hemorrhage
Extracranial Bleed / No / 569.86 / Dieulafoy lesion (hemorrhagic) of intestine
Extracranial Bleed / No / 573.8 / Other specified disorders of liver
Extracranial Bleed / No / 578.0 / Hematemesis
Extracranial Bleed / No / 578.1 / Blood in stool
Extracranial Bleed / No / 578.9 / Hemorrhage of gastrointestinal tract, unspecified
Extracranial Bleed / No / 593.81 / Vascular disorders of kidney
Extracranial Bleed / No / 599.70 / Hematuria, unspecified
Extracranial Bleed / No / 599.71 / Gross hematuria
Extracranial Bleed / No / 599.72 / Microscopic hematuria
Extracranial Bleed / No / 719.1x / Hemarthrosis
Extracranial Bleed / No / 772.4 / Gastrointestinal hemorrhage of fetus or newborn
Extracranial Bleed / No / 784.7 / Epistaxis
Extracranial Bleed / No / 784.8 / Hemorrhage from throat
Extracranial Bleed / No / 786.3x / Hemoptysis
Extracranial Bleed / No / 864.01 / Injury to liver without mention of open wound into cavity, hematoma and contusion
Extracranial Bleed / No / 865.01 / Injury to spleen without mention of open wound into cavity, hematoma without rupture of capsule
Extracranial Bleed / No / 866.01 / Injury to kidney without mention of open wound into cavity, hematoma without rupture of capsule
Extracranial Bleed / No / 997.02 / Iatrogenic cerebrovascular infarction or hemorrhage
Extracranial Bleed / No / 998.11 / Hemorrhage complicating a procedure

Table S2.Other demographic and clinical characteristics among NVAF patients before and after propensity score matching

Characteristics / Pre-matching / Post-matching
Dabigatran
(n = 20,348) / Warfarin
(n =43,514) / Dabigatran
(n = 18,980) / Warfarin
(n =18,980)
Age group (years), n (%)
18-34 / 103 (0.5) / 160 (0.4)* / 95 (0.5) / 101 (0.5)
35-44 / 423 (2.1) / 573 (1.3)** / 379 (2.0) / 374 (2.0)
45-54 / 2,151 (10.6) / 2,879 (6.6)** / 1,938 (10.2) / 1,886 (9.9)
55-64 / 6,405 (31.5) / 9,463 (21.8)** / 5,846 (30.8) / 5,722 (30.2)
65-74 / 4,868 (23.9) / 10,024 (23.0)* / 4,569 (24.1) / 4,637 (24.4)
75-84 / 4,848 (23.8) / 13,860 (31.9)** / 4,656 (24.5) / 4,718 (24.9)
≥85 / 1,550 (7.6) / 6,555 (15.1)** / 1,497 (7.9) / 1,542 (8.1)
Health plan type, n (%)
Comprehensive/Indemnity / 5,794 (28.5) / 14,345 (33.0)** / 5,491 (28.9) / 5,581 (29.4)
EPO/PPO / 9,996 (49.1) / 18,405 (42.3)** / 9,211 (48.5) / 9,220 (48.6)
POS with and without capitation / 1,190 (5.9) / 1,997 (4.6)** / 1,091 (5.8) / 1,064 (5.6)
HMO / 1,921 (9.4) / 6,501 (14.9)** / 1,841 (9.7) / 1,802 (9.5)
CDHP/HDHP/Other/Unknown / 1,447 (7.1) / 2,266 (5.2)** / 1,337 (7.1) / 1,322 (6.9)
Measures of overall health status
Number of unique medications, mean (SD) / 9.2 (6.0) / 9.9 (6.4)** / 9.3 (6.0) / 9.3 (6.1)
Number of hospitalizations, mean (SD) / 0.6 (0.7) / 0.9 (0.9)** / 0.6 (0.7) / 0.6 (0.7)
Number of physician visits, mean (SD) / 8.6 (6.5) / 9.3 (7.7)** / 8.6 (6.6) / 8.7 (7.4)
Presence of hip fracture, n (%) / 103 (0.5) / 778 (1.8)** / 101 (0.5) / 117 (0.6)
Use of other medications, n (%)
Beta blockers / 11,620 (57.1) / 24,177 (55.6)** / 10,782 (56.8) / 10,764 (56.7)
Antihyperlipidemics / 11,174 (54.9) / 23,741 (54.6) / 10,422 (54.9) / 10,473 (55.2)
Diuretics / 8,700 (42.8) / 20,941 (48.1)** / 8,191 (43.2) / 8,177 (43.1)
Corticosteroids / 7,730 (38.0) / 17,232 (39.6)** / 7,187 (37.9) / 7,243 (38.2)
Other antihypertensives / 7,378 (36.3) / 16,149 (37.1)* / 6,891 (36.3) / 6,952 (36.6)
Calcium channel blockers / 6,264 (30.8) / 14,198 (32.6)** / 5,850 (30.8) / 5,945 (31.3)
Antidiabetics / 4,332 (21.3) / 10,589 (24.3)** / 4,095 (21.6) / 4,063 (21.4)
Antiarrhythmics / 3,607 (17.7) / 5,413 (12.4)** / 3,224 (17.0) / 3,193 (16.8)
Antiplatelets / 2,518 (12.4) / 5,836 (13.4)** / 2,354 (12.4) / 2,338 (12.3)
Ketoconazole / 377 (1.9) / 827 (1.9) / 357 (1.9) / 383 (2.0)

*p<0.05 & **p<0.001 dabigatran versus warfarin cohorts

CDHP consumer driven health plan, EPOexclusive provider organization, HDHP high deductible health plan,HMO health maintenance organization,

NVAF non-valvularatrial fibrillation, POS point of service plan,PPO preferred provider organization,SD standard deviation

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Fig. S1 Unadjusted average PPPM all-cause healthcare expenditures among NVAF patientsa,b

aTotal outpatient costs included: emergency room visits, outpatient office visits and other outpatient visit costs

bTotal all-cause expenditures included: inpatient, total outpatient, and outpatient pharmacy costs

***p<0.001 dabigatran versus warfarin cohorts

PPPM per patient per month

Fig. S2 Unadjusted average PPPM stroke-specific healthcare expenditures among NVAF patientsa,b

aTotal outpatient costs included: emergency room visits, outpatient office visits and other outpatient visit costs

bTotal stroke-specific expenditures included: inpatient and total outpatient

*p<0.05 dabigatran versus warfarin cohorts

***p<0.001 dabigatran versus warfarin cohorts

PPPM per patient per month

Fig. S3 Unadjusted average PPPM bleed-specific healthcare expenditures among NVAF patientsa,b

aTotal outpatient costs included: emergency room visits, outpatient office visits and other outpatient visit costs

bTotal bleed-specific expenditures included: inpatient and total outpatient

**p<0.01 dabigatran versus warfarin cohorts

***p<0.001 dabigatran versus warfarin cohorts

PPPM per patient per month

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