Out-of-range international normalized ratio values and healthcare cost among new warfarin patients with non-valvular atrial fibrillation

Figures & data

Figure 1. Patient selection. AF, atrial fibrillation; INR, international normalized ratio; VHA, Veterans Health Administration.

Table 1. Baseline demographic and clinical characteristics for warfarin patients with NVAF (patients contribute to three cost groups).

	Warfarin patients with NVAF (n = 29,463)
	n/Mean	%/SD
Age
Age (mean)	70.77	10.09
Age 18–64	9553	32.42%
Age 65–74	8381	28.45%
Age 75+	11,529	39.13%
Gender
Male	28,988	98.39%
Female	475	1.61%
US geographic region
Northeast	4255	14.44%
Midwest	7378	25.04%
South	10,255	34.81%
West	6049	20.53%
Other region	1526	5.18%
Race
Black	2238	7.60%
Hispanic	957	3.25%
White	20,556	69.77%
Other race	5712	19.39%
Baseline comorbid conditions
Indices
Charlson comorbidity index score	1.93	1.98
Chronic disease score	7.66	4.43
CHADS2 score
Low (0)	3080	10.45%
Moderate (1)	7928	26.91%
High (>1)	18,455	62.64%
CHADS2 VASc score
Low (0)	1678	5.70%
Moderate (1)	3605	12.24%
High (>1)	24,180	82.07%
Atria bleeding risk score
Low (0–3)	23,656	80.29%
Moderate (4)	2099	7.12%
High (5–10)	3708	12.59%
Comorbidities
Congestive heart failure	5762	19.56%
Diabetes mellitus	11,758	39.91%
Hypertension	22,563	76.58%
Ischemic stroke	1386	4.70%
Transient ischemic attack	710	2.41%
Vascular disease	11,460	38.90%
End-stage renal disease	290	0.98%
Hospitalized hemorrhagic stroke	0	0.00%
Chronic kidney disease	3634	12.33%
Chronic obstructive pulmonary disease	1356	4.60%
Anemia	3783	12.84%
Hospitalized major bleeding	121	0.41%
Bleeding disorder	472	1.60%
Baseline medications
Use of rate control medications	19,415	65.90%
Use of rhythm control medications	2266	7.69%
Use of aspirin	8711	29.57%

NVAF, non-valvular atrial fibrillation; SD, standard deviation.

CHADS₂ score: Congestive heart failure (1 point), Hypertension (1 point), Age ≥75 years (1 point), Diabetes mellitus (1 point), prior Stroke or transient ischemic attack (2 points).

CHADS₂ VASc score27: Congestive heart failure (1 point), Hypertension (1 point), Age ≥75 years (2 points), Diabetes mellitus (1 point), prior Stroke or transient ischemic attack (2 points); Vascular disease (1 point), Age 65–74 years (1 point), female category (1 point).

Atria bleeding risk score: anemia = hemoglobin <13 g/dL (male), <12 g/dL (female) (3 points); severe renal disease = glomerular filtration rate <30 mL/min or dialysis-dependent (3 points); age ≥75 (2 points); any prior hemorrhage diagnosis (1 point); hypertension history (1 point).

Figure 2. Follow-up healthcare costs associated with out-of-range INR, within a 30-day period. Costs and utilization within a 30-day period were assessed starting from Month 2 (31 days post index date) through the end of the study period. In-range INR (2–3): randomly selected INR test occurrence (INR 2–3 result occurred at least 30 days apart and no other INR range type [<2 or >3] occurred within 30 days). Out-of-range INR (<2 or >3): randomly selected INR test occurrence (INR tests occurred at least 30 days apart; different range types occurring within 30 days were allowed). INR, international normalized ratio. *p-Values are based on multiple regression using a generalized linear model.

Figure 3. Follow-up healthcare resource use within a 30-day period, for the first 2–6 months and after 6 months of warfarin exposure. Patients with INR 2–3: randomly selected INR test for the 30-day period were collected from the second month through the end of warfarin exposure. Patients with INR <2 or >3: randomly selected INR test occurrence during the first 2–6 months and after 6 months of warfarin treatment. INR, international normalized ratio. *p-Values are based on multiple regression using a generalized linear model.

Codes used to identify warfarin initiator and comorbidities.

Diseases/condition	Codes (ICD-9 or CPT)
Transient perioperative AF diseases	36.10–36.19, 37.10–37.12, 37.31–37.33 or 37.40, 35.00–35.04, 35.31–35.39, 35.41–35.42, 35.50–35.56, 35.60–35.63 or 35.70–35.73
Mitral or aortic valve repair or replacement	394.0, 394.2, 396.0, 396.1, 396.8, V43.3, V42.2, 35.10, 35.14, 35.20, 35.28
Hyperthyroidism	242.0–242.9
Pregnancy	630–648
Cesarean delivery	74.xx
Vaginal delivery	72.xx, 73.xx, 75.xx, v27, 650–659
Congestive heart failure	428.xx
Diabetes mellitus	250.xx, 249.xx
Hypertension	401.xx, 405.xx
Ischemic stroke	433.xx, 434.01, 434.11, 434.91, and 437.1
Transient ischemic attack	435.xx
Vascular disease	410.xx, 411.1x, 411.8x, 414.xx, 443.9
End-stage renal disease	ICD-9-CM procedure: V42.0, V56.0, V56.8, 39.95, 54.98, and 55.69 CPT: 90921, 90925, 90935–90947, 99512, 99559, 50360, 50365
Hospitalized hemorrhagic stroke	430.xx, 431.xx and 432.xx, 852.xx, 853.xx, 854.xx accompanied by 438.xx during the same hospitalization
Chronic kidney disease	403.xx, 404.xx, 585.xx, 586.xx, 588.xx
Chronic obstructive pulmonary disease	491.2x, 492.xx, 518.1, 518.2
Anemia	280.xx, 281.xx, 282.xx, 283.xx, 284.xx, 285.xx

Lip GY, Nieuwlaat R, Pisters R, et al. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest 2010;137:263-72

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