Table 3.
Human Studies on Association of Warfarin Use With Calcification
| Study No. | Author | Type of Study | No. of Patients | Modality Used to Assess Calcification | Characteristic of Patients | Follow‐Up | Results |
|---|---|---|---|---|---|---|---|
| 1 | Yamamoto et al20 (2010) | Retrospective observational study | 556 | Echocardiogram | Age >50 years, calcification in any aortic valve leaflet or peak aortic jet velocity >2 ms−1 | Mean follow‐up: 2.8 years | Warfarin use was also associated with early‐stage CAVD progression (P = 0.03). |
| 2 | Villines et al15 (2009) | Cross‐sectional analysis | 70 | Electron beam CT | Patients with mean age 68 ± 13 y on warfarin | 3 groups of warfarin use duration: <6 m (n = 31), 6–24 m (n = 11), >24 m (n = 28) | Bivariate analysis revealed no correlation between warfarin duration and CAC score. |
| 3 | Lerner RG et al21 (2009) | Cross‐sectional analysis | 1155 | Echocardiogram | Nonvalvular AF: 725 (63%) patients and 430 (37%) controls | Unspecified | Valvular calcification present in 473 of 725 patients (65%) vs 225 of 430 controls (52%) (P<0.0001). Significant association between warfarin use and risk of calcification (OR: 1.71, 95% CI: 1.34–2.18). |
| 4 | Koos et al18 (2009) | Cross‐sectional analysis | 226 | Echocardiogram, multislice spiral CT, circulating ucMGP levels | 191 patients with CAVD vs 35 control subjects | Unspecified | Serum ucMGP levels were significantly lower in the study group (348.6 ± 123.1 nM vs 571.6 ± 153.9 nM, p<0.001). Patients on long‐term warfarin (n = 27) demonstrated lower serum ucMGP levels compared with patients without anticoagulation (n = 142). |
| 5 | Verdalles Guzmán et al14 (2008) | Retrospective observational study | 8 | Biopsy | Female patients on hemodialysis with calciphylaxis | Unspecified | Warfarin therapy is a risk factor for developing calciphylaxis. |
| 6 | Holden et al19 (2007) | Retrospective cohort study | 108 | Echocardiogram | Hemodialysis patients | 36.7 ± 19.7 mo | 18 subjects with long‐term warfarin exposure were more likely to have severe aortic valve calcification (P = 0.04). OR: 3.77, 95% CI: 0.97–14.70, P = 0.055). |
| 7 | Koos et al17 (2005) | Cross‐sectional analysis | 86 | Multislice spiral CT | CAVD; 23 patients vs 63 controls | 88 ± 113 mo | Patients on warfarin therapy had increased coronary calcium score (1561 ± 1141 vs 738 ± 978; P = 0.024) and valvular calcium score (2410 ± 1759 vs 1070 ± 1085, respectively; P = 0.002). |
| 8 | Schori and Stungis13 (2004) | Case report | 1 | Cardiac MRI | Otherwise healthy man found to have severe CAC on warfarin for 11 y | Unspecified | Long‐term warfarin treatment may have induced arterial calcification. |
Abbreviations: AF, atrial fibrillation; CAC, coronary artery calcification; CAVD, calcific aortic valve disease; CI, confidence interval; CT, computed tomography; MGP, matrix γ‐carboxyglutamate protein; MRI, magnetic resonance imaging; OR, odds ratio; ucMGP, inactive MGP.