Background: Warfarin blocks the synthesis and activity of matrix Gla protein (MGP), a vitamin K-dependent inhibitor of arterial calcification. The impact of warfarin on coronary arterial calcification in vivo is unknown. This study compared serial changes in coronary percent atheroma volume (PAV) and calcium index (CaI) in patients treated with and without warfarin.
Hypothesis: Serial changes in coronary CaI are greater in warfarin-treated patients compared with those not on warfarin, independent of changes in PAV
Methods: In a patient-level analysis of 8 prospective randomized trials using serial coronary intravascular ultrasound, we compared changes in PAV and CaI in matched arterial segments in patients with coronary artery disease treated with (n=171) and without (n=4129) warfarin during an 18-24-month period.
Results: Patients (age 57.9±9.2 yrs; male 73%; prior and concomitant statin use: 73 and 97% respectively) demonstrated an overall increase in PAV by 0.18±0.06% (p=0.003 compared with baseline) and CaI [median (IQR)] by 0.04 (0.00, 0.11) (p <0.001 compared with baseline). Following propensity-weighted adjustment for clinical trial, clinical characteristics and laboratory parameters, there was no difference in annualized ΔPAV in the presence and absence of warfarin treatment (0.08±0.05 vs. 0.13±0.04%, p=0.41). Following adjustment for PAV, a greater annualized increase in CaI was observed in warfarin treated patients [median (IQR) 0.03 (0.0-0.08) vs. no-warfarin: 0.02 (0.0-0.06) p<0.001)]. In a sensitivity analysis evaluating a 1:1 matched cohort (n=164 per group), significantly greater annualized changes in CaI were also observed in warfarin-treated patients. In a multivariable model, warfarin independently associated with an increasing CaI [Odds Ratio (95% confidence interval) 1.12 (1.01, 1.24), p=0.027].
Conclusion: Warfarin therapy associates with progressive coronary atheroma calcification, independent of changes in atheroma volume. The impact of these changes on plaque stability and cardiovascular outcomes require further investigation.