Objectives This study compared serial changes in coronary percent atheroma volume (PAV) and calcium index (CaI) in patients with coronary artery disease who were treated with and without warfarin.

Background Warfarin blocks the synthesis and activity of matrix Gla protein, a vitamin K–dependent inhibitor of arterial calcification. The longitudinal impact of warfarin on serial coronary artery calcification in vivo in humans is unknown.

Methods In a post hoc patient-level analysis of 8 prospective randomized trials using serial coronary intravascular ultrasound examinations, this study compared changes in PAV and CaI in matched arterial segments in patients with coronary artery disease who were treated with (n = 171) and without (n = 4,129) warfarin during an 18- to 24-month period.

Results Patients (mean age 57.9 ± 9.2 years; male 73%; prior and concomitant 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statin) use, 73% and 97%, respectively) demonstrated overall increases in PAV of 0.41 ± 0.07% (p = 0.001 compared with baseline) and in CaI (median) of 0.04 (interquartile range [IQR]: 0.00 to 0.11; p < 0.001 compared with baseline). Following propensity-weighted adjustment for clinical trial and a range of clinical, ultrasonic, and laboratory parameters, there was no significant difference in the annualized change in PAV in the presence and absence of warfarin treatment (0.33 ± 0.05% vs. 0.25 ± 0.05%; p = 0.17). A significantly greater annualized increase in CaI was observed in warfarin-treated compared with non–warfarin-treated patients (median 0.03; IQR: 0.0 to 0.08 vs. median 0.02; IQR: 0.0 to 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 compared with non–warfarin-treated patients. In a multivariate model, warfarin was independently associated with an increasing CaI (odds ratio: 1.16; 95% confidence interval: 1.05 to 1.28; p = 0.003).

Conclusions Warfarin therapy is associated with progressive coronary atheroma calcification independent of changes in atheroma volume. The impact of these changes on plaque stability and cardiovascular outcomes requires further investigation.

目的本研究比较了接受或不接受华法林治疗的冠心病患者的冠状动脉粥样硬化体积百分比（PAV）和钙指数（CaI）的系列变化。

背景华法令可阻断基质Gla蛋白（维生素K依赖性动脉钙化抑制剂）的合成和活性。华法林对人体体内系列冠状动脉钙化的纵向影响尚不清楚。

方法在一项采用串行冠状动脉内超声检查对8项前瞻性随机试验进行的事后患者水平分析中，本研究比较了接受（n = 171）和未接受治疗的冠心病患者的匹配动脉节段PAV和CaI的变化。 （n = 4,129）华法林，疗程为18到24个月。

结果患者（平均年龄57.9±9.2岁;男性73％;先前和同时使用3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂（他汀类药物）分别为73％和97％）证明PAV总体升高0.41±0.07％ （与基线相比，p = 0.001），CaI（中位数）为0.04（四分位间距[IQR]：0.00至0.11；与基线相比，p <0.001）。经过针对临床试验的倾向加权调整以及一系列临床，超声和实验室参数，在存在和不存在华法林治疗的情况下，PAV的年度变化无显着差异（0.33±0.05％vs. 0.25±0.05％ ； p ＝ 0.17）。与未经华法林治疗的患者相比，经华法林治疗的患者的CaI的年均升高幅度更大（中位数为0.03； IQR：0.0至0.08；中位数为0.02； IQR：0.0至0.06； p <0.001）。在评估1：1匹配队列的敏感性分析中（每组n = 164），与未用华法林治疗的患者相比，用华法林治疗的患者的CaI年度变化也显着更大。在多变量模型中，华法林与CaI升高独立相关（赔率：1.16； 95％置信区间：1.05至1.28； p = 0.003）。

结论华法林治疗与进行性冠状动脉粥样硬化钙化有关，而与钙化斑的变化无关。这些变化对斑块稳定性和心血管结局的影响需要进一步研究。