Vitamin K antagonists (VKA) such as phenprocoumon are the mainstay of therapy for patients with several specific indications for long-term oral anticoagulant therapy (OAT). Usage of VKAs have been linked to the development of increased cardiovascular calcification (CVC) through their interference with MatrixGla protein. 

The IRIVASC trial was a multi-center, prospective, controlled, open, randomized, interventional clinical trial (NCT02066662) and included 192 patients with atrial fibrillation or pulmonary embolism and an indication for oral anticoagulation > 12 months.Patients with an indication for OAT were randomized to receive either Rivaroxaban (n=96) or VKA (n=96) and followed over 12 months. MultiSlice CT (MSCT) was performed at baseline and after 12-month follow up. The primary endpoint of the study was the progression of coronary artery and aortic valve (AV) calcification, as determined by MSCT (volume score). 

Baseline demographic and laboratory values were comparable between the VKA and the Rivaroxaban groups.After 12-month follow-up complete data sets were available for 164 patients (86%) for coronary calcification and 67 patients for valvular calcification (per protocol analysis). 

We found no differences in the primary endpoints. Development of coronary artery calcification was similar within the 2 groups as evidenced by similar changes between the Rivaroxaban and the VKA groups of the coronary agatston score (307.3 IQR 1111.7 vs 353.6 IQR 1608.0 p=0,38), the coronary volume score (in ml) (275.4 IQR 939.3 vs 333.6 IQR 1326.8 p=0,359) and the coronary mass score (in mg) (51.8 IQR 179.2 vs. 62.5 IQR 275.3 p= 0,335) after 12 months. Similarly, there was no difference in the development of aortic valve calcification(AV Agatston score 157,4 IQR 477,8 vs. 86,2 IQR 222.1  p=0,621, AV volume score (in ml) 153,4 IQR 400,5 vs 83,3 IQR 277,3 p=0,824 and the AV Mass Score (in mg) 26,4 IQR 73 vs 15,0 IQR 39,5 p=0,626 ) (Table 1).

This is the first multicenter prospective, randomized trial to ever investigate the effects of VKA vs rivaroxaban onthe development of coronary and valvular calcification. Our findings are clinically relevant as VKA will remain the mainstay of treatment for several conditions including mechanical valve replacement or antiphospholipid syndrome and hence include patients at cardiovascular risk. Our data point towards a comparable risk of overt CVC progression as detectable by CT-scans in patients irrespective of VKA or NOAK treatment.