Thirty-five studies (23,145 participants) were included in the review.
Aortic valves.
There were less valve thrombosis events in the high-intensity VKA group than in the low-intensity group: 0.87 versus 1.16 per 1,000 patient-years (RR 0.75, 95% CI: 0.50, 1.13, P=0.126). There were less thromboembolisms in the high-intensity group than in the low-intensity group: 9.83 versus 13.09 per 1,000 patient-years (RR 0.75, 95% CI: 0.70, 0.81, P<0.0001). The total number of thromboembolic events was less in the high-intensity group than in the low-intensity group: 10.01 versus 13.69 per 1,000 patient-years (RR 0.73, 95% CI: 0.68, 0.78, P<0.0001). There was an increase in bleeding events in the high-intensity group compared with the low-intensity group: 14.89 versus 12.06 per 1,000 patient-years (RR=1.23, 95% CI: 1.16, 1.31, P<0.0001).
When all embolic and haemorrhagic events were combined, there was a reduction in the total number of all events in the high-intensity group compared with the low-intensity group: 23.84 versus 25.39 per 1,000 patient-years (RR 0.94, 95% CI: 0.88, 0.99, P=0.0067).
Mitral valves.
Patients in the high-intensity VKA group had a lower risk of valve thrombosis and thromboembolism than those in the low-intensity group: 2.06 versus 3.44 per 1,000 patient-years for valve thrombosis (RR 0.60, 95% CI: 0.47, 0.76 P<0.0001), and 15.91 versus 20.12 per 1,000 patient-years for thromboembolism (RR 0.79, 95% CI: 0.74, 0.84, P<0.0001). Bleeding events did not differ significantly between high- and low-intensity VKA: 12.94 versus 11.96 per 1,000 patient-years (RR 1.08, 95% CI: 1.00, 1.116, P=0.0524). The total number of events was 29.76 per 1,000 patient-years in the high-intensity group and 35.33 per 1,000 patient-years in the low-intensity group (RR 0.84, 95% CI: 0.79, 0.89, P<0.001).
Comparison between mitral and aortic prostheses.
The number of valve thrombosis and thromboembolic events was significantly lower in the aortic valve group than in the mitral valve group for both high- and low-intensity VKA. For high-intensity VKA, patients with aortic prostheses were more likely to haemorrhage than those with mitral prostheses (RR 1.15, 95% CI: 1.06, 1.25). However, there was no difference in bleeding complications for low-intensity VKA (RR 1.01, 95% CI: 0.94, 1.07).