Trial of Different Intensities of Anticoagulation in Patients with Prosthetic Heart Valves

Abstract

We compared the efficacy and complications of anticoagulation with warfarin in 258 patients with prosthetic heart valves treated with regimens of "moderate intensity" (prothrombin-time ratio, 1.5; international normalized ratio, 2.65) or "high intensity" (prothrombin-time ratio, 2.5; international normalized ratio, 9) in a prospective, randomized study. The two patient groups were followed up for 421 patient-years and 436 patient-years, respectively. Eleven patients were lost to follow-up. Thromboembolism occurred with similar frequency in the two groups (4.0 and 3.7 episodes per 100 patient-years, respectively), but there was a total of 6.2 bleeding episodes per 100 patient-years in the moderate-intensity group, as compared with 12.1 episodes in the high-intensity group (P less than 0.002). There were 5.2 episodes of minor bleeding per 100 patient-years in the moderate-intensity group, as compared with 10.1 episodes in the high-intensity group (P less than 0.01). Major bleeding was also more common in the high-intensity group (2.1 episodes per 100 patient-years--including the only two fatal hemorrhages--as compared with 0.95 episode in the moderate-intensity group), but the difference was not statistically significant. We conclude that a moderate anticoagulant effect (prothrombin-time ratio, about 1.5) in patients with a mechanical prosthetic heart valve offers protection equivalent to that of more intensive therapy, but at a significantly lower risk.

Achieved Anticoagulation vs Prosthesis Selection for Mitral Mechanical Valve Replacement

“…While anticoagulation is indispensable with mechanical MVR, the lack of association between TE rates and achieved anticoagulation reemphasizes the fact that aiming for higher INR goals to better prevent TEs is not appropriate. 16 Our results extend observations about aortic replacement, 10 that low-intensity anticoagulation is as effective as high-intensity anticoagulation in preventing TEs and should lead to recommending active but low-intensity anticoagulation after MVR. 2,13,22,23 Lower INRs may decrease bleeding, 10,16,17,19,34 while unstable anticoagulation predicts valve-related events.…”

“…16 Our results extend observations about aortic replacement, 10 that low-intensity anticoagulation is as effective as high-intensity anticoagulation in preventing TEs and should lead to recommending active but low-intensity anticoagulation after MVR. 2,13,22,23 Lower INRs may decrease bleeding, 10,16,17,19,34 while unstable anticoagulation predicts valve-related events. 33,35,36 In the present study, INR variability (ie, INR SD) tended to univariately predict TE risk and independently predict bleeding.…”

“…Furthermore, higher intensity anticoagulation never reduced TEs, complicating the use of mechanical prostheses. 10,16,17 The occurrence of excess TEs, particularly stroke, with use of a ball valve in MVR concurs with the results of small single-center studies 12,44 and is quite considerable (8.5 vs 3.1 per 100 patient-year, respectively; p Ͻ 0.0001), leading to excess MVRrelated events. An MVR ball prosthesis, the first successful prosthetic valve, 45 was a life saver in its time and has economic advantages for developing countries, 46 but it carries with it an unacceptable TE rate and should be retired from use worldwide.…”

“…The influence of anticoagulation on TE risk has been debated. Although intermittent or inadequate anticoagulation leads to a high TE risk, 7,15,16,21 randomized studies 3,10,21 have not observed lower TE rates with higher INR goals. However, clinical trials often enroll low-risk patients, which is not reflective of community practice, emphasizing the importance of our population-based study.…”

Role Of Acenocoumarol In Prosthetic Heart Valves

“…8 Addition of aspirin and dipyridamol results in reduction of anticoagulation therapy, thereby decreasing the incidence of thromboembolic and bleeding complications. 9 The oral anticoagulation should be started as early as possible, and not after 10 days as reported by others 10 . Normally, the INR should be titrated between 2.5 to 3.5, but should not be kept more than 3.5 in patients with prosthesis in mitral position and more than 3.0 in patients with prosthesis in aortic position.…”