Low-dose warfarin in high-risk pregnant patients with mechanical valves: A randomized clinical trial

Abstract

Low-dose Warfarin (LDW) throughout pregnancy was suggested to provide safe and effective anticoagulation in pregnant patients with mechanical heart valve prosthesis (MHVP). We aimed to study its rate of failure in achieving target INR of those patients. Methods: Group A: 100 pregnant patients with mitral (+aortic; 24%) MHVP were randomized in a 3:1 ratio, to either receive LDW (<5 mg/day) or phenindione (<100 mg/day) throughout pregnancy; respectively. Group B: 100 females in the child-bearing period with mitral (+aortic; 19%) MHVP were randomized similarly and followed same dosage limits. Both groups targeted an INR of 2.5–3.5. Patients failing to reach this target were shifted to the other oral anticoagulant (OA). Aspirin (100 mg/day) was supplemented on the 2nd trimester / 4th follow-up month (Group B). Results: Primary outcome: 20 patients in Group A (26.7%; 16.7–36.7%; P = 0.003) and 4 patients in Group B (5.3%; 0.23–10.37%; P = 0.5) failed to achieve target INR; all being on LDW. Secondary outcomes: Group A received larger doses of either OA (P < 0.0001) achieved lower INR values (P < 0.0001) and had higher failure rates, compared to Group B (relative risk: 5; 1.8–13.9); (P = 0.001). We had no patient mortality or fetal embryopathy but 9 spontaneous abortions and 2 stillbirths related to insignificantly higher OA doses and lower INR achieved (P = 0.039). Conclusions: LDW may be insufficient to reach INR target, especially in high-risk pregnant patients with MHVP. Phenindione can offer an effective and probably safe alternative. NCT01758640.