Safety And Efficacy of Low Dose Oral Anticoagulants And Aspirin Therapy Throughout Pregnancy In Patients With Mechanical Heart Valves Prosthesis

The patients were chosen from a main population of 3000 females in the child bearing period (18-40 years), with a bileaflet mechanical mitral (+ aortic) valve prosthesis, on regular follow-up at the outpatient clinic of Ain Shams University Hospitals. Patients were primarily screened for their wiliness to participate in the study by expressing their clear wish to become pregnant (Subpopulation A: 310 patients) or otherwise making a clear decision of not becoming pregnant by following a regular contraceptive measure (Subpopulation B: 660 patients).

Study groups A (pregnant) and B (non-pregnant) were then created by assessing the respective subpopulations for the following eligibility criteria (a) regular menstrual cycles and no history of congenital malformation, repeated abortions or still birth; (b) patient in NYHA class I or II c) regular INR records for the last 3 months, with the target INR being achieved with warfarin not exceeding 10 mg/day; d) patient accepting to participate in the study and; (d) getting pregnant for Group A patients, of course Patients were excluded from either groups if they refuse to participate in the study or to sign the informed consent. Pregnant patients were excluded from Group A if reporting their missed menstrual period or positive pregnancy test later than the 6th week of gestation. Patients were excluded from Group B whenever they get pregnant, of course.

A total of 100 patients were intended to be recruited in each group. Out of the 104 patients who met the inclusion criteria of Group A, 4 cases were excluded for reporting pregnancy late at the 9th and 12th week (2 cases; 1.9%) and for refusing to sign the informed consent (2 cases; 1.9%). Out of the 135 patients who met the inclusion criteria of Group B, as much as 35 patients (25.9%) were excluded for refusing to participate in the study.

Randomization and treatment allocation:

In order to become a formal Group A member, patients in subpopulation A were followed up until conception, with clear instructions to report after 3 days of missing a menstrual period and to confirm pregnancy by repeatedly performing pregnancy test every 3 days or until menstruating. Legible patients of both groups had to sign the informed consent before being randomized. We have used a simple 8 elements randomization table, with 6 elements being assigned to warfarin and 2 elements being assigned to phenindione, to create 2 separate randomization lists. Each list was used to randomize the recruited 100 patients of each group to either: low dose warfarin (<5 mg/day) or phenindione (<100 mg/day), in a 3:1 ratio; respectively. In patients assigned to the latter, phenindione replaced warfarin with a starting dose of 50 mg/day (25 mg /day in patients weighing <40 kg.), INR was repeated after 4 days and the dose was adjusted accordingly. All patients targeted an INR between 2.5 and 3.5.