الفهرس 
Review of LiteratureOnly 14 pages are availabe for public view
 |  | from | 146 |  |  |
| | | from | 146 | | |
Abstract
It has been estimated that 300,000 prosthetic heart valve replacements are performed each year worldwide (Sun et al., 2009). Mechanical heart valves are more durable than bio-prostheses but more thrombogenic. Hence, postoperative warfarin anticoagulation is recommended for all patients receiving mechanical aortic or mitral heart valve replacement (Whitlock et al., 2012),. Mechanical heart valves necessitate lifetime anticoagulation, with an international normalized ratio (INR) target range of 2.0 to 3.0 for aortic valves, and 2.5 to 3.5 for mitral valves. Warfarin starting doses between 5 and 10 mg per day given on the first 1 or 2 days of warfarin treatment were consistently accepted in earlier medical practice and were recommended by the American College of Chest Physicians (ACCP) to be applied for individuals who need long-term anticoagulation with consequent dose adjustment based on the INR findings (Ansell et al., 2008). The exaggerated sensitivity of warfarin after heart valve surgery is well recognized (Rose et al., 1998, Ageno and Turpie, 1999, Rahman et al., 2006). Many factors contribute to this postoperative sensitivity including; patient’s age, gender, body weight, concomitant medications like amiodarone and cefazoline, baseline INR, and serum albumin level (Mohammadi and Kargar, 2018). Owing to lack of evidence in this field, currently available guidelines offer no clear recommendation concerning warfarin initiation after heart valve surgery (Ageno et al., 2012, Vahanian et al., 2012b, Nishimura et al., 2014a, Baumgartner et al., 2018, Otto et al., 2021).
The previous warfarin commencement protocols were addressed for use in populations other than MVR (Heneghan et al., 2010, Mahtani et al., 2012). This has hindered the use of the established warfarin initiation protocols, mostly with a 5 mg dose in the clinical practice after heart valve surgery. Consequently, warfarin initiation in this group has reverted sometimes to empirical dosing depending on clinical judgment, with the commencement of a 3 mg dose targeting a more conservative initiation and transition to a stable INR.
The current study aimed to compare the efficacy and safety of warfarin initiation at two dose levels (3 versus 5 mg) for early postoperative anticoagulation of MVR patients, in terms of reaching optimum anticoagulation and occurrence of bleeding/thromboembolic events. Also calculating the enoxaparin cost used as the bridging agent during the study period.
This study was a single-blinded randomized controlled clinical trial. The study was conducted on 50 patients with mechanical mitral valve replacement patients on warfarin. Eligible patients were randomly assigned to either:
The 5 mg Group: received 5mg warfarin (Marevan ®) tablets initiation warfarin dose in the combination with enoxaparin (Clexane®) as a bridging agent
The 3 mg Group: Twenty-five patients received 3mg warfarin (Marevan ®) tablets initiation warfarin dose in the combination of enoxaparin (Clexane®) as a bridging agent
Patients’ demographic information including age, gender, body weight and height, smoking status as well as clinical data comprising co-morbid diseases, medication history, family history, and allergy were all collected from the patient daily notes using a predesigned follow-up sheet. Their comorbidities were identified where they included hypertension, diabetes, hyperlipidemia, hypothyroidism, atrial fibrillation, and rheumatic disease.
The study patients were initiated on warfarin for postoperative anticoagulation combined with enoxaparin as a bridging agent. INR was monitored daily, and dose adjustments were done to reach the therapeutic INR range (2.5-3.5) at which the enoxaparin was discontinued. Follow-up was continued daily till reaching the therapeutic INR range for at least two successive readings. All patients’ co-administered medications during the follow-up period were recorded. All patients were followed up for a minimum of 4 consecutive days.
Warfarin dose adjustments and enoxaparin injection doses were determined using the anticoagulation toolkit produced by the Michigan Anticoagulation Quality Improvement Initiative (MAQI2) (Barnes and Kline-Rogers, 2015).
Bleeding events due to over anticoagulation, as well as thromboembolic events, were monitored through the follow-up period.
All of the following were recorded for all patients in both groups:
• Daily INR value
• Time to reach INR value of 2.5
• Total enoxaparin dose administered
• Occurrence of bleeding episodes (major or minor)
• Occurrence of thromboembolic complications
• Warfarin dose adjustments
The primary outcome measure, at the end of the study, was Time to Reach Therapeutic INR (TRT). This is defined as the time in days required to reach the lower limit (2.5) of the target INR range.
The secondary outcome measures included:
• Percentage of patients who reached target INR range within 3-5 days
• Minor and major bleeding occurrence
• Thromboembolic events occurrence
• Total dose of the bridging agent given (therapeutic dose of enoxaparin)
• Cost of the bridging agent given (overall cost of enoxaparin)
• Number of in-range and INR readings above 4
The current study showed that:
• At baseline, both groups were comparable in their baseline characteristics and demographic data, except for age which was statistically higher in the 3 mg group versus the 5 mg group. However, all statistical analyses were adjusted for age.
• After the follow-up period, the 5 mg group achieved a therapeutic INR more rapidly than the 3 mg group.
• Percentage of patients who reached the target INR range within 3-5 days, was not significantly different between the two study groups.
• The percentages of patients who experienced any type of bleeding events as well as the total number of bleeding events in each group were not significantly different between the groups. But patients in the 5 mg group had a higher number of INR readings above 4 which is indicative of over-anticoagulation.
• The cost of enoxaparin consumption per patient was significantly lower in the 5 mg group compared to the 3 mg group
Finally, the present study showed that the efficacy of anticoagulation management using the 5 mg warfarin initiation in Egyptian MVR patients appeared to be more favorable than that of the 3 mg. This was determined by the time required to achieve the target INR. The number of bleeding events was comparable between the groups. The cost of bridging was higher in the 3 mg group patients.