Cardiovascular disease (CVD) associated mortality is steadily on the rise and comprised of almost one-third of all deaths globally in 2019(1). According to WHO, in Pakistan, 46 people die of cardiovascular causes every hour (2). Cardiovascular diseases are defined as any disease that affects the structure and function of the heart, which includes ischemic heart disease, valvular heart disease, rheumatic heart disease, arrhythmias, and stroke (3). Among valvular heart diseases, mitral valve is the most effective valve followed by the aortic valve. The mitral valve is located between the left heart chambers (4). There are various diseases that affect the functioning of the mitral valve. Mitral valve prolapse which is the bulging back of valve leaflets into the left atrium ultimately leading to a condition called mitral valve regurgitation which is the leaking back of blood to the left atrium because of the inability of valve leaflets to close tightly(5). Another condition requiring MVR is mitral valve stenosis in which the leaflets become thick and may fuse together resulting in a narrowed valve and reduced blood flow(6),(7). Treatment of which depends on the severity of the condition. Several surgical procedures exist to repair or replace the valves, including open-heart surgery or minimally invasive heart surgery(8). Post-op treatment of mitral valve repair mainly involves the use of lifelong oral anticoagulants(9). The most widely used OAC is warfarin, but like all other drugs, warfarin requires its regulation and if consumed unregulated it causes complications(10). There are multiple factors that affect the metabolism of warfarin. Besides warfarin’s own drug interactions and side effects, patient’s knowledge about its functioning and monitoring also holds great importance. A study conducted at Kathmandu hospital on the Evaluation of patients’ knowledge on warfarin concluded that the knowledge was poor, and regular assessment of knowledge as well as their understanding should be done(11). Another study conducted at the University of Sydney, Australia, on warfarin-related knowledge in specifically older patients concluded that 80% of older patients had inadequate knowledge about the basic aspects of warfarin therapy and required education on different aspects of warfarin therapy. Besides knowledge, the proper monitoring of warfarin’s functioning is also important(12). Current American and European clinical guidelines recommend a higher international normalized ratio (INR) for anticoagulant therapy after mechanical MVR. A target INR range of 2.5–3.5 is the current recommendation in patients who have undergone mechanical mitral valve replacement(13). Warfarin is a lifesaving drug in these patients but if INR is not monitored properly or if doses are changed without proper checks it might lead to severe complications(14). A study conducted in Botswana, Africa, on Incidence of thromboembolism and bleeding in patients with mechanical heart valves concluded that a long duration of warfarin use was associated with an increased risk of both bleeding and thromboembolic complications, therefore requiring the doctors to properly make patients understand its complications and maintenance(15). The current study, therefore, aims to evaluate the patient’s knowledge of warfarin, its mechanism of action, side effects, interactions, and monitoring. This study also aims to assess the average number of years lived per patient post MVR.

The prospective descriptive cross-sectional study was conducted at tertiary care hospital. Data was collected from patients who had undergone MVR between July 2017 to October 2020 in the Cardiothoracic surgery department of our hospital. 164 patients underwent mitral valve replacement at our center, of which records and contact details of 110 patient were present. However, 18 patients were found to have died at the time of data collection, therefore a total of 92 patients participated in our questionnaire. Data base was searched for all patients who underwent isolated mitral valve replacement surgery. A total of 110 patients were traced and telephoned. Over the phone call, the interviewer filled a pre-designed questionnaire, comprising of variables; demographic data, regular check-ups, warfarin use, complications, dietary and drug complications, from the patient which was then used to evaluate the patient’s knowledge on warfarin, its monitoring, interactions, and complications of warfarin. The inclusion criteria include patients aged 18 years and older, who underwent mitral mechanical valve replacement surgery at least 6 months prior to data collection, currently on Warfarin therapy, patients who consented for the study. The exclusion criteria include patients who had bio-prosthesis valve replacement. Patients with contraindications to Warfarin therapy. Sampling technique: Purposive sampling Study design: Descriptive cross-sectional study

Table 1 shows demographic data according to which there were 61 males (55.45%) and 49 females (44.5%). The maximum number of patients belongs to the 41-50 age groups whereas the minimum number of age group was recorded as 71+. The patients were divided geographically with 78 (70.9%) from Pakistan and 32 (29%) from Afghanistan

Table 1: Demographics of MVR patients

 Table 2 Shows post-MVR survival rate with a maximum of 92 (83.6%) alive and 18 (16%) expiries. Among the patients who expired, 5 (27.7%) survived less than 6 months. 7 (38.8%) survived 6-12 months and 6 (33.3%) survived more than 12 months.

Table 2: Post MVR Survival rate

Table 3 shows comorbidities in which 47(51%) people were hypertensive, 21(22.8%) were diabetic, 8 (8.6%) had a stroke, 12 (13.0%) people had atrial fibrillation. About post-warfarin induction complication 23 (25%) people had bleeding per nose, 17 (18.4%) had bruises, 16 (17.3%) had increased menstrual flow and 36 people had no complaints.

Table 3: Comorbidities

Table 4 shows knowledge, attitude, practice about warfarin and INR. 83 (90%) knew about the function of warfarin while 9(10%) didn’t know about the function of warfarin. 56 (60%) patients knew about the effectiveness of warfarin (INR) while 36 (40%) didn’t know about the function of warfarin. 65 (70%) got their INR tested regularly while 27(30%) didn’t get their INR tested regularly. 24(21%) knew about the diet and drug interaction of warfarin while 68 (61%) didn’t know about diet and drug interaction of warfarin.

Table 4: Knowledge, attitude, practice about warfarin, INR

Table 5 shows a comparison between people who changed their dose of warfarin themselves or without a prescription versus warfarin-induced complications

Table 5: Crosstab between un-prescribed warfarin dose Vs nasal bleed, bruises, increased menstrual flow

The American Heart Association guidelines currently advise lifelong anticoagulation to maintain a target INR in patients who undergo Mitral Valve replacement with a mechanical valve (16) The recommended oral anticoagulant for these patients is Warfarin (17) Warfarin is unique in that the anticoagulant effect of the same dose of warfarin varies from patient-to-patient. This means that a “one-size-fits-all” strategy does not apply. In addition, the effect of warfarin is affected a great deal by its interactions with other drugs and food items. Consequently, every patient on warfarin will require regular checks on their INR levels to ensure that the goal of anticoagulation is achieved. In the developing world, access to warfarin clinics is scarce and therefore a spectrum of complications with valve thrombosis on one end and bleeding coagulopathies on the other end are frequently seen. This has led to a growing number of surgeons who prefer using a bio prosthetic valve instead of a mechanical valve despite the added risk of a re-do procedure, just to avoid the complications associated with warfarin therapy (18) Our study delved into this misconception.

We had a long-term mortality rate of 16%. This is higher than most estimates of mortality in other studies (19) The definite cause of mortality in these patients was beyond the scope of this article. Whether the mortality was due to cardiovascular disease or otherwise was not established. It must, however, be stated that a number of patients that present to our cardiac surgery department are in the advanced stages of their pathologies with frequent occurrences of giant Left Atrium, enlarged left ventricular volumes, impaired left ventricular functions, and severe pulmonary hypertension. Therefore, it is deduced that the incidence of heart failure in these patients will also be high. Effective management of heart failure is paramount for the survival of these patients, and patients who are lost to follow-up are at high risk of succumbing to the drastic consequences of heart failure.

Amongst our study group, we found that an overwhelming majority of patients, contrary to popular belief, understood the need for warfarin with 90% of the patients being able to identify Warfarin and its role in preventing complications associated with a mechanical valve. All patients admitted to our center are counseled prior to surgery and discharge about warfarin, its side effects, the need and mechanism of monitoring. Despite that, it was seen that only 60% of the patients knew what test is performed to check the effectiveness of warfarin (i.e., PT/INR). Nevertheless, 70% of patients were getting their INR levels checked regularly. It can be concluded from this that in terms of compliance with doctors’ instructions, a majority of the patients were following the advice of the primary physician. These findings are comparable to those from the developed world. A study done in China published a 94% adherence rate to warfarin (20). Another study done showed very poor knowledge about warfarin and the test used to test its efficacy. In the study, it was found that 68% of the patients did not have sufficient knowledge of warfarin (21) It must be stated that in the mentioned study the warfarin questionnaire was more complex compared to ours and this might be the reason for the varied result. Nevertheless, this is still encouraging for surgeons who wish to continue to use mechanical prosthetic valves in patients who do not fulfill the criteria for a bioprosthetic valve. If we continue to educate our patients, we can achieve good long-term outcomes with warfarin use.

In those patients who survived, it was found, as expected, that 56 patients (62%) developed some bleeding complication since their surgery. The most common bleeding complication encountered was epistaxis. A study done in Nepal also supports epistaxis being the most common bleeding complication (16.8%) whereas other common complications include hemoptysis (15.3) and menorrhagia in females (15.3%) (22)

The most troubling part of prescribing warfarin and maintaining a therapeutic INR is to be able to understand its interactions with various foods and drugs, information about which is still poorly understood by doctors let alone the patients. Our study participants proved this point, with only 21% of the patients having knowledge of its interactions with drugs and food items. A Chinese study done to see if the knowledge of warfarin correlated with good anticoagulation control also pointed out that patients did not fully grasp the interactions that warfarin had with diet and other drugs (20) Similarly, a study conducted in the US distributed questionnaires amongst patients on warfarin therapy found that only 56% of the patients had unaware knowledge about the interactions of warfarin with drugs and food items (23).

After going through the results of our study we concluded that prescribing warfarin therapy must always be followed by frequent counseling of the patient and caregivers so as to repeatedly ingrain the importance of maintaining a therapeutic INR. However, further work must be done to find out the exact incidence of thromboembolism and bleeding that is associated with the warfarin use so as to confirm whether or not the risk of warfarin associated complications is higher in our population compared to the developed world

Limitations

It was a single-center study therefore generalization of the findings may be done with caution. The sample size was small. Many patients were lost to follow-up. The exact cause of mortality in patients could not be establisheded