Anticoagulants are commonly used in medicine in the prevention and treatment of thromboembolic diseases [1] [2] [3] and vitamin K antagonists (VKAs) were the only oral anticoagulants available for decades. However, VKAs have a narrow therapeutic index and require regular monitoring of their anticoagulant activity, which involves measuring the Prothrombin Time, expressed in international normalized ratio (INR) [4] . Since the availability of direct oral anticoagulants (DOACs), the use of VKAs is experiencing a sharp decline at the expense of the former, even if they remain the oral anticoagulants of choice in some indications such as atrial fibrillation associated with mitral stenosis or mechanical valve prosthesis [5] . Indeed, DOACs are immediately active, not necessarily requiring prior use of heparin [6] ; they do not require monitoring of their anticoagulant activity, which exempts patients from repetitive blood sampling and they do not present food interactions [7] . Furthermore, they would be safer than VKAs with regard to bleeding complications [8] [9] [10] [11] .

But in low and middle-income countries, such as Togo, it is a challenge to obtain DOACs due to their high cost compared to the standard of living of the populations and their lack of availability in pharmacies. In these countries, VKAs remain widely used.

The time in therapeutic range (TTR) estimates the percentage of time a patient’s INR is within the desired range. It evaluates the quality of VKA treatment and constitutes an important tool for evaluating the benefit-risk ratio [12] . A TTR > 70% indicates good anticoagulation [13] even if in the literature, a threshold of 65% is sometimes found [14] [15] . Several Western studies have evaluated the quality of oral anticoagulation by VKA using TTR. Anticoagulation was generally of poor quality [16] [17] [18] [19] as well as in the scares African studies on this topic [15] [20] [21] . In Togo, we did not find any data on this subject, hence the interest of the present study. The objective of the present study was to evaluate the quality of anticoagulation by VKA in Lomé, using TTR, and describe associated factors.

This study was carried out in the cardiology departments of two University teaching hospital (CHU Sylvanus Olympio and CHU Campus) in Lomé, Togo. This was a cross-sectional study with descriptive and analytical aims, carried out from November 2019 to October 2020.

In this sample of patients undergoing VKA treatment living in a low-income country of West African, we assessed the quality of anticoagulation using the TTR. Mean TTR was 47.6% ± 20.8%. The rate of good anticoagulation (TTR > 70%) was 17.7%. After multivariate logistic regression analysis, three variables were statistically associated with good anticoagulation: use of fluindione, concomitant low-dose aspirin and the monitoring of INR exclusively by the patient himself.

Quality of anticoagulation was generally poor in this study. This pattern of poor anticoagulation has also been observed in Cote d’Ivoire [20] and Tunisia [28] and in South Africa [29] where the rates of good anticoagulation defined by a TTR ≥ 65% were respectively 11%, 22% and 25.1%. These results from African studies are below those observed in Europe. Indeed, Cotté et al. observed that the proportion of patients with atrial fibrillation on VKA and having a TTR > 70% was 47.8% in France, 44.2% in Germany, 46.1% in Italy and 65.4% in the United Kingdom [19] . i.e., a rate of good anticoagulation 2 or 3 times higher than those observed in Africa. Even if these results from European studies were better than those observed in our study, it must be emphasized that anticoagulation by VKA was also of poor quality in these countries. The poor quality of oral anticoagulation by VKA in our area can be explained by the lack of therapeutic education of patients [30] . Therapeutic education can be improved by anticoagulation clinics which are services dedicated to the therapeutic education of patients as well as the collection of INRs and the adjustment of VKA dosages. Use of prescription assistance software in anticoagulation clinics has also demonstrated its effectiveness in this study [31] [32] . Based on the INR results, such software automatically suggests the VKA drug management including drug dosage and the date of next INR: they thus help to limit the risk of error on the part of the nursing staff. Other factors such as genetic variability and dietary interference may also explain the difficulty in having effective anticoagulation thresholds by VKA [20] .

INR monitoring performed exclusively by the patient himself without intervention of a companion favored good anticoagulation in this study. The intervention of companions can lead to an alteration of the messages sent by the doctor or the nurse to the patient. When presenting INR results the patient who monitors his INR can directly ask the doctor questions regarding his treatment. These discussions can be an opportunity to evaluate the patient’s level of knowledge regarding VKA treatment as well as the related measures. Such visit may be an occasion to remind him about taking medications and foods which can unbalance the INR. Monitoring of INRs by patients themselves should be encouraged whenever possible.

Patients treated with fluindione had better anticoagulation than those treated with acenocoumarol. This may be explained by the fact that fluindione has a longer half-life than acenocoumarol. Indeed, it has been reported that the longer the half-life of VKA is, the more it guarantees better stability of the INR [33] .

Concomitant use of low-dose aspirin was associated with good anticoagulation in the present study even if it also increased the risk of bleeding. This may be explained by the fact that low-dose aspirin potentiates the anticoagulant action of VKA [4] .

Mean number of medications in our patients was 3.5 ± 2. A number of medications greater than or equal to 3 was associated with poor anticoagulation in univariate analysis but this association did not persist after adjustments. Such threshold was higher in Iran where Farsad et al. [14] reported increased risk of poor anticoagulation with a number of medications ≥ 5 (OR = 2.06; 95% CI, 1.87 - 2.23). It was reported that polypharmacy can be a factor in poor anticoagulation due to interactions between VKAs and some medications [4] . It is therefore necessary to take into account the pharmacological properties of any medication before prescribing it in combination with a VKA drug since it can modify the INR [4] .

The Rosendaal method which was used to calculate the TTR has certain limitations. First, it uses interpolation which is a mathematical operation allowing a curve to be constructed from a finite number of values; for the calculation of the TTR, the interpolation is assumed to be linear, but the changes in the INR are not necessarily linear. Then, the TTR is very sensitive to the frequency of the INRs, but the delay between the different INRs carried out in this study was not uniform. Second, the TTR is indifferent to large variations in INR values: the risk of immediate hemorrhagic complications may thus be underestimated [28] .

Another limitation of this study was the impossibility of assessing complications in real time and objectively, particularly hemorrhagic complications. This could explain their relatively low rate; then minor hemorrhages may have been trivialized or forgotten by patients. Additionally, for patients who did not monitor INR themselves, information was collected by hetero anamnesis, which could represent recruitment bias.

Quality of oral anticoagulation by VKAs was poor in our practice. Factors associated with good anticoagulation were the use of fluindione (vs acenocoumarol), concomitant low-dose aspirin and monitoring of INR exclusively by the patient himself. The quality of oral anticoagulation by VKAs could be improved in our practice by the creation of anticoagulation clinics for better therapeutic education of patients and efficient management of VKAs dose, and the use of prescription assistance software. Weak anticoagulation quality of VKAs could justify an expansion of the prescription of DOACs if they are available and accessible.

KY: designed the study, wrote the protocol and corrected the manuscript;

TT, EHL: managed analysis and discussion and corrected the manuscript;

APD, ET, MK, EHL: managed the literature searches;

AA, SP, SB, and DF: managed data collection.

The authors declare that they have no competing interests.

Ethical approval was obtained from the Institutional Review Board of the Faculty Health Sciences of the University of Lomé (Togo). We also obtained administrative approval from the General Managers of the two hospitals. Oral consent has been obtained for each patient. For the purpose of confidentiality, participant’s data were processed using specific unique identifiers.

Yayehd, K., Tcherou, T., Edorh, H.L.A., Defodji, A., Kpelafia, M., Togbossi, E., Adzodo, A., Pessinaba, S., Pio, M., Baragou, S. and Damorou, F. (2024) Assessment of Oral Anticoagulation with Vitamin K Antagonists in Patients Living in a Low-Income Country of West Africa. World Journal of Cardiovascular Diseases, 14, 27-42. https://doi.org/10.4236/wjcd.2024.141004

Individual Survey Form

Assessment of oral anticoagulation with vitamin K antagonist (VKA) in patients living in a low-income century of West Africa.

Study center: /………….../ University Teaching Hospital Campus ¹; University Teaching Hospital Sylvanus Olympio ²

PATIENTS Id

Ÿ Last name + first name (initials): …………………………………………

Ÿ Age: ……………years

Ÿ gender: …………. □M ¹ □F ²

Ÿ contact: …………………………….

Ÿ Occupation: /…../

□civil servant/employee ¹ □individual ² □artisan ³ □housewife ⁴ □retired ⁵ □other ⁶: specify if other: ………………………

Ÿ Patient’s education level: /………../

Not in school ¹ primary ² secondary ³ higher ⁴

Ÿ Educational level accompaniment if non-autonomous or unavailable patient: /………../

Not in school ¹ primary ² secondary ³ higher ⁴

Ÿ Residence: /……/

Lomé ¹ other city ² rural ³ other ⁴: specify if other………………………..

Ÿ Ethnicity: ………...………………………

Ÿ Blood group-Rhesus factor: /………./

HISTORY /…………….……………….. / (Many possible responses)

None ¹ -stroke ² -hypertension ³ -diabetes ⁴ -obesity ⁵ -dyslipidemia ⁶ -alcohol ⁷ -tobacco ⁸ -heredity ⁹ -menopause ¹⁰ -heart failure ¹¹ -cardiopathy ¹² …………… -hepatopathy ¹³ …………………….. -Hepatocellular insufficiency ¹⁴ -renal insufficiency ¹⁵; GFR (MDRD) …………….. nephropathy ¹⁶ ………..-hemopathy ¹⁷ ……………… -neuropathy ¹⁸ ……………. -neoplasia ¹⁹ ……………….. -HIV ²⁰ -asthma ²¹ -sickle cell disease ²² -hyperthyroidism ²³ -hypothyroidism ²⁴ -Pulmonary embolism ²⁵ -Deep vein thrombosis ²⁶ -severe pulmonary hypertension ²⁷ -Other ²⁸; specify if other …………

Cognitive Functions: /……………/

autonomous ¹ semi-autonomous ² dependent ³

Indication for VKA treatment: /……..…/

Deep vein thrombosis ¹; Pulmonary embolism ²; Deep vein thrombosis + Pulmonary embolism ³; recurrence of venous thromboembolic disease ⁴; severe pulmonary hypertension ⁵; non-valvular atrial fibrillation ⁶; valvular atrial fibrillation ⁷; severe left ventricular dysfunction ⁸; mechanical valve prosthesis ⁹; or bioprosthesis ¹⁰; other ¹¹; specify other: …………………….

VKA molecule: /……….……/

Acenocoumarol (SINTROM) ¹; Fluindione (previscan) ²; Warfarin (coumadin) ³; other ⁴; specify if other…………………………….

Change of VKA molecule: /………..…/

Yes ¹ no ²

If yes, specify reason: /…………../

Outage on market ¹; inefficacy ²; other ³: …………

Expected duration of treatment with VKA: /……….…/

3 months ¹; 6 months ²; long term/indeterminate ³; for life ⁴

Total number of patient’s medications: including VKA: /……../

Molecules co-prescribed in association with VKA: /………………../

Furosemide ¹; spironolactone ²; bisoprolol ³; nebivolol ⁴; metoprolol ⁵; propanolol ⁶; other beta-blocker ⁷; perindopril ⁸; rampipril ⁹; enalapril ¹⁰; ACE inhibitor ¹¹; ARB ¹²; digoxin ¹³; amiodarone ¹⁴; neomercazole ¹⁵; omeprazole ¹⁶; lansoprazole ¹⁷; rabeprazole ¹⁸; pantoprazole ¹⁹; aspirin ²⁰; others ²¹ …………….

Baseline prothrombin time ………… or spontaneous INR …………….

INR TABLE

Results:

Time spent under VKA: ………………………………..…………….. Days

Total number of INR performed: ………………………….

Percentage of INR between 2 and 3: ……………………

Number of days in the effectiveness zone: ……………………………….

TTR according to the Rosendaal method: ……………………………….%

Percentage of time spent below the therapeutic range: ……………………%

Percentage of time spent above the therapeutic margin: ……………………%

Thromboembolic outcomes: /……………../

if yes specify: …………………………………………………………………

Hemorrhagic outcomes: /……………../

if yes specify:……………………………………………………………………

Evolution of the outcomes: /……………/

favorable ¹, death ², other ³ ……………………..