PATIENT-RELATED CHALLENGES
The importance of pharmacogenetic variability on warfarin dose requirements in SSA was demonstrated in a recent systematic review.[104] For example, three variants that are more prevalent in Black Africans than in other populations, CYP2C9*5 ,CYP2C9*6 , and CYP2C9*11 , affected warfarin dose requirements by -13, -8, and -5 mg/week respectively.[104]
Potential drug-drug interactions between warfarin and co-prescribed medications hinder good anticoagulation control. In SSA, antiretroviral therapy is a significant source of potential drug-drug interactions.[18,20,22,70,92,93,105] Tuberculosis is also common in SSA, and rifampicin use induces multiple cytochrome P450 isoforms resulting in a reduced warfarin effect. In a Kenyan case series of patients on concurrent rifampicin and warfarin, the median warfarin dose increase with rifampicin was 16%, but some patients required dose increases up to +441%.[106] In a Ugandan case series, patients concomitantly prescribed rifampicin, antiretroviral therapy, and warfarin had highly labile INRs and warfarin dose requirements, and it was not possible to predict the course of INR results in any individual patient.[107] In Kenya, VTE patients with advanced HIV and tuberculosis required a median 8 additional clinic visits to achieve or maintain a therapeutic INR.[108]
Despite widespread herbal medicine use in SSA[109,110] there is very little data on how this influences anticoagulation.[111,112] Nevertheless, it is plausible that some herbal medicines may interact with warfarin.
Anticoagulation patients in SSA are younger than those in high-income settings. For example, in Uganda and South Africa the median age of patients attending five anticoagulation services was 56 years,[22] and in a Kenyan service the mean age was 43 years.[20] Younger patients often show reduced adherence compared to older patients. Two possible reasons for this are that they are economically active and therefore may be unable to attend follow-up appointments, and that they may have reproductive wishes and expectations and therefore intentionally reduce their intake of a potentially teratogenic medicine.[113,114]
Four studies reporting patients’ self-reported adherence to anticoagulants in SSA are summarised in Table 4. Notably, from these, fewer than half of patients considered themselves highly adherent to warfarin. One study suggested that warfarin non-availability may contribute to poor adherence.[29] In an analysis of the “care cascade” of RHD patients in Uganda, retention in care was the stage with the highest patient drop-out.[48]
{Table 4 here}
We are not aware of any studies reporting SSA patients’ attitudes and beliefs about anticoagulation. A few studies (Table 5) reported on patients’ anticoagulation knowledge, with generally low levels of knowledge found. Only two studies investigated whether participants’ anticoagulation knowledge correlated with their anticoagulation control, and these reached conflicting results.[10,119] Levels of knowledge were generally associated with participants’ level of education and with the provision of written educational materials. Topics on which participants’ knowledge was low were drug and food interactions, the effect of missing a dose, the interpretation of INR values, recognizing the symptoms of over- or underdosing, contraception, and pregnancy planning.[10,82,120]
{Table 5 here}