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}