We sought to determine the anticoagulation control among patients on VKA in SSA. Data from our study indicate that the proportions of INR values in the therapeutic range, the median TTR and the proportion of patients with TTR ≥ 65% are all low. In all nine countries, the median TTR values were below 65%, ranging from 0 to 44.6%. In addition, we consistently observed poor anticoagulation control in patients with all VKA indications (mechanical heart valves, atrial fibrillation, and venous thromboembolism). For those with suboptimal control, under-anticoagulation is more frequent than over-anticoagulation. Universal health coverage was more likely associated with optimal anticoagulation control. Our analysis also showed a lower frequency of INR measurements among the study participants.

The high burden of suboptimal anticoagulation control in the current study is consistent with the findings in similar studies in SSA, where the TTR values ranged from 13.7% to 47% and the proportion of patients with TTR ≥ 65% as low as 15% [16, 28]. Our findings are consistent with the global GARFIELD study, which also reported a low proportion of patients with TTR ≥ 65%, varying from 16.7% in Asia to 49.4% in Europe [13]. Therefore, real-world data, including ours, indicate that optimal anticoagulation is often not achieved in routine clinical practice. This apparent suboptimal anticoagulation in VKA-treated individuals is concerning, given the increased mortality risk of as much as fourfold when TTR falls below 30% [15]. Our findings strengthen the argument for improving anticoagulation quality, particularly in SSA, where VKAs are the primary anticoagulants [13]. Evidence suggests that VKA at stable optimal anticoagulation has comparable efficacy and safety to NOACs [19,20,21].

The relatively high proportion of sub-therapeutic INRs is consistent with a previous meta-analysis and meta-regression conclusion, which reported predominantly under-anticoagulated in patients on VKA anticoagulation [14]. Although most studies typically report 25–36% of INRs below the range, the proportion of sub-therapeutic INRs in our cohorts was almost 50% [13, 14, 29,30,31,32]. Our findings not only depict suboptimal anticoagulation control but also that when patients were out of range, they were more likely to be sub-therapeutic and at an increased risk of thrombosis than supratherapeutic with an increased risk of bleeding. This is a concern as subtherapeutic anticoagulation may cause up to a 16-fold increase in the rate of thromboembolism [33]. Though the reasons are unclear, subtherapeutic anticoagulation is likely related to a lack of dedicated anticoagulation clinics and less stringent monitoring, VKA non-adherence, dosage interruption for several reasons, a recent dose reduction in response to a previously recorded high INR value and clinicians' using low dosage due to fears of inducing a major haemorrhage [33]. Regardless of the reason, our results call for efforts to reduce or eliminate sub-therapeutic anticoagulation to improve patient outcomes.

Better anticoagulation control has been attained in clinical trials performed in the SSA [2]. In the Investigation of Rheumatic AF Treatment Using VKA, Rivaroxaban or Aspirin Studies (INVICTUS) trial that involved several African countries, 56.1% to 65.3% of INR tests were in the therapeutic range during the four years of follow-up, rising from 33.2% before the trial. The INVICTUS study reported a lower rate of a composite of stroke, systemic embolism or myocardial infarction, or death in patients with rheumatic heart disease–associated atrial fibrillation on warfarin than rivaroxaban therapy. The improved quality of anticoagulation is a significant determinant of thrombotic and bleeding events in patients receiving a vitamin K antagonist and likely influenced outcomes in the INVICTUS trial. Although these results show that optimal quality of anticoagulation can be achieved in resource-limited countries, the trial's rigorous follow-up and strict inclusion criteria make it difficult to extrapolate the results to real-life VKA-treated patients [2]. Due to frequent anticoagulation monitoring, patients in the VKA arm had frequent physician interactions, which could have resulted in better clinical outcomes. Our study analysed anticoagulation data routinely collected from different levels of healthcare and likely reflects the accurate picture of the quality of anticoagulation in non-trial clinical sub-Saharan African settings. Putting these results into perspective, the benefits seen in the INVICTUS trial are difficult to replicate in sub-Saharan Africa, where time, distance, economic or other access-to-care issues impede access to anticoagulation care.

Our analyses noted an association between optimal quality of anticoagulation and universal health coverage. This finding is consistent with previous evidence linking out-of-pocket expenses for VKA services and suboptimal quality of the anticoagulation [13, 16, 18]. Owing to the underfunding of the health systems in Africa, patients travel a long distance to access the few unreliably running centralised VKA services [17].

The limitations of this study are those typical of a retrospective design. Although the analysis of variables in medical charts and electronic records was limited by missed information, the extracted information provided an accurate picture of the quality of anticoagulation in daily clinical practice. The convenient inclusion of sites and investigators may have potentially selected more motivated investigators and participants, with a consequential overestimation of the anticoagulation control. The distribution of the clinics in selected countries may not have yielded a representative sample as they were predominantly in urban settings. However, most anticoagulation services in SSA are often centralised, caring for urban and rural patients who often travel long distances to access these services[17]. The small number of participants in some countries and clinics may also have affected the representativeness of our sample and the generalisation of the findings in such settings. However, the quality of anticoagulation management in our analysis is consistent with that reported in other studies in SSA. Therefore, our results can be extrapolated to most SSA settings. Although data entries from different sites may have been prone to errors, site investigators were responsible for supervising and ensuring correct data entry. In addition, the REDCap dataset included customised validation rules to ensure that valid data are entered.