To our knowledge, this is the first study to report the incidence of bleeding and performance of a predictive model in patients on DAPT in both private and public settings in East Africa.
According to our results, the incidence of overall bleeding was low (6.93%), and most bleeding events were minimal (5.4%) and did not require any interventions to stop. The incidence of major TIMI bleeding was 0%.
This is in contrast to other studies performed elsewhere. In the TRITON-TIMI trial, the rates of major non-CABG-related bleeding were 2.4% and 1.8% in patients receiving prasugrel and clopidogrel, respectively. This included life-threatening bleeding of 1.4% vs 0.9% for the two groups, respectively (4). In the landmark PLATO trial (5), the rates of major bleeding were 4.5% and 3.8% in patients receiving ticagrelor and clopidogrel, respectively.
Some of the possible explanations as to why our study revealed low incidences of major bleeding compared with other studies include the low number of patients on ticagrelor and prasugrel, both of which were associated with slightly higher incidences than clopidogrel in the TRITON-TIMI and PLATO trials. However, this may not explain the difference entirely because even in the clopidogrel versus aspirin trials, such as the CHARISMA trial(14), the rates of major bleeding were still higher than those in our study (1.7% vs. 1.3%, p = 0.09) in the clopidogrel vs. aspirin arms, respectively.
Another possible explanation is the greater use of glycoprotein IIb/IIIa receptor antagonists (54%) in the TRITON-TIMI trial (4) than in our trial (30.7%).
The populations studied also differed. The TRITON-TIMI trial was predominantly a Caucasian population (92%), whereas our study was predominantly {, #58}a black African cohort (69.8%). However, in a study by Brittain et al. (15) comparing the risk of bleeding while on DAPT among US Black and White adults, there was no difference in post-discharge BARC 2–5 bleeding between the two groups of patients. Therefore, the racial difference in the studied population may not entirely explain the low incidence of bleeding in our study.
Although there was no difference between the incidence of bleeding and the type of DAPT used, possibly due to the small sample size, the use of ticagrelor/prasugrel or a GP IIb/IIIa inhibitor had an increasing effect on bleeding of 46% and 72%, respectively, compared with the use of clopidogrel and not using any GP IIb/IIIa inhibitor.
Although not widely used in clinical practice, international guidelines encourage the weighting of bleeding risk before the selection of the duration of DAPT. They suggest that patients with a high risk of bleeding should have a shorter period of DAPT (Updated ESC Guideline 2017: Dual Antiplatelet Therapy; PMID 30060279; DOI: 10.1055/a-0549-8230). Different tools have been validated for the assessment of bleeding risk at the time of initiation of DAPT to tailor the duration on the basis of bleeding risk. Although the PRECISE-DAPT Score has been validated by the PLATO trial validation cohort and the BernPCI registry validation cohort, it has not been studied in a low-resource setting.
In our study, the ability of the PRECISE-DAPT score to predict the one-year risk of bleeding was good, with an area under the curve of 0.699 (95% CI: 0.564–0.835) and a Hosmer–Lemeshow goodness-of-fit test, chi-square value of 6.53 and a p value of 0.588.
These findings are similar to those of other studies performed elsewhere. Fracesco Costa et al. (12) on derivation and validation of PRECISE-DAPT Score through a pooled analysis of patient’s datasets from clinical trials showed a c-index for out-of-hospital TIMI major and minor bleeding of 0.70 (95% CI 0.65–0.74) in the trial validation cohort and 0.66 (95% CI 0.61–0.71) in the Bern PCI registry validation cohort, similar to our study. Liang Dong, in a study evaluating the performance of the PRECISE-DAPT Score in predicting bleeding in Chinese elderly patients(16), reported that the C statistic of the PRECISE-DAPT model for the prediction of BARC > 2 bleeding in overall patients was 0.717 (95% CI, 0.656–0.777). The c-indexes for the PRECISE-DAPT Score in the GLOBAL LEADERS and GLASSY trials(17) were 0.67 (95% confidence interval [CI]: 0.63–0.71) vs. 0.63 (95% CI: 0.59–0.67) (p = 0.27) and 0.67 (95% CI: 0.61–0.73) vs. 0.66 (95% CI: 0.61–0.72), respectively. The SMART DATE Trial (18) analysed the clinical usefulness of the PRECISE-DAPT Score for predicting bleeding events in patients with ACS undergoing PCI. In patients with a non-high PRECISE-DAPT Score < 25, a 6-month DAPT was associated with a higher ischemic risk with similar bleeding risk, whereas in patients with a high PRECISE-DAPT Score > 25, a 6-month DAPT presented a similar ischemic risk with significantly reduced major bleeding risk. Although we did not analyse ischemic risk, the utility of the PRECISE-DAPT Score in predicting bleeding risk in this study is similar to that in our study. Thus, the determination of the PRECISE-DAPT Score could improve clinical outcomes in patients with ACS undergoing PCI.
The discriminative ability of the PRECISE DAPT Score in our study was good (goodness-of-fit chi-square value of 6.53, p value of 0.588), similar to the findings of other studies, such as the study by Liang Dong et al. (16), which reported a chi-square value of 0.432 and a p value of 0.806 for the calibration of BARC > 2 bleeding in a 65-year-old or older Asian cohort of patients.
Limitations
Our study had several limitations. First, despite being a multicenter study, most of the patients were recruited from a tertiary private hospital, and as such, the findings may not be valid across all ACS populations in Kenya.
Second, it was difficult to carry out subgroup analysis, including the association of PRECISE DAPT and different antiplatelet use, due to the size of the sample.
There is also the potential to miss some bleeding events since these events were reported by the patient, which may have led to recall bias. Although we assessed many possible risk factors associated with bleeding, other possible predisposing factors, such as malignancy and revascularization procedures, were not assessed. Furthermore, we did not evaluate ischemic risk, which has risk factors similar to those associated with bleeding. A randomized trial with a larger sample size is needed to support or refute our findings.