CARDIOVASCULAR JOURNAL OF AFRICA • Volume 35, No 2, May – August 2024 104 AFRICA in reduced haemoglobin levels. On the other hand, bleeding events were observed in two (6.7%) cases in group 2, both of which involved major bleeding from the GIS (p = 0.237). The bleeding events are presented in Table 2. Discussion Our study presents the one-year results of two groups receiving ASA in slightly different doses (75 vs 81 mg) as part of dual antiplatelet therapy. To the best of our knowledge, this is the first study to compare the use of dual antiplatelet therapy in the form of two separate tablets taken at two different times daily (75 mg of clopidogrel in the morning and 81 mg of ASA in the evening) with a combination preparation taken as a single dose (75 mg of ASA plus 75 mg of clopidogrel in the morning). Our results show that the form taken as a single tablet in the morning had slightly higher patency rates but also yielded a higher incidence of major bleeding in the long term. Although antiplatelet therapy has become a standard protocol in PAH, there is still no clear consensus on how long this process should be continued and which molecules and doses provide optimal treatment.8,9 Moreover, in the medical management of PAH, apart from the role of antiplatelet therapy in preventing major cardiovascular events, post-interventional plans for the advanced stages of the disease have not been clearly established. While discussions continue about the role of DAPT in standard treatment in recent guidelines, the advantages of its use after revascularisation have been emphasised.10,11 The data on prolonged DAPT application, especially after revascularisation, have also been discussed. It has been emphasised that discontinuation of DAPT before six months may be associated with early restenosis, and it has been suggested that prolonging it for more than six months may provide a prolonged patency rate. Although DAPT administered over six months reduced the risk of major cardiovascular events, prolonged treatment was associated with greater incidences of all-cause death, re-interventions for target lesions and major amputation.8-12 In our study, DAPT treatment was applied for one year in both groups and followed up. Abdullah et al. found that 12-month primary patency rates after peripheral revascularisation with drug eluting stents (DES) ranged from 54 to 85%, regardless of additional factors.13 DES has been reported to be more advantageous than bare stents. Singh et al. presented baseline demographic variables, medications, co-morbidity and procedure-related findings in their study investigating different combinations of single antiaggregant, DAPT and anticoagulation after peripheral vascular intervention.14 While advanced age andmale gender predominated in their study, as in ours, the frequency of diabetes and smoking was higher in their study. In this study, DAPT prescription after peripheral intervention was reported as over 90%.14 Kronlage et al. investigated the results of long- and shortterm DAPT treatment. The one-year open rates were 83.94% short-term versus 79.8% long-term DAPT. As a result, they stated that long-term DAPT treatment had no effect.15 In our study, DAPT was applied to all groups for 12 months, and the patency rate was found to be more than 80% in both groups. In the review by Tsai et al., many comprehensive studies are discussed, and it was emphasised that DAPT application after peripheral intervention provided benefits in terms of patency rate, need for re-intervention, amputation rates and major cardiovascular events.16 In the same study, it was emphasised that DPT did not increase major bleeding compared to monotherapy, but it did cause an increase in minor bleeding. However, data on the relationship between treatment duration and bleeding rates were not presented.16 In the study by Mauri et al., one-year DAPT treatment after peripheral revascularisation was compared with ASA treatment alone. It was determined that stent thrombosis as well as major cerebral and cardiovascular events were significantly reduced in the DAPT group. This study also focused on the relationship between prolonged DAPT administration and increased bleeding rates.17 The most important parameter of concern in the prolonged DAPT regimen is the increased risk of bleeding.18 The MIRROR study compared six months of DAPT and ASA monotherapy and found no difference in major bleeding rates.19 Cho et al. also found no increase in the frequency of major bleeding after prolonged DAPT.8 In our study, the effects of DAPT regimens taken simultaneously (in a single preparation) or in two separate doses, on major bleeding were evaluated in addition to the effectiveness of prolonged treatment. It was determined that the simultaneous intake of ASA and clopidogrel may cause more bleeding. A similar exploration of this issue has not been found in the literature. In pharmacokinetic and pharmacodynamic investigations, the time taken for 100 mg of oral ASA to reach its maximum plasma concentration (tmax: 1.00 hour) has been reported as one hour on average.20 This time was determined as 1.17 hours for 75 mg of oral clopidogrel (tmax: 1.17 hours). 21 The times for these molecules to reach similar peak plasma concentrations may be associated with increased bleeding times in concomitant administration. However, more comprehensive studies should be designed to clarify the mechanism of action behind the increased bleeding. One of the major limitations of this study is the relatively small study population. Larger cohorts would be useful for confirmation of the results. Another limitation is that the results presented here were collected from a single centre. Multicentre studies would produce more comprehensive conclusions. Conclusion Prolonged DAPT treatment, either in a single tablet or two separate doses, seems to be similarly effective in preventing stent restenosis. However, single-tablet administration seems to increase major bleeding events. Therefore, even if the use of a single tablet is advantageous, patients at risk should be followed closely and stringent anti-bleeding measures should be taken. Comprehensive studies are needed to definitively understand the pharmacodynamic effects discussed here. References 1. Conte SM, Vale PR. Peripheral arterial disease. Heart Lung Circ 2018; 27(4): 427–432. 2. Zemaitis MR, Boll JM, Dreyer MA. Peripheral arterial disease. [Updated 2022 Jul 7]. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2022 Jan. Available from: https://www.ncbi.nlm.nih.gov/ books/NBK430745/ 3. Kim TI, Brahmandam A, Sarac TP, Orion KC. Trends and perioperative outcomes of patients with human immunodeficiency virus (HIV) under-
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