Study search and study characteristics

After removing duplicates, a total of 2267 potentially relevant articles were screened. Eventually, 12 eligible RCTs were identified, involving a total of 59,284 older patients. These 12 studies were TWILIGHT-ACS [18], TRITON-TIMI 38 [19], PLATO [20], TRILOGY ACS [21], PRASFIT ACS [22], Wang et al. 2016 [23], PRAGUE-18 [24], Elderly ACS II [25], ISAR-REACT5 [26], POPular AGE [27], TICO [28], and TICAKOREA [29]. Regarding anti-platelet therapies strategies, four trials examined prasugrel to clopidogrel, while four trials compared ticagrelor to clopidogrel. Two trials compared prasugrel to ticagrelor. The median follow-up duration of the included studies was 12 months. Six trials reported the results based on intention-to-treat analysis [18,19,20, 26, 27, 29]. The process of study selection is illustrated in Fig. 1, and detailed information of the included studies is summarized in Table 1. The outcomes of all included and the definitions of MACE and bleeding are list in Supplemental Tables 1 and 2. The risk of bias was assessed by ROB-2 for each RCT and the barplot shown in Supplemental Fig. 1.

Fig. 1

Selection of studies. The preferred reporting items for systematic review and meta-analyses (PRISMA) flow diagram of study selection

Table 1 Characteristics of studies included in the systematic review and meta-analysisPrimary outcome: MACE

In total, 5666 (9.56%) patients experienced MACEs, with 1540 (9.93%) of the 15,514 with prasugrel, 1595 (9.42%) of the 16,940 with ticagrelor, and 3036 (12.60%) of the 24,099 treated with clopidogrel.

Standard meta-analysis of these studies revealed that DAPT of prasugrel 3.75 or 5 mg [1.2 (0.72, 2.0)], prasugrel 10 mg [0.68 (0.42,1.1)], ticagrelor 180 mg [0.89 (0.57, 1.4)] and ticagrelor monotherapy after 3 months DAPT [0.73 (0.32, 1.6)] showed similar primary endpoints when compared to clopidogrel (Fig. 2). The P score indicated that prasugrel 10 mg (0.528) as the most effective treatment for MACE, followed by ticagrelor monotherapy after 3 months DAPT (0.410), ticagrelor 180 mg (0.035) and clopidogrel 75 mg (0.018), while prasugrel 3.75 or 5 mg (0.015) was ranked the lowest (Fig. 3). Nonetheless, SUCRA Bayesian analysis demonstrated that prasugrel 10 mg (0.835) and ticagrelor monotherapy after 3 months DAPT (0.717) were the preferable treatment compared with ticagrelor 180 mg (0.490), clopidogrel 75 mg (0.333) and prasugrel 3.75 or 5 mg (0.124) for the primary endpoints of MACE.

Fig. 2Fig. 3Secondary outcomes: all-death mortality, CV death, stroke, MI, revascularization and stent thrombosis

Compared with DAPT of clopidogrel 75 mg, there was no significant difference in secondary outcomes, such as all-cause death, CV death, stroke, MI, revascularization and stent thrombosis, with prasugrel 3.75 or 5 mg, prasugrel 10 mg, ticagrelor 180 mg or ticagrelor monotherapy after 3 months DAPT, as illustrated in Fig. 4.

Fig. 4

Secondary outcomes compared with clopidogrel 75mg

According to P score analysis, ticagrelor monotherapy after 3 months DAPT was the most beneficial treatment for all deaths (0.627), cardiovascular deaths (0.667) and revascularization (0.585). Prasugrel 3.75 or 5 mg was identified as the most effective treatment for stroke (0.463) and ischemic stroke (0.650), while prasugrel 10 mg was most likely the optimal treatment for hemorrhagic stroke (0.717), MI (0.697), and stent thrombosis (0.442), as demonstrated in Fig. 5. However, SUCRA Bayesian analysis revealed that ticagrelor monotherapy after 3 months DAPT was the superior treatment strategy for primary endpoint of all death (0.863), cardiovascular death (0.806) and revascularization (0.774). SUCRA Bayesian analysis also showed that prasugrel 3.75 or 5 mg was the most effective for stroke (0.743) and ischemic stroke (0.800), while prasugrel 10 mg was the ideal treatment in terms of hemorrhagic stroke (0.850), MI (0.866) and stent thrombosis (0.746).

Fig. 5

Ranking plots for secondary outcomes

Bleeding outcome

There was heterogeneity in the definition of bleeding (Supplemental Table 1) among the RCTs that were included, but this standard was deemed acceptable for the purpose of this analysis. Through standard meta-analytic approach, DAPT of prasugrel 3.75 or 5 mg [0.85 (0.30, 2.4)], prasugrel 10 mg [1.2 (0.74, 2.3)], ticagrelor 180 mg [1.4 (0.97, 2.3)], and ticagrelor monotherapy after 3 months DAPT [0.75 (0.37, 1.7)] showed similar primary endpoints in comparison to clopidogrel (as shown in Fig. 6). The P score indicated that ticagrelor monotherapy after 3 months DAPT (0.519) was the optimal treatment for bleeding, followed by prasugrel 10 mg (0.025), prasugrel 3.75 mg (0.383) and clopidogrel 75 mg (0.072), whereas ticagrelor 180 mg (0.0006) was ranked the lowest (as shown in Fig. 7). Nonetheless, SUCRA Bayesian analysis demonstrated that ticagrelor monotherapy after 3 months DAPT (0.806) was the superior treatment concerning bleeding when compared to clopidogrel 75 mg (0.597), prasugrel 3.75 mg (0.660), prasugrel 10 mg (0.296) and ticagrelor 180 mg (0.142).

Fig. 6Fig. 7

Ranking plots for major bleedings

Sensitivity analysis and publication bias

In the sensitivity analysis, we used a fixed-effects model to re-analyze the data, and the results remained relatively consistent, indicating robust and trustworthy results (Supplement 6). The funnel plot did not reveal significant publication bias regarding (Supplement Fig. 5).