Search results:
The systematic search outputted 16,042 citations and 42 articles were subsequently scrutinized. Then, the TICO trial was incorporated. Eventually, 24 randomized controlled trials with aggregately 81,376 participants were deemed eligible for inclusion (Fig. 1) [7-10, 13-17, 23-37].
Characteristics of included studies and bias assessment:
The fundamental features of enrolled studies, baseline characteristics of participants, definitions of endpoints, outcomes of enrolled trials, and the network plots are summarized in additional file 2. Generally, 15,158 participants were randomly assigned to the L-DAPT arm, 35,743 to the DAPT 12Mo arm, 14,418 to the S-DAPT+ASA arm, and 16,057 to the S-DAPT+P2Y12 arm. The median follow-up duration was 18 months, with an interquartile range of 12 to 24 months. The distribution of baseline characteristics of patients was balance across comparisons.
An overwhelming majority of RCTs were judged to be low-risk categories according to the Cochrane Risk of Bias Tool, and other sources of bias made a huge contribution to the risk of bias (Additional file 2 table 5).
Outcomes of network meta-analysis:
Fig. 2 gives a representation of network meta-analysis results under the consistency model, and pooled estimates are presented in table 6 in additional file 2.
All-cause mortality and cardiac death:
We synthesized 24 studies reporting all-cause mortality and 21 studies with 60,112 patients altogether reporting cardiac death. Although S-DAPT+P2Y12 resulted in diminished all-cause mortality and cardiac death compared with other DAPT durations, they demonstrated no significant differences (Fig. 2).
Ischemic endpoints:
Overall, L-DAPT had advantages in reducing the probabilities of ischemic complications (Fig. 2). There was a decreasing risk of MI in participants treated with L-DAPT compared with S-DAPT+ASA (OR 0.60, 95%CI 0.46-0.82) and S-DAPT+P2Y12 (OR 0.69, 95%CI 0.44-1.08), but no significant differences were found when compared with S-DAPT+P2Y12. Simultaneously, pooled analysis for definite or probable ST proved to be without statistically significant when L-DAPT compared with S-DAPT+P2Y12 (OR 0.52, 95%CI 0.26-1.10).
Hemorrhagic endpoints:
Results of 18 studies with 54,746 participants about any bleeding and 22 studies with 79,009 participants about major bleeding were pooled. Short term DAPT, especially S-DAPT+P2Y12, was proved to honor overwhelming superiority (Fig. 2). The mate-analysis showed that L-DAPT resulted in an increased risk of major bleeding (OR 2.37, 95%CI 1.32-5.03) and any bleeding (OR 2.95, 95%CI 1.91-4.34) when compared with S-DAPT+P2Y12.
Stroke:
A total of 23 studies with 79,896 patients reported the data of stroke. We observed that 4 different therapies presented similar rates, and the differences were not statistically significant among them (Fig. 2).
Rank probabilities:
The rank probabilities were in accordance with the pooled results quantified by OR ( Fig. 3). S-DAPT+P2Y12 was ranked the best therapy for reducing all-cause mortality, cardiac death, major bleeding, and any bleeding. Besides, L-DAPT honored admiration in limiting myocardial infarction and definite or probable ST.
Network coherence:
The node-splitting analysis confirmed there was no significant difference between direct and indirect effects in closed loops, which verified favorable coherence in all endpoints (Additional file 2 table7).
Sensitivity analysis:
The SMART-DATE trial which defined duration of long term DAPT as 12-month or longer might weaken the contradistinction among different interventions. We excluded it and redefined long-term arm as received DAPT 18 months or longer. Results of sensitivity analysis did not in contradiction compared with the original meta-analysis but had more prominent differences (Additional file 2 table 8). Longer than 18 months of DAPT evaluated in higher rates of major bleeding (OR 2.16, 95%CI 1.27-4.17 compared with S-DAPT+ASA; OR 2.45, 95%CI 1.34-5.58 compared with S-DAPT+P2Y12) and any bleeding (OR 2.37, 95%CI 1.66-3.36 compared with S-DAPT+ASA; OR 3.13, 95%CI 2.03-4.70 compared with S-DAPT+P2Y12; OR 1.68, 95%CI 1.20 -2.21 compared with DAPT 12Mo). The robustness of outcomes could also be confirmed in the pooled analysis of the remaining treatments.
Subgroup analysis:
We conducted subgroup analyses among patients with ACS for their higher ischemic risks relative to those with stable CAD, and among patients after newer-generation DES implantation owning to its superiority in ischemic outcomes [38, 39].
Ten trials reported endpoints of ACS subgroup with a total of 25,189 participants and were included for further synthesis (Additional file 2 table 9) [7, 9, 13, 23, 25, 40-44]. L-DAPT was observed an increased risk of any bleeding when compared with DAPT 12Mo S-DAPT+ASA (OR 2.46, 95%CI 1.23-6.76), and S-DAPT+P2Y12 (Additional file 2 table 10).
Table 12 in additional file 2 showed that 18 trials with 58228 patients reported endpoints of newer-generation DES subgroup [7-10, 13-17, 23-27, 30, 32,34,36,45,46]. As for S-DAPT+P2Y12, lower risks of major bleeding (OR 0.60, 95%CI 0.34-0.96 when compared with DAPT 12Mo; OR 0.34, 95%CI 0.13-0.79 when compared with L-DAPT), any bleeding, as well as all-cause mortality were confirmed when compared with other strategies (Additional file 2 table 13).