Dual antiplatelet therapy (DAPT) remains the gold standard in patients who underwent percutaneous coronary intervention (PCI). This meta-analysis aims to evaluate the clinical safety of 1-month DAPT followed by aspirin or a P2Y12 receptor inhibitor after PCI with drug-eluting stents (DES). We searched PubMed, MEDLINE, Embase, Scopus, Google Scholar, Cochrane Central Registry, and ClinicalTrials.gov databases and identified 5 randomized controlled trials with 29,831 patients who underwent PCI with DES and compared 1-month versus >1-month DAPT. The primary end point was major bleeding, and the co-primary end point was stent thrombosis. The secondary end point included all-cause mortality, cardiovascular death, myocardial infarction, stroke, and major adverse cardiovascular or cerebrovascular events. Compared with >1-month DAPT, the 1-month DAPT was associated with a lower rate of major bleeding (odds ratio [OR] 0.66, 95% confidence interval [CI] 0.45 to 0.97, p = 0.03, I 2 = 71%), whereas stent thrombosis had a similar rate in both study groups (OR 1.08, 95% CI 0.81 to 1.44, p = 0.60, I 2 = 0.0%). The study groups had similar risks for all-cause mortality (OR 0.89, 95% CI 0.77 to 1.04, p = 0.14, I 2 = 0.0%), cardiovascular death (OR 0.84, 95% CI 0.59 to 1.19, p = 0.32, I 2 = 0.0%), myocardial infarction (OR 1.04, 95% CI 0.89 to 1.21, p = 0.62, I 2 = 0.0%), and stroke (OR 0.82, 95% CI 0.64 to 1.05, p = 0.11, I 2 = 6%). The risk of major adverse cardiovascular or cerebrovascular events was lower (OR 0.86, 95% CI 0.76 to 0.97, p = 0.02, I 2 = 25%) in the 1-month DAPT compared with >1-month DAPT. In conclusion, in patients who underwent PCI with DES, 1-month DAPT followed by aspirin or a P2Y12 receptor inhibitor reduced major bleeding with no risk of increased thrombotic risk compared with longer-term DAPT.
Graphical-abstract
Introduction
Despite the permanent improvement in the diagnosis and treatment, coronary artery disease (CAD) remains a major cause of morbidity and mortality worldwide, particularly in patients with acute coronary syndrome (ACS). , In patients with CAD, percutaneous coronary intervention (PCI) is the treatment of choice, both in those with ACS and with stable CAD. The current clinical guidelines recommend 6 to 12 months of dual antiplatelet therapy (DAPT), with aspirin and P2Y12 receptor inhibitors, as a protective measure against arterial thrombosis, after PCI and implantation of drug-eluting stent (DES) in these patients. , However, it has been shown that DAPT is associated with an increased risk of bleeding, which devalues the benefits of reduced ischemic events ; hence, attempts to shorten the duration of DAPT to a maximum of 1 month have recently been sought and evaluated. These studies showed noninferiority of 1 month of DAPT followed by aspirin or a P2Y12 receptor inhibitor compared with guidelines-based conventional longer-term treatment with DAPT. These 4 randomized clinical trials (RCTs) showed similar results in patients at high bleeding risk and in all comers , , who underwent PCI, but their conclusion has not reached clinical guidelines yet. Most recently, data from “Ticagrelor alone versus ticagrelor plus aspirin from month 1 to month 12 after percutaneous coronary intervention in patients with acute coronary syndromes (ULTIMATE-DAPT)” RCT showed that patients with ACS who underwent primary PCI, who remained free after 1 month on DAPT treated with ticagrelor alone, had less bleeding without increased thrombotic risk. The objective of the present systematic review was to provide a comprehensive evaluation of short-term (1 month) DAPT in patients who underwent PCI with DES by performing a meta-analysis including the most recent RCT, ULTIMATE-DAPT trial.
Methods
We followed the PRISMA guidelines of the 2020 preferred reporting items for systematic reviews and meta-analysis statements. Because of the study design (meta-analysis), neither institutional review board approval nor patient’s informed consent was needed.
Search strategy
we systematically searched PubMed-Medline, EMBASE, Scopus, Google Scholar, Cochrane Central Registry of Controlled Trials, and ClinicalTrial.gov from inception to April 13, 2024, using the following keywords: (“percutaneous coronary intervention” OR “PCI”) AND (“drug-eluting stent”) AND (“dual antiplatelet therapy” OR “DAPT”) AND (“randomized controlled trial” OR “RCT”) AND (“1-month” OR “1 month”). In this meta-analysis, we also included abstracts from selected congresses, including Scientific Sessions of the American Heart Association, European Society of Cardiology, American College of Cardiology, and European Society of Atherosclerosis. Only articles published in English were included in the analysis. No filters were applied. GA and PI independently and separately evaluated all articles. The finally selected articles were obtained in full-text and were searched carefully by the same 2 researchers, who extracted necessary data and evaluated the articles’ quality. Disagreements were resolved by discussion with a third party (MYH).
Eligibility criteria
studies eligible for inclusion were those fulfilling the following criteria: (1) randomized design comparing the efficacy and safety of 1-month DAPT with that >1-month DAPT treatment in patients who underwent PCI for ACS or stable CAD; (2) minimum follow-up period of 10 months; and (3) full-text studies published in peer-reviewed journals. The exclusion criteria were (1) nonrandomized studies, (2) unpublished studies, and (3) ongoing trials. Observational and unpublished studies were not included in the meta-analysis.
Data extraction
qualified studies were searched, and the following data were collected, including (1) first author’s name, (2) date of publication, (3) clinical trial name, (4) place where the study was conducted, (5) number of centers involved, (6) study design, (7) number of patients in each of the 2 study arms who received 1-month or >1-month DAPT treatment, (8) follow-up period, and (9) detailed clinical outcome and nature of events in the 2 groups.
Outcomes and definitions
End points
the primary end point was major bleeding based on Bleeding Academic Research Consortium type 3 or 5 bleeding, and major or clinically relevant nonmajor bleeding was defined as a bleeding event of Bleeding Academic Research Consortium type 2, 3, or 5. The co-primary end point was stent thrombosis, according to the Academic Research Consortium definitions. Secondary end points included all-cause death, cardiovascular (CV) death, major adverse CV or cerebrovascular events (MACCEs), myocardial infarction (MI), and stroke. MACE was defined as the combination of all-cause death, CV death, MI, major bleeding, stent thrombosis, and stroke.
Acute MI was defined according to symptoms, electrocardiographic signs, and biomarkers elevation above the upper normal limit. , Stroke was defined as an acute symptomatic episode of neurologic dysfunction >24 hours in duration in the absence of therapeutic intervention and neuroimaging evidence of cerebral, spinal, or retinal tissue injury.
Quality assessment
the risk of bias assessment in the included studies was evaluated by the same investigators for each study and was performed systematically using the revised Cochrane RoB2 tool involving 5 domains (randomization process, deviation from intended interventions, missing outcome data, outcome measurement, and selection of reported results). The risk of bias in each study was conventionally classified as “low,” “high,” or “unclear” ( Supplementary Table 1 ).
Statistical analysis
we performed the pooled analyses of treatment effects and clinical outcomes using the Cochrane Collaborative software, RevMan 5.3.5 (Nordic Cochrane Center, Cochrane Collaboration, 2014, Copenhagen). Baseline characteristics are reported as median and range. Mean and SD values were estimated using the method described by Hozo et al. Analysis was presented in forest plots. A 2-tailed p value <0.05 was considered significant. Meta-analyses were performed using the fixed-effects model, and the random-effect model was used if heterogeneity was encountered. Heterogeneity between studies was assessed using the Cochrane Q test and I 2 index, with I 2 < 25% indicating low, 25% to 50% moderate and >50% high heterogeneity. Based on a hazard ratio value of 1, above or below, we calculated the relative risk for CV events. Publication bias was assessed using Egger’s test and visual inspection of funnel plots. To test the possible effect of trials with large sample sizes on the direction of clinical outcomes, we performed influence analysis.
Results
Search results and trial flow
of 3,402 articles identified in the initial searches, 32 studies were initially considered as potentially relevant. After a stringent selection process, 5 articles met the inclusion criteria ( Supplementary Figure 1 ).
Characteristics of included studies
four studies, with a total of 29,831 patients, met all the inclusion criteria, 14,891 patients had been randomized to receive DAPT for 1 month, and 14,940 received DAPT for >1 month according to conventional recommendations ( Supplementary Table 2 ). The mean follow-up duration was 14.2 months in the 2 groups.
Demographic and clinical data of 1-month DAPT versus >1-month DAPT
the 2 patient groups were not different in age (68.3 ± 10 vs 68.9 ± 9 years, p = 0.72) and proportion of female participants (27.8% vs 26.9%, p = 0.46, respectively). Similarly, cardiac risk factors of the 1-month DAPT group were almost similar to those of the >1-month DAPT group: arterial hypertension (71.6% vs 71.9%, p = 0.86), diabetes (33.9% vs 33.6%, p = 0.52), dyslipidemia (72.7% vs 73.6%, p = 0.56), and current smokers (20.4% vs 19.2%, p = 0.28). Previous coronary intervention procedures and events, including coronary artery bypass graft surgery (CABG), PCI, MI, and bleeding, were also not different between the 2 treatment groups (p >0.05, for all; Supplementary Table 3 ).
Angiographic data of 1-month DAPT versus >1-month DAPT
angiographic data of the 1-month DAPT group were not different from the >1-month DAPT group: left main (2.9% vs 2.53%, p = 0.13), left anterior descending artery (46.5% vs 41.6%, p = 0.10), left circumflex artery (21.4 vs 22.9%, p = 0.50), right coronary artery (30.4% vs 28.9%, p = 0.33), and CABG (7.1% vs 6.5%, p = 0.22). Patients in the 2 treatment groups, 1-month and >1-month, did not differ in the number of vessels treated per patient, 1, 2, or 3 (p >0.05 for all). Moreover, access site procedures were not significantly different between the 2 treatment groups (p >0.05 for all; Supplementary Table 4 ).
Primary outcomes
the treatment group of 1-month DAPT had a lower risk for major bleeding (1.72% vs 2.12%, odds ratio [OR] 0.66, 95% confidence interval [CI] 0.45 to 0.97, p = 0.03, I 2 = 71%; Figure 1) but a similar risk for stent thrombosis (0.66% vs 0.60%, OR 1.08, 95% CI 0.81 to 1.44, p = 0.60, I 2 = 0.0%) to the group who received >1-month DAPT ( Figure 1 ).
