Dataset Information

Effect of P2Y12 Inhibitor Monotherapy vs Dual Antiplatelet Therapy on Cardiovascular Events in Patients Undergoing Percutaneous Coronary Intervention: The SMART-CHOICE Randomized Clinical Trial.

ABSTRACT:

Importance

Data on P2Y12 inhibitor monotherapy after short-duration dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention are limited.

Objective

To determine whether P2Y12 inhibitor monotherapy after 3 months of DAPT is noninferior to 12 months of DAPT in patients undergoing PCI.

Design, setting, and participants

The SMART-CHOICE trial was an open-label, noninferiority, randomized study that was conducted in 33 hospitals in Korea and included 2993 patients undergoing PCI with drug-eluting stents. Enrollment began March 18, 2014, and follow-up was completed July 19, 2018.

Interventions

Patients were randomly assigned to receive aspirin plus a P2Y12 inhibitor for 3 months and thereafter P2Y12 inhibitor alone (n = 1495) or DAPT for 12 months (n = 1498).

Main outcomes and measures

The primary end point was major adverse cardiac and cerebrovascular events (a composite of all-cause death, myocardial infarction, or stroke) at 12 months after the index procedure. Secondary end points included the components of the primary end point and bleeding defined as Bleeding Academic Research Consortium type 2 to 5. The noninferiority margin was 1.8%.

Results

Among 2993 patients who were randomized (mean age, 64 years; 795 women [26.6%]), 2912 (97.3%) completed the trial. Adherence to the study protocol was 79.3% of the P2Y12 inhibitor monotherapy group and 95.2% of the DAPT group. At 12 months, major adverse cardiac and cerebrovascular events occurred in 42 patients in the P2Y12 inhibitor monotherapy group and in 36 patients in the DAPT group (2.9% vs 2.5%; difference, 0.4% [1-sided 95% CI, -∞% to 1.3%]; P = .007 for noninferiority). There were no significant differences in all-cause death (21 [1.4%] vs 18 [1.2%]; hazard ratio [HR], 1.18; 95% CI, 0.63-2.21; P = .61), myocardial infarction (11 [0.8%] vs 17 [1.2%]; HR, 0.66; 95% CI, 0.31-1.40; P = .28), or stroke (11 [0.8%] vs 5 [0.3%]; HR, 2.23; 95% CI, 0.78-6.43; P = .14) between the 2 groups. The rate of bleeding was significantly lower in the P2Y12 inhibitor monotherapy group than in the DAPT group (2.0% vs 3.4%; HR, 0.58; 95% CI, 0.36-0.92; P = .02).

Conclusions and relevance

Among patients undergoing percutaneous coronary intervention, P2Y12 inhibitor monotherapy after 3 months of DAPT compared with prolonged DAPT resulted in noninferior rates of major adverse cardiac and cerebrovascular events. Because of limitations in the study population and adherence, further research is needed in other populations.

Trial registration

ClinicalTrials.gov Identifier: NCT02079194.

SUBMITTER: Hahn JY

PROVIDER: S-EPMC6593635 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Increasing evidence has shown P2Y12 inhibitor monotherapy is a feasible alternative treatment for patients after percutaneous coronary intervention (PCI) with stent implantation in the modern era. However, patients with diabetes mellitus (DM) have a higher risk of ischemic events and more complex coronary artery disease. The purpose of this study is to evaluate the efficacy and safety of this novel approach among patients with DM and those without DM. We conducted a systematic review and meta-analysis of randomized controlled trials that compared P2Y12 inhibitor monotherapy with 12 months of dual antiplatelet therapy (DAPT) in patients who underwent PCI with stent implantation. PubMed, Embase, Cochrane library database, ClinicalTrials.gov, and three other websites were searched for our data from the earliest report to January 2022. The primary efficacy outcome was major adverse cardiovascular and cerebrovascular events (MACCE): a composite of all-cause mortality, myocardial infarction, stent thrombosis, and stroke. The primary safety outcome was major or minor bleeding events. The secondary endpoint was net adverse clinical events (NACE) which are defined as a composite of major bleeding and adverse cardiac and cerebrovascular events. A total of four randomized controlled trials with 29,136 patients were included in our meta-analysis. The quantitative analysis showed a significant reduction in major or minor bleeding events in patients treated with P2Y12 inhibitor monotherapy compared to standard DAPT (OR: 0.68, 95% CI: 0.46-0.99, p = 0.04) without increasing the risk of MACCE (OR: 0.96, 95% CI: 0.85-1.09, p = 0.50). The number of NACE was significantly lower in the patients treated with P2Y12 inhibitor monotherapy (OR: 0.84, 95% CI: 0.72-0.97, p = 0.019). In DM patients, P2Y12 inhibitor monotherapy was associated with a lower risk of MACCE compared to standard DAPT (OR: 0.85, 95% CI: 0.74-0.98, p = 0.02). Furthermore, P2Y12 inhibitor monotherapy was accompanied by a favorable reduction in major or minor bleeding events (OR: 0.80, 95% CI: 0.64-1.05, p = 0.107). In non-DM patients, P2Y12 inhibitor monotherapy showed a significant reduction in major or minor bleeding events (OR: 0.58, 95% CI: 0.38-0.88, p = 0.01), but without increasing the risk of MACCE (OR: 0.99, 95% CI: 0.82-1.19, p = 0.89). Based on these findings, P2Y12 inhibitor monotherapy could significantly decrease bleeding events without increasing the risk of stent thrombosis or myocardial infarction in the general population. The benefit of reducing bleeding events was much more significant in non-DM patients than in DM patients. Surprisingly, P2Y12 inhibitor monotherapy could lower the risk of MACCE in DM patients. Our study supports that P2Y12 inhibitor monotherapy is a promising alternative choice of medical treatment for patients with DM undergoing PCI with stent implantation in the modern era.

Project description:ImportanceAlthough P2Y12 inhibitor monotherapy after a minimum period of dual antiplatelet therapy (DAPT) is a well-known way to reduce the risk of bleeding after percutaneous coronary intervention (PCI), data comparing long-term clinical outcomes between P2Y12 inhibitor monotherapy and extended DAPT in patients undergoing PCI have been unavailable.ObjectiveTo identify the long-term safety and efficacy of P2Y12 inhibitor monotherapy following 3 months of DAPT after PCI.Design, setting, and participantsThe Smart Angioplasty Research Team: Comparison Between P2Y12 Antagonist Monotherapy and Dual Antiplatelet Therapy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents (SMART-CHOICE) trial was an open-label, noninferiority, randomized clinical trial, enrolling patients who underwent PCI with drug-eluting stent at 33 hospitals in Korea from March 2014 through July 2017. Clinical follow-up was extended to 3 years and completed in August 2020.InterventionsPatients were randomly assigned to either P2Y12 inhibitor monotherapy after 3 months of DAPT or DAPT for 12 months or longer.Main outcomes and measuresThe primary end point was major adverse cardiac and cerebrovascular events (a composite of all-cause death, myocardial infarction, or stroke) at 3 years. The secondary end points included the components of the primary end point, bleeding (defined as Bleeding Academic Research Consortium [BARC] types 2-5), and major bleeding (BARC types 3-5).ResultsIn total, 2993 patients were randomly assigned to receive P2Y12 inhibitor monotherapy after 3 months of DAPT (1495 patients [50%]; mean [SD] age, 64.6 [10.7] years; 1087 [72.7%] male) or prolonged DAPT (1498 patients [50%]; mean [SD] age, 64.6 [10.7] years; 1111 [74.2%] male) after PCI. At 3 years, the primary end point occurred in 87 individuals (6.3%) in the P2Y12 inhibitor monotherapy group and 83 (6.1%) in the prolonged DAPT group (hazard ratio [HR], 1.06 [95% CI, 0.79-1.44]; P = .69). P2Y12 inhibitor monotherapy significantly reduced the risk of bleeding (BARC types 2-5: 112 [3.2%] vs 44 [8.2%]; HR, 0.39 [95% CI, 0.28-0.55]; P < .001) and major bleeding (BARC types 3-5; 17 [1.2%] vs 31 [2.4%]; HR, 0.56 [95% CI, 0.31-0.99]; P = .048), compared with prolonged DAPT. The landmark analyses between 3 months and 3 years and per-protocol analyses showed consistent results.Conclusions and relevanceAmong patients who underwent PCI and completed 3-month DAPT, P2Y12 inhibitor monotherapy was associated with a lower risk of clinically relevant major bleeding than prolonged DAPT. Although the 3-year risk of ischemic cardiovascular events was comparable between the 2 groups, this result should be interpreted with caution owing to the limited number of events and sample size.Trial registrationClinicalTrials.gov Identifier: NCT02079194.

Project description:ObjectiveTo assess the risks and benefits of P2Y12 inhibitor monotherapy compared with dual antiplatelet therapy (DAPT) and whether these associations are modified by patients' characteristics.DesignIndividual patient level meta-analysis of randomised controlled trials.Data sourcesSearches were conducted in Ovid Medline, Embase, and three websites (www.tctmd.com, www.escardio.org, www.acc.org/cardiosourceplus) from inception to 16 July 2020. The primary authors provided individual participant data.Eligibility criteriaRandomised controlled trials comparing effects of oral P2Y12 monotherapy and DAPT on centrally adjudicated endpoints after coronary revascularisation in patients without an indication for oral anticoagulation.Main outcome measuresThe primary outcome was a composite of all cause death, myocardial infarction, and stroke, tested for non-inferiority against a margin of 1.15 for the hazard ratio. The key safety endpoint was Bleeding Academic Research Consortium (BARC) type 3 or type 5 bleeding.ResultsThe meta-analysis included data from six trials, including 24 096 patients. The primary outcome occurred in 283 (2.95%) patients with P2Y12 inhibitor monotherapy and 315 (3.27%) with DAPT in the per protocol population (hazard ratio 0.93, 95% confidence interval 0.79 to 1.09; P=0.005 for non-inferiority; P=0.38 for superiority; τ2=0.00) and in 303 (2.94%) with P2Y12 inhibitor monotherapy and 338 (3.36%) with DAPT in the intention to treat population (0.90, 0.77 to 1.05; P=0.18 for superiority; τ2=0.00). The treatment effect was consistent across all subgroups, except for sex (P for interaction=0.02), suggesting that P2Y12 inhibitor monotherapy lowers the risk of the primary ischaemic endpoint in women (hazard ratio 0.64, 0.46 to 0.89) but not in men (1.00, 0.83 to 1.19). The risk of bleeding was lower with P2Y12 inhibitor monotherapy than with DAPT (97 (0.89%) v 197 (1.83%); hazard ratio 0.49, 0.39 to 0.63; P<0.001; τ2=0.03), which was consistent across subgroups, except for type of P2Y12 inhibitor (P for interaction=0.02), suggesting greater benefit when a newer P2Y12 inhibitor rather than clopidogrel was part of the DAPT regimen.ConclusionsP2Y12 inhibitor monotherapy was associated with a similar risk of death, myocardial infarction, or stroke, with evidence that this association may be modified by sex, and a lower bleeding risk compared with DAPT.RegistrationPROSPERO CRD42020176853.

Project description:BackgroundThe benefit of clopidogrel monotherapy after 1-month dual antiplatelet therapy (DAPT) compared with 12-month DAPT with aspirin and clopidogrel was demonstrated in the STOPDAPT-2 (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2), but not in the STOPDAPT-2 acute coronary syndrome (ACS); however, both trials were underpowered based on the actual event rates.MethodsWe obtained the prespecified pooled population of 5997 patients as the STOPDAPT-2 total cohort (STOPDAPT-2: N=3009/STOPDAPT-2 ACS: N=2988; ACS: N=4136/chronic coronary syndrome [CCS]: N=1861), comprising 2993 patients assigned to 1-month DAPT followed by clopidogrel monotherapy, and 3004 patients assigned to 12-month DAPT with aspirin and clopidogrel after percutaneous coronary intervention. The primary end point was the composite of cardiovascular (cardiovascular death, myocardial infarction, definite stent thrombosis, or any stroke) or bleeding (Thrombolysis in Myocardial Infarction major/minor) end points at 1 year.ResultsOne-month DAPT was noninferior to 12-month DAPT for the primary end point (2.84% versus 3.04%; hazard ratio [HR], 0.94 [95% CI, 0.70-1.27]; Pnoninferiority=0.001; Psuperiority=0.68). There was no significant risk-difference for the cardiovascular end point between the 1- and 12-month DAPT groups (2.40% versus 1.97%; HR, 1.24 [95% CI, 0.88-1.75]; Pnoninferiority=0.14; Psuperiority=0.23). There was a lower risk of the bleeding end point with 1-month DAPT relative to 12-month DAPT (0.50% versus 1.31%; HR, 0.38 [95% CI, 0.21-0.70]; Psuperiority=0.002). One-month DAPT relative to 12-month DAPT was associated with a lower risk for major bleeding regardless of ACS or CCS (ACS: HR, 0.46 [95% CI, 0.23-0.94]; P=0.03, and CCS: HR, 0.26 [95% CI, 0.09-0.79]; P=0.02; Pinteraction=0.40), while it was associated with a numerical increase in cardiovascular events in ACS patients, but not in CCS patients, although not statistically significant and without interaction (ACS: HR, 1.50 [95% CI, 0.99-2.27]; P=0.053, and CCS: HR, 0.74 [95% CI, 0.38-1.45]; P=0.39; Pinteraction=0.08).ConclusionsClopidogrel monotherapy after 1-month DAPT compared with 12-month DAPT with aspirin and clopidogrel had a benefit in reducing major bleeding events without being associated with increase in cardiovascular events.RegistrationURL: https://www.Clinicaltrialsgov; Unique identifiers: NCT02619760, NCT03462498.