Comparison of one-month versus twelve-month dual antiplatelet therapy after implantation of drug-eluting stents guided by either intravascular ultrasound or angiography in patients with acute coronary syndrome: rationale and design of prospective, multicenter, randomized, controlled IVUS-ACS and ULTIMATE-DAPT trial.

BACKGROUND: Current guidelines recommend administering dual antiplatelet therapy (DAPT) for 12 months to patients with acute coronary syndromes (ACS) and without contraindications after drug-eluting stent (DES) implantation. A recent study reported that 3 months of DAPT followed by ticagrelor monotherapy is effective and safe in ACS patients undergoing DES implantation compared with the standard duration of DAPT. However, it is unclear whether antiplatelet monotherapy with ticagrelor alone versus ticagrelor plus aspirin reduces the incidence of clinically relevant bleeding without increasing the risk of major adverse cardiovascular and cerebrovascular events (MACCEs) in ACS patients undergoing percutaneous coronary intervention (PCI) with DES implantation guided by either intravascular ultrasound (IVUS) or angiography who have completed a 1-month course of DAPT with aspirin plus ticagrelor. METHODS: The IVUS-ACS and ULTIMATE-DAPT is a prospective, multicenter, randomized, controlled trial designed to determine (1) whether IVUS-guided versus angiography-guided DES implantation in patients with ACS reduces the risk of target vessel failure (TVF) at 12 months and (2) whether ticagrelor alone versus ticagrelor plus aspirin reduces the risk of clinically relevant bleeding without increasing the risk of MACCE 1-12 months after the index PCI in ACS patients undergoing DES implantation guided by either IVUS or angiography. This study will enroll 3486 ACS patients eligible for DES implantation, as confirmed by angiographic studies. The patients who meet the inclusion criteria and none of the exclusion criteria will be randomly assigned in a 1:1 fashion to the IVUS- or angiography-guided group (first randomization). All enrolled patients will complete a 1-month course of DAPT with aspirin plus ticagrelor after the index PCI. Patients with no MACCEs or major bleeding (≥Bleeding Academic Research Consortium (BARC) 3b) within 30 days will be randomized in a 1:1 fashion to either the ticagrelor plus matching placebo (SAPT)group or ticagrelor plus aspirin (DAPT)group for an additional 11 months (second randomization). The primary endpoint of the IVUS-ACS trial is TVF at 12 months, including cardiac death, target vessel myocardial infarction (TVMI), or clinically driven target vessel revascularization (CD-TVR). The primary superiority endpoint of the ULTIMATE-DAPT trial is clinically relevant bleeding, defined as BARC Types 2, 3, or 5 bleeding, and the primary non-inferiority endpoint of the ULTIMATE-DAPT trial is MACCE, defined as cardiac death, myocardial infarction, ischemic stroke, CD-TVR, or definite stent thrombosis occurring 1-12 months in the second randomized population. CONCLUSION: The IVUS-ACS and ULTIMATE-DAPT trial is designed to test the efficacy and safety of 2 different antiplatelet strategies in ACS patients undergoing PCI with DES implantation guided by either IVUS or angiography. This study will provide novel insights into the optimal DAPT duration in ACS patients undergoing PCI and provide evidence on the clinical benefits of IVUS-guided PCI in ACS patients.

Obstructive Sleep Apnea Affecting Platelet Reactivity in Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: The relationship between obstructive sleep apnea (OSA) and platelet reactivity in patients undergoing percutaneous coronary intervention (PCI) has not been defined. The present prospective, single-center study explored the relationship between platelet reactivity and OSA in patients with PCI. METHODS: A total of 242 patients were finally included in the study. OSA was screened overnight by polysomnography. Platelet reactivity was assessed with a sequential platelet counting method, and the platelet maximum aggregation ratio (MAR) and average aggregation ratio were calculated. All patients were assigned per apnea-hypopnea index (AHI) to non-OSA (n = 128) and OSA (n = 114) groups. The receiver operating characteristic curve analysis was used to evaluate the accuracy of AHI for high platelet reactivity (HPR) on aspirin and clopidogrel, and multivariable logistic regression was used to determine the independent predictors of HPR on aspirin and clopidogrel. RESULTS: Median AHI was significantly higher in the OSA group than in the non-OSA group (34.5 events/h vs. 8.1 events/h, Z = -13.422, P < 0.001). Likewise, median arachidonic acid- and adenosine diphosphate-induced maximum aggregation rate (MAR) in the OSA group was significantly higher than those in the non-OSA group (21.1% vs. 17.7%, Z = -3.525, P < 0.001 and 45.8% vs. 32.2%, Z = -5.708, P < 0.001, respectively). Multivariable logistic regression showed that OSA was the only independent predictor for HPR on aspirin (odds ratio [OR]: 1.055, 95% confidence interval [CI]: 1.033-1.077, P < 0.001) and clopidogrel (OR: 1.036, 95% CI: 1.017-1.056, P < 0.001). The cutoff value of AHI for HPR on aspirin was 45.2 events/h (sensitivity 47.1% and specificity 91.3%), whereas cutoff value of AHI for HPR on clopidogrel was 21.3 events/h (sensitivity 68.3% and specificity 67.7%). CONCLUSION: Platelet reactivity appeared to be higher in OSA patients with PCI despite having received a loading dose of aspirin and clopidogrel, and OSA might be an independent predictor of HPR on aspirin and clopidogrel.