Aims : The aim of this study was to determine the effect of ticagrelor monotherapy on clinically relevant bleeding and major ischaemic events in relation to clinical presentation with and without non-ST elevation acute coronary syndromes (NSTE-ACS) among patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Methods and results : We conducted a pre-specified subgroup analysis of The Ticagrelor With Aspirin or Alone in High Risk Patients After Coronary Intervention (TWILIGHT) trial, which enrolled 9006 patients with high-risk features undergoing PCI with DES. After 3 months of dual antiplatelet therapy (DAPT) with ticagrelor plus aspirin, 7119 adherent and event-free patients were randomized in a double-blind manner to ticagrelor plus placebo versus ticagrelor plus aspirin for 12 months. The primary outcome was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding while the composite of all-cause death, myocardial infarction (MI), or stroke was the key secondary outcome. Among patients with NSTE-ACS (n = 4614), ticagrelor monotherapy reduced BARC 2, 3, or 5 bleeding by 53% [3.6% vs. 7.6%; hazard ratio (HR) 0.47; 95% confidence interval (CI) 0.36–0.61; P < 0.001) and in stable patients (n = 2503) by 24% (4.8% vs. 6.2%; HR 0.76; 95% CI 0.54–1.06; P = 0.11; nominal P int = 0.03). Rates of all-cause death, MI, or stroke among those with (4.3% vs. 4.4%; HR 0.97; 95% CI 0.74–1.28; P = 0.84) and without (3.1% vs. 3.2%; HR 0.96; 95% CI 0.61–1.49; P = 0.85) NSTE-ACS were similar between treatment arms irrespective of clinical presentation (P int = 0.96). Conclusion : Among patients with or without NSTE-ACS who have completed an initial 3-month course of DAPT following PCI with DES, ticagrelor monotherapy reduced clinically meaningful bleeding events without increasing ischaemic risk as compared with ticagrelor plus aspirin. The benefits of ticagrelor monotherapy with respect to bleeding events were more pronounced in patients with NSTE-ACS. Trial registration: Clinicaltrials.gov identifier: NCT02270242.

Patients at high bleeding risk (HBR) represent a prevalent subgroup among those undergoing percutaneous coronary intervention (PCI). Early aspirin discontinuation after a short course of dual antiplatelet therapy (DAPT) has emerged as a bleeding avoidance strategy. The aim of this study was to assess the effects of ticagrelor monotherapy after 3-month DAPT in a contemporary HBR population. This prespecified analysis of the TWILIGHT trial evaluated the treatment effects of early aspirin withdrawal followed by ticagrelor monotherapy in HBR patients undergoing PCI with drug-eluting stents. After 3 months of ticagrelor plus aspirin, event-free patients were randomized to 12 months of aspirin or placebo in addition to ticagrelor. A total of 1064 (17.2%) met the Academic Research Consortium definition for HBR. Ticagrelor monotherapy reduced the incidence of the primary endpoint of Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding compared with ticagrelor plus aspirin in HBR (6.3% vs. 11.4%; hazard ratio (HR) 0.53, 95% confidence interval (CI) 0.35–0.82) and non-HBR patients (3.5% vs. 5.9%; HR 0.59, 95% CI 0.46–0.77) with similar relative (P_interaction = 0.67) but a trend towards greater absolute risk reduction in the former [−5.1% vs. −2.3%; difference in absolute risk differences (ARDs) −2.8%, 95% CI −6.4% to 0.8%, P = 0.130]. A similar pattern was observed for more severe BARC 3 or 5 bleeding with a larger absolute risk reduction in HBR patients (−3.5% vs. −0.5%; difference in ARDs −3.0%, 95% CI −5.2% to −0.8%, P = 0.008). There was no significant difference in the key secondary endpoint of death, myocardial infarction, or stroke between treatment arms, irrespective of HBR status. Among HBR patients undergoing PCI who completed 3-month DAPT without experiencing major adverse events, aspirin discontinuation followed by ticagrelor monotherapy significantly reduced bleeding without increasing ischaemic events, compared with ticagrelor plus aspirin. The absolute risk reduction in major bleeding was larger in HBR than non-HBR patients. Effects of ticagrelor plus placebo vs. ticagrelor plus aspirin on bleeding and ischaemic events among high bleeding risk and non-high bleeding risk patients who tolerated 3 months of dual antiplatelet therapy after percutaneous coronary intervention with a drug-eluting stent. BARC, Bleeding Academic Research Consortium; CI, confidence interval; DAPT, dual antiplatelet therapy; HBR, high bleeding risk; HR, hazard ratio; MI, myocardial infarction; PCI, percutaneous coronary intervention; tica, ticagrelor.

Background— Intravascular ultrasound (IVUS) studies have shown that a mechanism of plaque compression/embolization contributes toward the poststenting increase in lumen area. The aim of this IVUS study was to compare the mechanisms of lumen enlargement after coronary stenting in 54 consecutive patients with unstable angina (UA) (group 1) and 56 with stable angina (group 2) to verify whether plaque embolization plays a major role in the former. Methods and Results— Both groups underwent the IVUS assessment (speed, 0.5 mm/sec) before the intervention and after stent implantation. The lumen area, the external elastic membrane area, and the plaque+media area (PA) were measured at 0.5-mm intervals. PA reduction in the lesion site was significantly greater in group 1 (−2.50±1.97 versus −0.53±1.43 mm ² , P <0.001). After stenting, 47% of the lumen area increase in group 1 was obtained by means of PA reduction, and 53% was attributable to external elastic membrane area increase; the corresponding figures in group 2 were 13% and 87% ( P <0.05). Decrease in PA after stenting was the only significant predictor of the MB fraction of creatinine kinase (CK-MB) release in a multiple regression model ( P =0.047). Conclusions— Serial volumetric IVUS assessment revealed in UA lesions a marked poststenting reduction in plaque volume, which is significantly greater than in stable angina and is associated with postprocedural CK-MB release. The decrease in PA during the procedure predicts CK-MB release in a multiple regression model. These findings suggest that stent deployment is often associated with plaque embolization in patients with UA.

Endothelial dysfunction and plaque formation are features of atherosclerosis. Inhibition of L-type calcium channels or HMG-CoA pathway improves endothelial function and reduces plaque size. Thus, we investigated in stable coronary artery disease (CAD) the effects of a calcium antagonist on coronary endothelial function and plaque size. In 454 patients undergoing PCI, acetylcholine (10⁻⁶ to 10⁻⁴ M) was infused in a coronary segment without significant CAD. Changes in coronary diameter were measured and an intravascular ultrasound examination (IVUS) was performed. On top of statin therapy, patients were randomized in a double-blind fashion to placebo or nifedipine GITS 30–60 mg/day and followed for 18–24 months. Blood pressure was lower on nifedipine than on placebo by 5.8/2.1 mmHg (P < 0.001) as was total and LDL cholesterol (4.8 mg/dL; P = 0.495), while HDL was higher (3.6 mg/dL; P = 0.026). In the most constricting segment, nifedipine reduced vasoconstriction to acetylcholine (14.0% vs. placebo 7.7%; P < 0.0088). The percentage change in plaque volume with nifedipine and placebo, respectively, was 1.0 and 1.9%, ns. The ENCORE II trial demonstrates in a multi-centre setting that calcium channel blockade with nifedipine for up to 2 years improves coronary endothelial function on top of statin treatment, but did not show an effect of nifedipine on plaque volume.