Abstract Background Dual antiplatelet therapy (DAPT) is necessary to prevent thrombosis yet increases bleeding after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). ...Antiplatelet monotherapy with a potent P2Y12 receptor antagonist may reduce bleeding while maintaining anti thrombotic efficacy compared with conventional DAPT. Methods TWILIGHT is a randomized, double blind placebo-controlled trial evaluating the comparative efficacy and safety of antiplatelet monotherapy versus DAPT in up to 9000 high-risk patients undergoing PCI with DES. Upon enrollment after successful PCI, all patients will be treated with open label low-dose aspirin (81–100 mg daily) plus ticagrelor (90 mg twice daily) for 3 months. Event-free patients will then be randomized in a double-blind fashion to low-dose aspirin versus matching placebo with continuation of open-label ticagrelor for an additional 12 months. The primary hypothesis is that a strategy of ticagrelor monotherapy will be superior with respect to the primary endpoint of bleeding academic research consortium (BARC) type 2, 3 or 5, while maintaining non-inferiority for ischemic events compared with ticagrelor plus ASA. Conclusions TWILIGHT is the largest study to date that is specifically designed and powered to demonstrate reductions in bleeding with ticagrelor monotherapy versus ticagrelor plus ASA beyond 3 months post-procedure in a high-risk PCI population treated with DES. The trial will provide novel insights with respect to the potential role of ticagrelor monotherapy as an alternative for long-term platelet inhibition in a broad population of patients undergoing PCI with DES.
Objectives The aim of this study was to report the frequency, patient and lesion-related characteristics, and outcomes of subclinical, nonculprit plaque ruptures in the PROSPECT (Providing Regional ...Observations to Study Predictors of Events in the Coronary Tree) study. Background Plaque rupture and subsequent thrombosis is the most common cause of acute coronary syndrome (ACS). Secondary, subclinical, nonculprit plaque ruptures have been seen in both stable patients and patients with ACS; however, reports of the natural history of these secondary plaque ruptures are limited. Methods After successful stenting in 697 patients with ACS, 3-vessel grayscale and intravascular ultrasound virtual histology (IVUS-VH) was performed in the proximal-mid segments of all 3 coronary arteries as part of a prospective multicenter study. Results Among 660 patients with complete IVUS data, 128 plaque ruptures were identified in 105 nonculprit lesions in 100 arteries from 93 patients (14.1%). Although the minimum lumen area (MLA) was similar, the plaque burden was significantly greater in nonculprit lesions with a plaque rupture compared with nonculprit lesions without a plaque rupture (66.0% 95% confidence interval: 64.5% to 67.4% vs. 56.0% 95% confidence interval: 55.6% to 56.4%; p < 0.0001). IVUS-VH analysis revealed that a nonculprit lesion with a plaque rupture was more often classified as a fibroatheroma than a nonculprit lesion without a plaque rupture (77.1% vs. 51.4%; p < 0.0001). Independent predictors of a plaque rupture were lesion length (per 10 mm; odds ratio: 1.30; p < 0.0001), plaque burden at the MLA site (per 10%; odds ratio: 2.56; p < 0.0001), vessel area at the MLA site (per 1 mm2 ; odds ratio: 1.13; p < 0.0001), and VH–thin-cap fibroatheroma (odds ratio: 1.80; p = 0.016). During 3 years of follow-up, the incidence of overall major adverse cardiac events did not differ significantly between the patients with and patients without subclinical, nonculprit plaque ruptures. Conclusions Secondary, nonculprit plaque ruptures were seen in 14% of patients with ACS and were associated with a fibroatheroma phenotype with a residual necrotic core but not with adverse outcomes if patients were treated with optimal medical therapy as part of a multicenter study. (Providing Regional Observations to Study Predictors of Events in the Coronary Tree PROSPECT; NCT00180466 )
Objectives This study sought to investigate whether the everolimus-eluting stent (EES) is superior to the paclitaxel-eluting stent (PES) with respect to long-term individual clinical outcomes. ...Background Individual studies have indicated a clinical advantage of coronary EES compared with PES with respect to restenosis and the composite endpoint of major adverse cardiac events. However, these trials were not powered for superiority in low-frequency event rates and have reported limited data beyond 1-year follow-up. Methods We conducted a meta-analysis of the final 3-year results from the international SPIRIT (Clinical Evaluation of the Xience V Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions) II, III, and IV clinical trials. Individual patient data from 4,989 patients who were prospectively randomized to treatment with EES (n = 3,350) or PES (n = 1,639) were pooled for analysis. Results At 3-year follow-up, EES was superior to PES in reducing the following event rates: target lesion failure (8.9% vs. 12.5%, hazard ratio HR: 0.71, 95% confidence interval CI: 0.59 to 0.85; p = 0.0002), all-cause mortality (3.2% vs 5.1%, HR: 0.65, 95% CI: 0.49 to 0.86; p = 0.003), myocardial infarction (3.2% vs. 5.1%, HR: 0.64, 95% CI: 0.48 to 0.85; p = 0.002), cardiac death or myocardial infarction (4.4% vs. 6.3%, HR: 0.70, 95% CI: 0.54 to 0.90; p = 0.005), ischemia-driven target lesion revascularization (6.0% vs. 8.2%, HR: 0.72, 95% CI: 0.58 to 0.90; p = 0.004), stent thrombosis (0.7% vs. 1.7%, HR: 0.45, 95% CI: 0.26 to 0.78; p = 0.003), and major adverse cardiac events (9.4% vs. 13.0%, HR: 0.71, 95% CI: 0.60 to 0.85; p = 0.0002). No interaction was present between stent type and the 3-year relative rates of target lesion failure across a broad range of subgroups, with the exception of diabetes and vessel (left anterior descending vs. other). Conclusions In this large dataset with 3-year follow-up, coronary implantation of EES compared with PES resulted in reduced rates of all-cause mortality, myocardial infarction, ischemia-driven target lesion revascularization, stent thrombosis, and target lesion failure. Further research is warranted to characterize possible interactions between stent type, diabetes, and vessel.
Abstract Objectives The aim of this study was to investigate the clinical correlates and prognostic impact of coronary artery calcification (CAC) in women undergoing percutaneous coronary ...intervention with drug-eluting stents (DES). Background The clinical correlates and the prognostic significance of CAC in women undergoing percutaneous coronary intervention with DES remain unclear. Methods Patient-level data from female participants in 26 randomized trials of DES were pooled. Study population was categorized according to the presence of moderate or severe versus mild or no target lesion CAC, assessed through coronary angiography. Co–primary endpoints of interest were the composite of death, myocardial infarction (MI), or target lesion revascularization and death, MI, or stent thrombosis at 3-year follow-up. Results Among 11,557 women included in the pooled dataset, CAC status was available in 6,371 women. Of these, 1,622 (25.5%) had moderate or severe CAC. In fully adjusted models, independent correlates of CAC were age, hypertension, hypercholesterolemia, smoking, previous coronary artery bypass graft surgery, and worse left ventricular and renal function. At 3 years, women with CAC were at higher risk for death, MI, or target lesion revascularization (18.2% vs. 13.1%; adjusted hazard ratio: 1.56; 95% confidence interval: 1.33 to 1.84; p < 0.0001) and death, MI, or stent thrombosis (12.7% vs. 8.6%; adjusted hazard ratio: 1.48; 95% confidence interval: 1.21 to 1.80; p = 0.0001). The adverse effect of CAC on ischemic outcomes appeared to be consistent across clinical and angiographic subsets of women, including new-generation DES. Conclusions Women undergoing PCI of calcified lesions tend to have worse clinical profile and remain at increased ischemic risk, irrespective of new-generation DES.
Most intravascular ultrasound (IVUS)-identifiable myocardial bridges (MBs) were not appreciated angiographically, especially when they occurred adjacent to fixed proximal obstructive disease. The ...impact of MB stent placement on clinical outcome was determined in 317 consecutive patients with obstructive left anterior descending coronary artery lesions undergoing coronary stent placement. In these patients, IVUS identified 70 MBs, defined as a segment of coronary artery with both systolic compression and perivascular echolucent muscle. IVUS showed that the stent extended into the MB segment beyond the obstructive lesion in 24 patients (34%; MB stent group), although significant plaque was not observed within any MB segment. In the remaining 46 patients, the left anterior descending artery stent was implanted in only the obstructive lesion, avoiding the distal MB segment (non-MB stent group). Minimum stent area was significantly smaller in the MB stent group than non-MB stent group (4.8 ± 1.1 vs 5.8 ± 1.8 mm2 ; p = 0.02). Rates of target-lesion revascularization, target-vessel revascularization, and composite end point (death/myocardial infarction/target-lesion revascularization/target-vessel revascularization, evaluated at a mean follow-up of 358 ± 252 days) were more common in patients with versus without MB stent placement. Specifically, target-lesion revascularization rates were 24% versus 3%, respectively (log-rank p = 0.003). In-stent restenosis occurred within the stented MB segment in 3 of 5 MB stent group patients who required target-lesion revascularization (60%). In conclusion, inadvertent MB stent placement in left anterior descending artery lesions occurred commonly and may have been associated with an increased incidence of late events.
Background The aim of the study was to investigate the incidence and clinical consequences of acquired thrombocytopenia in patients with acute coronary syndromes (ACS) in the ACUITY trial. Methods We ...examined 10,836 patients with ACS randomized to receive heparin plus glycoprotein (GP) IIb/IIIa inhibitor, bivalirudin plus GP IIb/IIIa inhibitor, or bivalirudin monotherapy. Results Acquired thrombocytopenia developed in 740 (6.8%) patients; mild (100,000-150,000 platelets/mm3 ), moderate (50,000-100,000 platelets/mm3 ), and severe (<50,000 platelets/mm3 ) developed in 656 (6%), 51 (0.5%), and 33 (0.3%) patients, respectively. Patients with acquired thrombocytopenia, compared with those without, were more likely to develop major bleeding (14% vs 4.3%, P < .0001) at 30 days and had higher rates of mortality (6.5% vs 3.4%, P < .0001) at 1 year. By multivariate analysis, acquired thrombocytopenia was an independent predictor of major bleeding at 30 days (hazard ratio HR 1.68, 95% CI 1.04-2.72, P = .03). Moderate and severe acquired thrombocytopenia were predictors of mortality at 1 year (HR 2.89, 95% CI 0.92-9.06, P = .06, and HR 3.41, 95% CI 1.09-10.68, P = .03, respectively). Compared to heparin plus GP IIb/IIIa inhibitor, bivalirudin monotherapy was associated with less declines in platelet count by >25% (7.6% vs 5.6%, P = .0009) and >50% (1.4% vs 0.7%, P = .004) from baseline. Conclusions Acquired thrombocytopenia occurs in approximately 1 in 14 patients with ACS treated with antithrombin and antiplatelet medications and is strongly associated with hemorrhagic and ischemic complications. Compared to an anticoagulant regimen including a GP IIb/IIIa inhibitor, administration of bivalirudin monotherapy appears to be associated with less frequent declines in platelet count.
Although interventional technology and skills have markedly advanced, percutaneous coronary intervention (PCI) for coronary chronic total occlusion (CTO) lesions remains challenging. Indeed, CTO PCI ...is technically complex, carries the potential for a relatively high likelihood of failure and acute complications, and requires specifically skilled operators and a demanding use of resources. In addition, controversy persists surrounding appropriate indications for attempting CTO revascularization. Finally, there is a wide uncertainty on the actual benefits achieved with successful CTO recanalization. A growing number of studies have reported procedural results and/or assessed functional effects and long-term clinical outcomes of CTO PCI. We therefore sought to review and critically appraise the evidence base for procedural outcomes and potential clinical benefits of CTO PCI.
Objectives We compared intravascular ultrasound findings of drug-eluting stent (DES)–treated lesions that developed thrombosis versus in-stent restenosis (ISR). Background Stent underexpansion is a ...predictor of both DES thrombosis and ISR. However, all underexpanded DES may not be equal. Methods Intravascular ultrasound findings from 20 definite DES thrombosis patients (representing all definite thromboses from 1,407 consecutive DES patients undergoing intravascular ultrasound imaging) were compared with 50 risk-factor-balanced ISR patients with no evidence of stent thrombosis and 50 risk-factor-balanced “no-event” patients with neither thrombosis nor ISR. Results Minimum stent area (3.9 ± 1.0 mm2 vs. 5.0 ± 1.7 mm2 , p = 0.008), mean stent area (5.3 ± 1.0 mm2 vs. 7.2 ± 2.0 mm2 , p = 0.001), and both focal (55.4 ± 13.2% vs. 74.9 ± 19.9%, p < 0.001) and diffuse stent expansion (77.4 ± 19.3% vs. 109.5 ± 23.1%, p < 0.001) were significantly smaller in the stent thrombosis group versus ISR and in both groups versus the “no-event” group. Minimum stent area <4.0 mm2 (65% vs. 32%, p = 0.01) or <5.0 mm2 (85% vs. 52%, p = 0.01) was more common in the stent thrombosis versus the ISR group and in both groups vs. “no-event” patients; and the relative length of the stent area <5 mm2 was greatest in the stent thrombosis group (36.6 ± 37.7%), intermediate in the ISR group (22.8 ± 35.6%), and least in the “no-event” group (10.9 ± 26.4%), p = 0.04. In the stent thrombosis group, the minimum stent area site occurred in the proximal stent segment in 50% versus 24% in the ISR group (p = 0.03). There were no differences in edge dissection, stent fracture, or stent-vessel-wall malapposition among the groups. Conclusions The DES-treated lesions that develop thrombosis or restenosis are often underexpanded, but underexpansion associated with thrombosis is more severe, diffuse, and proximal in location.
Objective: This study sought to investigate the effect of body mass index on outcomes in patients with severe aortic valve stenosis undergoing transcatheter aortic valve implantation. Methods: A ...total of 12,381 patients undergoing transfemoral transcatheter aortic valve implantation were divided into body mass index categories: underweight (<18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), and obesity (>30 kg/m2). Primary endpoints were differences in 30-day and 1-year all-cause mortality. Secondary endpoints included all other clinical endpoints such as stroke. Univariate and multivariate odds ratios were calculated using logistic and cox regression analyses. Results: Two percent (n = 205) of patients were underweight, 29% (n = 3564) were normal weight, 44% (n = 5460) were overweight, and 25% (n = 3152) were obese. Thirty-day mortality was lower in overweight (5.3%, odds ratio, 0.73; 95% confidence interval, 0.61-0.88; P = .001) and obese patients (5.2%, odds ratio, 0.74; 95% confidence interval, 0.60-0.92; P = .006), but higher in underweight (9.8%, odds ratio, 1.51; 95% confidence interval, 0.92-2.47; P = .010) as compared to normal weight patients (6.9%). After multivariate adjustment, 30-day mortality was not significantly different across body mass index categories. However, 1-year mortality was higher in underweight patients (hazard ratio, 1.52; 95% confidence interval, 1.10-2.09; P = .011). Stroke rates were comparable between body mass index groups. Conclusions: For overweight and obese patients with severe aortic valve stenosis undergoing transcatheter aortic valve implantation, there was no 30-day difference in mortality compared with patients with normal weight. However, underweight patients showed higher rates of 1-year mortality after transcatheter aortic valve implantation.
Gender-Specific Outcomes After Sirolimus-Eluting Stent Implantation Emilia Solinas, Eugenia Nikolsky, Alexandra J. Lansky, Ajay J. Kirtane, Marie-Claude Morice, Jeffrey J. Popma, Joachim Schofer, ...Erick Schampaert, Tereza Pucelikova, Jiro Aoki, Martin Fahy, George D. Dangas, Jeffrey W. Moses, Donald E. Cutlip, Martin B. Leon, Roxana Mehran In this analysis of pooled data from the RAVEL (Randomized Comparison of a Sirolimus-Eluting Stent with a Standard Stent for Coronary Revascularization), SIRIUS (SIRolImUS-coated Bx velocity balloon expandable stent in the treatment of patients with de novo coronary artery lesions), E-SIRIUS (Sirolimus-eluting stents for treatment of patients with long atherosclerotic lesions in small coronary arteries), and C-SIRIUS (Canadian study of the sirolimus-eluting stent in the treatment of patients with long de novo lesions in small native coronary arteries) trials, sirolimus-eluting stent (SES) versus bare metal-stent (BMS) implantation was associated with significant reductions in rates of in-segment binary restenosis both in women (6.3% vs. 43.8%) and in men (6.4% vs. 35.6%), as well as reductions in adverse clinical outcomes in both genders. By multivariable analysis, female gender was not an independent predictor of restenosis and clinical outcomes in SES- or BMS-treated patients.
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