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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. 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 type 2, 3 or 5, while maintaining non-inferiority for ischemic events compared with ticagrelor plus ASA. 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.

Older patients who undergo coronary interventions are at greater risk of ischemic events and less likely to tolerate prolonged dual antiplatelet therapy (DAPT) due to bleeding risk. The COMBO biodegradable polymer sirolimus-eluting stent promotes rapid endothelialization through endothelial progenitor cell capture technology which may be advantageous in elderly patients. We compared 1-year clinical outcomes and DAPT cessation events in patients >75 versus ≤75 years from the MASCOT registry. MASCOT was a prospective, multicenter cohort study of all-comers undergoing attempted COMBO stenting. The primary endpoint was 1-year target lesion failure (TLF), composite of cardiac death, myocardial infarction (MI) not clearly attributed to a nontarget vessel or clinically driven target lesion revascularization. Bleeding was adjudicated using the Bleeding Academic Research Consortium criteria. Adjusted outcomes were analyzed using Cox regression methods. The study included 18% (n = 479) patients >75 years and 72% (n = 2,135) patients ≤75 years. One-year TLF occurred in 4.6% patients >75 years versus 3.1% patients ≤75years of age, p = 0.10; adj hazard ratio 1.36, 95% confidence intervals 0.77 to 2.38, p = 0.29. There were no significant differences in cardiac death (1.7% vs 1.3%, p = 0.55), MI (2.1% vs 1.2%, p = 0.14), target lesion revascularization (1.7% vs 1.4%, p = 0.60) and definite stent thrombosis (0.8% vs 0.4%, p = 0.19). Major Bleeding Academic Research Consortium 3,5 bleeding (3.1% vs 1.5%, p = 0.01) and DAPT cessation rates (32.4% vs 23.0%, p <0.001) were significantly higher in elderly patients. In conclusion, elderly patients >75 years treated with COMBO stents had similar TLF but significantly greater incidence of bleeding than younger patients and DAPT cessation in one-third of patients over 1 year.

We sought to determine the frequency of use and association between prasugrel and outcomes in acute coronary syndrome patients undergoing percutaneous coronary intervention (PCI) in clinical practice. PROMETHEUS was a multicenter observational registry of acute coronary syndrome patients undergoing PCI from 8 centers in the United States that maintained a prospective PCI registry for patient outcomes. The primary end points were major adverse cardiovascular events at 90days, a composite of all-cause death, nonfatal myocardial infarction, stroke, or unplanned revascularization. Major bleeding was defined as any bleeding requiring hospitalization or blood transfusion. Hazard ratios (HRs) were generated using multivariable Cox regression and stratified by the propensity to treat with prasugrel. Of 19,914 patients (mean age 64.4years, 32% female), 4,058 received prasugrel (20%) and 15,856 received clopidogrel (80%). Prasugrel-treated patients were younger with fewer comorbid risk factors compared with their counterparts receiving clopidogrel. At 90days, there was a significant association between prasugrel use and lower major adverse cardiovascular event (5.7% vs 9.6%, HR 0.58, 95% CI 0.50-0.67, P<.0001) and bleeding (1.9% vs 2.9%, HR 0.65, 95% CI 0.51-0.83, P<.001). After propensity stratification, associations were attenuated and no longer significant for either outcome. Results remained consistent using different approaches to adjusting for potential confounders. In contemporary clinical practice, patients receiving prasugrel tend to have a lower-risk profile compared with those receiving clopidogrel. The lower ischemic and bleeding events associated with prasugrel use were no longer evident after accounting for these baseline differences.

Temporary interruption of dual antiplatelet therapy (DAPT) is not infrequently required in patients undergoing percutaneous coronary intervention (PCI). We sought to describe the procedures and outcomes associated with DAPT interruption in patients treated with DAPT following successful PCI from the Patterns of non-adherence to anti-platelet regimens in stented patients registry (n = 5018). DAPT interruption was prespecified as physician recommended cessation for <14 days. Of the study cohort, 490 patients (9.8%) experienced 594 DAPT interruptions over 2 years following PCI. Only 1 antiplatelet agent was interrupted in 57.2% cases and interruption was frequently recommended by noncardiologists (51.3%). Where type of surgery was reported, majority of DAPT interruptions occurred for minor surgery (68.4% vs 31.6%) and a similar cessation pattern of single versus dual antiplatelet cessation was observed regardless of minor or major surgery. Subsequent to DAPT interruption, 12 patients (2.4%) experienced 1 thrombotic event each, of which 5 (1.0%) occurred during the interruption period. All events occurred in patients who either stopped both agents (8 of 12) or clopidogrel-only (4 of 12), with no events occurring due to aspirin cessation alone. In conclusion, in the Patterns of Non-adherence to Anti-platelet Regiments in Stented Patients registry, 1 in 10 patients were recommended DAPT interruption for surgery within 2 years of PCI. Interruption was more common for a single agent rather than both antiplatelet agents regardless of severity of surgery, and was frequently recommended by noncardiologists. Only 1% of patients with DAPT interruption experienced a subsequent thrombotic event during the interruption period, which mainly occurred in patients stopping both antiplatelet agents.

Studies have shown worse outcome for women compared with men after percutaneous coronary intervention (PCI), especially in the presence of diabetes mellitus (DM). We aimed to investigate the risk of ischemic events after PCI in women versus men stratified by the presence or absence of DM. A total of 17,154 consecutive patients from a single-center PCI registry enrolled from January 2009 to December 2014 were categorized accordingly: female/non-DM, female/DM, male/non-DM, and male/DM. End points included death and myocardial infarction (MI) at 1 year. Of the overall population, 15% (n = 2,631) were female/non-DM, 17% (n = 2,891) were female/DM, 38% (n = 6,483) were male/non-DM, and 30% (n = 5,149) were male/DM. Within the 4 study groups, female/DM had the highest risk, whereas female/non-DM and male/DM showed similar risks and male/non-DM showed lowest risk for death (4.64% vs 3.08% vs 2.93% vs 2.31%; p-trend <0.0001 over all groups and p = 0.69 between female/non-DM and male/DM, respectively) and MI (4.15% vs 3.99% vs 3.71% vs 2.55%; p trend <0.0001 over all groups and p = 0.97 between female/non-DM and male/DM, respectively). After multivariate adjustment findings were largely unchanged suggesting highest risk for adverse events in diabetic women compared with other groups and comparable risks for death and MI in nondiabetic women compared with diabetic men. In conclusion, these findings highlight the combined influence of DM and female gender as strong determinants of post-PCI risk while also illustrating “risk equivalence” between nondiabetic women versus diabetic men.

BackgroundPrasugrel is a potent thienopyridine that may be preferentially used in younger patients with lower bleeding risk.ObjectiveWe compared prasugrel use and outcomes by age from the PROMETHEUS study. We also assessed age-related trends in treatment effects with prasugrel versus clopidogrel.MethodsPROMETHEUS was a multicenter acute coronary syndrome (ACS) percutaneous coronary intervention (PCI) registry. We compared patients in age tertiles (T1 < 60 years, T2 60–70 years, T3 > 70 years). Major adverse cardiac events (MACE) were a composite of death, myocardial infarction, stroke or unplanned revascularization. Data were adjusted using multivariable Cox regression for age-related risks and propensity score stratification for thienopyridine effects.ResultsThe study included 19,914 patients: 7045 (35.0%) in T1, 6489 (33.0%) in T2 and 6380 (32.0%) in T3. Prasugrel use decreased from T1 to T3 (29.2% vs. 23.5% vs. 7.5%, p < 0.001). Crude 1-year MACE rates were highest in T3 (17.4% vs. 16.8% vs. 22.7%, p < 0.001), but adjusted risk was similar between the groups (p-trend 0.52). Conversely, crude incidence (2.8% vs. 3.8% vs. 6.9%, p < 0.001) and adjusted bleeding risk were highest in T3 (HR 1.24, 95% CI 0.99–1.55 in T2; HR 1.83, 95% CI 1.46–2.30 in T3; p-trend < 0.001; reference = T1). Treatment effects with prasugrel versus clopidogrel did not demonstrate age-related trends for MACE (p-trend = 0.91) or bleeding (p-trend = 0.28).ConclusionsAge is a strong determinant of clinical risk as well as prasugrel prescription in ACS PCI with much lower use among older patients. Prasugrel did not have a differential treatment effect by age for MACE or bleeding.Graphic abstractFrequency of prasugrel use and age-related temporal risks of all-cause death and bleeding after ACS PCI.

PurposeThe COMBO biodegradable polymer sirolimus-eluting stent includes endothelial progenitor cell capture (EPC) technology for rapid endothelialization, which may offer advantage in acute coronary syndromes (ACS). We sought to analyze the performance of the COMBO stent by ACS status and ACS subtype.MethodsThe COMBO collaboration (n = 3614) is a patient-level pooled dataset from the MASCOT and REMEDEE registries. We evaluated outcomes by ACS status, and ACS subtype in patients with ST segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) versus unstable angina (UA). The primary endpoint was 1-year target lesion failure (TLF), composite of cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization. Secondary outcomes included stent thrombosis (ST).ResultsWe compared 1965 (54%) ACS and 1649 (46.0%) non-ACS patients. ACS presentations included 40% (n = 789) STEMI, 31% (n = 600) NSTEMI, and 29% (n = 576) UA patients. Risk of 1-year TLF was greater in ACS patients (4.5% vs. 3.3%, HR 1.51 95% CI 1.01–2.25, p = 0.045) without significant differences in definite/probable ST (1.1% vs 0.5%, HR 2.40, 95% CI 0.91–6.31, p = 0.08). One-year TLF was similar in STEMI, NSTEMI, and UA (4.8% vs 4.8% vs. 3.7%, p = 0.60), but definite/probable ST was higher in STEMI patients (1.9% vs 0.5% vs 0.7%, p = 0.03). Adjusted outcomes were not different in MI versus UA patients.ConclusionsDespite the novel EPC capture technology, COMBO stent PCI was associated with somewhat greater risk of 1-year TLF in ACS than in non-ACS patients, without significant differences in stent thrombosis. No differences were observed in 1-year TLF among ACS subtypes.

Increasing numbers of balloon aortic valvuloplasty (BAV) are performed in the management of symptomatic aortic stenosis as bridge and therapeutic challenge in the work-up for transcatheter aortic valve replacement. However, the significance of gender in outcomes following BAV remains controversial. We retrospectively reviewed 664 consecutive patients who underwent BAV from January 2005 to December 2012. Patients were stratified according to gender. Clinical and procedural characteristics as well as in-hospital outcomes and 1-year mortality were collected. Cumulative survival curves for women and men were constructed using the Kaplan-Meier method and were compared by the log-rank test. Cox regression analysis was performed to identify the independent effect of sex on 1-year mortality. Of the 664 patients, 333 (52%) were women. Women had lower body surface area, tended to be frailer and were less likely to have history of coronary artery disease. Women were more likely to present with heart failure whereas men presented more commonly with chest pain. In hospital death was significantly higher in women compared to men, mainly driven by the difference in cardiac death (8.1% vs 3.9%, P = .02 and 6.3% vs 2.6%, P = .02 respectively). One-year mortality rates were similar in women and men (25.4% vs 29.4%, P = .42) and after multivariate analysis gender had no association with 1-year mortality (HR = 0.9, P = .65). Significant differences exist in baseline characteristics and presentation between genders. Although in hospital mortality after BAV was significantly higher in women, 1-year mortality was similar between women and men.

Eosinophilic esophagitis (EoE) is a chronic antigen mediated disease associated with substantial esophageal remodeling and fibrosis. The functional TGFβ1 promoter SNP C-509 associates with renal fibrosis and asthma. The effect of TGFβ1 genotype and EoE severity or potential gene-environment interactions have not been previously reported in EoE. Genotype at TGFβ1 C-509T and remodeling was analyzed in 144 subjects with EoE. The severity of remodeling and inflammation was analyzed in the context of IgE sensitization to food antigens and C-509T genotype. The TGFβ1 promoter C-509 genotypes CC, CT, and TT were 35%, 52%, and 13%, respectively. Sixty-six percent of subjects were sensitized to foods by positive skin prick test (SPT) or serum specific IgE. TT genotype subjects had significantly more TGFβ1 (CC subjects = 1300 per mm2; TT = 2250 per mm2) (p<0.05) and tryptase (CC subjects = 145 per mm2: TT = 307 per mm2) (p<0.05) positive cells and higher epithelial remodeling scores (2.4 vs 3.7, p<0.001) than CC subjects. The differences in TGFβ1 and tryptase positive cells as well as fibrosis were significantly increased when there was concurrent food sensitization. Food sensitization alone did not associate with any parameters of inflammation or remodeling. Our data support a gene-environment interaction between food and genotype at C-509 that modulates disease severity in EoE. Since EoE subjects often continue to consume foods to which they are sensitized, these findings may have clinical relevance for disease management.

Assessment of platelet reactivity alone for thienopyridine selection with percutaneous coronary intervention (PCI) has not been associated with improved outcomes. In TRIAGE, a prospective multicenter observational pilot study we sought to evaluate the benefit of an integrated algorithm combining clinical risk and platelet function testing to select type of thienopyridine in patients undergoing PCI. Patients on chronic clopidogrel therapy underwent platelet function testing prior to PCI using the VerifyNow assay to determine high on treatment platelet reactivity (HTPR, ≥230 P2Y 12 reactivity units or PRU). Based on both PRU and clinical (ischemic and bleeding) risks, patients were switched to prasugrel or continued on clopidogrel per the study algorithm. The primary endpoints were (i) 1-year major adverse cardiovascular events (MACE) composite of death, non-fatal myocardial infarction, or definite or probable stent thrombosis; and (ii) major bleeding, Bleeding Academic Research Consortium type 2, 3 or 5. Out of 318 clopidogrel treated patients with a mean age of 65.9 ± 9.8 years, HTPR was noted in 33.3 %. Ninety (28.0 %) patients overall were switched to prasugrel and 228 (72.0 %) continued clopidogrel. The prasugrel group had fewer smokers and more patients with heart failure. At 1-year MACE occurred in 4.4 % of majority HTPR patients on prasugrel versus 3.5 % of primarily non-HTPR patients on clopidogrel (p = 0.7). Major bleeding (5.6 vs 7.9 %, p = 0.47) was numerically higher with clopidogrel compared with prasugrel. Use of the study clinical risk algorithm for choice and intensity of thienopyridine prescription following PCI resulted in similar ischemic outcomes in HTPR patients receiving prasugrel and primarily non-HTPR patients on clopidogrel without an untoward increase in bleeding with prasugrel. However, the study was prematurely terminated and these findings are therefore hypothesis generating.