To date, limited information is available on the long-term discontinuation rates of antiplatelet therapy after drug-eluting stent implantation. The aim of the present study was to determine the ...prevalence and predictors of premature discontinuation of oral antiplatelet therapy after drug-eluting stent implantation and to evaluate its effects on long-term prognosis. We studied 1,358 consecutive patients successfully treated with drug-eluting stents and discharged with dual oral antiplatelet therapy. Aspirin was to be maintained lifelong, and clopidogrel was prescribed for 12 months. The patients were followed for 36 months. The prevalence and predictors of aspirin and clopidogrel discontinuation were assessed. Major adverse cardiac events, defined as death, myocardial infarction, destabilizing symptoms leading to hospitalization, and nonfatal stroke, were recorded. Definite, probable, and possible stent thrombosis (ST) and major and minor bleeding were also determined. Of the 1,358 patients, 8.8% had discontinued one or both antiplatelet agents within the first 12 months (“early” discontinuation) and 4.8% had discontinued aspirin after 1 year (“late” discontinuation). Early discontinuation was predicted by in-hospital major bleeding, the use of oral anticoagulants at discharge, and the lack of a statin prescription. Previous stroke was the only independent predictor of late discontinuation. Patients with early discontinuation experienced a greater incidence of major adverse cardiac events (28.6% vs 13.7%, p <0.001) and ST (7.6% vs 3.4%, p = 0.038). All-cause mortality (13.4% vs 4.7%, p <0.001) and cardiovascular death (5% vs 1.2%, p = 0.007) were significantly more frequent among patients with early discontinuation. In patients with late discontinuation, a nonstatistically significant increase was seen in major adverse cardiac events (20% vs 13.3%, p = 0.128) and ST (6.2% vs 3.2%, p = 0.275). In conclusion, premature discontinuation of antiplatelet therapy is relatively common, especially within the first year, and strongly associated with increased cardiovascular events, including ST and death.
The impact of gender-related pathophysiologic features of severe aortic stenosis on transcatheter aortic valve implantation (TAVI) outcomes remains to be determined, as does the consistency of ...predictors of mortality between the genders. All consecutive patients who underwent TAVI at 6 institutions were enrolled in this study and stratified according to gender. Midterm all-cause mortality was the primary end point, with events at 30 days and at midterm as secondary end points. All events were adjudicated according to Valve Academic Research Consortium definitions. Eight hundred thirty-six patients were enrolled, 464 (55.5%) of whom were female. At midterm follow-up (median 365 days, interquartile range 100 to 516) women had similar rates of all-cause mortality compared with men (18.1% vs 22.6%, p = 0.11) and similar incidence of myocardial infarction and cerebrovascular accident. Gender did not affect mortality also on multivariate analysis. Among clinical and procedural features, glomerular filtration rate <30 ml/min/1.73 m2 (hazard ratio HR 2.55, 95% confidence interval CI 1.36 to 4.79) and systolic pulmonary arterial pressure >50 mm Hg (HR 2.26, 95% CI 1.26 to 4.02) independently predicted mortality in women, while insulin-treated diabetes (HR 3.45, 95% CI 1.47 to 8.09), previous stroke (HR 3.42, 95% CI 1.43 to 8.18), and an ejection fraction <30% (HR 3.82, 95% CI 1.41 to 10.37) were related to mortality in men. Postprocedural aortic regurgitation was independently related to midterm mortality in the 2 groups (HR 11.19, 95% CI 3.3 to 37.9). In conclusion, women and men had the same life expectancy after TAVI, but different predictors of adverse events stratified by gender were demonstrated. These findings underline the importance of a gender-tailored clinical risk assessment in TAVI patients.
Objective Severe carotid stenosis is a frequent cause of stroke in both men and women. Whereas several sex-related comparisons are available on coronary atherosclerosis, there are few data appraising ...gender-specific features of carotid plaques. We aimed to systematically compare the pathology and inflammatory features of carotid plaques in men vs women. Methods Carotid plaque specimens were collected from patients undergoing surgical endarterectomy for asymptomatic or symptomatic carotid stenosis. Histologic analysis was performed, as well as measurements of plaque composition and inflammation. Results A total of 457 patients were included (132 women, 325 men). Baseline analyses showed a greater prevalence of hypercholesterolemia, hypertension, and former smoking status in women, despite a higher Framingham Heart Score in men (all P < .05). Women had a lower prevalence of thrombotic plaques, smaller percentage area of necrotic core, and hemorrhage extension (all P < .05). Plaque inflammation analysis showed a lower concentration of inflammatory and, in particular, of macrophage foam cells in the plaque cap of women (both P < .05). These differences were, however, no longer significant at multivariable analysis, including several baseline features, such as symptom status and stenosis severity. Conclusions Carotid plaques seem significantly different in women and men, but the main drivers of such pathologic differences are baseline features, including stenosis severity and symptom status.
Objectives We designed a randomized trial exploiting optical coherence tomography (OCT) to assess coverage and apposition of overlapping bare-metal stents (BMS) and drug-eluting stents (DES) in human ...coronary arteries. Background Overlapping DES impair healing in animals. Optical coherence tomography allows accurate in vivo assessment of stent strut coverage and apposition. Methods Seventy-seven patients with long coronary stenoses were randomized to overlapping sirolimus-eluting stents (SES), paclitaxel-eluting stents (PES), zotarolimus-eluting stents (ZES), or BMS. The primary goal of the study was to determine the rate of uncovered/malapposed struts in overlap versus nonoverlap segments, according to stent type, at 6-month follow-up with OCT. Results A total of 53,047 struts were analyzed. The rate of uncovered/malapposed struts was 1.5 ± 3.4% and 0.6 ± 2.7% in overlap versus nonoverlap BMS (p = NS), respectively, and 4.3 ± 11% and 3.6 ± 8% in overlap versus nonoverlap DES (p = NS), respectively. There were no differences in the rates of uncovered/malapposed struts between overlapping BMS and DES, likely due to low frequency of uncovered/malapposed struts in ZES (0.1 ± 0.4%), which offset the higher rates observed in SES (6.7 ± 9.6%) and PES (6.7 ± 16.5%, p < 0.05). Overlap segments showed greater neointimal volume obstruction versus nonoverlap segments in all DES (p < 0.05 for all DES types). Strut-level neointimal thickness at overlap and nonoverlap segments were lowest in SES (0.16 ± 0.1 mm and 0.12 ± 0.1 mm, respectively) compared with PES (0.27 ± 0.1 mm and 0.20 ± 0.1 mm, respectively), ZES (0.40 ± 0.16 mm and 0.33 ± 0.13 mm, respectively), and BMS (0.55 ± 0.31 mm and 0.53 ± 0.25 mm, respectively, p < 0.05). Conclusions As assessed by OCT the impact of DES on vascular healing was similar at overlapping and nonoverlapping sites. However, strut malapposition, coverage pattern, and neointimal hyperplasia differ significantly according to DES type. (Optical Coherence Tomography for Drug Eluting Stent Safety ODESSA; NCT00693030 )
It remains undefined if transradial coronary angiography from a right or left radial arterial approach differs in real-world practice. To address this issue, we performed a subanalysis of the PREVAIL ...study. The PREVAIL study was a prospective, multicenter, observational survey of unselected consecutive patients undergoing invasive cardiovascular procedures over a 1-month observation period, specifically aimed at assessing the outcomes of radial approach in the contemporary real world. The choice of arterial approach was left to the discretion of the operator. Prespecified end points of this subanalysis were procedural characteristics. Of 1,052 patients consecutively enrolled, 509 patients underwent transradial catheterization, 304 with a right radial and 205 with a left radial approach. Procedural success rates were similar between the 2 groups. Compared to the left radial group, the right radial group had longer procedure duration (46 ± 29 vs 33 ± 24 minutes, p <0.0001) and fluoroscopy time (765 ± 787 vs 533 ± 502, p <0.0001). At multivariate analysis, including a parsimonious propensity score for the choice of left radial approach, duration of procedure (beta coefficient 11.38, p <0.001) and total dose–area product (beta coefficient 11.38, p <0.001) were independently associated with the choice of the left radial artery approach. The operator's proficiency in right/left radial approach did not influence study results. In conclusion, right and left radial approaches are feasible and effective to perform percutaneous procedures. In the contemporary real world, however, the left radial route is associated with shorter procedures and lower radiologic exposure than the right radial approach, independently of an operator's proficiency.
Background The vascular safety of electronic cigarettes (e-Cigarettes) must still be clarified. We compared the impact of e-Cigarettes vs traditional tobacco cigarettes on oxidative stress and ...endothelial function in healthy smokers and nonsmoker adults. Methods A crossover, single-blind study was performed in 40 healthy subjects (20 smokers and 20 nonsmokers, matched for age and sex). First, all subjects smoked traditional tobacco cigarettes. One week later, the same subjects smoked an e-Cigarette with the same nominal nicotine content. Blood samples were drawn just before and after smoking, and markers of oxidative stress, nitric oxide bioavailability, and vitamin E levels were measured. Flow-mediated dilation (FMD) was also measured. Results Smoking both e-Cigarettes and traditional cigarettes led to a significant increase in the levels of soluble NOX2-derived peptide and 8-iso-prostaglandin F2α and a significant decrease in nitric oxide bioavailability, vitamin E levels, and FMD. Generalized estimating equation analysis confirmed that all markers of oxidative stress and FMD were significantly affected by smoking and showed that the biologic effects of e-Cigarettes vstraditional cigarettes on vitamin E levels ( P = .413) and FMD ( P = .311) were not statistically different. However, e-Cigarettes seemed to have a lesser impact than traditional cigarettes on levels of soluble NOX2-derived peptide ( P = .001), 8-iso-prostaglandin F2α ( P = .046), and nitric oxide bioavailability ( P = .001). Conclusions Our study showed that both cigarettes have unfavorable effects on markers of oxidative stress and FMD after single use, although e-Cigarettes seemed to have a lesser impact. Future studies are warranted to clarify the chronic vascular effects of e-Cigarette smoking.
Acute myocardial infarction (AMI) initiates an intense inflammatory response in which interleukin-1 (IL-1) plays a central role. The IL-1 receptor antagonist is a naturally occurring antagonist, and ...anakinra is the recombinant form used to treat inflammatory diseases. The aim of the present pilot study was to test the safety and effects of IL-1 blockade with anakinra on left ventricular (LV) remodeling after AMI. Ten patients with ST-segment elevation AMI were randomized to either anakinra 100 mg/day subcutaneously for 14 days or placebo in a double-blind fashion. Two cardiac magnetic resonance (CMR) imaging and echocardiographic studies were performed during a 10- to 14-week period. The primary end point was the difference in the interval change in the LV end-systolic volume index (LVESVi) between the 2 groups on CMR imaging. The secondary end points included differences in the interval changes in the LV end-diastolic volume index, and C-reactive protein levels. A +2.0 ml/m2 median increase (interquartile range +1.0, +11.5) in the LVESVi on CMR imaging was seen in the placebo group and a −3.2 ml/m2 median decrease (interquartile range −4.5, −1.6) was seen in the anakinra group (p = 0.033). The median difference was 5.2 ml/m2 . On echocardiography, the median difference in the LVESVi change was 13.4 ml/m2 (p = 0.006). Similar differences were observed in the LV end-diastolic volume index on CMR imaging (7.6 ml/m2 , p = 0.033) and echocardiography (9.4 ml/m2 , p = 0.008). The change in C-reactive protein levels between admission and 72 hours after admission correlated with the change in the LVESVi (R = +0.71, p = 0.022). In conclusion, in the present pilot study of patients with ST-segment elevation AMI, IL-1 blockade with anakinra was safe and favorably affected by LV remodeling. If confirmed in larger trials, IL-1 blockade might represent a novel therapeutic strategy to prevent heart failure after AMI.
Study objective Primary angioplasty is associated with benefits in survival as compared with thrombolysis among patients with ST-segment elevation myocardial infarction (STEMI). However, in daily ...practice only a minority of STEMI patients are admitted to 24-hour primary percutaneous coronary intervention hospitals. A previous meta-analysis failed to show significant benefits in terms of survival, potentially because of a limited statistical power. Thus, the aim of the current study is to perform an updated meta-analysis of randomized trials to evaluate whether transfer for primary angioplasty provides significant benefits in terms of survival compared with on-site thrombolysis among STEMI patients. Methods The literature was scanned by formal searches of electronic databases (MEDLINE, CENTRAL, EMBASE) and the Cochrane Central Register of Controlled trials ( http://www.mrw.interscience.wiley.com/cochrane/Cochrane_clcentral_articles_ fs.html ) from January 1990 to April 2008. The following key words were used: “randomized trial;” “myocardial infarction;” “reperfusion;” “thrombolysis;” “primary angioplasty;” “angioplasty;” “mechanical reperfusion;” “facilitation;” “transfer;” “transportation;” “mortality;” and “survival.” Inclusion criteria were (1) randomized comparison between on-site thrombolysis and transferring for primary angioplasty; and (2) complete data on mortality. We did not exclude trials or trial arms that specifically addressed transfer for percutaneous coronary intervention after thrombolysis. Crude data were extracted by 2 investigators. No language restrictions were enforced. The relationship between benefits in mortality and reinfarction, baseline mortality of the thrombolytic group in each study (study level variable), and percutaneous coronary intervention-related time delay was evaluated by using a weighted least-square regression. Results A total of 11 randomized trials were identified, including 5,741 patients (51.8% transferred for primary angioplasty and 48.2% treated with thrombolysis). Transfer for primary angioplasty was associated with a significant reduction in mortality (5.6% versus 6.8%; P =.02), reinfarction (2.1% versus 4.7%; P <.0001 and stroke (0.7% versus 1.7%, P =.0005) at 30-day follow-up. The benefits in mortality and reinfarction of transfer for primary percutaneous coronary intervention over thrombolysis were not significantly related to baseline mortality of the lytic group or to percutaneous coronary intervention-related time delay. Conclusion This meta-analysis demonstrates that, among STEMI patients, transfer for mechanical reperfusion is associated, in addition to benefits in reinfarction and stroke, with a significant reduction in mortality at 30-day follow-up.
Surgical risk scores fail to accurately predict mortality after transcatheter aortic valve implantation (TAVI). The aim of this study was to develop and validate a dedicated risk score for accurate ...estimation of mortality risk in these patients. All consecutive patients who underwent TAVI at 6 international institutions were enrolled. Predictors for 1-year all-cause mortality were identified by means of Cox multivariate analysis and incorporated in a prediction score. Accuracy of the score was derived and externally validated for 30-day and 1-year mortality. The net classification improvement compared with the Society of Thoracic Surgeons (STS) score was appraised. A total of 1,064 patients constituted the derivation cohort and 180 patients constituted the external validation cohort. A total of 165 patients (15%) died at 1-year follow-up. Previous stroke (odds ratio OR 1.80, 1.4 to 3), inverse of renal clearance (OR 8, 6 to 14), and systolic pulmonary arterial pressure ≥50 mm Hg (OR 2.10, 1.5 to 3) were independently related to 1-year mortality. Area under the curve (AUC) of the survival post TAVI (STT) for 1-year mortality was 0.68 (0.62 to 0.71). At 30 days, 65 patients (7%) had died and the AUC for the STT at this time point was 0.66 (0.64 to 0.75). In the external validation cohorts, the AUC of the STT were 0.66 (0.56 to 0.7) for 30-day and 0.67 (0.62 to 0.71) for 1-year mortality. Net reclassification improvement for STT compared with STS was 31% (p <0.001) for 30-day mortality and 14% (p <0.001) for 1-year mortality. In conclusion, the STT score represents an easy and accurate tool to assess the risk of short-term and mid-term mortality in patients undergoing TAVI.
The management of individual patients requiring anthracyclines remains challenging because uncertainty persists on predictors of cardiotoxicity. We aimed to perform a systematic review and ...meta-analysis on incidence and predictors of anthracycline chemotherapy in patients with cancer. Databases were searched for pertinent studies. Meta-analytic pooling with random-effects methods was performed for incidence estimates, while relying on descriptive statistics for prevalence and strength of association of predictors. From 16,054 retrieved citations, 18 studies reporting on 49,017 patients with cancer were included, with 22,815 treated with anthracyclines. After a median follow-up of 9 years, clinically overt cardiotoxicity occurred in 6% (95% confidence interval 3% to 9%), whereas subclinical cardiotoxicity developed in 18% (95% confidence interval 12% to 24%). Appraisal of independent risk factors of cardiotoxicity showed that cumulative anthracycline dose was most consistently reported as an accurate and robust predictor of cardiotoxicity, with an acceptable prognostic role also for chest radiotherapy, African-American ethnicity, very young or very old age, diabetes, hypertension, very high or very low body weight, or severe co-morbidities. In conclusion, despite ongoing refinements in chemotherapy regimens, anthracyclines still pose a significant risk of cardiotoxicity, especially in those requiring a high cumulative dose or chest radiotherapy.
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