Comparative Effectiveness and Safety of New-Generation Versus Early-Generation Drug-Eluting Stents According to Complexity of Coronary Artery Disease: A Patient-Level Pooled Analysis of 6,081 Patients.

OBJECTIVES The purpose of this study was to compare the 2-year safety and effectiveness of new- versus early-generation drug-eluting stents (DES) according to the severity of coronary artery disease (CAD) as assessed by the SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score. BACKGROUND New-generation DES are considered the standard-of-care in patients with CAD undergoing percutaneous coronary intervention. However, there are few data investigating the effects of new- over early-generation DES according to the anatomic complexity of CAD. METHODS Patient-level data from 4 contemporary, all-comers trials were pooled. The primary device-oriented clinical endpoint was the composite of cardiac death, myocardial infarction, or ischemia-driven target-lesion revascularization (TLR). The principal effectiveness and safety endpoints were TLR and definite stent thrombosis (ST), respectively. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated at 2 years for overall comparisons, as well as stratified for patients with lower (SYNTAX score ≤11) and higher complexity (SYNTAX score >11). RESULTS A total of 6,081 patients were included in the study. New-generation DES (n = 4,554) compared with early-generation DES (n = 1,527) reduced the primary endpoint (HR: 0.75 [95% CI: 0.63 to 0.89]; p = 0.001) without interaction (p = 0.219) between patients with lower (HR: 0.86 [95% CI: 0.64 to 1.16]; p = 0.322) versus higher CAD complexity (HR: 0.68 [95% CI: 0.54 to 0.85]; p = 0.001). In patients with SYNTAX score >11, new-generation DES significantly reduced TLR (HR: 0.36 [95% CI: 0.26 to 0.51]; p < 0.001) and definite ST (HR: 0.28 [95% CI: 0.15 to 0.55]; p < 0.001) to a greater extent than in the low-complexity group (TLR pint = 0.059; ST pint = 0.013). New-generation DES decreased the risk of cardiac mortality in patients with SYNTAX score >11 (HR: 0.45 [95% CI: 0.27 to 0.76]; p = 0.003) but not in patients with SYNTAX score ≤11 (pint = 0.042). CONCLUSIONS New-generation DES improve clinical outcomes compared with early-generation DES, with a greater safety and effectiveness in patients with SYNTAX score >11.

Anatomic characteristics and clinical implications of angiographic coronary thrombus: insights from a patient-level pooled analysis of SYNTAX, RESOLUTE, and LEADERS Trials.

BACKGROUND The distribution of thrombus-containing lesions (TCLs) in an all-comer population admitted with a heterogeneous clinical presentation (stable, ustable angina, or an acute coronary syndrome) and treated with percutaneous coronary intervention is yet unclear, and the long-term prognostic implications are still disputed. This study sought to assess the distribution and prognostic implications of coronary thrombus, detected by coronary angiography, in a population recruited in all-comer percutaneous coronary intervention trials. METHODS AND RESULTS Patient-level data from 3 contemporary coronary stent trials were pooled by an independent academic research organization (Cardialysis, Rotterdam, the Netherlands). Clinical outcomes in terms of major adverse cardiac events (major adverse cardiac events, a composite of death, myocardial infarction, and repeat revascularization), death, myocardial infarction, and repeated revascularization were compared between patients with and without angiographic TCL. Preprocedural TCL was present in 257 patients (5.8%) and absent in 4193 (94.2%) patients. At 3-year follow-up, there was no difference for major adverse cardiac events (25.3 versus 25.4%; P=0.683); all-cause death (7.4 versus 6.8%; P=0.683); myocardial infarction (5.8 versus 6.0%; P=0.962), and any revascularizations (17.5 versus 17.7%; P=0.822) between patients with and without TCL. The comparison of outcomes in groups weighing the jeopardized myocardial by TCL also did not show a significant difference. TCL were seen more often in the first 2 segments of the right (43.6%) and left anterior descending (36.8%) coronary arteries. The association of TCL and bifurcation lesions was present in 40.1% of the prespecified segments. CONCLUSIONS TCL involved mainly the proximal coronary segments and did not have any effect on clinical outcomes. A more detailed thrombus burden quantification is required to investigate its prognostic implications. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00114972, NCT01443104, NCT00617084.

"Attacks" or "Whistling": Impact of Questionnaire Wording on Wheeze Prevalence Estimates.

BACKGROUND Estimates of prevalence of wheeze depend on questionnaires. However, wording of questions may vary between studies. We investigated effects of alternative wording on estimates of prevalence and severity of wheeze, and associations with risk factors. METHODS White and South Asian children from a population-based cohort (UK) were randomly assigned to two groups and followed up at one, four and six years (1998, 2001, 2003). Parents were asked either if their child ever had "attacks of wheeze" (attack group, N=535), or "wheezing or whistling in the chest" (whistling group, N=2859). All other study aspects were identical, including questions about other respiratory symptoms. RESULTS Prevalence of wheeze ever was lower in the attack group than in the whistling group for all surveys (32 vs. 40% in white children aged one year, p<0.001). Prevalence of other respiratory symptoms did not differ between groups. Wheeze tended to be more severe in the attack group. The strength of association with risk factors was comparable in the two groups. CONCLUSIONS The wording of questions on wheeze can affect estimates of prevalence, but has less impact on measured associations with risk factors. Question wording is a potential source of between-study-heterogeneity in meta-analyses.

Reference values for digital X-ray radiogrammetry parameters in children and adolescents in comparison to estimates in patients with distal radius fractures.

The first objective of this study was to determine normative digital X-ray radiogrammetry (DXR) values, based on original digital images, in a pediatric population (aged 6-18 years). The second aim was to compare these reference data with patients suffering from distal radius fractures, whereas both cohorts originated from the same geographical region and were evaluated using the same technical parameters as well as inclusion and exclusion criteria. DXR-BMD and DXR-MCI of the metacarpal bones II-IV were assessed on standardized digital hand radiographs, without printing or scanning procedures. DXR parameters were estimated separately by gender and among six age groups; values in the fracture group were compared to age- and gender-matched normative data using Student's t tests and Z scores. In the reference cohort (150 boys, 138 girls), gender differences were found in bone mineral density (DXR-BMD), with higher values for girls from 11 to 14 years and for boys from 15 to 18 years (p < 0.05). Girls had higher normative metacarpal index (DXR-MCI) values than boys, with significant differences at 11-14 years (p < 0.05). In the case-control investigation, the fracture group (95 boys, 69 girls) presented lower DXR-BMD at 15-18 years in boys and 13-16 years in girls vs. the reference cohort (p < 0.05); DXR-MCI was lower at 11-18 years in boys and 11-16 years in girls (p < 0.05). Mean Z scores in the fracture group for DXR-BMD were -0.42 (boys) and -0.46 (girls), and for DXR-MCI were -0.51 (boys) and -0.53 (girls). These findings indicate that the fully digital DXR technique can be accurately applied in pediatric populations ≥ 6 years of age. The lower DXR-BMD and DXR-MCI values in the fracture group suggest promising early identification of individuals with increased fracture risk, without the need for additional radiation exposure, enabling the initiation of prevention strategies to possibly reduce the incidence of osteoporosis later in life.

Global Estimates of the Prevalence and Incidence of Four Curable Sexually Transmitted Infections in 2012 Based on Systematic Review and Global Reporting.

BACKGROUND Quantifying sexually transmitted infection (STI) prevalence and incidence is important for planning interventions and advocating for resources. The World Health Organization (WHO) periodically estimates global and regional prevalence and incidence of four curable STIs: chlamydia, gonorrhoea, trichomoniasis and syphilis. METHODS AND FINDINGS WHO's 2012 estimates were based upon literature reviews of prevalence data from 2005 through 2012 among general populations for genitourinary infection with chlamydia, gonorrhoea, and trichomoniasis, and nationally reported data on syphilis seroprevalence among antenatal care attendees. Data were standardized for laboratory test type, geography, age, and high risk subpopulations, and combined using a Bayesian meta-analytic approach. Regional incidence estimates were generated from prevalence estimates by adjusting for average duration of infection. In 2012, among women aged 15-49 years, the estimated global prevalence of chlamydia was 4.2% (95% uncertainty interval (UI): 3.7-4.7%), gonorrhoea 0.8% (0.6-1.0%), trichomoniasis 5.0% (4.0-6.4%), and syphilis 0.5% (0.4-0.6%); among men, estimated chlamydia prevalence was 2.7% (2.0-3.6%), gonorrhoea 0.6% (0.4-0.9%), trichomoniasis 0.6% (0.4-0.8%), and syphilis 0.48% (0.3-0.7%). These figures correspond to an estimated 131 million new cases of chlamydia (100-166 million), 78 million of gonorrhoea (53-110 million), 143 million of trichomoniasis (98-202 million), and 6 million of syphilis (4-8 million). Prevalence and incidence estimates varied by region and sex. CONCLUSIONS Estimates of the global prevalence and incidence of chlamydia, gonorrhoea, trichomoniasis, and syphilis in adult women and men remain high, with nearly one million new infections with curable STI each day. The estimates highlight the urgent need for the public health community to ensure that well-recognized effective interventions for STI prevention, screening, diagnosis, and treatment are made more widely available. Improved estimation methods are needed to allow use of more varied data and generation of estimates at the national level.

Effect of Chronic Kidney Disease in Women Undergoing Percutaneous Coronary Intervention With Drug-Eluting Stents: A Patient-Level Pooled Analysis of Randomized Controlled Trials.

OBJECTIVES This study sought to evaluate: 1) the effect of impaired renal function on long-term clinical outcomes in women undergoing percutaneous coronary intervention (PCI) with drug-eluting stent (DES); and 2) the safety and efficacy of new-generation compared with early-generation DES in women with chronic kidney disease (CKD). BACKGROUND The prevalence and effect of CKD in women undergoing PCI with DES is unclear. METHODS We pooled patient-level data for women enrolled in 26 randomized trials. The study population was categorized by creatinine clearance (CrCl) <45 ml/min, 45 to 59 ml/min, and ≥60 ml/min. The primary endpoint was the 3-year rate of major adverse cardiovascular events (MACE). Participants for whom baseline creatinine was missing were excluded from the analysis. RESULTS Of 4,217 women included in the pooled cohort treated with DES and for whom serum creatinine was available, 603 (14%) had a CrCl <45 ml/min, 811 (19%) had a CrCl 45 to 59 ml/min, and 2,803 (66%) had a CrCl ≥60 ml/min. A significant stepwise gradient in risk for MACE was observed with worsening renal function (26.6% vs. 15.8% vs. 12.9%; p < 0.01). Following multivariable adjustment, CrCl <45 ml/min was independently associated with a higher risk of MACE (adjusted hazard ratio: 1.56; 95% confidence interval: 1.23 to 1.98) and all-cause mortality (adjusted hazard ratio: 2.67; 95% confidence interval: 1.85 to 3.85). Compared with older-generation DES, the use of newer-generation DES was associated with a reduction in the risk of cardiac death, myocardial infarction, or stent thrombosis in women with CKD. The effect of new-generation DES on outcomes was uniform, between women with or without CKD, without evidence of interaction. CONCLUSIONS Among women undergoing PCI with DES, CKD is a common comorbidity associated with a strong and independent risk for MACE that is durable over 3 years. The benefits of newer-generation DES are uniform in women with or without CKD.

Safety and Efficacy of New-Generation Drug-Eluting Stents in Women at High Risk for Atherothrombosis: From the Women in Innovation and Drug-Eluting Stents Collaborative Patient-Level Pooled Analysis

BACKGROUND The safety and efficacy of new-generation drug-eluting stents (DES) in women with multiple atherothrombotic risk (ATR) factors is unclear. METHODS AND RESULTS We pooled patient-level data for women enrolled in 26 randomized trials. Study population was categorized based on the presence or absence of high ATR, which was defined as having history of diabetes mellitus, prior percutaneous or surgical coronary revascularization, or prior myocardial infarction. The primary end point was major adverse cardiovascular events defined as a composite of all-cause mortality, myocardial infarction, or target lesion revascularization at 3 years of follow-up. Out of 10 449 women included in the pooled database, 5333 (51%) were at high ATR. Compared with women not at high ATR, those at high ATR had significantly higher risk of major adverse cardiovascular events (15.8% versus 10.6%; adjusted hazard ratio: 1.53; 95% confidence interval: 1.34-1.75; P=0.006) and all-cause mortality. In high-ATR risk women, the use of new-generation DES was associated with significantly lower risk of 3-year major adverse cardiovascular events (adjusted hazard ratio: 0.69; 95% confidence interval: 0.52-0.92) compared with early-generation DES. The benefit of new-generation DES on major adverse cardiovascular events was uniform between high-ATR and non-high-ATR women, without evidence of interaction (Pinteraction=0.14). At landmark analysis, in high-ATR women, stent thrombosis rates were comparable between DES generations in the first year, whereas between 1 and 3 years, stent thrombosis risk was lower with new-generation devices. CONCLUSIONS Use of new-generation DES even in women at high ATR is associated with a benefit consistent over 3 years of follow-up and a substantial improvement in very-late thrombotic safety.

Impact of Diabetic Status on Outcomes After Revascularization With Drug-Eluting Stents in Relation to Coronary Artery Disease Complexity: Patient-Level Pooled Analysis of 6081 Patients.

BACKGROUND Diabetes mellitus and angiographic coronary artery disease complexity are intertwined and unfavorably affect prognosis after percutaneous coronary interventions, but their relative impact on long-term outcomes after percutaneous coronary intervention with drug-eluting stents remains controversial. This study determined drug-eluting stents outcomes in relation to diabetic status and coronary artery disease complexity as assessed by the Synergy Between PCI With Taxus and Cardiac Surgery (SYNTAX) score. METHODS AND RESULTS In a patient-level pooled analysis from 4 all-comers trials, 6081 patients were stratified according to diabetic status and according to the median SYNTAX score ≤11 or >11. The primary end point was major adverse cardiac events, a composite of cardiac death, myocardial infarction, and clinically indicated target lesion revascularization within 2 years. Diabetes mellitus was present in 1310 patients (22%), and new-generation drug-eluting stents were used in 4554 patients (75%). Major adverse cardiac events occurred in 173 diabetics (14.5%) and 436 nondiabetic patients (9.9%; P<0.001). In adjusted Cox regression analyses, SYNTAX score and diabetes mellitus were both associated with the primary end point (P<0.001 and P=0.028, respectively; P for interaction, 0.07). In multivariable analyses, diabetic versus nondiabetic patients had higher risks of major adverse cardiac events (hazard ratio, 1.25; 95% confidence interval, 1.03-1.53; P=0.026) and target lesion revascularization (hazard ratio, 1.54; 95% confidence interval, 1.18-2.01; P=0.002) but similar risks of cardiac death (hazard ratio, 1.41; 95% confidence interval, 0.96-2.07; P=0.08) and myocardial infarction (hazard ratio, 0.89; 95% confidence interval, 0.64-1.22; P=0.45), without significant interaction with SYNTAX score ≤11 or >11 for any of the end points. CONCLUSIONS In this population treated with predominantly new-generation drug-eluting stents, diabetic patients were at increased risk for repeat target-lesion revascularization consistently across the spectrum of disease complexity. The SYNTAX score was an independent predictor of 2-year outcomes but did not modify the respective effect of diabetes mellitus. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00297661, NCT00389220, NCT00617084, and NCT01443104.