Clinical trials in peripheral vascular disease: pipeline and trial designs: an evaluation of the ClinicalTrials.gov database.

BACKGROUND: Tremendous advances have occurred in therapies for peripheral vascular disease (PVD); until recently, however, it has not been possible to examine the entire clinical trial portfolio of studies for the treatment of PVD (both arterial and venous disease). METHODS AND RESULTS: We examined interventional trials registered in ClinicalTrials.gov from October 2007 through September 2010 (n=40,970) and identified 676 (1.7%) PVD trials (n=493 arterial only, n=170 venous only, n=13 both arterial and venous). Most arterial studies investigated lower-extremity peripheral artery disease and acute stroke (35% and 24%, respectively), whereas most venous studies examined deep vein thrombosis/pulmonary embolus prevention (42%) or venous ulceration (25%). A placebo-controlled trial design was used in 27% of the PVD trials, and 4% of the PVD trials excluded patients >65 years of age. Enrollment in at least 1 US site decreased from 51% of trials in 2007 to 41% in 2010. Compared with noncardiology disciplines, PVD trials were more likely to be double-blinded, to investigate the use of devices and procedures, and to have industry sponsorship and assumed funding source, and they were less likely to investigate drug and behavioral therapies. Geographic access to PVD clinical trials within the United States is limited to primarily large metropolitan areas. CONCLUSIONS: PVD studies represent a small group of trials registered in ClinicalTrials.gov, despite the high prevalence of vascular disease in the general population. This low number, compounded by the decreasing number of PVD trials in the United States, is concerning and may limit the ability to inform current clinical practice of patients with PVD.

Comparative effectiveness of endovascular and surgical revascularization for patients with peripheral artery disease and critical limb ischemia: systematic review of revascularization in critical limb ischemia.

BACKGROUND: For patients with critical limb ischemia (CLI), the optimal treatment to enhance limb preservation, prevent death, and improve functional status is unknown. We performed a systematic review and meta-analysis to assess the comparative effectiveness of endovascular revascularization and surgical revascularization in patients with CLI. METHODS: We systematically searched PubMed, Embase, and the Cochrane Database of Systematic Reviews for relevant English-language studies published from January 1995 to August 2012. Two investigators screened each abstract and full-text article for inclusion, abstracted the data, and performed quality ratings and evidence grading. Random-effects models were used to compute summary estimates of effects, with endovascular treatment as the control group. RESULTS: We identified a total of 23 studies, including 1 randomized controlled trial, which reported no difference in amputation-free survival at 3 years (odds ratio [OR] 1.22, 95% CI 0.84-1.77) and all-cause mortality (OR 1.07, 0.73-1.56) between the 2 treatments. Meta-analysis of the observational studies showed a statistically nonsignificant reduction in all-cause mortality at 6 months (11 studies, OR 0.85, 0.57-1.27) and amputation-free survival at 1 year (2 studies, OR 0.76, 0.48-1.21) in patients treated with endovascular revascularization. There was no difference in overall death, amputation, or amputation-free survival at ≥2 years. CONCLUSIONS: The currently available literature suggests that there is no difference in clinical outcomes for patients with CLI treated with endovascular or surgical revascularization. There is a paucity of high-quality data available to guide clinical decision making, especially as it pertains to patient subgroups or anatomical considerations.

Do patients treated at academic hospitals have better longitudinal outcomes after admission for non-ST-elevation myocardial infarction?

BACKGROUND: Prior studies have found that academic hospitals provide more consistent use of guideline-recommended therapies in patients with non-ST-segment myocardial infarction (NSTEMI) compared with nonacademic centers, yet it is unclear whether these care differences translate into longer-term outcome differences. METHODS: Using data from the CRUSADE Registry linked to Center for Medicare & Medicaid Services claims, we compared 30-day and 1-year all-cause mortality among 12,194 older patients with NSTEMI (age ≥65 years) treated at 103 academic centers and 28,335 patients treated at 302 nonacademic centers from February 2003 to December 2006. Outcomes were first adjusted for clinical characteristics, followed by adjustment for hospital performance, on 13 acute and discharge guideline-recommended therapies using a shared frailty model (an extension of the Cox proportional hazard model). RESULTS: Compared with older patients with NSTEMI treated at nonacademic hospitals, those treated at academic hospitals had greater and more consistent use of evidence-based acute and discharge therapies, were more likely to receive in-hospital revascularization (61.1% vs 54.2%; P < .0001), and had modestly lower risk-adjusted 30-day mortality after adjustment for patient-level clinical characteristics (8.9% vs 10.2%, adjusted hazard ratio [HR] 0.89, 95% CI 0.80-0.99). These differences were attenuated (HR 0.94, 95% CI 0.83-1.02) after further adjustment for hospital delivery of evidence-based treatments, yet did not persist out to 1 year (unadjusted HR 0.92, 95% CI 0.84-1.01, P = .089). CONCLUSIONS: Patients with NSTEMI treated at academic centers are more likely to receive guideline-recommended therapies and had modestly better 30-day outcomes. Nevertheless, these differences do not persist out to 1 year.

Missed opportunities: despite improvement in use of cardioprotective medications among patients with lower-extremity peripheral artery disease, underuse remains.

BACKGROUND: Patients with peripheral artery disease (PAD) are at high risk of cardiovascular events and benefit from aggressive secondary prevention; however, changes in the use of cardioprotective medications after incident diagnosis of PAD have not been well described. METHODS AND RESULTS: We used Danish nationwide administrative registries (2000-2007) to identify 2 groups with incident PAD: PAD alone (n=34 160) and PAD with history of coronary artery disease (CAD) (n=9570). With the use of a comparator with incident CAD alone (n=154 183), we assessed temporal trends and comparative use of cardioprotective medications. Relative differences in medication use were examined by using multivariable logistic regression. Use of medications improved temporally among both groups: for PAD alone, any antiplatelet use increased from 29% to 59% from 2000 to 2007 (P<0.0001), whereas statin use increased 6-fold (9%-56%; P<0.0001). However, use of these therapies by 18 months after incident diagnosis for both PAD groups remained modest and lower in comparison with CAD alone (any antiplatelet, 53% versus 66%; statins, 40% versus 52%; angiotensin-converting enzyme inhibitors, 20% versus 29%). Relative to CAD alone, patients with PAD alone were less likely to use any antiplatelet (adjusted odds ratio, 0.50; 95% confidence interval, 0.49-0.52), statins (adjusted odds ratio, 0.50; 95% confidence interval, 0.48-0.52), or angiotensin-converting enzyme inhibitors (adjusted odds ratio, 0.51; 95% confidence interval, 0.49-0.53) by 18 months. CONCLUSIONS: Despite improvement in the use of cardioprotective medications over time, patients with PAD alone remain less likely than those with CAD alone to use these agents.

Admission international normalized ratio levels, early treatment strategies, and major bleeding risk among non-ST-segment-elevation myocardial infarction patients on home warfarin therapy: insights from the National Cardiovascular Data Registry.

BACKGROUND: Non-ST-segment-elevation myocardial infarction patients on home warfarin pose treatment concerns because of their potential increased risk of bleeding. Expert opinion from the American College of Cardiology/American Heart Association guidelines suggest holding anticoagulants and initiating antiplatelet therapy among therapeutically anticoagulated non-ST-segment-elevation myocardial infarction patients. Yet, little is known about contemporary treatment patterns and bleeding risks in this population. METHODS AND RESULTS: We stratified 5787 non-ST-segment-elevation myocardial infarction patients on home warfarin therapy using data from the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With the Guidelines by admission international normalized ratio (INR) levels: subtherapeutic (INR <2), therapeutic (INR, 2-3), and supratherapeutic (INR >3). Multivariable logistic generalized estimating equations models were constructed to examine the associations between admission INR level, early antithrombotic treatment and invasive therapy, and risk of in-hospital major bleeding. Among these patients, 46%, 35%, and 19% had subtherapeutic, therapeutic, and supratherapeutic admission INR levels, respectively. Risk of major bleeding was higher among patients with therapeutic (15%; adjusted odds ratio, 1.25; 95% confidence interval [CI], 1.03-1.50) and supratherapeutic (22%; odds ratio, 1.60; 95% CI, 1.30-1.97) anticoagulation compared with the subtherapeutic group (12%). Among patients with admission INR ≥2, 45% were treated with early (within 24 hours) heparin, 35% with early clopidogrel, 14% with early glycoprotein IIb/IIIa inhibitor, and 36% with early invasive strategy. Early antithrombotic treatment was associated with increased bleeding risk (odds ratio, 1.40 [95% CI, 1.14-1.72] for heparin; 1.50 [95% CI, 1.22-1.84] for clopidogrel; and 1.82 [95% CI, 1.43-2.32] for glycoprotein IIb/IIIa inhibitor); however, an early invasive strategy was not (odds ratio, 1.09; 95% CI, 0.86-1.37). No significant interactions were observed between INR level and use of each early treatment in its association with bleeding. CONCLUSIONS: National patterns of early antithrombotic treatment for non-ST-segment-elevation myocardial infarction patients on home warfarin diverge from expert opinion provided by current practice guidelines. Early antithrombotic treatment was associated with increased bleeding risk regardless of admission INR level.

High mortality risks after major lower extremity amputation in Medicare patients with peripheral artery disease.

BACKGROUND: Little is known regarding the contemporary outcomes of older patients with peripheral artery disease (PAD) undergoing major lower extremity (LE) amputation in the United States. We sought to characterize clinical outcomes and factors associated with outcomes after LE amputation in patients with PAD. METHODS: Using data from the Centers for Medicare and Medicaid Services from January 1, 2000, to December 31, 2008, we examined the national patterns of mortality after major LE amputation among patients 65 years or older with PAD. Cox proportional hazards models were used to investigate the association between clinical variables, comorbid conditions, year of index amputation, geographic variation, and major LE amputation. RESULTS: Among 186,338 older patients with identified PAD who underwent major LE amputation, the mortality rate was 13.5% at 30 days, 48.3% at 1 year, and 70.9% at 3 years. Age per 5-year increase (hazard ratio [HR] 1.29, 95% CI 1.29-1.29), history of heart failure (HR 1.71, 95% CI 1.71-1.72), renal disease (HR 1.84. 95% CI 1.83-1.85), cancer (HR 1.71, 95% CI 1.70-1.72), and chronic obstructive pulmonary disease (HR 1.33, 95% CI, 1.32-1.33) were all independently associated with death after major LE amputation. Subjects who underwent above knee amputation had a statistically higher hazard of death when compared with subjects who underwent LE amputation at more distal locations (HR with above the knee amputation 1.31, 95% CI 1.25-1.36). CONCLUSIONS: Older patients with PAD undergoing major LE amputation still face a slightly high mortality risk, with almost half of all patients with PAD dying within a year of major LE amputation.

Incorporation of bleeding as an element of the composite end point in clinical trials of antithrombotic therapies in patients with non-ST-segment elevation acute coronary syndrome: validity, pitfalls, and future approaches.

With the large number of antithrombotic therapies available and under investigation for the treatment of non-ST-segment elevation acute coronary syndromes (NSTE ACS), practice guidelines now stress the importance of selecting an antithrombotic strategy according to the efficacy and safety profiles of the chosen agent. Contemporary trials have incorporated bleeding along with ischemic end points into a composite end point commonly referred to as net clinical benefit, which allows for simultaneous evaluation of the differences between benefit and harm for an investigational antithrombotic therapy. However, incorporating major bleeding into a composite end point that includes ischemic events is not warranted and is associated with many pitfalls. In this article, we discuss the validity of combining efficacy and safety end points to form a net clinical benefit composite end point with the traditional time-to-event analysis for trials evaluating antithrombotic therapies for NSTE ACS. We describe alternative statistical approaches for concurrent assessment of the safety and efficacy of antithrombotic therapies used to treat patients with NSTE ACS.

The association of in-hospital major bleeding with short-, intermediate-, and long-term mortality among older patients with non-ST-segment elevation myocardial infarction.

AIMS: Bleeding complications have been associated with short-term mortality in patients with non-ST-segment elevation myocardial infarction (NSTEMI). Their association with long-term outcomes is less clear. This study examines mortality associated with in-hospital bleeding during NSTEMI over time intervals starting from hospital discharge and extending past 3 years. METHODS AND RESULTS: We studied 32 895 NSTEMI patients aged ≥65 years, using patient-level data from the CRUSADE registry linked with Medicare claims data. We assessed the association of in-hospital major bleeding with short (30 days), intermediate (1 year), and long-term (3 years) mortality among hospital survivors overall, as well as in those patients treated with or without a percutaneous coronary intervention (PCI). We calculated adjusted hazard ratios (HRs) for mortality for bleeders vs. non-bleeders over time intervals from: (i) discharge to 30 days; (ii) 31 days to 1 year; (iii) 1 year to 3 years; and (iv) beyond 3 years. Overall, 11.9% (n = 3902) had an in-hospital major bleeding event. Cumulative mortality was higher in those who had a major bleed vs. those without at 30 days, 1 year, and 3 years. Even after adjustment, major bleeding continued to be significantly associated with higher mortality over time in the overall population: (i) discharge to 30 days [adjusted HR 1.33; 95% confidence interval (CI) 1.18-1.51]; (ii) 31 days to 1 year (1.19; 95% CI 1.10-1.29); (iii) 1 year to 3 years (1.09; 95% CI 1.01-1.18), and (iv) attenuating beyond 3 years (1.14; 95% CI 0.99-1.31). In-hospital bleeding among patients treated with PCI continued to be significantly associated with higher adjusted mortality even beyond 3 years (1.25; 95% CI 1.01-1.54). CONCLUSION: In-hospital major bleeding is associated with short-, intermediate-, and long-term mortality among older patients hospitalized for NSTEMI-this association is strongest within the first 30 days, but remains significant long term, particularly among PCI-treated patients. Despite a probable early hazard related to bleeding, the longer duration of risk in patients who bleed casts doubt on its causal relationship with long-term mortality. Rather, major bleeding likely identifies patients with an underlying risk for mortality.

Baseline risk of major bleeding in non-ST-segment-elevation myocardial infarction: the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA Guidelines) Bleeding Score.

BACKGROUND: Treatments for non-ST-segment-elevation myocardial infarction (NSTEMI) reduce ischemic events but increase bleeding. Baseline prediction of bleeding risk can complement ischemic risk prediction for optimization of NSTEMI care; however, existing models are not well suited for this purpose. METHODS AND RESULTS: We developed (n=71 277) and validated (n=17 857) a model that identifies 8 independent baseline predictors of in-hospital major bleeding among community-treated NSTEMI patients enrolled in the Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines (CRUSADE) Quality Improvement Initiative. Model performance was tested by c statistics in the derivation and validation cohorts and according to postadmission treatment (ie, invasive and antithrombotic therapy). The CRUSADE bleeding score (range 1 to 100 points) was created by assignment of weighted integers that corresponded to the coefficient of each variable. The rate of major bleeding increased by bleeding risk score quintiles: 3.1% for those at very low risk (score < or = 20); 5.5% for those at low risk (score 21-30); 8.6% for those at moderate risk (score 31-40); 11.9% for those at high risk (score 41-50); and 19.5% for those at very high risk (score >50; P(trend) <0.001). The c statistics for the major bleeding model (derivation=0.72 and validation=0.71) and risk score (derivation=0.71 and validation=0.70) were similar. The c statistics for the model among treatment subgroups were as follows: > or = 2 antithrombotics=0.72; <2 antithrombotics=0.73; invasive approach=0.73; conservative approach=0.68. CONCLUSIONS: The CRUSADE bleeding score quantifies risk for in-hospital major bleeding across all postadmission treatments, which enhances baseline risk assessment for NSTEMI care.

Central aortic pressure is independently associated with diastolic function.

BACKGROUND: Studies investigating the association between central aortic pressures and diastolic function have been limited. METHODS: Consecutive ambulatory patients (n = 281, mean age 49 +/- 13 years, 49% male) with normal left ventricular (LV) systolic function were included. The LV filling pressure (E/Em) was estimated by Doppler-derived ratio of mitral inflow velocity (E) to septal (Em) by tissue Doppler, LV relaxation by Em, and central aortic pressures by radial tonometry. Central aortic systolic (cSBP), diastolic (cDBP), mean (cMAP) and pulse pressure (cPP) were entered individually into stepwise linear regression models to determine their association with E/Em or Em. RESULTS: In univariate analysis, cPP correlated most strongly with E/Em (Spearman's rho = 0.45, P < .001), whereas cSBP correlated most strongly with Em (Spearman's rho = -0.51, P < .001). Multivariate analysis demonstrated that the pulsatile component of afterload, cPP, contributed most to E/Em (partial r(2) = 23%); meanwhile, the nonpulsatile components (cDBP and cMAP) were significant but small contributors (partial r(2) of 6% and 5%, respectively) of LV relaxation (Em). CONCLUSION: The nonpulsatile components of aortic afterload (cMAP and cDBP) exhibited a weak but significant association with LV relaxation, whereas the pulsatile component of afterload, cPP, exhibited strong association with LV filling pressure.

Comparative Effectiveness of Medical Therapy, Supervised Exercise, and Revascularization for Patients With Intermittent Claudication: A Network Meta-analysis.

BACKGROUND: There are limited data on the comparative effectiveness of medical therapy, supervised exercise, and revascularization to improve walking and quality of life in patients with intermittent claudication (IC). HYPOTHESIS: Supervised exercise and revascularization was superior to medical therapy in IC. METHODS: We studied the comparative effectiveness of exercise training, medications, endovascular intervention, and surgical revascularization on outcomes including functional capacity (walking distance and timing), quality of life, and mortality. We searched PubMed, EMBASE, and the Cochrane Database of Systematic Reviews from January 1995 to August 2012 for relevant English-language studies. Two investigators independently collected data. Meta-analyses with random-effects models of direct comparisons were supplemented by mixed-treatment analyses to incorporate data from placebo comparisons, head-to-head comparisons, and multiple treatment arms. RESULTS: Thirty-five unique studies evaluated treatment modalities in 7475 patients with IC. Compared with usual care, only exercise training improved both maximal walking distance (150 meters; 95% confidence interval: 35-266 meters, P = 0.01) and initial claudication distance (39 meters; 95% confidence interval: 9-65 meters, P = 0.003). All modalities were associated with improved quality of life (Short Form-36 physical functioning score) compared with usual care, but there were no differences between treatments. There were insufficient safety data to assess treatment-related complications. All-cause mortality was not significantly different between modalities. CONCLUSIONS: Evidence is insufficient to determine treatment superiority for improving quality of life and walking parameters in IC patients. Further studies with attention to study design, standardized efficacy and safety endpoints, and appropriate subgroup reporting are necessary to determine comparative effectiveness.

Peripheral artery disease is a coronary heart disease risk equivalent among both men and women: results from a nationwide study.

AIMS: Lower extremity peripheral artery disease (PAD) has been proposed as a 'coronary heart disease (CHD) risk equivalent'. We aimed to examine whether PAD confers similar risk for mortality as incident myocardial infarction (MI) and whether risk differs by gender. METHODS: Using nationwide Danish administrative registries (2000-2008), we identified patients aged ≥40 years with incident PAD (PAD only, n = 35,628), incident PAD with a history of MI (PAD + MI, n = 7029), and incident MI alone (MI alone, n = 71,115). RESULTS: Patients with PAD only tended to be younger, female, and have less comorbidity than the other groups. During follow up (median 1051 d, IQR 384-1938), we found that MI-alone patients had greater risk of adverse outcomes in the acute setting (first 90 d); however, the PAD-only and PAD + MI groups had higher long-term mortality at 7 years than those with MI alone (47.8 and 60.4 vs. 36.4%, respectively; p < 0.0001). After adjustment, the PAD-only and PAD + MI groups had a higher long-term risk for mortality [hazard ratio (HR) 1.47, 95% confidence interval (CI) 1.44-1.51; and HR 1.65, 95% CI 1.58-1.72, respectively], cardiovascular mortality (HR 1.30, 95% CI 1.26-1.34; and HR 1.71, 95% CI 1.62-1.80, respectively), and composite of death, MI, and ischaemic stroke, 95% CI HR, 1.38, 95% CI 1.36-1.42; and HR 1.68, 95% CI 1.61-1.75, respectively). The greater long-term risks of PAD were seen for both women and men. CONCLUSIONS: Both women and men with incident PAD have greater long-term risks of total and cardiovascular mortality vs. those with incident MI. PAD should be considered a CHD risk equivalent, warranting aggressive secondary prevention.

Sources of hospital-level variation in major bleeding among patients with non-st-segment elevation myocardial infarction: a report from the National Cardiovascular Data Registry (NCDR).

BACKGROUND: Major bleeding has received increasing attention as a target for quality improvement in care of patients with acute myocardial infarction. However, little is known about variation in bleeding across hospitals and whether variation is attributable to quality of hospital care, treatments, or case mix. METHODS AND RESULTS: We characterized hospital variation in major bleeding events (an absolute hemoglobin drop ≥4 g/dL, intracranial hemorrhage, retroperitoneal bleed, or transfusion) among 99 200 patients with non-ST-segment elevation myocardial infarction in the National Cardiovascular Data Registry (NCDR) Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With the Guidelines (ACTIOM Registry-GWTG) between January 2007 and June 2010. A total of 9566 (9.6%) patients experienced a major bleeding event during hospitalization. The median of the estimated distribution of major bleeding rates across hospitals was 9.4% (interquartile range, 7.5%-11.7%), with some hospitals having bleeding rates >2.3 times higher than others (10th-90th percentile, 6.1%-14.2%). Multivariable hierarchical models revealed that differences in case mix explained 19.2% of the hospital variation in bleeding complications, where anticoagulation and antiplatelet strategies explained an incremental 9.9% and 6.8%, respectively. Together, 32.3% of hospital variation in major bleeding rates was attributable to differences in patient case mix and identifiable differences in treatment strategies in patients with non-ST-segment elevation myocardial infarction. CONCLUSIONS: In-hospital major bleeding rates varied widely across hospitals. Although patient factors and treatments explained less than one third of hospital-level variation, ≈70% of bleeding variation remains after adjustment. A better understanding of causes for substantial hospital-level bleeding variations is needed to help target high-risk patients or practices and to optimize care.

Comparison of bivalirudin and radial access across a spectrum of preprocedural risk of bleeding in percutaneous coronary intervention: analysis from the national cardiovascular data registry.

BACKGROUND: Bleeding is a common, noncardiac, preventable complication of percutaneous coronary intervention. We compared the relative safety of radial access and bivalirudin in percutaneous coronary intervention. METHODS AND RESULTS: From CathPCI Registry, we determined the association between the site of arterial access, bivalirudin, and periprocedural bleeding rates in 501 017 patients. Radial access patients receiving heparin (radial group) were compared with those receiving bivalirudin (radial combination group). Femoral access patients who had bivalirudin and a vascular closure device served as a reference group (femoral group). An inverse probability weighting analysis incorporating propensity scores was used to compare groups. The overall rate of bleeding was 2.59%. It was 2.71% in the femoral group, 2.5% in the radial group, and 1.82% in the radial combination groups (P<0.001). When compared with femoral group, the adjusted odds ratio for bleeding was significantly lower for patients with radial combination group (odds ratio, 0.79; 95% confidence interval, 0.72-0.86), but not for radial group (odds ratio, 0.96; 95% confidence interval, 0.88-1.05), unless patients treated with IIb/IIIa were excluded (radial group-IIb/IIIa odds ratio, 0.84; 95% confidence interval, 0.75-0.94).The number needed to treat to prevent 1 bleeding event with radial combination group was 138, whereas the number needed to treat to prevent 1 bleeding event in high-bleeding risk patients was 68. CONCLUSIONS: In this observational analysis, the combination of bivalirudin and radial access was associated with reduced bleeding event rate. This benefit was present across the entire spectrum of preprocedural risk of bleeding, with or without exposure to IIb/IIIa inhibitors. These data support an adequately powered randomized trial comparing bleeding avoidance strategies.

Patterns of use and comparative effectiveness of bleeding avoidance strategies in men and women following percutaneous coronary interventions: an observational study from the National Cardiovascular Data Registry.

OBJECTIVES: This study sought to compared the use and effectiveness of bleeding avoidance strategies (BAS) by sex. BACKGROUND: Women have higher rates of bleeding following percutaneous coronary intervention (PCI). METHODS: Among 570,777 men (67.5%) and women (32.5%) who underwent PCI in the National Cardiovascular Data Registry's CathPCI Registry between July 1, 2009 and March 31, 2011, in-hospital bleeding rates and the use of BAS (vascular closure devices, bivalirudin, radial approach, and their combinations) were assessed. The relative risk of bleeding for each BAS compared with no BAS was determined in women and men using multivariable logistic regressions adjusted for clinical characteristics and the propensity for receiving BAS. Finally, the absolute risk differences in bleeding associated with BAS were compared. RESULTS: Overall, the use of any BAS differed slightly between women and men (75.4% vs. 75.7%, p = 0.01). When BAS was not used, women had significantly higher rates of bleeding than men (12.5% vs. 6.2%, p < 0.01). Both sexes had similar adjusted risk reductions of bleeding when any BAS was used (women, odds ratio: 0.60, 95% confidence interval [CI]: 0.57 to 0.63; men, odds ratio: 0.62, 95% CI: 0.59 to 0.65). Women and men had lower absolute bleeding risks with BAS; however, these absolute risk differences were greater in women (6.3% vs. 3.2%, p < 0.01). CONCLUSIONS: Women continue to have almost twice the rate of bleeding following PCI. The use of any BAS was associated with a similarly lower risk of bleeding for men and women; however, the absolute risk differences were substantially higher in women. These data underscore the importance of applying effective strategies to limit post-PCI bleeding, especially in women.

The prevalence and outcomes of transradial percutaneous coronary intervention for ST-segment elevation myocardial infarction: analysis from the National Cardiovascular Data Registry (2007 to 2011).

OBJECTIVES: The purpose of this study was to examine use and describe outcomes of radial access for percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Transradial PCI (TRI) is associated with reduced risk of bleeding and vascular complications, as compared with femoral access PCI (FPCI). Studies have suggested that TRI may reduce mortality among patients with STEMI. METHODS: We examined 294,769 patients undergoing PCI for STEMI at 1,204 hospitals in the CathPCI Registry between 2007 and 2011. Patients were grouped according to access site used for PCI. The temporal trend in the rate of radial versus femoral approach was determined. For minimization of confounding, an inverse probability weighting analysis incorporating propensity scores was used to compare procedural success, post-PCI bleeding, door-to-balloon times, and in-hospital mortality between radial and femoral access. RESULTS: Over the 5-year period, the use of TRI versus FPCI in STEMI increased from 0.9% to 6.4% (p < 0.0001). There was no difference in procedural success. TRI was associated with longer median door-to-balloon time (78 vs. 74 min; p < 0.0001) but lower adjusted risk of bleeding (odds ratio [OR]: 0.62; 95% CI: 0.53 to 0.72; p < 0.0001) and lower adjusted risk of in-hospital mortality (OR: 0.76; 95% CI: 0.57 to 0.99; p = 0.0455). CONCLUSIONS: In this large national database, use of radial access for PCI in STEMI increased over the study period. Despite longer door-to-balloon times, the radial approach was associated with lower bleeding rate and reduced in-hospital mortality. These data provide support to execute an adequately powered randomized controlled trial comparing radial and femoral approaches for PCI in STEMI.

Socioeconomic disparities in the use of cardioprotective medications among patients with peripheral artery disease: an analysis of the American College of Cardiology's NCDR PINNACLE Registry.

OBJECTIVES: The aim of this paper was to examine disparities in the use of cardioprotective medications in the treatment of peripheral artery disease (PAD) by socioeconomic status (SES). BACKGROUND: PAD is associated with increased cardiovascular risk and is more prevalent among those of lower SES. However, the use of guideline-recommended secondary preventive measures for the treatment of PAD across diverse income subgroups and the influence of practice site on potential treatment disparities by SES are unknown. METHODS: Within the National Cardiovascular Disease Registry (NCDR) PINNACLE Registry, 62,690 patients with PAD were categorized into quintiles of SES, as defined by the median income of each patient's zip code. The association between SES and secondary preventive treatment with antiplatelet and statin medications was evaluated using sequential hierarchical modified Poison models, adjusting first for practice site and then for clinical variables. RESULTS: Compared with the highest SES quintile (median income: >$60,868), PAD patients in the lowest SES quintile (median income: <$34,486) were treated less often with statins (72.5% vs. 85.8%; RR: 0.84; 95% CI: 0.83 to 0.86; p < 0.001) and antiplatelet therapy (79.0% vs. 84.6%; RR: 0.93; 95% CI: 0.91 to 0.94; p < 0.001). These differences were markedly attenuated after controlling for practice site variation: statins (adjusted RR: 0.97; 95% CI: 0.95 to 0.99; p = 0.003) and antiplatelet therapy (adjusted RR: 0.98; 95% CI: 0.97 to 1.00; p = 0.012). Additional adjustment for patients' clinical characteristics had minimal impact, with slight further attenuation with statins (adjusted RR: 1.00: 95% CI: 0.99 to 1.01; p = 0.772) and antiplatelet therapy (adjusted RR: 1.00; 95% CI: 0.99 to 1.01; p = 0.878). CONCLUSIONS: Among PAD patients, the practice site at which patients received care largely explained the observed SES differences in treatment with guideline-recommended secondary preventive medications. Future efforts to reduce treatment disparities in these vulnerable populations should target systems improvement at practices serving high proportions of patients with low SES.

Temporal trends and geographic variation of lower-extremity amputation in patients with peripheral artery disease: results from U.S. Medicare 2000-2008.

OBJECTIVES: This study sought to characterize temporal trends, patient-specific factors, and geographic variation associated with amputation in patients with lower-extremity peripheral artery disease (LE PAD) during the study period. BACKGROUND: Amputation represents the end-stage failure for those with LE PAD, and little is known about the rates and geographic variation in the use of LE amputation. METHODS: By using data from the Centers for Medicare & Medicaid Services (CMS) from January 1, 2000, to December 31, 2008, we examined national patterns of LE amputation among patients age 65 years or more with PAD. Multivariable logistic regression was used to adjust regional results for other patient demographic and clinical factors. RESULTS: Among 2,730,742 older patients with identified PAD, the overall rate of LE amputation decreased from 7,258 per 100,000 patients with PAD to 5,790 per 100,000 (p < 0.001 for trend). Male sex, black race, diabetes mellitus, and renal disease were all independent predictors of LE amputation. The adjusted odds ratio of LE amputation per year between 2000 and 2008 was 0.95 (95% CI: 0.95-0.95, p < 0.001). CONCLUSIONS: From 2000 to 2008, LE amputation rates decreased significantly among patients with PAD. However, there remains significant patient and geographic variation in amputation rates across the United States.

Association between periprocedural bleeding and long-term outcomes following percutaneous coronary intervention in older patients.

OBJECTIVES: The authors sought to describe the association between post-procedural bleeding and long-term recurrent bleeding, major adverse cardiac events (MACE), and mortality among older patients undergoing percutaneous coronary intervention (PCI). BACKGROUND: Bleeding complications after PCI are associated with an increased risk for acute morbidity and long-term mortality, but the association of these bleeding complications with other events is unknown. METHODS: Patients entered into the National Cardiovascular Data Registry (NCDR) CathPCI Registry (n = 461,311; 946 sites) from January 2004 to December 2008 were linked with claims from the Centers for Medicare & Medicaid Services and grouped according to in-hospital post-PCI bleeding. The association between post-PCI bleeding and 1-, 12-, and 30-month readmission for bleeding, MACE, and all-cause mortality was examined with Cox regression that included patient and procedural characteristics using no bleeding as the reference. RESULTS: Overall, 3.1% (n = 14,107) of patients experienced post-PCI bleeding. Patients who bled were older, more often female, had more medical comorbidities, less often received bivalirudin, and more often underwent PCI via the femoral approach. After adjustment, bleeding after the index procedure was significantly associated with readmission for bleeding (adjusted hazard ratios [95% confidence interval]: 1 month, 1.54 [1.42 to 1.67]; 12 months, 1.52 [1.40 to 1.66]; 30 months, 1.29 [1.11 to 1.50]), MACE (1 month, 1.11 [1.07 to 1.15]; 12 months, 1.17 [1.13 to 1.21]; 30 months, 1.12 [1.06 to 1.19]) and all-cause mortality (1 month, 1.32 [1.26 to 1.38]; 12 months, 1.33 [1.27 to 1.40]); 30 months, 1.22 [1.15 to 1.30]). CONCLUSIONS: Post-PCI bleeding complications are associated with an increased risk for short- and long-term recurrent bleeding, MACE, and all-cause mortality. These data underscore the prognostic importance of periprocedural bleeding and the need for identifying strategies to reduce long-term bleeding risk among patients undergoing PCI.