Faculty Bibliography

A recent study has shown an association between high-potency statins and risk of acute kidney injury. However, these data are from observational studies, and it is not clear if similar signal is seen from randomized controlled trials. We evaluated the risk of renal-associated serious adverse events (SAEs) using statins versus placebo trials and the high-dose versus low-dose statin trials that were available to us. The outcome of interest was renal-related SAEs. The incidence of adverse events relating to kidney injury was determined through review of the adverse event database. The following outcomes were evaluated: (1) renal-related SAEs within 120 days of randomization (primary outcome), (2) renal-related SAEs after 120 days of randomization (secondary), and (3) drug discontinuation due to renal-related SAEs (secondary). There was no difference in the incidence of renal-related SAEs at 120 days (0.04% vs 0.10%, p = 0.162) between atorvastatin and placebo in the 24 placebo-controlled trials (10,345 patients on atorvastatin (10 to 80 mg/day) versus 8,945 patients on placebo) or in the high-dose versus low-dose statin trials including the Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) study (0.05% vs 0.02%, p = 0.625) or the Treating to New Targets (TNT) trial (0.0% vs 0.04%, p = 0.500) trial. Results were similar for renal-related SAEs after 120 days (placebo controlled trials [0.38% vs 0.36%, p = 0.905], IDEAL trial [0.56% vs 0.65%, p = 0.683], or the TNT trial [0.76% vs 1.04%, p = 0.168]) and for drug withdrawal due to renal-related SAE (placebo controlled trials [0.05% vs 0.04%, p = 1.00], IDEAL trial [0.02% vs 0.0%, p = 0.499], or the TNT trial [0.08% vs 0.12%, p = 0.754]). In conclusion, the results from clinical trials with data from 149,882 patient-years of follow-up fail to show any increase in renal-related SAEs with statins compared with controls.

BACKGROUND: The use of bivalirudin versus unfractionated heparin monotherapy in patients without ST-segment-elevation myocardial infarction is not well defined. METHODS AND RESULTS: The study population consisted of patients enrolled in the Evaluation of Drug-Eluting Stents and Ischemic Events (EVENT) registry with either non-ST-segment-elevation acute coronary syndromes or stable ischemic heart disease, who underwent percutaneous coronary intervention with either unfractionated heparin or bivalirudin monotherapy. Propensity score matching was used to adjust for baseline characteristics. The primary bleeding (in-hospital composite bleeding-access site bleeding, thrombolysis in myocardial infarction major/minor bleeding, or transfusion) and primary (in-hospital death/myocardial infarction) and secondary ischemic outcomes (death/myocardial infarction/unplanned repeat revascularization at 12 months) were evaluated. Propensity score matching yielded 1036 patients with non-ST-segment-elevation acute coronary syndromes and 2062 patients with stable ischemic heart disease. For the non-ST-segment-elevation acute coronary syndrome cohort, bivalirudin use was associated with lower bleeding (difference, -3.3% [-0.8% to -5.8%]; P=0.01; number need to treat=30) without increase in either primary (difference, 1.2% [4.1% to -1.8%]; P=0.45) or secondary ischemic outcomes, including stent thrombosis (difference, 0.0% [1.3% to -1.3%]; P=1.00). Similarly, in the stable ischemic heart disease cohort, bivalirudin use was associated with lower bleeding (difference, -1.8% [-0.4% to -3.3%]; P=0.01; number need to treat=53) without increase in either primary (difference, 0.4% [2.3% to -1.5%]; P=0.70) or secondary ischemic outcomes, including stent thrombosis (difference, 0.0% [0.7% to -0.7%]; P=1.00) when compared with unfractionated heparin monotherapy. CONCLUSIONS: Among patients with non-ST-segment-elevation acute coronary syndromes or stable ischemic heart disease undergoing percutaneous coronary intervention, bivalirudin use during percutaneous coronary intervention when compared with unfractionated heparin monotherapy was associated with lower bleeding without significant increase in ischemic outcomes or stent thrombosis.

BACKGROUND: Patients with stroke or transient ischemic attack are at increased risk of recurrent stroke. Transient ischemic attack is a harbinger for stroke merely hours to days after the initial transient ischemic attack. There is thus a narrow window of opportunity to initiate evidence-based therapies for secondary prevention of stroke. Our objective was to assess hospital adherence at discharge to secondary prevention measures after transient ischemic attack or ischemic stroke. METHODS: Observational study of patients in the Get With The Guidelines-Stroke registry from 2007 to 2011. Patients were divided into 2 cohorts based on presentation- transient ischemic attack vs. ischemic stroke. Adherence to evidence-based secondary prevention and other quality measures were assessed. RESULTS: Among the 858,835 patients with transient ischemic attack or ischemic stroke, 259,319 (30%) patients presented with a transient ischemic attack and 599,516 (70%) patients presented with an ischemic stroke. After adjusting for patient and hospital characteristics, adherence to secondary prevention measures was consistently lower for the transient ischemic attack cohort (vs. ischemic stroke cohort) who had lower odds of being discharged on antithrombotics (Odds Ratio (OR)=0.63; 95% confidence interval (CI) 0.59-0.66; P<0.0001), anticoagulants for atrial fibrillation (OR=0.65; 95% CI 0.61-0.68; P<0.0001), lipid lowering medication for LDL >100 mg/dl (OR=0.52; 95% CI 0.50-0.54; P<0.0001), intensive statin therapy (OR=0.74; 95% CI 0.72-0.76; P<0.0001), LDL cholesterol measurement (OR=0.66; 95% CI 0.64-0.68; P<0.0001), smoking cessation counseling (OR=0.83; 95% CI 0.78-0.89; P<0.0001), stroke education (OR=0.71; 95% CI 0.69-0.73; P<0.0001), or weight loss recommendations (OR=0.88; 95% CI 0.85-0.90; P<0.0001). The adherence to evidence-based therapies increased significantly (P<0.0001) over time (2007-2011) for both the cohorts, but the increasing trend was consistently lower for patients who presented with transient ischemic attack. CONCLUSIONS: In patients surviving an ischemic stroke or transient ischemic attack, adherence to evidence-based secondary prevention discharge measures were consistently less for patients with transient ischemic attack, thus representing a missed opportunity at instituting preventive measures to reduce the risk of recurrent stroke.

Research and development in the field of coronary stent design is a fast-evolving and fascinating journey. A device that was once introduced to salvage acute closure associated with balloon angioplasty is now the standard of care for many patients with coronary artery disease. Newer generation stents are the product of remarkable progress in technology and innovation, driven by the need to make the stents easier to deliver and to improve their safety and efficacy. As such, the design of these stents has become quite sophisticated and complex. The number of available stents has increased giving patients and physicians more choices on one hand, but also created confusion in selecting the optimal stent for a given patient. Although a 'one size fits all' approach may not be reasonable, several randomized trials have attested to the efficacy and safety of newer generation durable polymer drug eluting stents. This article discusses the evidence base to support various stent choices in contemporary practice.

Background: The Third Universal Definition of Myocardial Infarction (MI) designates an increase in cardiac troponin concentration (cTn) > 99th percentile of a normal reference population as the decision level for MI diagnosis. The variability among hospitals in the lab-determined cTn level to diagnose MI [cTn decision level] relative to the assay manufacturer determined 99th percentile has not been well characterized. Methods: We surveyed 93 sites from 15 countries participating in the NHLBI ISCHEMIA trial to ascertain the cTn assay used at their hospital labs, its 99th percentile, as well as the cTn MI decision level. The ratio of cTn MI decision level to cTn 99th percentile was calculated for each lab. Results: Laboratories employed 32 unique cTn assays from 7 manufacturers; 77% used cTnI assays and 23% used cTnT assays. Highly sensitive assays were used in 18 labs (19.4%). The ratio of cTn MI decision level to cTn 99th percentile was <1 at 7 labs (7.5%), equal to 1 at 29 labs (31.2%) and >10 at 18 labs (19.4%) (Figure). Substantial variability was observed in cTn MI decision level even among labs using the same assay. Conclusion: Significant variability exists in the cTn MI decision level used by hospital laboratories relative to the assay cTn 99th percentile. Only one-third of labs follow the Third Universal Definition of MI. These data have important implications for the diagnosis of MI in clinical practice and adjudicating MI endpoints in clinical trials. (Figure Presented)

Background: A meta-analyses of randomized clinical trials (RCT) was performed to evaluate the risk of gastrointestinal bleeding with new oral anticoagulants (NOACs) compared with conventional anticoagulants (CAG). Methods: Electronic databases were searched from January 01, 2001 through February 28, 2013. RCTs comparing NOACs (apixaban, dabigatran, or rivaroxaban) with pharmacologically active CAG were selected. Results: Seventeen RCTs including 91,933 patients met our inclusion criteria. NOACs were associated with a significantly higher GI bleeding compared with conventional anticoagulants [Peto's odds ratio (POR) 1.23, 95% confidence interval [CI] 1.10 to 1.36; number needed to harm (NNH)=295 patients]. Trial sequential analysis (TSA) confirms a 20% relative risk increase (RRI) of any GI bleeding with NOACs versus CAG. Compared with controls, risk of GI bleeding was significantly higher with dabigatran (POR 1.31, 1.10 to 1.57; NNH=205) and rivaroxaban (POR 1.35, 1.16 to 1.57; NNH=139) but not with apixaban (POR 0.85, 0.67 to 1.08). TSA support a RRI of 20% for dabigatran and rivaroxaban and showed insufficient data for apixaban. NOACs caused significantly higher risk of any GI bleeding compared with warfarin (NNH=212) and LMWH followed by warfarin (NNH=134), but not against LMWH alone. Conclusion: The GI bleeding risk may differ among NOACs and is definitely higher with dabigatran and rivaroxaban, but we lack sufficient evidence for apixaban. These risks should be addressed in large RCTs. (Table Presented)

BACKGROUND: The 2013 American College of Cardiology Foundation/American Heart Association ST-segment elevation myocardial infarction (STEMI) guidelines have shifted focus from door-to-balloon (D2B) time to the time from first medical contact to device activation (contact-to-device time [C2D] ). HYPOTHESIS: This study investigates the impact of prehospital wireless electrocardiogram transmission (PHT) on reperfusion times to assess the impact of the new guidelines. METHODS: From January 2009 to December 2012, data were collected on STEMI patients who received percutaneous coronary interventions; 245 patients were included for analysis. The primary outcome was median C2D time in the PHT group and the secondary outcome was D2B time. RESULTS: Prehospital wireless electrocardiogram transmission was associated with reduced C2D times vs no PHT: 80 minutes (interquartile range [IQR], 64-94) vs 96 minutes (IQR, 79-118), respectively, P < 0.0001. The median D2B time was lower in the PHT group vs the no-PHT group: 45 minutes (IQR, 34-56) vs 63 minutes (IQR, 49-81), respectively, P < 0.0001. Multivariate analysis showed PHT to be the strongest predictor of a C2D time of <90 minutes (odds ratio: 3.73, 95% confidence interval: 1.65-8.39, P = 0.002). Female sex was negatively predictive of achieving a C2D time <90 minutes (odds ratio: 0.23, 95% confidence interval: 0.07-0.73, P = 0.01). CONCLUSIONS: In STEMI patients, PHT was associated with significantly reduced C2D and D2B times and was an independent predictor of achieving a target C2D time. As centers adapt to the new guidelines emphasizing C2D time, targeting a shorter D2B time (<50 minutes) is ideal to achieve a C2D time of <90 minutes.

BACKGROUND: Recent initiatives have focused on primary prevention to delay time to first myocardial infarction (MI). The aim of this study was to evaluate the change in risk factor profile over time in patients without known cardiovascular disease presenting with first MI. METHODS: In the American Heart Association's Get With The Guidelines-Coronary Artery Disease national registry, 100,884 patients without known cardiovascular disease presenting with acute MI from 408 hospitals were evaluated between 2002 and 2008. The time trends of the proportion of patients with cardiovascular risk factors (nonmodifiable: age >45 years for men or >55 years for women, male sex, modifiable: diabetes mellitus, hypertension, hyperlipidemia, tobacco use) were analyzed. Analyses were stratified by non-ST-segment elevation MI (NSTEMI) versus ST-segment elevation MI (STEMI). RESULTS: The proportion of patients with >/=3 of 6 traditional risk factors slightly decreased over time in the NSTEMI (69.5%-66.8%, P < .0001) and STEMI (68.9%-66.4%, P < .0001) cohorts. The proportion of patients with >/=2 of 4 modifiable risk factors increased from 52% to 59% and then declined to 52.1% (P < .0001) in the NSTEMI cohort but declined slightly in the STEMI cohort (50.9%-47.3%, P < .0001). After adjusting for age and gender, the time trend of proportion with diabetes mellitus, hypertension, and tobacco use declined in both cohorts. However, the proportion of patients with hyperlipidemia remained similar. CONCLUSIONS: Although risk factor profiles in patients presenting with first MI have shown improvements over time, the changes are modest.