USE OF DRUG ELUTING STENTS AS A FUNCTION OF PREDICTED BENEFIT: CLINICAL AND ECONOMIC IMPLICATIONS OF CURRENT PRACTICE

Background: Benefits of drug-eluting stents (DES) in percutaneous coronary intervention (PCI) are greatest in those at the highest risk of target vessel revascularization (TVR). While DES reduce restenosis, they cost more than bare metal stents (BMS), and necessitate prolonged dual antiplatelet therapy (DAPT) that increases costs, bleeding risk, and risk of complications if DAPT is prematurely discontinued. Our objectives were to assess if DES are preferentially used in those with higher predicted TVR risk, and to estimate whether lower use of DES (50% less DES use among patients with low predicted TVR risk) would be more cost-effective as compared with the existing pattern of DES use. Methods: We analyzed ~1.5 million PCI procedures in the NCDR CathPCI registry from Apr 2003 - Sept 2010. We estimated 1-year TVR risk assuming PCI with BMS using a previously validated prediction model. The main outcome measures were the rate of DES use and projected annual US societal costs at one year after PCI. We assessed the association between TVR risk with BMS DES use, and performed cost-effectiveness analysis of a lower use of DES (50% less DES use among patients with low predicted TVR risk) vs. existing DES use. Results: There was marked variation in physicians' use of DES (range = 2-100%). DES use was relatively high across all categories of predicted TVR risk (73.9% in patients with TVR risk 20%), with a modest correlation between predicted TVR risk and DES use (RR 1.005/1% increase in predicted TVR risk [95% CI = 1.005, 1.006]). Reducing DES use by 50% among the lowest risk patients was projected to lower US healthcare costs by $205 million/year while increasing the overall TVR event rate by 0.5% (95% CI= 0.49%, 0.51%) in absolute terms. Conclusions: DES use in the U.S. varies widely among physicians, with only modest correlation to patients' risk of restenosis. Less DES use among patients with low risk of restenosis has the potential for significant cost savings for the US healthcare system, while minimally increasing restenosis events

A simple method to combine multiple molecular biomarkers for dichotomous diagnostic classification

BACKGROUND: In spite of the recognized diagnostic potential of biomarkers, the quest for squelching noise and wringing in information from a given set of biomarkers continues. Here, we suggest a statistical algorithm that – assuming each molecular biomarker to be a diagnostic test – enriches the diagnostic performance of an optimized set of independent biomarkers employing established statistical techniques. We validated the proposed algorithm using several simulation datasets in addition to four publicly available real datasets that compared i) subjects having cancer with those without; ii) subjects with two different cancers; iii) subjects with two different types of one cancer; and iv) subjects with same cancer resulting in differential time to metastasis. RESULTS: Our algorithm comprises of three steps: estimating the area under the receiver operating characteristic curve for each biomarker, identifying a subset of biomarkers using linear regression and combining the chosen biomarkers using linear discriminant function analysis. Combining these established statistical methods that are available in most statistical packages, we observed that the diagnostic accuracy of our approach was 100%, 99.94%, 96.67% and 93.92% for the real datasets used in the study. These estimates were comparable to or better than the ones previously reported using alternative methods. In a synthetic dataset, we also observed that all the biomarkers chosen by our algorithm were indeed truly differentially expressed. CONCLUSION: The proposed algorithm can be used for accurate diagnosis in the setting of dichotomous classification of disease states

The Roles of the Saccharomyces cerevisiae RecQ Helicase SGS1 in Meiotic Genome Surveillance

leads to an increase in synapsis initiation complexes and axial associations leading to the proposal that it has an early role in unwinding surplus strand invasion events. Physical studies of recombination intermediates implicate it in the dissolution of double Holliday junctions between sister chromatids. chromosomes may sometimes remain entangled at the end of pre-meiotic replication. This, combined with reciprocal crossing over, could lead to physical destruction of the recombined and entangled chromosomes. We hypothesise that Sgs1, acting in concert with the topoisomerase Top2, resolves these structures.This work provides evidence that Sgs1 interacts with various partner proteins to maintain genome stability throughout meiosis

Impact of Clopidogrel Pretreatment on Ischemic Complications of PCI among Bivalirudin-Treated Patients: Results from the EVENT Registry

Computational Infrastructure and Informatics Poster SessionBackground: Although clopidogrel (CLO) pretreatment benefits PCI patients with acute coronary syndromes, these benefits are less well-established among elective PCI patients—particularly when treated with the direct thrombin inhibitor (DTI), bivalirudin. The effect of timing of CLO pretreatment on ischemic complications in these patients is also unknown. Methods: We used data from the multicenter EVENT registry to assess the association of clopidogrel pretreatment (600 mg 2 hr pre-PCI, 300 mg 6 hrs pre-PCI, or 75 mg/d for 1 week) with PCI-related complications in patients undergoing elective PCI with a DTI as planned antithrombotic. The primary endpoint was the composite of in-hospital death or MI (peak CKMB > 3 x ULN). Results: Between 01/05 and 12/07, 3568 pts underwent elective PCI and 1913 (54%) received DTI as planned anticoagulant (37% diabetics, age 65±10 y). Clopidogrel pre-treatment was used in 923 (48%). There were no differences in in-hospital or 1 year ischemic or bleeding events in relation to clopidogrel pretreatment in both unadjusted and adjusted analyses (see Table). There was a trend toward lower rates of death or MI with earlier pretreatment, however [Odds ratios vs. no pretreatment: >1 week 0.48 (95% CI 0.08 - 2.73); > 6 h OR 0.69 (95% CI 0.11 - 4.45) and 2-6 h OR 0.77 (95% CI 0.18 - 3.31)]. Conclusion: Among unselected patients undergoing elective PCI with DTI as the planned anticoagulant, clopidogrel pretreatment was common, but was not associated with a reduced risk of ischemic complications

Minimizing radiographic contrast administration during coronary angiography using a novel contrast reduction system: A multicenter observational study of the DyeVert™ plus contrast reduction system

ObjectiveTo evaluate contrast media (CM) volume (CMV) saved using the DyeVert™ Plus Contrast Reduction System (DyeVert Plus System, Osprey Medical) in patients undergoing diagnostic coronary angiogram (CAG) and/or percutaneous coronary interventional (PCI) procedures performed with manual injections.BackgroundCurrent guidelines advocate for monitoring and minimization of the total volume of CM in chronic kidney disease (CKD) patients undergoing invasive cardiac procedures. The DyeVert Plus System is an FDA cleared device designed to reduce CMV delivered during angiography and permit real‐time CMV monitoring.MethodsWe performed a multicenter, single‐arm, observational study. Eligible subjects were ≥ 18 years old with baseline estimated glomerular filtration rate (eGFR) 20–60 mL/min/1.73 m2. The primary endpoint was % CMV saved over the total procedure. A secondary objective was to evaluate adverse events (AEs) related to DyeVert Plus System or to CM use.ResultsA total of 114 subjects were enrolled at eight centers. Mean age was 72 ± 9 years, 72% were male, and mean body mass index was 29 ± 5. Baseline eGFR was 43 ± 11 mL/min/1.73 m2. CAG‐only was performed in 65% of cases. One hundred and five subjects were evaluable for the primary endpoint. Mean CMV attempted was 112 ± 85 mL (range 22–681) and mean CMV delivered was 67 ± 51 mL (range 12–403), resulting in an overall CMV savings of 40.1 ± 8.8% (95% CI 38.4, 41.8; P 0.3 mg/dL from baseline) was reported in 11 cases with seven occurring in subjects with baseline eGFR < 30 and three AKI events were attributed to CM. AKI rates increased as CMV/eGFR ratios increased.ConclusionsThese data suggest DyeVert Plus System use in CKD patients undergoing CAG and/or PCI results in clinically meaningful CMV savings while maintaining image quality.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149537/1/ccd27935_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149537/2/ccd27935.pd

Trends in the Prevalence of Acute Kidney Injury in Patients with Acute Myocardial Infarction

Comparative Medicine - OneHealth and Comparative Medicine Poster SessionIntroduction: Acute kidney injury (AKI) is common in patients (pts) with acute myocardial infarction (AMI), and associated with permanent renal impairment and death. While guidelines increasingly emphasize the importance of AKI prevention, whether the rates of AKI changed over time is unknown. Methods: We studied 35,425 pts hospitalized with AMI in 66 U.S. centers from 2000-08 using Health Facts, a national database with detailed information on in-hospital renal function. AKI was defined as absolute creatinine increase of ≥ 0.3 mg/dL or relative increase of ≥50%. Temporal trends in AKI during the 9-year study period were evaluated using hierarchical logistic regression, adjusting for secular changes in baseline creatinine and other known AKI predictors. Results: From 2000-08, mean age increased (66.9 vs 68.8 yrs), as did baseline creatinine (1.4 vs 1.5 mg/dL), rate of cardiogenic shock (5.1 vs 6.3%), diabetes (30.4 vs 35.8%), coronary angiography (57 vs 68%), and PCI (30.2 vs 45.2%, P<0.001 for all comparisons). Despite increase in AKI risk factors, the rates of AKI declined steadily (Figure). The trend of decreasing AKI rates persisted after multivariable adjustment (P=0.01). Conclusions: While AKI still affects nearly 1 in 4 AMI pts, the rates of AKI declined significantly from 2000-08, despite the aging population and rising prevalence of AKI risk factors. These findings may reflect the impact of increased clinician awareness, better risk stratification, and AKI prevention efforts during this time period

Nuisance Bleeding With Prolonged Dual Antiplatelet Therapy After Acute Myocardial Infarction and its Impact on Health Status

ObjectivesThe purpose of this study was to examine the incidence of nuisance bleeding after AMI and its impact on QOL.BackgroundProlonged dual antiplatelet therapy (DAPT) is recommended after acute myocardial infarction (AMI) to reduce ischemic events, but it is associated with increased rates of major and minor bleeding. The incidence of even lesser degrees of post-discharge “nuisance” bleeding with DAPT and its impact on quality of life (QOL) are unknown.MethodsData from the 24-center TRIUMPH (Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients' Health Status) study of 3,560 patients, who were interviewed at 1, 6, and 12 months after AMI, were used to investigate the incidence of nuisance bleeding (defined as Bleeding Academic Research Consortium type 1). Baseline characteristics associated with “nuisance” bleeding and its association with QOL, as measured by the EuroQol 5 Dimension visual analog scale, and subsequent re-hospitalization were examined.ResultsNuisance (Bleeding Academic Research Consortium type 1) bleeding occurred in 1,335 patients (37.5%) over the 12 months after AMI. After adjusting for baseline bleeding and mortality risk, ongoing DAPT was the strongest predictor of nuisance bleeding (rate ratio [RR]: 1.44, 95% confidence interval [CI]: 1.17 to 1.76 at 1 month; RR: 1.89, 95% CI: 1.35 to 2.65 at 6 months; and RR: 1.39, 95% CI: 1.08 to 1.79 at 12 months; p < 0.01 for all comparisons). Nuisance bleeding at 1 month was independently associated with a decrement in QOL at 1 month (−2.81 points on EuroQol 5 Dimension visual analog scale; 95% CI: 1.09 to 5.64) and nonsignificantly toward higher re-hospitalization (hazard ratio: 1.20; 95% CI: 0.95 to 1.52).ConclusionsNuisance bleeding is common in the year after AMI, associated with ongoing use of DAPT, and independently associated with worse QOL. Improved selection of patients for prolonged DAPT may help minimize the incidence and adverse consequences of nuisance bleeding