Matthew W. Mell

Complications of spinal fluid drainage in thoracoabdominal aortic aneurysm repair: A report of 486 patients treated from 1987 to 2008

OBJECTIVE Spinal fluid drainage reduces paraplegia risk in thoracic (TAA) and thoracoabdominal (TAAA) aortic aneurysm repair. There has not been a comprehensive study of the risks of spinal fluid drainage and how these risks can be reduced. Here we report complications of spinal fluid drainage in patients undergoing TAA/TAAA repair. METHODS The study comprised 648 patients who had TAA or TAAA repair from 1987 to 2008. Spinal drains were used in 486 patients. Spinal fluid pressure was measured continuously, except when draining fluid, and was reduced to <6 mm Hg during thoracic aortic occlusion and reperfusion. After surgery, spinal fluid pressure was kept <10 mm Hg until patients were awake with normal leg lift. Drains were removed 48 hours after surgery. Spinal and head computed tomography (CT) scans were performed in patients with bloody spinal fluid or neurologic deficit. We studied the incidence of headache treated with epidural blood patch, infection, bloody spinal fluid, intracranial and spinal bleeding on CT, as well as the clinical consequences. RESULTS Twenty-four patients (5%) had bloody spinal fluid. CT exams showed seven had no evidence of intracranial hemorrhage, 14 (2.9%) had intracranial blood without neurologic deficit, and three with intracranial bleeding and cerebral atrophy had neurologic deficits (1 died, 1 had permanent hemiparesis, and 1 with transient ataxia recovered fully). Two patients without bloody spinal fluid or neurologic deficit after surgery presented with neurologic deficits 5 days postoperatively and died from acute on chronic subdural hematoma. Neurologic deficits occurred after spinal fluid drainage in 5 of 482 patients (1%), and 3 died. The mortality from spinal fluid drainage complications was 0.6% (3 of 482). By univariate and multivariate analysis, larger volume of spinal fluid drainage (mean, 178 mL vs 124 mL, P < .0001) and higher central venous pressure before thoracic aortic occlusion (mean, 16 mm Hg vs 13 mm Hg, P < .0012) correlated with bloody spinal fluid. CONCLUSION Strategies that reduce the volume of spinal fluid drainage but still control spinal fluid pressure are helpful in reducing serious complications. Patients with cerebral atrophy are at increased risk for complications of spinal fluid drainage.

Causes and Implications of Readmission after Abdominal Aortic Aneurysm Repair

Objective:To determine the frequency, causes, predictors, and consequences of 30-day readmission after abdominal aortic aneurysm (AAA) repair. Background Data:Centers for Medicare & Medicaid Services (CMS) will soon reduce total Medicare reimbursements for hospitals with higher-than-predicted 30-day readmission rates after vascular surgical procedures, including AAA repair. However, causes and factors leading to readmission in this population have never before been systematically analyzed. Methods:We analyzed elective AAA repairs over a 2-year period from the CMS Chronic Conditions Warehouse, a 5% national sample of Medicare beneficiaries. Results:A total of 2481 patients underwent AAA repair–-1502 endovascular aneurysm repair (EVAR) and 979 open aneurysm repair. Thirty-day readmission rates were equivalent for EVAR (13.3%) and open repair (12.8%). Although wound complication was the most common reason for readmission after both procedures, the relative frequency of other causes differed—eg, bowel obstruction was common after open repair, and graft complication after EVAR. In multivariate analyses, preoperative comorbidities had a modest effect on readmission; however, postoperative factors, including serious complications leading to prolonged length of stay and discharge destination other than home, had a profound influence on the probability of readmission. The 1-year mortality in readmitted patients was 23.4% versus 4.5% in those not readmitted (P < 0.001). Conclusions:Early readmission is common after AAA repair. Adjusting for comorbidities, postoperative events predict readmission, suggesting that proactively preventing, detecting, and managing postoperative complications may provide an approach to decreasing readmissions, with the potential to reduce cost and possibly enhance long-term survival.

Cost-Effectiveness of Genotype-Guided and Dual Antiplatelet Therapies in Acute Coronary Syndrome

Context Several options for antiplatelet therapy after percutaneous coronary intervention for acute coronary syndrome are available. Contribution This cost-effectiveness analysis compared drug-only strategies (generic clopidogrel, prasugrel, or ticagrelor) and genotype-guided strategies targeting ticagrelor or prasugrel. Ticagrelor was the most cost-effective strategy. The genotyping-with-prasugrel strategy was superior to giving all patients prasugrel. The genotyping-with-ticagrelor strategy was clinically superior but more expensive than clopidogrel. Caution No randomized trials have directly compared genotyping strategies or prasugrel with ticagrelor. Implication Genotype-guided personalization of antiplatelet therapy could improve cost-effectiveness in some situations, but ticagrelor for all without genotyping also seems reasonable. The Editors Dual antiplatelet therapy combining aspirin with a second agent is the mainstay of therapy after acute coronary syndrome (ACS), particularly among patients who receive a percutaneous coronary intervention (PCI) (1). Antiplatelet agents reduce thrombotic events, such as myocardial infarction (MI) and stent thrombosis, but increase risk for bleeding (2). Approximately one half of the 1.1 million ACS events in the United States every year are treated with a PCI, making the choice of antiplatelet therapy a common and important clinical decision (3, 4). Clopidogrel has been the standard of care after PCI for nearly a decade (5). Until recently, it was the second-largest drug in terms of sales, and much of the

Effect of early plasma transfusion on mortality in patients with ruptured abdominal aortic aneurysm

12 billion spent on it each year was for use after ACS (6). However, many patients receiving clopidogrel and aspirin have recurrent cardiovascular events (7, 8), and on-treatment platelet inhibition varies considerably (9, 10). Patients who carry a loss-of-function polymorphism of CYP2C19 (a key enzyme involved in the hepatic activation of clopidogrel) achieve less platelet inhibition with clopidogrel and have more thrombotic events (1113) and less bleeding. However, carriers of gain-of-function alleles of the CYP2C19 enzyme achieve greater platelet inhibition with clopidogrel and have fewer thrombotic events and more bleeding (14, 15). Two new drugs, prasugrel and ticagrelor, are approved for use in patients having PCI for ACS (1619). The greater antiplatelet activity of these agents reduces the rate of MI and cardiovascular death compared with clopidogrel. However, prasugrel increases fatal bleeding so that its net effect on mortality rates is neutral (16, 17). Ticagrelor is dosed twice daily and causes mild to moderate dyspnea in some patients (18, 19), which may adversely affect adherence. Both agents are expensive, particularly when compared with generic formulations of clopidogrel that are now available. Further, commercial availability of genetic testing may allow clinicians to personalize antiplatelet therapy so that the new, more expensive drugs could be selectively prescribed to patients most likely to benefit (11, 12, 20, 21). These recent developments have altered the therapeutic landscape, highlighting the need for a comprehensive evaluation of alternative strategies for dual antiplatelet therapy. There are no head-to-head clinical trials of ticagrelor with prasugrel and no prospective studies of genotype-based treatment decisions. In this article, we present a simulation that addresses uncertainties about the role of genotyping and identifies the most cost-effective strategies for dual antiplatelet therapy after PCI for ACS. Methods We developed a discrete-state Markov model to compare 5 strategies of dual antiplatelet therapy (22). Drug-Only Strategies Drug-only strategies were generic clopidogrel, prasugrel, or ticagrelor. We assumed that generic clopidogrel had the same efficacy as the proprietary formulation. On the basis of the results of TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With PrasugrelThrombolysis in Myocardial Infarction), we assumed that prasugrel led to fewer cardiovascular deaths but more fatal bleeding compared with clopidogrel (16, 17). On the basis of the PLATO (Platelet Inhibition and Patient Outcomes) study, we assumed that ticagrelor reduced cardiovascular deaths without a corresponding increase in fatal bleeding (18, 19) and that some patients had dyspnea and bradyarrhythmias while on treatment (23, 24). We did not distinguish between patients who presented with or without ST-segment elevations because this feature did not modify the effect of prasugrel or ticagrelor on the primary end point in either TRITON-TIMI 38 or PLATO (16, 18). Genotype-Guided Strategies We modeled the genotype-guided regimens on the basis of the recently published guidelines of the Clinical Pharmacogenetics Implementation Consortium (25) (Table 1 of the Supplement). In the 2 genotype-guided strategies, we assumed that carriers of 1 or 2 loss-of-function alleles would receive prasugrel (genotyping-with-prasugrel strategy) or ticagrelor (genotyping-with-ticagrelor strategy), whereas patients with 2 gain-of-function alleles, 1 gain-of-function allele and 1 wild-type allele, or 2 wild-type alleles would be treated with clopidogrel. Because 1 gain-of-function allele does not completely compensate for 1 loss-of-function allele (25), such persons would receive prasugrel or ticagrelor after genotyping. We did not evaluate strategies using tests of platelet reactivity or clopidogrel dose-escalation because their clinical relevance was unclear (26, 27). Supplement. Modeling Details and Supplementary Results The base case was a hypothetical cohort of 100000 patients aged 65 years with ACS who had PCI with 1 or more drug-eluting stents. All patients received dual antiplatelet therapy with 1 of the previously mentioned agents and aspirin for 12 months after the last PCI or MI and low-dose aspirin daily thereafter unless contraindicated. We assumed the societal perspective (28), considering all direct and induced medical costs and relevant clinical outcomes. Utilities and costs were assigned to each clinical event in 1-month cycles and discounted at 3% annually (29). We conducted extensive deterministic, probabilistic, and scenario-based sensitivity analyses to account for uncertainty in the input variables. We adhered to the recommendations of the Panel on Cost-Effectiveness in Health and Medicine (30). We reported results in 2011 U.S. dollars, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) (30). For each ICER evaluation, the comparator was the strategy that produced the next-most QALYs, excluding strategies that cost more (strictly dominated) or had a greater ICER (dominated by extension). Because of the inherent challenges of indirect comparisons between the 2 drugs, we did tiered comparisons: We first compared the drug-only strategies (to distinguish the drug effect from the effect of genetic testing), then we examined the effect of genotyping on prasugrel and ticagrelor separately; finally, we did a global comparison across all 5 strategies. Where required, we applied a willingness-to-pay threshold of

For-profit hospital status and rehospitalizations at different hospitals: an analysis of Medicare data.

50000 per QALY. Modeling was done using TreeAge Pro 2009 (TreeAge Software, Williamstown, Massachusetts) and Excel 2007 (Microsoft, Redmond, Washington), and statistical analyses were done using Stata, version 11 (StataCorp, College Station, Texas). Model Structure After the initial PCI, patients were at risk for stent thrombosis, nonfatal MI (unrelated to stent thrombosis), percutaneous or surgical revascularization, intracranial and extracranial bleeding, and death of cardiovascular and noncardiovascular causes (Figure 1 of the Supplement). Three additional states were modeled: Post-MI (patients who had an MI after entering the model had an increased risk for future MIs and cardiovascular death); intracranial bleed; and a steady state, into which all patients entered after a coronary artery bypass graft or 4 years after their initial PCI, whichever was sooner. The steady state accounted for age-specific medical costs and QALYs without tracking individual clinical events. Model Inputs Details can be found in the Appendix Table. For patients in the clopidogrel group, we estimated the incidence and management of major coronary events from trials (8, 16, 18, 19, 3137), observational data (4, 3854), U.S. life tables (55), U.S. Food and Drug Administration publications (56), Medicare claims data (57, 58), clinical guidelines (5, 5961), and other publications (48, 62). Event rates in the other groups were estimated using rate ratios relative to patients on clopidogrel (1619, 3335). Long-term survival of patients with ACS was estimated using Medicare claims data from 2002 to 2006 (Figure 2 of the Supplement) (57, 58). See the Supplement for additional information. Appendix Table. Summary of Key Model Variables We estimated the prevalence of loss-of-function polymorphisms from published studies (25, 34, 6365). Although some studies showed that loss-of-function carriers had a greater rate of thrombotic events than noncarriers when treated with clopidogrel (66), 2 recent reviews estimated different degrees of association between carrier states and thrombotic events. In a collaborative, random-effects model meta-analysis of 9 studies including 9685 patients (91% of whom had a PCI), Mega and colleagues (12) found that carriers of 1 or 2 CYP2C19 loss-of-function alleles had a hazard ratio of 1.57 for thrombotic events (95% CI, 1.13 to 2.16) relative to noncarriers. In a fixed-effects model meta-analysis of 42016 patients from 32 clopidogrel trials that were not limited to patients with PCI, Holmes and colleagues (67) found that carriers of loss-of-function alleles had a relative risk of 1.18 (CI, 1.09 to 1.28) for thrombotic events relative to noncarriers. In light of this uncertainty in the ability of loss-of-function alleles to discriminate between high- and low-risk patien

Outcomes after endarterectomy for chronic mesenteric ischemia

BACKGROUND The ratio of red blood cell (PRBC) transfusion to plasma (FFP) transfusion (PRBC:FFP ratio) has been shown to impact survival in trauma patients with massive hemorrhage. The purpose of this study was to determine the effect of the PRBC:FFP ratio on mortality for patients with massive hemorrhage after ruptured abdominal aortic aneurysm (RAAA). METHODS A retrospective review was performed of patients undergoing emergent open RAAA repair from January 1987 to December 2007. Patients with massive hemorrhage (≥10 units of blood products transfused prior to conclusion of the operation) were included. The effects of patient demographics, admission vital signs, laboratory values, peri-operative variables, amount of blood products transfused, and the PRBC:FFP ratio on 30-day mortality were analyzed by multivariate analysis. RESULTS One hundred and twenty-eight of the 168 (76%) patients undergoing repair for RAAA received at least 10 units of blood products within the peri-operative period. Mean age was 73.1 ± 9.1 years, and 109 (85%) were men. Thirty-day mortality was 22.6% (29/128), including 11 intra-operative deaths. By multivariate analysis, 30-day mortality was markedly lower (15% vs 39%; P < .03) for patients transfused at a PRBC:FFP ratio ≤2:1 (HIGH FFP group) compared with those transfused at a ratio of >2:1 (LOW FFP), and the likelihood of death was more than 4-fold greater in the LOW FFP group (odds ratio 4.23; 95% confidence interval, 1.2-14.49). Patients in the HIGH FFP group had a significantly lower incidence of colon ischemia than those in the LOW FFP group (22.4% vs 41.1%; P = .004). CONCLUSION For RAAA patients requiring massive transfusion, more equivalent transfusion of PRBC to FFP (HIGH FFP) was independently associated with lower 30-day mortality. The lower incidence of colonic ischemia in the HIGH FFP group may suggest an additional benefit of early plasma transfusion that could translate into further mortality reduction. Analysis from this study suggests the potential feasibility for a more standardized protocol of initial resuscitation for these patients, and prospective studies are warranted to determine the optimum PRBC:FFP ratio in RAAA patients.

Impact of the screening abdominal aortic aneurysms very efficiently (SAAAVE) act on abdominal ultrasonography use among medicare beneficiaries

BACKGROUND About one quarter of rehospitalized Medicare patients are admitted to hospitals different from their original hospital. The extent to which this practice is related to for-profit hospital status and affects payments and mortality is unknown. OBJECTIVE To describe and examine predictors of and payments for rehospitalization at a different hospital among Medicare patients rehospitalized within 30 days at for-profit and nonprofit or public hospitals. DESIGN Cohort study of patients discharged and rehospitalized from January 2005 to November 2006. SETTING Medicare fee-for-service hospitals throughout the United States. PARTICIPANTS A 5% random national sample of Medicare patients with acute care rehospitalizations within 30 days of discharge (n = 74,564). MEASUREMENTS 30-day rehospitalizations at different hospitals and total payments or mortality over the subsequent 30 days. Multivariate logistic and quantile regression models included index hospital for-profit status, discharge counts, geographic region, rural-urban commuting area, and teaching status; patient sociodemographic characteristics, disability status, and comorbid conditions; and a measure of risk adjustment. RESULTS 16 622 patients (22%) in the sample were rehospitalized at a different hospital. Factors associated with increased risk for rehospitalization at a different hospital included index hospitalization at a for-profit, major medical school-affiliated, or low-volume hospital and having a Medicare-defined disability. Compared with patients rehospitalized at the same hospital, patients rehospitalized at different hospitals had higher adjusted 30-day total payments (median additional cost,

The Society for Vascular Surgery practice guidelines on the care of patients with an abdominal aortic aneurysm

1308 per patient; P < 0.001) but no statistically significant differences in 30-day mortality, regardless of index hospital for-profit status. LIMITATION The database lacked detailed clinical information about patients and did not include information about specific provider practice motivations or the role of patient choice in hospitalization venues. CONCLUSION Rehospitalizations at different hospitals are common among Medicare patients, are more likely among those initially hospitalized at a for-profit hospital, and are related to increased overall payments without improved mortality. PRIMARY FUNDING SOURCE University of Wisconsin Hartford Center of Excellence in Geriatrics, National Institutes of Health.

Low frequency of primary lipid screening among Medicare patients with rheumatoid arthritis

OBJECTIVES A retrospective study was performed to identify optimal factors affecting outcomes after open revascularization for chronic mesenteric ischemia. METHODS All patients who underwent open surgery for chronic mesenteric ischemia from 1987 to 2006 were reviewed. Patients with acute mesenteric ischemia or median arcuate ligament syndrome were excluded. Mortality, recurrent stenosis, and symptomatic recurrence were analyzed using logistic regression, and univariate and multivariate analysis. RESULTS We identified 80 patients (69% women, 31% men). Mean age was 64 years (range, 31-86 years). Acute-on-chronic symptoms were present in 26%. Presenting symptoms included postprandial pain (91%), weight loss (69%), and food fear and diarrhea (25%). Preoperative imaging demonstrated severe (>70%) stenosis of the superior mesenteric artery in 75 patients (24 occluded), the celiac axis in 63 (20 occluded), and the inferior mesenteric artery in 53 (20 occluded). Multivessel disease was present in 72 patients (90%), and 40 (50%) underwent multivessel reconstruction. Revascularization was achieved by endarterectomy in 37 patients, mesenteric bypass in 29, and combined procedures in 14. Concurrent aortic reconstruction was required in 13 patients (16%). Three hospital deaths occurred (3.8%). Mean follow-up was 3.8 years (range, 0-17.2 years). One- and 5-year survival was 92.2% and 64.5%. Mortality was associated with age (P = .019) and renal insufficiency (P = .007), but not by clinical presentation. Symptom-free survival was 89.7% and 82.1% at 1 and 5 years, respectively. Symptoms requiring reintervention occurred in nine patients (11%) at a mean of 29 months (range, 5-127 months). Multivariate analysis showed that freedom from recurrent symptoms correlated with endarterectomy for revascularization (5.2% vs 27.6%; hazard ratio, 0.20; 95% confidence interval, 0.04-0.92; P = .02). CONCLUSION For open surgical candidates, endarterectomy appears to provide the most durable long-term symptom relief in patients with chronic mesenteric ischemia.

Presurgical Localization of the Artery of Adamkiewicz with Time-resolved 3.0-T MR Angiography

BACKGROUND Since January 1, 2007, Medicare has covered abdominal aortic aneurysm (AAA) screening for new male enrollees with a history of smoking under the Screening Abdominal Aortic Aneurysms Very Efficiently (SAAAVE) Act. We examined the association between this program and abdominal ultrasonography for AAA screening, elective AAA repair, hospitalization for AAA rupture, and all-cause mortality. METHODS We used a 20% sample of traditional Medicare enrollees from 2004 to 2008 to identify 65-year-old men eligible for screening and 3 control groups not eligible for screening (70-year-old men, 76-year-old men, and 65-year-old women). We used logistic regression to examine the change in outcomes at 365 days for eligible vs ineligible beneficiaries before and after SAAAVE Act implementation, adjusting for comorbidities, state-level smoking prevalence, geographic variation, and time trends. RESULTS Fewer than 3% of abdominal ultrasonography claims after 2007 were for SAAAVE-specific AAA screening. There was a significantly greater increase in abdominal ultrasonography use among SAAAVE-eligible beneficiaries (2.0 percentage points among 65-year-old men, from 7.6% in 2004 to 9.6% in 2008; 0.7 points [8.9% to 9.6%] among 70-year-old men; 0.7 points [10.8% to 11.5%] among 76-year-old men; and 0.9 points [7.5% to 8.4%] among 65-year-old women) (P < .001 for all comparisons with 65-year-old men). The SAAAVE Act was associated with increased use of abdominal ultrasonography in 65-year-old men compared with 70-year-old men (adjusted odds ratio [AOR], 1.15; 95% CI, 1.11-1.19) (P < .001), and this increased use remained even when SAAAVE-specific AAA screening was excluded (AOR, 1.12; 95% CI, 1.08-1.16) (P < .001). Implementation of the SAAAVE Act was not associated with changes in rates of AAA repair, AAA rupture, or all-cause mortality. CONCLUSIONS The impact of the SAAAVE Act on AAA screening was modest and was based on abdominal ultrasonography use that it did not directly reimburse. The SAAAVE Act had no discernable effect on AAA rupture or all-cause morality.