Xuerong Wen

Evidence of Pre-Procedural Statin Therapy : A Meta-Analysis of Randomized Trials

OBJECTIVES The purpose of this study was to summarize the evidence of pre-procedural statin therapy to reduce periprocedure cardiovascular events. BACKGROUND Invasive procedures can result in adverse cardiovascular events, such as myocardial infarction (MI) and death. We hypothesized that statins might improve clinical outcomes when used before invasive procedures. METHODS We searched the MEDLINE, Cochrane, and clinicaltrials.gov databases from inception to February 2010 for randomized, controlled trials that examined statin therapy before invasive procedures. Invasive procedures were defined as percutaneous coronary intervention, coronary artery bypass grafting (CABG), and noncardiac surgery. We required that studies initiated statins before the procedure and reported clinical outcomes. A DerSimonian-Laird model was used to construct random-effects summary risk ratios. RESULTS Eight percent of the screened trials (21 of 270) met our selection criteria, which included 4,805 patients. The use of pre-procedural statins significantly reduced post-procedural MI (risk ratio [RR]: 0.57, 95% confidence interval [CI]: 0.46 to 0.70, p < 0.0001). This benefit was seen after both percutaneous coronary intervention (p < 0.0001) and noncardiac surgical procedures (p = 0.004), but not CABG (p = 0.40). All-cause mortality was nonsignificantly reduced by statin therapy (RR: 0.66, 95% CI: 0.37 to 1.17, p = 0.15). Pre-procedural statins also reduced post-CABG atrial fibrillation (RR: 0.54, 95% CI: 0.43 to 0.68, p < 0.0001). CONCLUSIONS Statins administered before invasive procedures significantly reduce the hazard of post-procedural MI. Additionally, statins reduce the risk of atrial fibrillation after CABG. The routine use of statins before invasive procedures should be considered.

Efficacy and Safety of Glycoprotein IIb/IIIa Inhibitors During Elective Coronary Revascularization A Meta-Analysis of Randomized Trials Performed in the Era of Stents and Thienopyridines

OBJECTIVES The purpose of this study was to investigate the efficacy and safety of glycoprotein IIb/IIIa inhibitors (GPIs) during elective percutaneous coronary intervention (PCI). BACKGROUND Studies have documented that GPIs are useful during PCI; however, much of this research was conducted before the routine use of coronary stents and thienopyridines. METHODS We searched the MEDLINE, Cochrane clinical trials, and ClinicalTrials.gov databases from inception for studies that randomly assigned patients undergoing elective PCI to a GPI versus control. Trials were included if stents and thienopyridines were used routinely and clinical outcomes were reported. Outcomes were assessed within 30 days. A DerSimonian-Laird model was used to construct random effects summary risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS Our search yielded 22 studies with 10,123 patients. The incidence of nonfatal myocardial infarction was 5.1% with GPI versus 8.3% with control (RR: 0.66, 95% CI: 0.55 to 0.79, p < 0.0001). Major bleeding was 1.2% versus 0.9% (RR: 1.37, 95% CI: 0.83 to 2.25, p = 0.22), minor bleeding was 3.0% versus 1.7% (RR: 1.70, 95% CI: 1.28 to 2.26, p < 0.0001), and mortality was 0.3% versus 0.5% (RR: 0.70, 95% CI: 0.36 to 1.33, p = 0.27), respectively. CONCLUSIONS In the current era of elective PCI performed with stents and thienopyridines, GPIs provide clinical benefit. These agents reduce nonfatal myocardial infarction without a notable increase in major bleeding; however, they increase the risk of minor bleeding. All-cause mortality is not reduced.

Antiepileptic drug use by pregnant women enrolled in Florida Medicaid

Objective: The study aims were to investigate secular trends in antiepileptic drug (AED) use in women during pregnancy, and to compare the use of first- and second-generation AEDs. Methods: Study participants consisted of female Florida Medicaid beneficiaries, older than 15 years, and pregnant within the time period 1999 to 2009. Fifteen AEDs were categorized into first and second generation of AEDs. Continuous use of AEDs was defined as at least 2 consecutive AED prescriptions totaling more than a 30-day supply. Polytherapy was defined as 2 or more AEDs continuously used for at least 30 overlapping days. Annual prevalence was estimated and compared. Results: We included 2,099 pregnant women who were enrolled in Florida Medicaid from 1999 to 2009 and exposed to AEDs during pregnancy. Although there were fluctuations, overall AED use in the study cohort did not increase from 2000 to 2009 (β ± standard error [SE]: −0.07 ± 0.06, p = 0.31). The use of first-generation AEDs decreased (β ± SE: −6.21 ± 0.47, p < 0.0001), whereas the use of second-generation AEDs increased (β ± SE: 6.27 ± 0.52, p < 0.0001) from 2000 to 2009. AED use in polytherapy did not change through the study period. Valproate use reduced from 23% to 8% in the study population (β ± SE: −1.61 ± 0.36, p = 0.0019), but this decrease was only for women receiving an AED for epilepsy and was not present for other indications. Conclusion: The second-generation AEDs are replacing first-generation AEDs in both monotherapy and polytherapy. Valproate use has declined for epilepsy but not other indications. Additional changes in AED use are expected in future years.

Effect of Phosphodiesterase Type 5 Inhibition on Microvascular Coronary Dysfunction in Women: A Women’s Ischemia Syndrome Evaluation (WISE) Ancillary Study

Microvascular coronary dysfunction (MCD) is associated with symptoms and signs of ischemia, and also adverse outcomes in women without macrovascular obstructive coronary artery disease (M‐CAD). Although MCD can be quantified using coronary flow reserve (CFR), treatment is poorly defined.

Complete Versus Culprit-Only Revascularization for Patients With Multi-Vessel Disease Undergoing Primary Percutaneous Coronary Intervention: An Updated Meta-Analysis of Randomized Trials: Complete versus Culprit PCI in STEMI

To perform an updated meta‐analysis to determine whether complete revascularization of significant coronary lesions at the time of primary percutaneous coronary intervention (PCI) would be associated with better outcomes compared with culprit‐only revascularization.

Prolonged immunosuppression preserves nonsensitization status after kidney transplant failure.

Background When kidney transplants fail, transplant medications are discontinued to reduce immunosuppression-related risks. However, retransplant candidates are at risk for allosensitization which prolonging immunosuppression may minimize. We hypothesized that for these patients, a prolonged immunosuppression withdrawal after graft failure preserves nonsensitization status (PRA 0%) better than early immunosuppression withdrawal. Methods We retrospectively examined subjects transplanted at a single center between July 1, 1999 and December 1, 2009 with a non–death-related graft loss. Subjects were stratified by timing of immunosuppression withdrawal after graft loss: early (⩽3 months) or prolonged (>3 months). Retransplant candidates were eligible for the main study where the primary outcome was nonsensitization at retransplant evaluation. Non-retransplant candidates were included in the safety analysis only. Results We found 102 subjects with non–death-related graft loss of which 49 were eligible for the main study. Nonsensitization rates at retransplant evaluation were 30% and 66% for the early and prolonged immunosuppression withdrawal groups, respectively (P=0.01). After adjusting for cofactors such as blood transfusion and allograft nephrectomy, prolonged immunosuppression withdrawal remained significantly associated with nonsensitization (adjusted odds ratio=5.78, 95% CI [1.37–24.44]). No adverse safety signals were seen in the prolonged immunosuppression withdrawal group compared to the early immunosuppression withdrawal group. Conclusions These results suggest that prolonged immunosuppression may be a safe strategy to minimize sensitization in retransplant candidates and provide the basis for larger or prospective studies for further verification.

Is antiepileptic drug use related to depression and suicidal ideation among patients with epilepsy

Depression and suicide are increased in patients with epilepsy. The U.S. Food and Drug Administration warns that antiepileptic drugs (AEDs) are associated with increased risk of suicidality. This study examines the relationship among depression, suicidal ideation, and AEDs in a prospective cohort of 163 patients with epilepsy from a registry at the University of Florida (January 2006 to August 2008). The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) was used to measure mood and suicidal ideation across two time points (median = 154 days). Groups included: (1) No AED Change, (2) New AED Added, (3) AED Dose Increased, (4) AED Reduced/Stopped, (5) Multiple AED Changes, and (6) Combined Any AED Change (groups 2-5 combined). No group had worsening mood or suicidal ideation. Significant improvements in proportions of depression and suicidal ideation were seen only for the No AED Change group, which differed only with the AED Dose Increased group with respect to suicidal ideation.

Impact of donor obesity and donation after cardiac death on outcomes after kidney transplantation.

The effect of donor body mass index (BMI) and donor type on kidney transplant outcomes has not been well studied. Scientific Registry of Transplant Recipients data on recipients of deceased‐donor kidneys between 1997 and 2010 were reviewed. Donors were categorized by DCD status (DCD, 6932; non‐DCD, 90,158) and BMI groups at 5 kg/m2 increments: 18.5–24.9, 25–29.9, 30–34.9, 35–39.9, 40–44.9, and ≥ 45 kg/m2. The primary outcome, death‐censored graft survival (DCGS), was adjusted for donor, recipient, and transplant characteristics. Among recipients of non‐DCD kidneys, donor BMI was not associated with DCGS. Among DCD recipients, donor BMI was not associated with DCGS for donor BMI categories <45 kg/m2; however, donor BMI ≥45 kg/m2 was independently associated with DCGS compared to BMI of 20–24.9 kg/m2 (adjusted hazard ratio, 1.84; 95% CI, 1.23, 2.74). The adjusted odds of delayed graft function (DGF) was greater for each level of BMI above reference for both DCD and non‐DCD groups. There was no association of donor BMI with one‐yr acute rejection for either type of donor. Although BMI is associated with DGF, long‐term graft survival is not affected except in the combination of DCD with extreme donor BMI ≥45.

Kidney transplantation from small pediatric donors: does recipient body mass index matter?

Background. The influence of recipient body mass index (BMI) on pediatric-donor kidney transplant outcomes is unclear. We aimed to determine graft survival and functional outcomes of pediatric-donor kidneys compared with adult kidneys stratified by recipient BMI group. Methods. Scientific Registry of Transplant Recipients data for recipients from 1996 to 2010 were reviewed. Donors were categorized by transplant type, pediatric single kidney transplant (SKT, n=3712), en bloc kidney transplant (EBK, n=1517), or adult standard criteria donor (SCD, n=66,741). Recipients were stratified by BMI tertiles (<24, 24–29, and >29 kg/m2). Results. SKT and EBK from donors ⩽40 kg conferred similar risks of adjusted death-censored graft survival relative to SCDs regardless of recipient BMI except for EBK transplants in recipients with BMI <24 where the effect was protective (adjusted hazard ratio [aHR] 0.71, 95% confidence interval [CI] 0.56–0.94). SKT from donors ⩽20 kg conferred worse death-censored graft survival in recipients with BMI <24 (aHR 1.3, 95% CI 1.0–1.6) and BMI >29 (aHR 1.5, 95% CI 1.1–2.0); however, most of the risk appeared early, and the effect was abrogated with reanalysis conditional on 1-year graft survival. Compared with SCDs, 1-year glomerular filtration rates of SKT from donors ⩽20 kg were significantly higher when transplanted into recipients with BMI <24 (P<0.01) and similar in the other BMI groups. Conclusion. Increasing recipient BMI is not a clear risk factor for outcomes or graft function after transplantation with small pediatric-donor kidneys.

Outcomes and survival analysis of old‐to‐old simultaneous pancreas and kidney transplantation

Outcomes of old‐donor simultaneous pancreas–kidney transplantation (SPKT) have not been thoroughly studied. Scientific Registry of Transplant Recipients data reported for SPKT candidates receiving dialysis wait‐listed between 1993 and 2008 (n = 7937) were analyzed for outcomes among those who remained listed (n = 3301) and of SPKT recipients (n = 4636) using multivariable time‐dependent regression models. Recipients were stratified by donor/recipient age (cutoff 40 years) into: young‐to‐young (n = 2099), young‐to‐old (n = 1873), old‐to‐young (n = 293), and old‐to‐old (n = 371). The overall mortality was 12%, 14%, 20%, and 24%, respectively, for those transplanted, and 50% for those remaining on the waiting list. On multivariable analysis, old‐donor SPKT was associated with significantly higher overall risks of patient death, death‐censored pancreas, and kidney graft failure in both young (73%, 53%, and 63% increased risk, respectively) and old (91%, 124%, and 85% increased risk, respectively) recipients. The adjusted relative mortality risk was similar for recipients of old‐donor SPKT compared with wait‐listed patients including those who subsequently received young‐donor transplants (aHR 0.95; 95% CI 0.78, 1.12) except for candidates in OPOs with waiting times ≥604 days (aHR 0.65, 95% CI 0.45–0.94). Old‐donor SPKT results in significantly worse graft survival and patient mortality without any waiting‐time benefit as compared to young‐donor SPKT, except for candidates with expected long waiting times.