Adjusted Cox Analysis Research Articles

Body mass index and the risk of all-cause mortality among patients with nonvalvular atrial fibrillation: a multicenter prospective observational study in China.

High body mass index (BMI) is associated with increased incident atrial fibrillation (AF) and mortality rate. In patients presenting with nonvalvular AF (NVAF), the prognostic relevance of BMI remains unclear. In this prospective observational study, a total of 1759 patients with NVAF (69.9±12.9 years old, 47.9% male) were divided into three clinical settings according to estimated stroke risks (CHADS2 score ⩽1 (low), =2 (moderate) and ⩾3 (high)). The primary outcome was all-cause mortality, and the secondary outcomes included thromboembolism and major bleeding. Cox-proportional hazard models were used to estimate the association between BMI levels and clinical outcomes. During a mean follow-up of 1 year representing 1974 patient-years at risk, 256 patients died, 142 suffered from thromboembolism and 17 developed major bleeding. Multivariate adjusted Cox analysis indicated that a BMI of 24.0-27.9 kg/m2 was independently associated with improved survival among all patients (hazard ratio (HR) 0.689, 95% confidence interval (CI) 0.512-0.928; P=0.018) and patients at high stroke risk (HR 0.622, 95% CI 0.410-0.943; P=0.024), but not among those at low or moderate stroke risks. No associations were observed between BMI levels and the incidence of thromboembolic events in various clinical settings. A paradoxical BMI-all-cause mortality risk association was observed in Chinese patients with NVAF, and this association was pronounced among patients at high stroke risk rather than in those at low stroke risk.

Low parathyroid hormone status induced by high dialysate calcium is an independent risk factor for cardiovascular death in hemodialysis patients

Here we studied a possible association between low parathyroid hormone (PTH) status and mortality in incident patients undergoing hemodialysis . A total of 1983 patients were included at baseline and prospectively followed for 24months. Patients were classified according to their Kidney Disease: Improving Global Outcomes PTH status at baseline and at 12 months, and mortality evaluated at 12 to 24 months using adjusted Cox analysis. Factors potentially involved in PTH status variability between baseline and 12months were analyzed. A decrease in serum PTH from normal or high to low values between baseline and 12months was associated with significantly increased cardiovascular mortality at 12 to 24 months (hazard ratio, 2.03; 95% confidence interval, 1.22-3.36). For patients with high or normal baseline PTH levels, the main independent factor at 6 months for a decrease to low PTH levels at 12months was high dialysate calcium (1.75 mmol/L), whereas prescription of non-calcium-based phosphate binders was associated with a lower risk of PTH decrease. Inthe high cardiovascular (CV) mortality risk subgroup of patients who acquired a low PTH status at 12 months, the main independent factor at 12 months associated with significant 12- to 24-month CV mortality was high dialysate calcium (odds ratio, 5.44; 95% CI, 2.52-11.75). Thus, patients with a serum PTH decrease to low values after 1year of hemodialysis treatment are at high risk of short-term CV death. High dialysate calcium was an important contributor to PTH oversuppression, and continued use was associated with increased CV mortality.

Serum Alkaline Phosphatase Levels are Not Associated with Increased Death Risk in Prevalent Hemodialysis Patients: 5-Year Experience in a Single Hemodialysis Center

Background/Aims: Although high serum alkaline phosphatase (ALP) levels were reported as predictive factors for death risk in dialysis patients on the basis of large databank analyses, the real scenario in a single hemodialysis (HD) center is unknown. Methods: In this study, a 5-year cohort of 1126 prevalent HD patients in the largest HD center in Taiwan was studied. The associations of ALP levels expressed as baseline, time-average, and time-dependent with all-cause mortality and cardiovascular mortality were evaluated by using adjusted Cox regression models. Results: At baseline, levels of serum parathyroid hormone, calcium, and liver enzymes are increased in parallel with ALP quartiles. The hazard ratio (HR) for all-cause mortality was significantly increased in time-average and time-dependent ALP quartile in the unadjusted Cox analysis. The significance disappeared when multivariate adjusted Cox analysis was used. Similarly, HR was not significantly increased for cardiovascular mortality with ALP quartile expressed as baseline, time-average, and time-dependent in three models of Cox analyses. Conclusion: Our study demonstrated that serum ALP levels were not associated with increased death risk in prevalent HD patients over a 5-year interval.

Drug-eluting stents appear superior to bare metal stents for vein-graft PCI in vessels up to a stent diameter of 4 mm.

Research trials have shown improved short-term outcome with drug-eluting stents (DES) over bare metal stents (BMS) in saphenous vein graft (SVG) percutaneous coronary intervention (PCI), primarily by reducing target vessel revascularization (TVR) for in-stent restenosis. We compared the outcomes in patients undergoing SVG stent implantation treated with DES or BMS. In exploratory analyses we investigated the influence of stent generation and diameter. Data were obtained from a prospective database of 657 patients who underwent PCI for SVG lesions between 2003 and 2011. A total of 344 patients had PCI with BMS and 313 with DES. Propensity scores were developed based on 15 observed baseline covariates in a logistic regression model with stent type as the dependent variable. The nearest-neighbour-matching algorithm with Greedy 5-1 Digit Matching was used to produce two patient cohorts of 313 patients each. We assessed major adverse cardiac events (MACE) out to a median of 3.3 years (interquartile range: 2.1-4.1). MACE was defined as all-cause mortality, myocardial infarction (MI), TVR and stroke. There was a significant difference in MACE between the two groups in favour of DES (17.9% DES vs. 31.2% BMS group; p = 0.0017) over the 5-year follow-up period. MACE was driven by increased TVR in the BMS group. There was no difference in death, MI or stroke. Adjusted Cox analysis confirmed a decreased risk of MACE for DES compared with BMS 0.75 (95% confidence interval (CI) 0.52-0.94), with no difference in the hazard of all-cause mortality (hazard ratio: 1.08; 95% CI: 0.77-1.68). However, when looking at stent diameters greater than 4 mm, no difference was seen in MACE rates between BMS and DES. Overall in our cohort of patients who had PCI for SVG disease, DES use resulted in lower MACE rates compared with BMS over a 5-year follow-up period; however, for stent diameters over 4 mm no difference in MACE rates was seen.

Continuous positive airway pressure and survival of very elderly persons with moderate to severe obstructive sleep apnea

ObjectiveThere is evidence of a beneficial effect of long-term continuous positive airway pressure (CPAP) on survival in elderly persons with obstructive sleep apnea (OSA), although the usual age cut off is between 60 and 70 years of age. Our objective was to determine this effect in very elderly patients (ie, those ≥80 years of age). MethodsAn observational study of a historic cohort of very elderly persons with moderate to severe OSA (apnea–hypopnea index ≥20) and the effect of long-term CPAP on their survival was performed. Two groups were formed: one prescribed CPAP treatment (≥4 hours per night), and one without CPAP treatment. Survival analyses, including Kaplan–Meier curves and Cox models, were carried out to determine the association of long-term CPAP with longer survival, ResultsA total of 155 very elderly persons (84 men and 71 women, mean age 81.5 ± 1.5 years) were followed up for 53 months (interquartile range, 41–77 months); 83 deaths occurred. CPAP was prescribed to 132 patients, and adherence was observed in 79 (60%). Kaplan–Meier curves showed longer survival in the treated OSA group (91 months, 95% confidence interval [CI] = 76–106) than in the untreated OSA group (52 months, 95% CI 41–64), which was statistically significant (log-rank 16.9, p < 0.0001). Although history of stroke was significantly associated with higher mortality (hazard ratio [HR] = 2.18, 95% CI = 1.14–4.17, p = 0.02), CPAP treatment was associated with higher survival rates (HR = 0.46, 95% CI = 0.27–0.78, p = 0.004) in an adjusted Cox analysis. ConclusionsCPAP treatment might be associated with a longer survival in very elderly persons with moderate to severe OSA.

The prognostic effects of ventricular heart rate among patients with permanent atrial fibrillation with and without coronary artery disease: a multicenter prospective observational study.

Heart rate control is important among patients with either atrial fibrillation (AF) or coronary artery disease (CAD). However, the relationship between the ventricular heart rate and adverse outcomes among patients with AF and CAD remains unclear. This study aimed to assess the prognostic effects of ventricular heart rate in patients with permanent AF (permAF) and CAD.We performed a multicenter, prospective, observational study of patients with AF in China. Patients≥18 years old with permAF were included and divided into a CAD group and a non-CAD group. All patients underwent 1 year of follow-up. The primary outcome was total mortality. Cox proportional hazard models were used to evaluate the relationship between risk factors and the survival rate in the study population.A total of 852 patients (69.1±12.7 years old, 43.3% male, 44.7% with CAD) were included in the analysis. Patients with CAD were older, were more likely to be male and exhibited higher prevalences of hypertension, diabetes mellitus, LV dysfunction, chronic obstructive pulmonary disease (COPD) and stroke compared with patients without CAD. During the follow-up period, a higher total mortality rate was noted in the CAD group than in the non-CAD group (21.5% vs 15.5%, P = 0.023). In the patients without CAD, the lowest quartile (≤76 beats/min) exhibited the best 1-year survival rate; however, in the patients with CAD, the highest quartile (>110 beats/min) exhibited the worst survival rate. Multivariate adjusted Cox analysis indicated that age (HR 1.039, 95% CI 1.025–1.055, P < 0.001) and heart rate (P = 0.004) were each independently associated with total mortality.Patients with CAD have more risk factors, and comorbidities and higher mortality rates than patients without CAD. In the patients with permAF without CAD, a ventricular rate of ≤76 beats/minute was associated with the best survival rate; however, among the patients with CAD, no increased mortality was observed unless the heart rate was >110 beats/min.

Risk of intracranial hemorrhage associated with autosomal dominant polycystic kidney disease in patients with end stage renal disease

BackgroundAn analysis of intracranial hemorrhage (ICH) in a national sample of autosomal dominant polycystic kidney disease (ADPKD) patients receiving long-term dialysis has not been reported. It is often assumed that patients with ADPKD are not at increased risk of ICH after starting dialysis. We hypothesized that patients with ADPKD would have a higher subsequent risk of ICH even after the start of chronic dialysis.MethodsRetrospective cohort study of Medicare primary patients with and without ADPKD in the United States Renal Data System (USRDS), initiated on chronic dialysis or transplanted between 1 January 1999 and 3 July 2009, and followed until 31 December 2009. Covariates included age, gender, race, prior stroke, diabetes mellitus, dialysis modality, body mass index, serum albumin and other co-morbid conditions from the Medical Evidence Form. Primary outcome was ICH, based on inpatient and outpatient Medicare claims, and all-cause mortality. Kaplan-Meier analysis was used for unadjusted assessment of time to events. Cox regression was used for assessment of factors associated with ICH and mortality. We performed competing risk regression using kidney transplant and death as competing risks. Kidney transplant was also modeled as a time-dependent covariate in Cox regression.ResultsCompeting risk regression demonstrated that ADPKD had a subhazard ratio 2.97 for ICH (95% CI 2.27-3.89). Adjusted Cox analysis showed that ADPKD patients had an AHR for death of 0.59 vs. non-ADPKD patients (95% CI 0.57-0.61).ConclusionsADPKD is a significant risk factor for ICH among patients on maintenance dialysis. Our Medicare primary cohort was older than in previous studies of intracranial aneurysm rupture among ADPKD patients. There are also limitations inherent to using the USRDS database.

High-Sensitivity Troponin I for Risk Assessment in Patients With Atrial Fibrillation

Background— High-sensitivity troponin-I (hs-TnI) measurement improves risk assessment for cardiovascular events in many clinical settings, but the added value in atrial fibrillation patients has not been described. Methods and Results— At randomization, hs-TnI was analyzed in 14 821 atrial fibrillation patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial comparing apixaban with warfarin. The associations between hs-TnI concentrations and clinical outcomes were evaluated by using adjusted Cox analysis. The hs-TnI assay detected troponin (≥1.3 ng/L) in 98.5% patients, 50% had levels &gt;5.4, 25% had levels &gt;10.1, and 9.2% had levels ≥23 ng/L (the 99th percentile in healthy individuals). During a median of 1.9 years follow-up, annual rates of stroke or systemic embolism ranged from 0.76% in the lowest hs-TnI quartile to 2.26% in the highest quartile (&gt;10.1 ng/L). In multivariable analysis, hs-TnI was significantly associated with stroke or systemic embolism, adjusted hazard ratio 1.98 (1.42–2.78), P =0.0007. hs-TnI was also significantly associated with cardiac death; annual rates ranged from 0.40% to 4.24%, hazard ratio 4.52 (3.05–6.70), P &lt;0.0001, in the corresponding groups, and for major bleeding hazard ratio 1.44 (1.11–1.86), P =0.0250. Adding hs-TnI levels to the CHA 2 DS 2 VASc score improved c-statistics from 0.629 to 0.653 for stroke or systemic embolism, and from 0.591 to 0.731 for cardiac death. There were no significant interactions with study treatment. Conclusions— Troponin-I is detected in 98.5% and elevated in 9.2% of atrial fibrillation patients. The hs-TnI level is independently associated with a raised risk of stroke, cardiac death, and major bleeding and improves risk stratification beyond the CHA 2 DS 2 VASc score. The benefits of apixaban in comparison with warfarin are consistent regardless of hs-TnI levels. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00412984.

Abstract 9364: Drug Eluting Stents Appear Superior to Bare Metal Stents for Vein Graft Pci in a Propensity Matched Cohort

Background: Research trials have shown improved short-term outcome with drug-eluting stents (DES) over bare metal stent (BMS) in Saphenous vein graft (SVG) PCI, primarily by reducing target vessel revascularization (TVR) for In-Stent Restenosis (ISR). Because of the high event rates in these patients it is not clear if these benefits are maintained long term. We compared the outcomes in patients undergoing SVG stent implantation treated with DES or BMS, over a prolonged follow-up period using a propensity matched analysis. Methods: Clinical information was analysed from a prospective database on 512 patients who underwent PCI for SVG lesions between 2003 and 2010. 293 patients had PCI with BMS and 219 with DES. Propensity scores representing the estimated probabilities of patients receiving either DES or BMS were developed based on 15 observed baseline covariates in a logistic regression model with stent type as the dependent variable. The nearest-neighbour-matching algorithm with Greedy 5-1 Digit Matching was used to produce two patient cohorts of 219 patients each balanced for baseline factors. We assessed major adverse cardiac events (MACE) ) out to a median of 3.3 years (IQR: 2.1-4.1) MACE defined as •All Cause mortality •Myocardial infarction (MI) •Target vessel revascularisation (TVR) •Stroke Results There was a significant difference in MACE between the two groups in favour of DES (17.9% DES v 31.2% BMS group [P=0.04] over the 5-year follow-up. MACE was driven by ISR in both groups and the difference between groups was due to increased TVR in the BMS group. There was no difference in death, MI or stroke.(Figure 1) Adjusted Cox analysis confirmed a decreased risk of MACE for DES compared with BMS 0.75 (95% confidence intervals 0.52-0.94) with no difference in the hazard of all cause mortality (HR: 1.08 95% CI: 0.77-1.68). Conclusion: In our cohort of patients who had PCI for treatment of SVG disease the use of DES resulted in lower MACE rate compared to BMS over a 5-year follow-up.

Immunoglobulin (Ig)M antibodies against oxidized cardiolipin but not native cardiolipin are novel biomarkers in haemodialysis patients, associated negatively with mortality

The risk of premature death is high in haemodialysis (HD) patients. Antibodies against cardiolipin (anti-CL) are thrombogenic in diseases such as systemic lupus erythematosus (SLE). CL is easily oxidized (Ox) and plays a role in apoptosis. In this work we studied immunoglobulin (Ig)M anti-CL and anti-OxCL in HD-patients. We conducted an observational study with a prospective follow-up examining the relationship between anti-CL, anti-OxCL and mortality risk in a well-characterized cohort of 221 prevalent HD patients [56% men, median age 66 (interquartile range 51-74) years, vintage time 29 (15-58) months] with a mean follow-up period of 41 (20-48 months). According to the receiver operator characteristic (ROC) analysis, anti-OxCL [area under the curve (AUC) 0·62, P < 0·01], but not anti-CL (AUC 0·52, P = 0·2), is associated with mortality. In crude and adjusted Cox analysis, every log increase in anti-OxCL inversely predicted all-cause [adjusted hazard ratios (HR) 0·62 (0·43-0·89)] and CVD-related [adjusted HR 0·56 (0·32-0·98)] mortality. Patients with anti-OxCL levels below median also had increased all-cause and cardiovascular disease (CVD)-related mortality. Although anti-OxCL and anti-phosphorylcholine (PC) were related positively to each other (ρ = 0·57, P < 0·01), patients with one or two of these autoantibody levels below the median were associated with an incrementally increased death risk. Anti-OxCL were co-factor β2-GPI-independent; anti-CL from patients with anti-phospholipid antibody syndrome were β2-GPI-dependent, while sera from HD-patients less so. Sera from healthy donors was not β2-GPI-dependent. Anti-OxCL IgM is β2-glycoprotein 1 (GPI)-independent and a novel biomarker; low levels are associated with death among HD patients (and high levels with decreased risk). Combination with anti-PC increases this association. Putative therapeutic implications warrant further investigation.

Serum and tumor biomarkers to predict outcome in the eLung trial, a multicenter, randomized phase IIb study of standard platinum doublets (PD) plus cetuximab (CET) as first-line treatment of advanced non-small cell lung cancer (NSCLC).

8044 Background: The eLung trial randomized chemotherapy naïve advanced NSCLC patients (pts) to 1 of 3 PD and concurrent CET followed by CET maintenance until progression, stratified by non-squamous (NSQ) and squamous (SQ) histology. Primary outcome results were reported (ESMO, Schwartzberg 2012). Pre-treatment tumor tissue and serum samples were prospectively collected. Methods: Tumor samples were analyzed for H-score (graded 0-300), calculated by the intensity and number of cells expressing EGFR by IHC; a score of &gt;200 was considered high (Pirker 2011). Mutation analysis of EGFR and KRAS was performed by PCR. The VeriStrat multivariate serum protein test was performed on available serum samples assigning good and poor classifications (Taguchi 2007). Results: Of 601 pts enrolled on the trial, 378 consented to blood/tissue or both. The available tissue (N=210) and serum subsets (N=203) had similar demographics and survival outcome to the full trial set. Results for biomarkers/cohorts in the Table demonstrate that VeriStrat was highly significant for OS in all pts and NSQ, while H-score and EGFR mutations were significant only in NSQ. In adjusted Cox analysis VeriStrat was an independent predictor for OS, HR=.665, p=.026; H-score was not. Conclusions: VeriStrat classification significantly correlated with survival outcome in all pts treated with PD and CET and the NSQ subset; tissue biomarkers correlated in NSQ only. Further evaluation of these markers is warranted. [Table: see text]

Increased Risk of Pneumonia Among Patients With Inflammatory Bowel Disease

Patients with inflammatory bowel disease (IBD) may be at increased risk for infections. We aimed to determine the pneumonia risk in IBD and how specific medications affect this risk. We performed a retrospective cohort and a nested case-control study using administrative data from IMS Health Inc., LifeLink Health Plan Claims Database. Limitations to this data set include lack of clinical details to validate exposures and outcomes. In the cohort, IBD patients were matched to four individuals without IBD. Pneumonia risk was evaluated by incidence rate ratio (IRR) and adjusted Cox proportional hazards models (hazard ratio (HR)). In the nested case-control, 4,856 IBD patients with pneumonia were matched to four IBD patients without pneumonia by incidence density sampling. We used conditional logistic regression to determine the associations between medications and pneumonia. The cohort included 50,932 patients with Crohn's disease (CD), 56,403 patients with ulcerative colitis (UC), and 1,269 with unspecified IBD; matched to 434,416 individuals without IBD. Median follow-up within the cohort was 24 months. The IBD cohort had an increased pneumonia risk when compared with non-IBD (IRR 1.82, 95% confidence interval (CI) 1.75-1.88). In adjusted Cox analysis, pneumonia risk remained increased for the IBD vs. non-IBD cohort (HR 1.54, 95% CI 1.49-1.60), with increased risk in both CD (HR 1.71, 95% CI 1.62-1.80) and UC (HR 1.41, 95% CI 1.34-1.48). In the nested case-control analysis, use of biologic medications (odds ratio (OR) 1.32, 95% CI 1.11-1.57), corticosteroids (OR 1.91, 95% CI 1.72-2.12), thiopurines (OR 1.13, 95% CI 1.00-1.27), proton-pump inhibitors (PPIs) (OR 1.15, 95% CI 1.04-1.26), or narcotics (2.28, 95% CI 2.09-2.48) was independently associated with pneumonia. Patients with IBD are at increased risk for pneumonia. Medications such as corticosteroids and narcotics are particularly associated with pneumonia in this population. An emphasis upon primary prevention of pneumonia through vaccination and reduction of risk factors is warranted.

Lysophosphatidylcholine, Oxidized Low-Density Lipoprotein and Cardiovascular Disease in Korean Hemodialysis Patients: Analysis at 5 Years of Follow-up

Although oxidized low-density lipoprotein (LDL) and lysophosphatidylcholine (LPC) have been proposed as important mediators of the atherosclerosis, the long-term contribution to the risk of cardiovascular disease (CVD) in hemodialysis patients has not been evaluated. This study investigated the relation between oxidized LDL and LPC levels with long term risk of CVD. Plasma oxidized LDL and LPC levels were determined in 69 Korean hemodialysis patients as a prospective observational study for 5 yr. During the observation period, 18 cardiovascular events (26.1%) occurred including 6 deaths among the hemodialysis patients. The low LPC level group (≤ 254 µM/L, median value) had much more increased risk of CVD compared to the high LPC level group (> 254 µM/L) (P = 0.01). However, serum levels of oxidized LDL were not significantly different between groups with and without CVD. In adjusted Cox analysis, previous CVD, (hazard ratio [HR], 5.68; 95% confidence interval [CI], 1.94-16.63, P = 0.002) and low LPC level (HR, 3.45; 95% CI, 1.04-11.42, P = 0.04) were significant independent risk factors for development of CVD. It is suggested that low LPC, but not oxidized LDL, is associated with increased risk of CVD among a group of Korean hemodialysis patients.

Deployment of drug‐eluting stents for isolated proximal lad disease is associated with lower major adverse cardiac events and no increase in stent thrombosis when compared with bare metal stents: A 5‐year observational cohort study

Drug-eluting stents (DES) may be associated with an increased risk of late stent thrombosis (ST) compared with bare metal stents (BMS). We compared major adverse cardiac events (MACE) and long term all cause mortality in patients with isolated proximal LAD disease treated with DES or BMS. This study of 1653 patients with isolated proximal LAD disease, includes 643 treated with BMS and 1010 treated with DES. All patients received standard dual antiplatelet treatment. MACE after 5 years were less frequent in DES compared with BMS (12.1% 95% CI 9.3-14.2 versus 21.3% 95% CI: 16.9-25.1, P < 0.0001), driven largely by a decreased rate of both target vessel and lesion revascularization (TVR: 6.3%, 95% CI 4.0-7.5% versus 14.7%, 95% CI 11.0-17.3%, P < 0.0001, TLR: (5.3%, 95% CI 3.2-7.1% versus 13.2%, 95% CI 9.8.0-15.4%, P < 0.0001). There was no difference in the rate of death, myocardial infarction, or CVA. Incidence of stent thrombosis was also comparable (1.2% 95% CI: 0.6-2.6% versus 1.1% 95% CI: 0.6-2.5%, P = 0.8). Adjusted Cox analysis confirmed a decreased risk of MACE for DES compared with BMS 0.55 (95% confidence intervals 0.41-0.73) with no difference in the hazard of all cause mortality (HR: 1.04 95% CI: 0.67-1.61). When treating proximal LAD disease, use of DES was associated with a lower MACE rate than BMS, with no differences in the incidence of stent thrombosis, myocardial infarction or 5 year all cause mortality. Our data suggests that despite the adverse prognostic correlates of proximal LAD disease, DES deployment in this location is both safe and clinically more effective than BMS.

No Advantage of Quadruple- or Triple-Class Antiretroviral Therapy as Initial Treatment in Patients with Very High Viraemia

We assessed whether quadruple or triple-class therapy for the initial treatment of HIV-1 infection provides a virological benefit over standard triple therapy in patients with very high plasma viraemia. The assessment was made based on a national observational HIV cohort in the Netherlands. Inclusion criteria were age ≥18 years, treatment-naive, plasma viral load (pVL) ≥500,000 copies/ml and initiation of quadruple or triple therapy between 2001 and 2011. Time to viral suppression, defined as pVL<50 copies/ml, was compared between the two groups using Kaplan-Meier plots and multivariate Cox regression analysis. A total of 675 patients were included: 125 (19%) initiated quadruple and 550 (81%) triple therapy. Median pVL was 5.9 (IQR 5.8-6.1) log(10) copies/ml in both groups (P=0.49). 22 (18%) patients on quadruple and 63 (12%) on triple therapy interrupted the treatment regimen because of drug-related toxicity (P=0.06). Median time to viral suppression was 5.8 (IQR 4.6-7.9) and 6.0 (4.0-9.4) months in the patients on quadruple and triple therapy, respectively (log-rank, P=0.42). In the adjusted Cox analysis, quadruple therapy was not associated with time to viral suppression (HR 1.07 [95% CI 0.86, 1.33], P=0.53). Similar results were seen when comparing triple- versus dual-class therapy (n=72 versus n=601, respectively). Initial quadruple- or triple-class therapy was equally effective as standard triple therapy in the suppression of HIV-1 in treatment-naive patients with very high viraemia and did not result in faster pVL decreases, but did expose patients to additional toxicity.

Use of N -acetylcysteine during liver procurement: A prospective randomized controlled study

Antioxidant agents have the potential to reduce ischemia/reperfusion damage to organs for liver transplantation (LT). In this prospective, randomized study, we tested the impact of an infusion of N-acetylcysteine (NAC) during liver procurement on post-LT outcomes. Between December 2006 and July 2009, 140 grafts were transplanted into adult candidates with chronic liver disease who were listed for first LT, and according to a sequential, closed-envelope, single-blinded procedure, these patients were randomly assigned in a 1/1 ratio to an NAC protocol (69 patients) or to the standard protocol without NAC [71 patients (the control group)]. The NAC protocol included a systemic NAC infusion (30 mg/kg) 1 hour before the beginning of liver procurement and a locoregional NAC infusion (300 mg through the portal vein) just before cross-clamping. The primary endpoint was graft survival. The graft survival rates at 3 and 12 months were 93% and 90%, respectively, in the NAC group and 82% and 70%, respectively, in the control group (P = 0.02). An adjusted Cox analysis showed a significant NAC effect on graft survival at both 3 months [hazard ratio = 1.65, 95% confidence interval (CI) = 1.01-2.93, P = 0.04] and 12 months (hazard ratio = 1.73, 95% CI = 1.14-2.76, P ≤ 0.01). The incidence of postoperative complications was lower in the NAC group (23%) versus the control group (51%, P < 0.01). In the subgroup of 61 patients (44%) receiving suboptimal grafts (donor risk index > 1.8), the incidence of primary dysfunction of the liver was lower (P = 0.09) for the NAC group (15%) versus the control group (32%). In conclusion, the NAC harvesting protocol significantly improves graft survival. The effect of NAC on early graft function and survival seems higher when suboptimal grafts are used.

No treatment versus 24 or 60 weeks of antiretroviral treatment during primary HIV infection: the randomized Primo-SHM trial.

The objective of this study was to assess the benefit of temporary combination antiretroviral therapy (cART) during primary HIV infection (PHI). Adult patients with laboratory evidence of PHI were recruited in 13 HIV treatment centers in the Netherlands and randomly assigned to receive no treatment or 24 or 60 wk of cART (allocation in a 1∶1∶1 ratio); if therapy was clinically indicated, participants were randomized over the two treatment arms (allocation in a 1∶1 ratio). Primary end points were (1) viral set point, defined as the plasma viral load 36 wk after randomization in the no treatment arm and 36 wk after treatment interruption in the treatment arms, and (2) the total time that patients were off therapy, defined as the time between randomization and start of cART in the no treatment arm, and the time between treatment interruption and restart of cART in the treatment arms. cART was (re)started in case of confirmed CD4 cell count < 350 cells/mm(3) or symptomatic HIV disease. In total, 173 participants were randomized. The modified intention-to-treat analysis comprised 168 patients: 115 were randomized over the three study arms, and 53 randomized over the two treatment arms. Of the 115 patients randomized over the three study arms, mean viral set point was 4.8 (standard deviation 0.6) log(10) copies/ml in the no treatment arm, and 4.0 (1.0) and 4.3 (0.9) log(10) copies/ml in the 24- and 60-wk treatment arms (between groups: p < 0.001). The median total time off therapy in the no treatment arm was 0.7 (95% CI 0.0-1.8) y compared to 3.0 (1.9-4.2) and 1.8 (0.5-3.0) y in the 24- and 60-wk treatment arms (log rank test, p < 0.001). In the adjusted Cox analysis, both 24 wk (hazard ratio 0.42 [95% CI 0.25-0.73]) and 60 wk of early treatment (hazard ratio 0.55 [0.32-0.95]) were associated with time to (re)start of cART. In this trial, temporary cART during PHI was found to transiently lower the viral set point and defer the restart of cART during chronic HIV infection.

Long-Term Clinical Outcome After Fractional Flow Reserve–Guided Percutaneous Coronary Revascularization in Patients With Small-Vessel Disease

Small coronary vessels supply small myocardial territories. The clinical significance of small-vessel stenoses is therefore questionable. Moreover, percutaneous coronary intervention (PCI) of nonfunctionally significant lesions does not improve clinical outcome and might be associated with potential procedural or stent related risks. The aim of this study was to assess the clinical outcome of fractional flow reserve (FFR)-guided PCI in the treatment of small coronary vessel lesions as compared with an angio-guided PCI. From January 2004 to December 2008, all patients treated with PCI for stable or unstable angina in small native coronary vessels (reference vessel diameter and stent size <3 mm) were retrospectively analyzed. Patients were divided into angio-guided and an FFR-guided PCI groups. A total of 717 patients were enrolled (495 angio-guided, 222 FFR-guided). End points were death, nonfatal myocardial infarction (MI), combined death or nonfatal MI, target vessel revascularization (TVR), and procedure costs. Major adverse cardiac events (MACE) were defined as death, nonfatal MI, and TVR. Clinical follow-up was obtained in 97.5% (median follow-up: 3.3 [from 0.01-5] years) of the patients. Seventy-eight patients (35%) had a significant FFR (<0.80) and underwent PCI. Using a propensity score adjusted Cox analysis, patients treated with FFR-guided PCI had significantly lower combined death or nonfatal MI (hazard ratio [HR], 0.413; 95% confidence interval [CI], 0.227-0.750; P=0.004), nonfatal MI (HR, 0.063; 95% CI, 0.009-0.462; P=0.007), TVR (HR, 0.517; 95% CI, 0.323-0.826; P=0.006), and MACE (HR, 0.458; 95% CI, 0.310-0.679; P<0.001). No difference was observed in mortality alone (HR, 0.684; 95% CI, 0.355-1.316; P=0.255). Procedure costs were also reduced in the FFR guided strategy (3253±102 Euros versus 4714±37 Euros, P<0.0001). FFR-guided PCI of small coronary arteries is safe and results in better clinical outcomes when compared with an angio-guided PCI.

The Clinical and Biologic Significance of Thrombocytosis in Myeloid Disorders

Abstract 5031 PurposeMyelodysplastic syndromes (MDS) are typically characterized by peripheral blood cytopenias. However, some MDS is associated with thrombocytosis rather than thrombocytopenia. The prognostic significance of thrombocytosis is unknown. The purpose of this study was to compare the overall survival (OS) of MDS patient based on their platelet count. MethodsWe reviewed a prospective cohort of patients with myeloid disorders from 1994 to present. Out of the 1,654 unique patients, 102 had platelets > 450,000 (5.7%) throughout their disease; 88 had stable platelet counts, 6 had varying platelet counts, and 12 were excluded because of missing information.OS of patients with thrombocytosis (>450,000 platelet count) was compared to FAB/WHO case matched patients with normal (100–450 platelet counts) and low platelet counts (<100 platelet count). OS was evaluated using unadjusted and adjusted Cox proportional hazard regression modeling with all-cause mortality as the dependent variable and demographic and clinical characteristics as independent variable; adjusted for IPSS risk group at first sample collection and age-adjusted mortality. The OS curves were constructed using Kaplan-Meier methods. ResultsThe worst OS occurred in patients with unstable platelet counts, followed by thrombocytopenia, and then thrombocytosis. Thrombocytopenia was associated with a poorer prognosis than thrombocytosis, although not significantly worse. Patients with normal platelet counts had the best prognosis. Thrombocytosis significantly reduced OS compared to patients with normal platelet counts (HR 1.44, p= 0.04) using adjusted Cox analysis. Thrombocytopenia had significantly reduced OS compared to patient with normal platelet counts (HR 1.8, p=0.0002) using unadjusted Cox regression. Patients who had unstable platelet counts had significantly the worst OS (HR 5.7, p= 0.0009). Both older age at diagnosis and IPSS independently and significantly affected OS. ConclusionMDS patients with both thrombocytopenia and thrombocytosis have significantly decreased OS compared to normal platelet counts.{abspict} [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Renin–angiotensin system blockade and kidney transplantation: a longitudinal cohort study

The beneficial effect of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB) in kidney transplant recipients on modern immunosuppression is not yet well established. Our objective was to investigate the impact of the use of ACEI/ARB on patient and graft survival in a cohort of kidney transplant recipients. A total of 990 patients, who received a single deceased donor kidney at our institution between 1996 and 2005, were included in this longitudinal cohort study. All-cause mortality and death-censored graft loss were the primary outcomes. We used traditional time-dependent Cox model (unweighted) and inverse-probability-of-treatment weighting of marginal structural models (weighted Cox model), controlling for time-dependent confounding by indication. A total of 414 patients (42%) received ACEI/ARB through the study period (median duration 14 months, interquartile range 6-40 months). ACEI/ARB use was associated with reduction of risk for mortality in the crude [hazard ratio (HR) 0.627, 95% confidence interval (CI) 0.412-0.953] and adjusted Cox analysis (HR 0.626, 95% CI 0.407-0.963). Similar results were observed after adjusting for confounding by indication (HR 0.629, 95% CI 0.407-0.973). By contrast, ACEI/ARB use was not associated with significant improvement of graft survival after kidney transplantation. ACEI/ARB prescription may be suggested as beneficial among multiple medications for reducing mortality in kidney transplant recipients, but its use was not associated with longer graft survival.