Umesh Tamhane

Association Between Admission Neutrophil to Lymphocyte Ratio and Outcomes in Patients With Acute Coronary Syndrome

The neutrophil/lymphocyte ratio (NLR) has recently been described as a predictor of mortality in patients who undergo percutaneous coronary intervention. The aim of this study was to investigate the utility of admission NLRs in predicting outcomes in patients with acute coronary syndromes (ACS). A total of 2,833 patients admitted to the University of Michigan Health System with diagnoses of ACS from December 1998 to October 2004 were followed. Patients were divided into tertiles according to NLR. The primary end point was all-cause in-hospital and 6-month mortality. The ACS cohort comprised 564 patients with ST-segment elevation myocardial infarctions and 2,269 patients with non-ST-segment elevation ACS. Patients in tertile 3 had higher in-hospital (8.5% vs 1.8%) and 6-month (11.5% vs 2.5%) mortality compared with those in tertile 1 (p <0.001). After adjusting for Global Registry of Acute Coronary Events risk profile, patients in the highest tertile were at an exaggerated risk for in-hospital (odds ratio 2.04, p = 0.013) and 6-month (odds ratio 3.88, p <0.001) mortality. Admission NLR is an independent predictor of in-hospital and 6-month mortality in patients with ACS. This relatively inexpensive marker of inflammation can aid in the risk stratification and prognosis of patients diagnosed with ACS.

The Relative Renal Safety of Iodixanol Compared With Low-Osmolar Contrast Media : A Meta-Analysis of Randomized Controlled Trials

OBJECTIVES We sought to compare the nephrotoxicity of the iso-osmolar contrast medium, iodixanol, to low-osmolar contrast media (LOCM). BACKGROUND Contrast-induced acute kidney injury (CI-AKI) is a common cause of in-hospital renal failure. A prior meta-analysis suggested that iodixanol (Visipaque, GE Healthcare, Princeton, New Jersey) was associated with less CI-AKI than LOCM, but this study was limited by ascertainment bias and did not include the most recent randomized controlled trials. METHODS We searched Medline, Embase, ISI Web of Knowledge, Google Scholar, Current Contents, and International Pharmaceutical Abstracts databases, and the Cochrane Central Register of Controlled Trials from 1980 to November 30, 2008, for randomized controlled trials that compared the incidence of CI-AKI with either iodixanol or LOCM. Random-effects models were used to calculate summary risk ratios (RR) for CI-AKI, need for hemodialysis, and death. RESULTS A total of 16 trials including 2,763 subjects were pooled. There was no significant difference in the incidence of CI-AKI in the iodixanol group than in the LOCM group overall (summary RR: 0.79, 95% confidence interval [CI]: 0.56 to 1.12, p = 0.19). There was no significant difference in the rates of post-procedure hemodialysis or death. There was a reduction in CI-AKI when iodixanol was compared with ioxaglate (RR: 0.58, 95% CI: 0.37 to 0.92; p = 0.022) and iohexol (RR: 0.19, 95% CI: 0.07 to 0.56; p = 0.002), but no difference when compared with iopamidol (RR: 1.20, 95% CI: 0.66 to 2.18; p = 0.55), iopromide (RR: 0.93, 95% CI: 0.47 to 1.85; p = 0.84), or ioversol (RR: 0.92, 95% CI: 0.60 to 1.39; p = 0.68). CONCLUSIONS This meta-analysis including 2,763 subjects suggests that iodixanol, when compared with LOCM overall, is not associated with less CI-AKI. The relative renal safety of LOCM compared with iodixanol may vary based on the specific type of LOCM.

Short term and intermediate term comparison of endarterectomy versus stenting for carotid artery stenosis: systematic review and meta-analysis of randomised controlled clinical trials

Objective To evaluate the relative short term safety and intermediate term efficacy of carotid endarterectomy versus carotid artery stenting. Design Systematic review and meta-analysis. Data sources BIOSIS, Embase, Medline, the Cochrane central register of controlled trials, International Pharmaceutical Abstracts database, ISI Web of Science, and Google scholar and bibliographies, from 1 January 1990 to 25 July 2009. Study selection Randomised controlled trials comparing carotid endarterectomy with carotid artery stenting in patients with carotid artery stenosis with or without symptoms. Data extraction Primary end point was a composite of mortality or stroke. Secondary end points were death, stroke, myocardial infarction, or facial neuropathy (as individual end points), and mortality or disabling stroke (as a composite end point). Data synthesis 11 trials were included (4796 patients); 10 reported on short term outcomes (n=4709) and nine on intermediate term outcomes (1-4 years). The periprocedural risk of mortality or stroke was lower for carotid endarterectomy (odds ratio 0.67, 95% confidence interval 0.47 to 0.95; P=0.025) than for carotid stenting, mainly because of a decreased risk of stroke (0.65, 0.43 to 1.00; P=0.049), whereas the risk of death (1.14, 0.56 to 2.31; P=0.727) and the composite end point mortality or disabling stroke (0.74, 0.53 to 1.05; P=0.088) did not differ significantly. The odds of periprocedural myocardial infarction (2.69, 1.06 to 6.79; P=0.036) or cranial nerve injury (10.2, 4.0 to 26.1; P<0.001) was higher in the carotid endarterectomy group than in the carotid stenting group. In the intermediate term, the two treatments did not differ significantly for stroke or death (hazard ratio 0.90, 95% confidence interval 0.74 to 1.1; P=0.314). Conclusions Carotid endarterectomy was found to be superior to carotid artery stenting for short term outcomes but the difference was not significant for intermediate term outcomes; this difference was mainly driven by non-disabling stroke. Significantly fewer cranial nerve injuries and myocardial infarctions occurred with carotid artery stenting.

Sodium bicarbonate-based hydration prevents contrast-induced nephropathy: a meta-analysis

BackgroundContrast-induced nephropathy is the leading cause of in-hospital acute renal failure. This side effect of contrast agents leads to increased morbidity, mortality, and health costs. Ensuring adequate hydration prior to contrast exposure is highly effective at preventing this complication, although the optimal hydration strategy to prevent contrast-induced nephropathy still remains an unresolved issue. Former meta-analyses and several recent studies have shown conflicting results regarding the protective effect of sodium bicarbonate. The objective of this study was to assess the effectiveness of normal saline versus sodium bicarbonate for prevention of contrast-induced nephropathy.MethodsThe study searched MEDLINE, EMBASE, Cochrane databases, International Pharmaceutical Abstracts database, ISI Web of Science (until 15 December 2008), and conference proceedings for randomized controlled trials that compared normal saline with sodium bicarbonate-based hydration regimen regarding contrast-induced nephropathy. Random-effects models were used to calculate summary odds ratios.ResultsA total of 17 trials including 2,633 subjects were pooled. Pre-procedural hydration with sodium bicarbonate was associated with a significant decrease in the rate of contrast-induced nephropathy (odds ratios 0.52; 95% confidence interval 0.34–0.80, P = 0.003). Number needed to treat to prevent one case of contrast-induced nephropathy was 16 (95% confidence interval 10–34). No significant differences in the rates of post-procedure hemodialysis (P = 0.20) or death (P = 0.53) was observed.ConclusionSodium bicarbonate-based hydration was found to be superior to normal saline in prevention of contrast-induced nephropathy in this updated meta-analysis.

Does Simplicity Compromise Accuracy in ACS Risk Prediction? A Retrospective Analysis of the TIMI and GRACE Risk Scores

Background The Thrombolysis in Myocardial Infarction (TIMI) risk scores for Unstable Angina/Non-ST–elevation myocardial infarction (UA/NSTEMI) and ST-elevation myocardial infarction (STEMI) and the Global Registry of Acute Coronary Events (GRACE) risk scores for in-hospital and 6-month mortality are established tools for assessing risk in Acute Coronary Syndrome (ACS) patients. The objective of our study was to compare the discriminative abilities of the TIMI and GRACE risk scores in a broad-spectrum, unselected ACS population and to assess the relative contributions of model simplicity and model composition to any observed differences between the two scoring systems. Methodology/Principal Findings ACS patients admitted to the University of Michigan between 1999 and 2005 were divided into UA/NSTEMI (n = 2753) and STEMI (n = 698) subpopulations. The predictive abilities of the TIMI and GRACE scores for in-hospital and 6-month mortality were assessed by calibration and discrimination. There were 137 in-hospital deaths (4%), and among the survivors, 234 (7.4%) died by 6 months post-discharge. In the UA/NSTEMI population, the GRACE risk scores demonstrated better discrimination than the TIMI UA/NSTEMI score for in-hospital (C = 0.85, 95% CI: 0.81–0.89, versus 0.54, 95% CI: 0.48–0.60; p<0.01) and 6-month (C = 0.79, 95% CI: 0.76–0.83, versus 0.56, 95% CI: 0.52–0.60; p<0.01) mortality. Among STEMI patients, the GRACE and TIMI STEMI scores demonstrated comparably excellent discrimination for in-hospital (C = 0.84, 95% CI: 0.78–0.90 versus 0.83, 95% CI: 0.78–0.89; p = 0.83) and 6-month (C = 0.72, 95% CI: 0.63–0.81, versus 0.71, 95% CI: 0.64–0.79; p = 0.79) mortality. An analysis of refitted multivariate models demonstrated a marked improvement in the discriminative power of the TIMI UA/NSTEMI model with the incorporation of heart failure and hemodynamic variables. Study limitations included unaccounted for confounders inherent to observational, single institution studies with moderate sample sizes. Conclusions/Significance The GRACE scores provided superior discrimination as compared with the TIMI UA/NSTEMI score in predicting in-hospital and 6-month mortality in UA/NSTEMI patients, although the GRACE and TIMI STEMI scores performed equally well in STEMI patients. The observed discriminative deficit of the TIMI UA/NSTEMI score likely results from the omission of key risk factors rather than from the relative simplicity of the scoring system.

A Comparison of Abciximab and Small-Molecule Glycoprotein IIb/IIIa Inhibitors in Patients Undergoing Primary Percutaneous Coronary Intervention A Meta-Analysis of Contemporary Randomized Controlled Trials

Background—Current guidelines recommend abciximab as the preferred agent for patients undergoing primary percutaneous coronary intervention, yet small-molecule glycoprotein IIb/IIIa inhibitors are more commonly used in clinical practice. The objective of our meta-analysis was to evaluate for differences in clinical outcome between small-molecule glycoprotein IIb/IIIa inhibitors and abciximab in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Methods and Results—Five randomized trials (n=2138 patients) comparing tirofiban or eptifibatide with abciximab as an adjunctive therapy to primary percutaneous coronary intervention were included in this meta-analysis. Summary odds ratios (ORs) for 30-day death, reinfarction, and major bleeding were calculated using random- and fixed-effect models. There were no differences in 30-day mortality (1.9% for small molecule versus 2.3% for abciximab; OR, 0.84; 95% CI, 0.46 to 1.55; P=0.58), reinfarction (1.3% versus 1.2%; OR, 1.22; 95% CI, 0.51 to 2.91; P=0.69), or major bleeding (1.7% versus 1.3%; OR, 1.21; 95% CI, 0.58 to 2.49; P=0.61) between the 2 adjunctive strategies. Similarly, there was no significant difference in the incidence of death (3.9% versus 5%; OR, 0.77; 95% CI, 0.41 to 1.46; P=0.43) or reinfarction on follow-up at 8 months between small-molecule glycoprotein IIb/IIIa inhibitors and abciximab. Conclusion—In patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction, no difference in outcome could be identified in patients treated with small-molecule glycoprotein IIb/IIIa inhibitor or abciximab.

Efficacy of Cilostazol in reducing restenosis in patients undergoing contemporary stent based PCI: a meta-analysis of randomised controlled trials

AIMS Cilostazol has been associated with reduction in restenosis in patients undergoing coronary and peripheral arterial angioplasty. Our objective was to evaluate the impact of cilostazol on restenosis in patients undergoing contemporary PCI with bare metal (BMS) or drug eluting stents (DES) and treated with aspirin and thienopyridine. METHODS AND RESULTS Ten randomised trials (n=2,809 patients) comparing triple antiplatelet therapy (aspirin, thienopyridine and cilostazol) with standard dual antiplatelet therapy were included. Summary risk ratios for restenosis, late loss, target lesion revascularisation (TLR) and target vessel revascularisation (TVR) were calculated using fixed-effects models. Cilostazol was associated with a significant reduction in late loss in BMS (mean difference 0.24 mm, 95% CI 0.15-0.33, p<0.001) and DES groups (mean difference 0.12 mm, 95% CI 0.07-0.18, p<0.001). Cilostazol therapy was associated with a significant reduction in angiographic restenosis (Odds ratio [OR] 0.52, 95% CI 0.41- 0.66, p<0.001) with consistent benefits in patients treated with BMS (OR 0.49, 95% CI 0.35-0.70, p<0.001) or DES (OR 0.54, 95% CI 0.38-0.76, p=0.001). Addition of cilostazol to dual antiplatelet therapy was associated with a significant reduction in TLR (OR 0.38, 95% CI 0.25-0.58, p<0.001), with no difference in subacute stent thrombosis (OR 1.91, 95% CI 0.33-11.08, p=0.47), or major bleeding (OR 0.87, 95% CI 0.44-1.74, P=0.69) but with an increased risk of skin rash (OR 3.67, 95% CI 1.86-7.24, p<0.001). CONCLUSIONS Cilostazol in addition to dual antiplatelet therapy is associated with a reduction in angiographic restenosis in patients undergoing stent based PCI. This inexpensive drug may be particularly beneficial in patients who are at high risk of restenosis and it should undergo further evaluation in large, definitive randomised controlled trials.

Safety and efficacy of thrombectomy in patients undergoing primary percutaneous coronary intervention for Acute ST elevation MI: A Meta-Analysis of Randomized Controlled Trials

BackgroundClinical trials comparing thrombectomy devices with conventional percutaneous coronary interventions (PCI) in patients with acute ST elevation myocardial infarction (STEMI) have produced conflicting results. The objective of our study was to systematically evaluate currently available data comparing thrombectomy followed by PCI with conventional PCI alone in patients with acute STEMI.MethodsSeventeen randomized trials (n = 3,909 patients) of thrombectomy versus PCI were included in this meta-analysis. We calculated the summary odds ratios for mortality, stroke, post procedural myocardial blush grade (MBG), thrombolysis in myocardial infarction (TIMI) grade flow, and post procedural ST segment resolution (STR) using random-effects and fixed-effects models.ResultsThere was no difference in risk of 30-day mortality (44/1914 vs. 50/1907, OR 0.84, 95% CI 0.54-1.29, P = 0.42) among patients randomized to thrombectomy, compared with conventional PCI. Thrombectomy was associated with a significantly greater likelihood of TIMI 3 flow (1616/1826 vs. 1533/1806, OR 1.41, P = 0.007), MBG 3 (730/1526 vs. 486/1513, OR 2.42, P < 0.001), STR (923/1500 vs. 715/1494, OR 2.30, P < 0.001), and with a higher risk of stroke (14/1403 vs. 3/1413, OR 2.88, 95% CI 1.06-7.85, P = 0.04). Outcomes differed significantly between different device classes with a trend towards lower mortality with manual aspiration thrombectomy (MAT) (21/949 vs.36/953, OR 0.59, 95% CI 0.35-1.01, P = 0.05), whereas mechanical devices showed a trend towards higher mortality (20/416 vs.10/418, OR 2.07, 95% CI 0.95-4.48, P = 0.07).ConclusionsThrombectomy devices appear to improve markers of myocardial perfusion in patients undergoing primary PCI, with no difference in overall 30-day mortality but an increased likelihood of stroke. The clinical benefits of thrombectomy appear to be influenced by the device type with a trend towards survival benefit with MAT and worsening outcome with mechanical devices.

A Prior Myocardial Infarction: How Does it Affect Management and Outcomes in Recurrent Acute Coronary Syndromes?

Despite improved secondary prevention efforts, acute coronary syndrome (ACS) recurrence among patients with prior history of coronary events remains high. The differences in presentation, management, and subsequent clinical outcomes in patients with and without a prior myocardial infarction (MI) and presenting with another episode of ACS remain unexplored.

The chimeric monoclonal antibody abciximab: a systematic review of its safety in contemporary practice.

Background: Abciximab is a monoclonal antibody that prevents platelet aggregation by blocking platelet glycoprotein (GP) IIb/IIIa receptor. Objective: To study the safety profile of this agent in contemporary clinical practice. Methods: We evaluated efficacy and safety end points (major and minor bleeding, thrombocytopenia) in patients treated with abciximab and compared them to those treated with placebo in main randomized clinical trials of patients with acute coronary syndromes (ACS) or those undergoing percutaneous coronary intervention (PCI). Results/conclusion: Use of abciximab is associated with an improved outcome in high-risk patients undergoing PCI but with a worse outcome in ACS patients treated conservatively. Use of abciximab is associated with an acceptable safety profile even when used on a background of aspirin and high doses of thienopyridine but has a potential to increase thrombocytopenia and minor bleeding. Small molecule GP IIb/IIIa antagonists are increasingly preferred over abciximab in clinical practice, and recent observational data have demonstrated these agents to have a similar efficacy and safety profile. As an increasing number of agents are being evaluated for peri-PCI anti-thrombotic therapy, the role of abciximab is likely to be further restricted to the highest risk patients.