Somjot Brar

Use of drug-eluting stents in acute myocardial infarction: a systematic review and meta-analysis

OBJECTIVES The primary aim of the analysis was to compare outcomes by stent type for death, myocardial infarction (MI), target vessel revascularization (TVR), and stent thrombosis in randomized trials of ST-segment elevation myocardial infarction (STEMI). A secondary analysis was performed among registry studies. BACKGROUND It is not known whether there are differences in outcomes between drug-eluting stents (DES) and bare-metal stents (BMS) for STEMI. METHODS We searched MEDLINE, EMBASE, the Cochrane Library, and Internet sources for articles comparing outcomes between DES and BMS among patients with STEMI between January 2000 and October 2008. Randomized controlled trials and registries including patients 18 years of age and older receiving a DES or BMS were included. We extracted variables related to the study design, setting, participants, and clinical end points. RESULTS Thirteen randomized trials were identified (N = 7,352). Compared with BMS, DES significantly reduced TVR (relative risk [RR]: 0.44; 95% confidence interval [CI]: 0.35 to 0.55), without increasing death (RR: 0.89; 95% CI: 0.70 to 1.14), MI (RR: 0.82; 95% CI: 0.64 to 1.05), or stent thrombosis (RR: 0.97; 95% CI: 0.73 to 1.28). These observations were durable over 2 years. Among 18 registries (N = 26,521), DES significantly reduced TVR (RR: 0.54; 95% CI: 0.40 to 0.74) without an increase in MI (RR: 0.87, 95% CI: 0.62 to 1.23). Death was significantly lower in the DES group within 1 year of the index percutaneous coronary intervention, but there were no differences within 2 years (p = 0.45). CONCLUSIONS The use of DES appears safe and efficacious in randomized trials and registries of patients with STEMI. The DES significantly reduce TVR compared with BMS, without an increase in death, MI, or stent thrombosis within 2 years of the index procedure.

Sodium bicarbonate for the prevention of contrast induced-acute kidney injury: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES Infusion of sodium bicarbonate has been suggested as a preventative strategy but reports are conflicting on its efficacy. The aim of this study was to assess the effectiveness of hydration with sodium bicarbonate for the prevention of contrast-induced acute kidney injury (CI-AKI). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Medline, EMBASE, Cochrane library, and the Internet were searched for randomized controlled trials comparing hydration between sodium bicarbonate and chloride for the prevention of CI-AKI between 1966 and November 2008. Fourteen trials that included 2290 patients were identified. There was significant heterogeneity between studies (P heterogeneity = 0.02; I(2) = 47.8%), which was largely accounted for by trial size (P = 0.016). Trials were therefore classified by size. RESULTS Three trials were categorized as large (n = 1145) and 12 as small (n = 1145). Among the large trials, the incidence of CI-AKI for sodium bicarbonate and sodium chloride was 10.7 and 12.5%, respectively; the relative risk (RR) [95% confidence interval (CI)] was 0.85 (0.63 to 1.16) without evidence of heterogeneity (P = 0.89, I(2) = 0%). The pooled RR (95% CI) among the 12 small trials was 0.50 (0.27 to 0.93) with significant between-trial heterogeneity (P = 0.01; I(2) = 56%). The small trials were more likely to be of lower methodological quality. CONCLUSIONS A significant clinical and statistical heterogeneity was observed that was largely explained by trial size and published status. Among the large randomized trials there was no evidence of benefit for hydration with sodium bicarbonate compared with sodium chloride for the prevention of CI-AKI. The benefit of sodium bicarbonate was limited to small trials of lower methodological quality.

Long-Term Outcomes by Clopidogrel Duration and Stent Type in a Diabetic Population With De Novo Coronary Artery Lesions

OBJECTIVES The purpose of this study was to determine whether long-term clinical outcomes differed between bare-metal stents (BMS) and drug-eluting stents (DES) by duration of clopidogrel use among diabetic patients. BACKGROUND There is concern that DES are associated with late adverse events such as death and myocardial infarction (MI) secondary to stent thrombosis. However, data on outcomes in diabetic patients remain limited. METHODS We identified 749 patients with diabetes mellitus who underwent stent implantation with either BMS (n = 251) or DES (n = 498) from October 2002 to December 2004. We performed survival analysis on the full cohort and on those event-free from death, MI, or repeat revascularization at 6 months (n = 671). RESULTS By clopidogrel duration, the event rate for death or MI was 3.2% in the >9-month group, 9.4% in the 6- to 9-month group, and 16.5% in the <6-month group, p < 0.001. For death alone, the event rate was 0.5% in the >9-month group, 4.3% in the 6- to 9-month group, and 10.0% in the <6-month group, p < 0.001. When taking BMS clopidogrel non-users as a referent in the multivariate analysis, the hazard ratio (95% confidence interval [CI]) for death and nonfatal MI for DES clopidogrel users, DES clopidogrel nonusers, and BMS clopidogrel users were: HR 0.22 (95% CI 0.08 to 0.62, p = 0.005), HR 0.39 (95% CI 0.13 to 1.13, p = 0.08), and HR 0.25 (95% CI 0.08 to 0.81, p = 0.02), respectively. CONCLUSIONS Longer duration of clopidogrel use was associated with a lower incidence of death or MI in both the BMS and DES groups. Among clopidogrel nonusers, the incidence of death/MI or death did not differ by stent type.

Bifurcation stenting with drug-eluting stents: a systematic review and meta-analysis of randomised trials.

AIMS We sought to determine if outcomes differ between provisional (elective side branch stenting) compared to a routine two-stent strategy (mandatory side branch stenting) for the treatment of bifurcation stenoses of the coronary arteries using drug-eluting stents. METHODS AND RESULTS We searched Medline, EMBASE, and the Cochrane library from January 2000 to February 2009 for studies comparing the provisional and two-stent strategies. Six randomised controlled trials, including 1,641 patients, were identified. The relative risk (95% confidence interval) for death, MI, target lesion revascularisation, and stent thrombosis within 1-year of the index procedure for a provisional vs. two-stent strategy were 1.12 (0.42-3.02), 0.57 (0.37-0.87), 0.91 (0.61-1.35), and 0.56 (0.23-1.35), respectively. By quantitative coronary angiography, there was no difference in the difference in means (95% CI) between the provisional and two-stent strategies for percent diameter stenosis (95% CI) in the main vessel or side branch, -1.08 (-2.91 to 0.74) and 1.30 (-3.35 to 5.96), respectively. CONCLUSION While death, stent thrombosis, and restenosis were similar between the treatment groups, MI was more common with the two-stent strategy. Thus, compared to a routine two-stent strategy, provisional stenting yields similar efficacy with superior safety and lower costs.

Racial/Ethnic differences in ischemic stroke rates and the efficacy of warfarin among patients with atrial fibrillation.

Background and Purpose— Warfarin reduces stroke risk in studies of predominantly white patients with atrial fibrillation (AF). Whether nonwhites also have lower rates of stroke while treated with warfarin is unclear. Methods— A multiethnic stroke-free cohort hospitalized with nonrheumatic AF was identified in a large health maintenance organization. Stroke risk factors (advanced age, diabetes, hypertension, and heart failure), warfarin use, and anticoagulation intensity were assessed. Crude ischemic stroke rates were calculated by Poisson regression for each group while using and not using warfarin. Cox proportional hazard models were constructed to assess the independent effect of race/ethnicity on ischemic stroke. Results— Between 1995 and 2000, we identified 18 867 AF hospitalizations (78.5% white, 8% black, 9.5% Hispanic, and 3.9% Asian). Over the course of 63 204 person-years follow-up (median, 3.3 years), 1226 ischemic strokes were identified. The percent-time on warfarin did not differ by race/ethnicity. The median percent-time on warfarin that international normalized ratio was 2 to 3 was 54.5% overall, but it was lower in blacks at 47.8%, whereas the other groups had a rate of ≈54%. The rate ratios (95% CI) of ischemic stroke with warfarin compared to without warfarin for whites, blacks, Hispanics, and Asians were 0.79 (0.68 to 0.90), 0.92 (0.65 to 1.30), 0.71 (0.48 to 1.05), and 0.65 (0.34 to 1.23), respectively. Conclusions— In this cohort, we did not observe a statistically significant lower rate of stroke with warfarin therapy among nonwhites (in particular blacks) with previous AF hospitalizations. The relatively small numbers of nonwhites renders our estimates less than precise and should be interpreted with caution.

Effect of Race/Ethnicity on the Efficacy of Warfarin : Potential Implications for Prevention of Stroke in Patients with Atrial Fibrillation

Atrial fibrillation (AF) is the most common sustained arrhythmia seen in clinical practice. It affects approximately 6% of persons over 65 years of age and is independently associated with a 4-to 5-fold higher risk of ischaemic stroke and a 2-fold higher risk of death. Randomized controlled trials have shown that treatment with adjusted-dose oral vitamin K antagonists (primarily warfarin with a target international normalized ratio [INR] of 2.0–3.0) reduces the relative risk of ischaemic stroke by two-thirds (an approximately 3% reduction in annual absolute risk), but is associated with a 0.2% excess annual absolute risk of intracranial haemorrhage (ICH). However, in ‘real world’ studies, the risk reductions in ischaemic stroke with warfarin have been significantly lower (25–50% relative risk reduction) than in selected trial samples. Moreover, more than 90% of patients enrolled in the sentinel trials were White/European. This raises the question of whether the beneficial results of warfarin can be extrapolated to persons of colour. Important differences in stroke risk profile and responsiveness to warfarin exist across racial/ethnic groups, such that one cannot assume a priori that there is a net benefit of warfarin therapy for AF patients of all racial/ethnic groups.Among patients with ischaemic stroke, AF is more likely to be implicated as the cause of stroke in the White population than in other racial/ethnic groups. Furthermore, AF may be a stronger predictor of ischaemic stroke among the White population than in Black or Hispanic/Latino populations. Approximately one-third of strokes in AF patients are noncardioembolic. Warfarin has been shown to be ineffective in preventing recurrent noncardioembolic strokes. Many persons of colour with AF have other risk factors that predispose them to noncardioembolic stroke, which may partially explain why warfarin has been reported to be less efficacious in preventing strokes in non-White patients with AF, even after adjustment for co-morbidities and anticoagulation monitoring. Notably, the background incidence of ICH is higher in Black, Hispanic and Asian patients than in White patients. Any greater than expected increases in bleeding secondary to anticoagulation may potentially offset any benefit gained from cardioembolic stroke reduction, although this has not been fully resolved.Finally, there are racial/ethnic differences in the prevalence of certain polymorphisms in genes that influence warfarin pharmacokinetics and pharmaco-dynamics (e.g. cytochrome P450 2C9 and vitamin K epoxide reductase). The Asian population generally appear to require the lowest daily dose of warfarin to maintain a given INR target, with the White population requiring an intermediate daily dose and the Black population requiring the highest daily dose. These differences must be taken into account when administering warfarin in order to minimize the risk of under-or over-anticoagulation.In summary, warfarin is highly effective in preventing ischaemic strokes in White patients with AF at a modestly higher risk of ICH. Whether the same net clinical benefit extends to persons of colour is unproven. Given the rapidly changing demographic nationally and internationally, additional research is needed to resolve this important question.

Implantable Defibrillators Improve Survival in End-Stage Renal Disease: Results from a Multi-Center Registry

Background: Small retrospective analyses suggest that end-stage renal disease (ESRD) patients do not obtain as much of a survival benefit from an implantable cardioverter-defibrillator (ICD) as non-ESRD patients do. We aimed to assess the survival effect of an ICD in ESRD patients with left ventricular dysfunction. Methods: Data from two registries identified ESRD patients with an ICD and ESRD patients with left ventricular dysfunction (defined as ejection fraction <0.35). Cox proportional hazards regression was performed, including certain predefined covariates to assess the effect of an ICD on survival. Results: Overall survival in the full cohort was a median of 4.7 years with 20 deaths in the ICD group and 29 deaths in the no-ICD group. The median survival in the ICD group was 8.0 years and 3.1 years in the no-ICD group. Crude analysis showed a better survival in the ICD group as compared to the no-ICD group (p = 0.016). The multivariable analysis confirmed that the ICD group had significantly less all-cause mortality compared to the no-ICD group (HR: 0.40; 95% CI: 0.19, 0.82; p = 0.013). Conclusion: An ICD is associated with a higher survival in ESRD patients with left ventricular dysfunction. This result merits further study in a larger cohort of patients.

Contrast-Induced Acute Kidney Injury: Underappreciated or a New Marker of Cardiovascular Mortality?⁎

Acute kidney injury (AKI) after exposure to intravenous or intra-arterial iodinated contrast material (contrast-induced [CI]-AKI) increases morbidity and length of hospital stay. Our group and others reported on the association of this complication with early and late clinical outcomes. Interesting

Comparison of Bivalirudin versus Bivalirudin plus glycoprotein IIb/IIIa inhibitor versus heparin plus glycoprotein IIb/IIIa inhibitor in patients with acute coronary syndromes having percutaneous intervention for narrowed saphenous vein aorto-coronary grafts (the ACUITY trial investigators).

Clinical outcomes in patients with acute coronary syndromes randomized in the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial who underwent percutaneous coronary intervention (PCI) of saphenous vein grafts (SVGs) were examined. The ACUITY trial assessed the safety and efficacy of bivalirudin alone versus bivalirudin plus a glycoprotein (GP) IIb/IIIa inhibitor versus heparin plus a GP IIb/IIIa inhibitor in 13,819 patients with moderate- and high-risk acute coronary syndromes, 7,789 of whom underwent PCI. A total of 329 patients (4.2%) underwent PCI of SVGs in ACUITY. The primary end points at 30 days were composite ischemia or major adverse cardiac events (death, myocardial infarction, or unplanned target vessel revascularization), major bleeding (unrelated to coronary artery bypass grafting), and net adverse clinical events (composite ischemia or major bleeding). The rates of ischemic, bleeding, and net clinical end points were similar with bivalirudin monotherapy, bivalirudin plus a GP IIb/IIIa inhibitor, and heparin plus a GP IIb/IIIa inhibitor. Net adverse clinical outcome rates at 30 days were 22%, 26%, and 22% (p = 0.67), respectively, for the 3 groups. Major adverse cardiac event rates at 1 year were 37%, 37%, and 43% (p = 0.95), respectively. Minor bleeding unrelated to coronary artery bypass grafting at 30 days was significantly lower with bivalirudin alone compared with heparin plus a GP IIb/IIIa inhibitor (26% vs 38%, p = 0.05). In conclusion, bivalirudin is an effective anticoagulant in PCI of SVGs in acute coronary syndromes, with similar rates of major adverse cardiac events and net adverse cardiac events and lower minor bleeding complications in comparison with heparin plus a GP IIb/IIIa inhibitor or bivalirudin plus a GP IIb/IIIa inhibitor.

Multi‐Center, Community‐Based Cardiac Implantable Electronic Devices Registry: Population, Device Utilization, and Outcomes

Background The purpose of this study is to describe key elements, clinical outcomes, and potential uses of the Kaiser Permanente–Cardiac Device Registry. Methods and Results This is a cohort study of implantable cardioverter defibrillators (ICD), pacemakers (PM), and cardiac resynchronization therapy (CRT) devices implanted between January 1, 2007 and December 31, 2013 by ≈400 physicians in 6 US geographical regions. Registry data variables, including patient characteristics, comorbidities, indication for procedures, complications, and revisions, were captured using the healthcare systems electronic medical record. Outcomes were identified using electronic screening algorithms and adjudicated via chart review. There were 11 924 ICDs, 33 519 PMs, 4472 CRTs, and 66 067 leads registered. A higher proportion of devices were implanted in males: 75.1% (ICD), 55.0% (PM), and 66.7% (CRT), with mean patient age 63.2 years (ICD), 75.2 (PM), and 67.2 (CRT). The 30‐day postoperative incidence of tamponade, hematoma, and pneumothorax were ≤0.3% (ICD), ≤0.6% (PM), and ≤0.4% (CRT). Device failures requiring revision occurred at a rate of 2.17% for ICDs, 0.85% for PMs, and 4.93% for CRTs, per 100 patient observation years. Superficial infection rates were <0.03% for all devices; deep infection rates were 0.6% (ICD), 0.5% (PM), and 1.0% (CRT). Results were used to monitor vendor‐specific variations and were systematically shared with individual regions to address potential variations in outcomes, utilization, and to assist with the management of device recalls. Conclusions The Kaiser Permanente–Cardiac Device Registry is a robust tool to monitor postprocedural patient outcomes and postmarket surveillance of implants and potentially change practice patterns.