Cardiac Implantable Electronic Device-Related Infection and Extraction Trends in the U.S.

BACKGROUND: Implantation of cardiac implanted electronic device (CIED) has surged lately. This resulted in a rise in cardiac device-related infections (CDI) and inevitably, lead extractions. We examined the recent national trend in the incidence of CIED infections and lead extractions in hospitalized patients and associated mortality. METHODS: Using the Nationwide Inpatient Sample for the years 2003-2011 we identified patients diagnosed with a CDI-associated infection as determined by discharge ICD-9 diagnostic codes. We examined the trend of device-related infections overall and in different subgroups. We studied mortality associated with device infections, lead extractions, associated costs, and length of stay. RESULTS: There is a significant increase in the number of hospitalizations due to CDI from 5,308 in the year 2003 to 9,948 in 2011. Males (68%), Caucasians (77%), and age group 65-84 years (56.4%) accounted for majority of CDI. The mortality associated with CDI was 4.5 %, and was worse in higher age groups (2.5% in 18-44 years compared to 5.3% in 85+ years, P < 0.001). Average length of stay was unchanged over the years remaining at 13.6 days; however, mean hospitalization charges increased from $91,348 in 2003 to $173,211 in 2011 (P < 0.001). Among all lead extraction procedures, the percentage of patients undergoing lead extraction secondary to CDI also increased from 2003 (59.1%) to 2011 (76.7%), P-value < 0.001. CONCLUSIONS: Healthcare burden associated with CDI infections and associated lead extractions has significantly increased in the recent years. Despite an increase in cost associated with CIED infections, mortality remains the same, and is higher in older patients.

Incremental value of left ventricular systolic and diastolic function to determine outcome in patients with acute ST-segment elevation myocardial infarction: the echocardiographic substudy of the OASIS-6 trial.

BACKGROUND: The echocardiographic substudy of the OASIS-6 trial evaluated the prognostic implications of left ventricle (LV) systolic and diastolic dysfunction early postacute ST-segment elevation myocardial infarction (STEMI) in patients treated with fondaparinux versus usual care. METHODS: Comprehensive echocardiograms were performed a median of 6 days after the index STEMI in 528 patients, 258 randomized to fondaparinux and 270 to usual care (unfractionated heparin or placebo), to assess LV systolic and diastolic function, LV mass, and LV end-systolic and end-diastolic volumes. A total of 245 (46.4%) patients were followed up for 3 months and 283 (53.6%) for 6 months. Major cardiac events (MACE) were defined as the composite of death, reinfarction, heart failure, or cardiogenic shock and resuscitated cardiac arrest. RESULTS: Patients with LV ejection fraction (LVEF) ≤ 45% and restrictive diastolic function (RDF) were at greatly increased risk of MACE (hazard ratio [HR] = 8.85, 95% CI, 4.21­18.60) compared to patients with LVEF ≥ 45% and without RDF. RDF remained a strong predictor for MACE in patients with LVEF ≥ 45% (HR = 4.38, 95% CI, 1.52­12.60) and in multivariate models adjusted for LVEF, LV end-systolic volume, and clinical variables. CONCLUSION: In this large international trial, LV systolic and diastolic function, as determined by echocardiography early following STEMI, are incremental predictors of MACE. In addition, RDF is a strong independent predictor of MACE after STEMI across a broad range of LVEF.

Comparison of risk factor reduction and tolerability of a full-dose polypill (with potassium) versus low-dose polypill (polycap) in individuals at high risk of cardiovascular diseases: the Second Indian Polycap Study (TIPS-2) investigators.

BACKGROUND: A daily single capsule (polycap) of 3 blood pressure (BP) lowering drugs (hydrochlorthiazide, 12.5 mg; atenolol, 50 mg; ramipril, 5 mg) at low doses, simvastatin (20 mg), and aspirin (100 mg) has been demonstrated to be well tolerated and to reduce BP and low-density lipoprotein cholesterol. We examined the incremental effects of 2 (full dose) plus K(+) supplementation versus single polycap (low dose) on risk factors and tolerability. METHODS AND RESULTS: After a run-in period, 518 individuals with previous vascular disease or diabetes mellitus from 27 centers in India were randomly assigned to a single-dose polycap or to 2 capsules of the polycap plus K(+) supplementation for 8 weeks. The effects on BP, heart rate (HR), serum lipids, serum and urinary K(+), and tolerability were assessed using an intention-to-treat analysis. The full-dose polycap (plus K(+) supplementation) reduced BP by a further 2.8 mm Hg systolic and 1.7 mm Hg diastolic, compared with that observed with the low-dose polycap (P=0.003; P=0.001), but there were no differences in HR (0.1 bpm). The differences in total and low-density lipoprotein cholesterol between the full-dose and low-dose polycap was 7.2 mg/dL (P=0.014) and 6.6 mg/dL (P=0.006), respectively, but there were no differences in high-density lipoprotein cholesterol or triglycerides. The rates of discontinuation of the study drug after randomization were similar in the 2 groups (6.9% low dose versus 7.8% full dose). CONCLUSIONS: The full-dose polycap (plus K(+) supplementation) reduces BP and low-density lipoprotein cholesterol to a greater extent compared with the low dose, with similar tolerability. Therefore, the full-dose polycap should potentially lead to larger benefits. Clinical Trial Registration- URL: http://www.ctri.nic.in. Unique identifier: CTRI/2010/091/000054.

Early invasive compared with a selective invasive strategy in women with non-ST-elevation acute coronary syndromes: a substudy of the OASIS 5 trial and a meta-analysis of previous randomized trials.

AIMS: The aim of this study was to compare benefits and risks of a routine invasive compared with a selective invasive strategy in women with non-ST-elevation acute coronary syndromes. METHODS AND RESULTS: We randomly assigned 184 women, either to a routine or to a selective invasive strategy as a substudy to the OASIS 5 trial, who were followed for 2 years. Meta-analysis of data from previous randomized trials was also done. There were no significant differences between the two treatment strategies in the primary outcome death/myocardial infarction (MI)/stroke [21.0 vs. 15.4%, HR = 1.46, 95% CI (0.73-2.94)], in the secondary outcome death/MI [18.8 vs. 14.3%, HR = 1.39, 95% CI (0.67-2.88)], or separately analysed outcomes MI [12.9 vs. 13.3%, HR = 0.95, 95% CI (0.42-2.19)] or stroke [2.3 vs. 4.4%, HR = 0.67, 95% CI (0.12-3.70)]. However, there were significantly more deaths after 1 year (8.8 vs. 1.1%, HR = 9.01, 95% CI (1.11-72.90) and a higher rate of major bleeding at 30 days [8.8 vs. 1.1%, HR = 11.45, 95% CI (1.43-91.96)] in the routine invasive strategy group. A meta-analysis including 2692 women in previous randomized trials, with a gender perspective, showed no significant difference in the composite outcome death/MI, OR = 1.18, 95% CI (0.92-1.53) but a higher mortality with a routine invasive strategy for women, OR = 1.51, 95% CI (1.00-2.29). CONCLUSION: The rate of death, MI, or stroke in women was not different in patients treated with a routine invasive strategy compared with a selective invasive strategy, but there was a concerning trend towards higher mortality. When combined with data from previous trials, there does not appear to be a benefit of an early invasive strategy in women with ACS, which differs from the results in men. These data emphasize the lack of clear evidence in favour of an invasive strategy in women and suggest caution in extrapolating the results from men to women.

Impact of transradial and transfemoral coronary interventions on bleeding and net adverse clinical events in acute coronary syndromes.

AIMS: The aim of the present study was to examine the impact of the transradial approach (TRA), in comparison to the transfemoral approach (TFA), on PCI-related bleeding and patient outcomes in acute coronary syndrome patients who underwent PCI in the OASIS-5 trial. METHODS AND RESULTS: The primary outcome (death, myocardial infarction, refractory ischaemia) at nine days was similar in both groups (7.1% in 872 TRA and 7.7% in 7,013 TFA). Major bleeding was significantly lower in patients who underwent PCI with TRA by comparison to TFA (1.6% vs 3.5%, p<0.003, respectively). No difference between patients treated by fondaparinux or enoxaparin was noted for ischaemic events at nine days according to the access site. The rate of major bleeding at nine days was markedly reduced with fondaparinux when compared to enoxaparin for both access sites (from 4.8% to 2.3%, HR 0.48 [0.37-0.62], p< 0.0001 for TFA and from 2.4 to 0.9%, HR 0.36 [0.11- 1.16], p<0.08 for TRA). CONCLUSIONS: TRA is associated with substantial decrease of PCI-related bleeding in current contemporary pharmacological environment in comparison to TFA. Even in the context of low access site complication rate provided by TRA, fondaparinux was effective in reducing major bleeding.

Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL): a randomised, parallel group, multicentre trial.

BACKGROUND: Small trials have suggested that radial access for percutaneous coronary intervention (PCI) reduces vascular complications and bleeding compared with femoral access. We aimed to assess whether radial access was superior to femoral access in patients with acute coronary syndromes (ACS) who were undergoing coronary angiography with possible intervention. METHODS: The RadIal Vs femorAL access for coronary intervention (RIVAL) trial was a randomised, parallel group, multicentre trial. Patients with ACS were randomly assigned (1:1) by a 24 h computerised central automated voice response system to radial or femoral artery access. The primary outcome was a composite of death, myocardial infarction, stroke, or non-coronary artery bypass graft (non-CABG)-related major bleeding at 30 days. Key secondary outcomes were death, myocardial infarction, or stroke; and non-CABG-related major bleeding at 30 days. A masked central committee adjudicated the primary outcome, components of the primary outcome, and stent thrombosis. All other outcomes were as reported by the investigators. Patients and investigators were not masked to treatment allocation. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, NCT01014273. FINDINGS: Between June 6, 2006, and Nov 3, 2010, 7021 patients were enrolled from 158 hospitals in 32 countries. 3507 patients were randomly assigned to radial access and 3514 to femoral access. The primary outcome occurred in 128 (3·7%) of 3507 patients in the radial access group compared with 139 (4·0%) of 3514 in the femoral access group (hazard ratio [HR] 0·92, 95% CI 0·72-1·17; p=0·50). Of the six prespecified subgroups, there was a significant interaction for the primary outcome with benefit for radial access in highest tertile volume radial centres (HR 0·49, 95% CI 0·28-0·87; p=0·015) and in patients with ST-segment elevation myocardial infarction (0·60, 0·38-0·94; p=0·026). The rate of death, myocardial infarction, or stroke at 30 days was 112 (3·2%) of 3507 patients in the radial group compared with 114 (3·2%) of 3514 in the femoral group (HR 0·98, 95% CI 0·76-1·28; p=0·90). The rate of non-CABG-related major bleeding at 30 days was 24 (0·7%) of 3507 patients in the radial group compared with 33 (0·9%) of 3514 patients in the femoral group (HR 0·73, 95% CI 0·43-1·23; p=0·23). At 30 days, 42 of 3507 patients in the radial group had large haematoma compared with 106 of 3514 in the femoral group (HR 0·40, 95% CI 0·28-0·57; p<0·0001). Pseudoaneurysm needing closure occurred in seven of 3507 patients in the radial group compared with 23 of 3514 in the femoral group (HR 0·30, 95% CI 0·13-0·71; p=0·006). INTERPRETATION: Radial and femoral approaches are both safe and effective for PCI. However, the lower rate of local vascular complications may be a reason to use the radial approach. FUNDING: Sanofi-Aventis, Population Health Research Institute, and Canadian Network for Trials Internationally (CANNeCTIN), an initiative of the Canadian Institutes of Health Research.

Apixaban in patients with atrial fibrillation.

BACKGROUND: Vitamin K antagonists have been shown to prevent stroke in patients with atrial fibrillation. However, many patients are not suitable candidates for or are unwilling to receive vitamin K antagonist therapy, and these patients have a high risk of stroke. Apixaban, a novel factor Xa inhibitor, may be an alternative treatment for such patients. METHODS: In a double-blind study, we randomly assigned 5599 patients with atrial fibrillation who were at increased risk for stroke and for whom vitamin K antagonist therapy was unsuitable to receive apixaban (at a dose of 5 mg twice daily) or aspirin (81 to 324 mg per day), to determine whether apixaban was superior. The mean follow up period was 1.1 years. The primary outcome was the occurrence of stroke or systemic embolism. RESULTS: Before enrollment, 40% of the patients had used a vitamin K antagonist. The data and safety monitoring board recommended early termination of the study because of a clear benefit in favor of apixaban. There were 51 primary outcome events (1.6% per year) among patients assigned to apixaban and 113 (3.7% per year) among those assigned to aspirin (hazard ratio with apixaban, 0.45; 95% confidence interval [CI], 0.32 to 0.62; P<0.001). The rates of death were 3.5% per year in the apixaban group and 4.4% per year in the aspirin group (hazard ratio, 0.79; 95% CI, 0.62 to 1.02; P=0.07). There were 44 cases of major bleeding (1.4% per year) in the apixaban group and 39 (1.2% per year) in the aspirin group (hazard ratio with apixaban, 1.13; 95% CI, 0.74 to 1.75; P=0.57); there were 11 cases of intracranial bleeding with apixaban and 13 with aspirin. The risk of a first hospitalization for cardiovascular causes was reduced with apixaban as compared with aspirin (12.6% per year vs. 15.9% per year, P<0.001). The treatment effects were consistent among important subgroups. CONCLUSIONS: In patients with atrial fibrillation for whom vitamin K antagonist therapy was unsuitable, apixaban reduced the risk of stroke or systemic embolism without significantly increasing the risk of major bleeding or intracranial hemorrhage. (Funded by Bristol-Myers Squibb and Pfizer; ClinicalTrials.gov number, NCT00496769.).

Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL): a randomised, parallel group, multicentre trial

Background Small trials have suggested that radial access for percutaneous coronary intervention (PCI) reducesvascular complications and bleeding compared with femoral access. We aimed to assess whether radial access was superior to femoral access in patients with acute coronary syndromes (ACS) who were undergoing coronaryangiography with possible intervention.Methods The RadIal Vs femorAL access for coronary intervention (RIVAL) trial was a randomised, parallel group,multicentre trial. Patients with ACS were randomly assigned (1:1) by a 24 h computerised central automated voiceresponse system to radial or femoral artery access. The primary outcome was a composite of death, myocardialinfarction, stroke, or non-coronary artery bypass graft (non-CABG)-related major bleeding at 30 days. Key secondary outcomes were death, myocardial infarction, or stroke; and non-CABG-related major bleeding at 30 days. A masked central committee adjudicated the primary outcome, components of the primary outcome, and stent thrombosis. All other outcomes were as reported by the investigators. Patients and investigators were not masked to treatment allocation. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, NCT01014273. Findings Between June 6, 2006, and Nov 3, 2010, 7021 patients were enrolled from 158 hospitals in 32 countries.3507 patients were randomly assigned to radial access and 3514 to femoral access. The primary outcome occurred in128 (3·7%) of 3507 patients in the radial access group compared with 139 (4·0%) of 3514 in the femoral access group (hazard ratio [HR] 0·92, 95% CI 0·72–1·17; p=0·50). Of the six prespecifi ed subgroups, there was a signifi cant interaction for the primary outcome with benefi t for radial access in highest tertile volume radial centres (HR 0·49, 95% CI 0·28–0·87; p=0·015)...

Apixaban in patients with atrial fibrillation

Background Vitamin K antagonists have been shown to prevent stroke in patients with atrial fibrillation. However, many patients are not suitable candidates for or are unwilling to receive vitamin K antagonist therapy, and these patients have a high risk of stroke. Apixaban, a novel factor Xa inhibitor, may be an alternative treatment for such patients.Methods In a double-blind study, we randomly assigned 5599 patients with atrial fibrillation who were at increased risk for stroke and for whom vitamin K antagonist therapy was unsuitable to receive apixaban (at a dose of 5 mg twice daily) or aspirin (81 to 324 mgper day), to determine whether apixaban was superior. The mean follow up period was 1.1 years. The primary outcome was the occurrence of stroke or systemic embolism.Results Before enrollment, 40% of the patients had used a vitamin K antagonist. The data and safety monitoring board recommended early termination of the study because of a clear benefit in favor of apixaban. There were 51 primary outcome events (1.6% per year) among patients assigned to apixaban and 113 (3.7% per year) among those assigned to aspirin (hazard ratio with apixaban, 0.45; 95% confidence interval [CI],0.32 to 0.62; P<0.001). The rates of death were 3.5% per year in the apixaban group and 4.4% per year in the aspirin group (hazard ratio, 0.79; 95% CI, 0.62 to 1.02; P = 0.07).There were 44 cases of major bleeding (1.4% per year) in the apixaban group and 39 (1.2% per year) in the aspirin group (hazard ratio with apixaban, 1.13; 95% CI, 0.74 to 1.75; P = 0.57); there were 11 cases of intracranial bleeding with apixaban and 13 with aspirin. The risk of a first hospitalization for cardiovascular causes was reduced with apixaban as compared with aspirin (12.6% per year vs. 15.9% per year, P<0.001). The treatment effects were consistent among important subgroups...

Efficacy and safety of fondaparinux in patients with ST-segment elevation myocardial infarction across the age spectrum. Results from the Organization for the Assessment of Strategies for Ischemic Syndromes 6 (OASIS-6) trial.

AIMS: The OASIS-6 trial demonstrated the benefit of fondaparinux in patients with ST-segment elevation myocardial infarction (STEMI) not undergoing primary percutaneous coronary intervention. Elderly compared to younger patients are at higher risk of bleeding and could have a different balance of benefits and risks when treated with antithrombotic therapy. METHODS AND RESULTS: We explored the efficacy and safety of fondaparinux compared to control according to age tertiles in 12,092 patients with STEMI in the OASIS-6 trial. Death or myocardial infarction rates were reduced by fondaparinux in tertile I (age<56 years, 4.5% vs 4.8%, hazard ratio [HR] 0.94, 95% CI 0.71-1.25), in tertile II (age 56-68 years, 7.9% vs 9.7%, HR 0.80, 0.65-0.98), and in tertile III (age≥69 years, 17.2% vs 19.8%, HR 0.87, 95% CI 0.75-1.01, P for heterogeneity=0.87). Severe hemorrhage rates were reduced in tertile I (0.5% vs 0.6%, HR 0.94, 95% CI 0.41-2.12), in tertile II (0.9% vs 1.5%, HR 0.63, 95% CI 0.35-1.11), and in tertile III (2.1% vs 2.4%, HR 0.86, 95% CI 0.56-1.33, P for heterogeneity=0.86). Death, myocardial infarction, or severe hemorrhage rates were reduced in tertile I (4.8% vs 5.0%, HR 0.95, 95% CI 0.72-1.25), in tertile II (8.1% vs 10.1%, HR 0.79, 95% CI 0.65-0.97), and in tertile III (17.6% vs 20.4%, HR 0.86, 95% CI 0.74-1.00, P for heterogeneity=0.77). CONCLUSION: The balance of benefits and risks of fondaparinux is consistent across age tertiles, supporting its use across the age spectrum of patients with STEMI who do not undergo primary percutaneous coronary intervention.

Dose comparisons of clopidogrel and aspirin in acute coronary syndromes.

BACKGROUND: Clopidogrel and aspirin are widely used for patients with acute coronary syndromes and those undergoing percutaneous coronary intervention (PCI). However, evidence-based guidelines for dosing have not been established for either agent. METHODS: We randomly assigned, in a 2-by-2 factorial design, 25,086 patients with an acute coronary syndrome who were referred for an invasive strategy to either double-dose clopidogrel (a 600-mg loading dose on day 1, followed by 150 mg daily for 6 days and 75 mg daily thereafter) or standard-dose clopidogrel (a 300-mg loading dose and 75 mg daily thereafter) and either higher-dose aspirin (300 to 325 mg daily) or lower-dose aspirin (75 to 100 mg daily). The primary outcome was cardiovascular death, myocardial infarction, or stroke at 30 days. RESULTS: The primary outcome occurred in 4.2% of patients assigned to double-dose clopidogrel as compared with 4.4% assigned to standard-dose clopidogrel (hazard ratio, 0.94; 95% confidence interval [CI], 0.83 to 1.06; P=0.30). Major bleeding occurred in 2.5% of patients in the double-dose group and in 2.0% in the standard-dose group (hazard ratio, 1.24; 95% CI, 1.05 to 1.46; P=0.01). Double-dose clopidogrel was associated with a significant reduction in the secondary outcome of stent thrombosis among the 17,263 patients who underwent PCI (1.6% vs. 2.3%; hazard ratio, 0.68; 95% CI, 0.55 to 0.85; P=0.001). There was no significant difference between higher-dose and lower-dose aspirin with respect to the primary outcome (4.2% vs. 4.4%; hazard ratio, 0.97; 95% CI, 0.86 to 1.09; P=0.61) or major bleeding (2.3% vs. 2.3%; hazard ratio, 0.99; 95% CI, 0.84 to 1.17; P=0.90). CONCLUSIONS: In patients with an acute coronary syndrome who were referred for an invasive strategy, there was no significant difference between a 7-day, double-dose clopidogrel regimen and the standard-dose regimen, or between higher-dose aspirin and lower-dose aspirin, with respect to the primary outcome of cardiovascular death, myocardial infarction, or stroke. (Funded by Sanofi-Aventis and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00335452.)

Low-dose vs standard-dose unfractionated heparin for percutaneous coronary intervention in acute coronary syndromes treated with fondaparinux: the FUTURA/OASIS-8 randomized trial.

CONTEXT: The optimal unfractionated heparin regimen for percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation acute coronary syndromes treated with fondaparinux is uncertain. OBJECTIVE: To compare the safety of 2 unfractionated heparin regimens during PCI in high-risk patients with non-ST-segment elevation acute coronary syndromes initially treated with fondaparinux. DESIGN, SETTING, AND PARTICIPANTS: Double-blind randomized parallel-group trial in 179 hospitals in 18 countries involving 2026 patients undergoing PCI within 72 hours, nested within a cohort of 3235 high-risk patients with non-ST-segment elevation acute coronary syndromes initially treated with fondaparinux enrolled from February 2009 to March 2010. INTERVENTIONS: Patients received intravenously either low-dose unfractionated heparin, 50 U/kg, regardless of use of glycoprotein IIb/IIIa (GpIIb-IIIa) inhibitors or standard-dose unfractionated heparin, 85 U/kg (60 U/kg with GpIIb-IIIa inhibitors), adjusted by blinded activated clotting time (ACT). MAIN OUTCOME MEASURES: Composite of major bleeding, minor bleeding, or major vascular access-site complications up to 48 hours after PCI. Key secondary outcomes include composite of major bleeding at 48 hours with death, myocardial infarction, or target vessel revascularization within day 30. RESULTS: The primary outcome occurred in 4.7% of those in the low-dose group vs 5.8% in the standard-dose group (odds ratio [OR], 0.80; 95% confidence interval [CI], 0.54-1.19; P = .27). The rates of major bleeding were not different but the rates of minor bleeding were lower with 0.7% in the low-dose group vs 1.7% in the standard-dose group (OR, 0.40; 95% CI, 0.16-0.97; P = .04). For the key secondary outcome, the rates for low-dose group were 5.8% vs 3.9% in the standard-dose group (OR, 1.51; 95% CI, 1.00-2.28; P = .05) and for death, myocardial infarction, or target vessel revascularization it was 4.5% for the low-dose group vs 2.9% for the standard-dose group (OR, 1.58; 95% CI, 0.98-2.53; P = .06). Catheter thrombus rates were very low (0.5% in the low-dose group and 0.1% in the standard-dose group, P = .15). CONCLUSION: Low-dose compared with standard-dose unfractionated heparin did not reduce major peri-PCI bleeding and vascular access-site complications. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00790907.

Meta-analysis of combined therapy with angiotensin receptor antagonists versus ACE inhibitors alone in patients with heart failure.

BACKGROUND: There is insufficient evidence whether the benefit of adding angiotensin II receptor blockers (ARBs) to angiotensin-converting enzyme (ACE) inhibitors outweighs the increased risk of adverse effects in patients with heart failure. METHODOLOGY/PRINCIPAL FINDINGS: Two independent reviewers searched and abstracted randomized controlled trials of ARBs and ACE inhibitors compared to ACE inhibitor therapy alone in patients with heart failure reporting mortality and hospitalizations having a follow-up of at least 6 months identified by a systematic literature search. Eight trials including a total of 18,061 patients fulfilled our inclusion criteria. There was no difference between patients treated with combination therapy and ACE inhibitor therapy alone for overall mortality, hospitalization for any reason, fatal or nonfatal MI. Combination therapy was, however, associated with fewer hospital admissions for heart failure (RR 0.81, 95%CI 0.72-0.91), although there was significant heterogeneity across trials (p-value for heterogeneity = 0.04; I(2) = 57% [95%CI 0-83%]). Patients treated with combination therapy had a higher risk of worsening renal function and symptomatic hypotension, and their trial medications were more often permanently discontinued. Lack of individual patient data precluded the analysis of time-to-event data and identification of subgroups which potentially benefit more from combination therapy such as younger patients with preserved renal function and thus at lower risk to experience worsening renal function or hyperkalemia. CONCLUSIONS/SIGNIFICANCE: Combination therapy with ARBs and ACE inhibitors reduces admissions for heart failure in patients with congestive heart failure when compared to ACE inhibitor therapy alone, but does not reduce overall mortality or all-cause hospitalization and is associated with more adverse events. Thus, based on current evidence, combination therapy with ARBs and ACE inhibitors may be reserved for patients who remain symptomatic on therapy with ACE inhibitors under strict monitoring for any signs of worsening renal function and/or symptomatic hypotension.

Mortality and morbidity following a major bleed in a registry population with acute ST elevation myocardial infarction.

Major bleeding has been associated with an increased risk of ischemic events and death in patients with acute coronary syndromes. We examined the relationship between bleeding and outcome in 1,389 consecutive patients with ST-elevation myocardial infarction (STEMI) presenting to a tertiary center between May 1, 2003 and July 10, 2007. We recorded bleeding, length of stay and death during the first 30 days after hospitalization. Major bleeding occurred in 10.9% (152/1389, 95% confidence interval [CI] 9.3-12.6%). In hospital mortality was significantly higher in patients with major bleeding compared to those without major bleeding (19.7 vs. 8.2%, odds ratio [OR] 2.8, 95% CI 1.8-4.3) and was evident in the subgroups of patients with a low TIMI STEMI risk score (7.9 vs. 1.8%, OR 4.6, 95% CI 1.2-17.0) and medium risk score (11.7 vs. 6.3%, OR 2.0, 95% CI 0.6-6.2) but not those with a high TIMI STEMI risk score (28.8 vs. 26.1%, OR 1.2, 95% CI 0.7-2.0) (P for interaction = 0.024). Our data indicate that serious bleeding is common in patients with STEMI treated with thrombolysis or PCI and is a powerful predictor of death, particularly in patients with a low TIMI risk score. Therapies that maintain efficacy while reducing bleeding and that reduce the risk of death in patients who develop bleeding are needed.

Safety and feasibility of early hospital discharge in ST-segment elevation myocardial infarction--a prospective and randomized trial in low-risk primary percutaneous coronary intervention patients (the Safe-Depart Trial).

BACKGROUND: Patients with ST-segment elevation myocardial infarction (STEMI) have traditionally been hospitalized for 5 to 7 days to monitor for serious complications such as heart failure, arrhythmias, reinfarction, and death. The Zwolle Primary Percutaneous Coronary Intervention (PCI) Index is an externally validated risk score that has been used to identify low-risk STEMI patients who have undergone primary PCI and can safely be discharged from hospital within 72 hours. Previous studies have shown that many low-risk patients remain in hospital significantly longer. METHODS: We randomly assigned 54 low-risk STEMI patients treated with primary or rescue PCI to 1 of 2 groups. Patients in the intervention group (n = 27) were actively targeted for early hospital discharge (48-72 hours) and received outpatient follow-up with an advanced practice nurse (APN). In the control group (n = 27), discharge planning and follow-up were left to the treating physician, and there was no added nursing intervention. The 2 primary outcomes of this pilot study were to demonstrate feasibility and safety. Secondary outcomes included compliance with medications, smoking cessation, attendance at cardiac rehabilitation, and quality of life, measured in both groups at 6 weeks time. RESULTS: In the intervention group, 74% of patients were discharged within 72 hours, 100% had follow-up with the APN within 3 days (74% in person, 26% by phone), and 100% had >/= 3 APN follow-ups in total, meeting our prespecified criteria for feasibility. The median length of stay was 55 hours in both groups. There were no deaths in either group, and there was no difference in rehospitalization between patients in the intervention and control groups (8% vs 4%, P = .56). There was no difference in rates of medication compliance, smoking cessation, attendance at cardiac rehabilitation, or quality of life between the 2 groups, although our small pilot study was not powered to detect a difference in these outcomes. CONCLUSION: In low-risk STEMI patients treated with primary or rescue PCI, a strategy of early hospital discharge facilitated by close nursing follow-up is feasible. Although our study did not identify differences in compliance or quality of life between the 2 groups, it did provide a functional study design for a larger trial powered to detect these important clinical end points.

Relationship between baseline haemoglobin and major bleeding complications in acute coronary syndromes.

AIMS: In patients with acute coronary syndromes (ACS), the negative impact of baseline haemoglobin levels on ischaemic events, particularly death, is well established, but the association with bleeding risk is less well studied. The aim of this study was to assess the impact of baseline haemoglobin levels on major bleeding complications. METHODS AND RESULTS: Pooled analysis of OASIS 5 and 6 data involving 32 170 patients with ACS with and without ST-segment elevation was performed. The association between baseline haemoglobin and major bleeding or ischaemic events was examined using multiple regression model. MAIN OUTCOME MEASURES: were 30-day rates of major bleeding, death, and death/myocardial infarction (MI) analysed according to baseline haemoglobin levels. Baseline haemoglobin level independently predicted the risk of overall, procedure-related, and non-procedure-related major bleedings at 30 days [odds ratio (OR) 0.94, 95% CI 0.90-0.98; OR 0.94, 95% CI 0.90-0.99; and OR 0.89, 95% CI 0.83-0.95, respectively, per 1 g/dL haemoglobin increment above 10 g/dL]. In addition, a curvilinear relationship between baseline haemoglobin levels and death at 30 days was observed with a 6% decrease in the risk for every 1 g/dL haemoglobin increment above 10 g/dL up to 15.9 g/dL (OR 0.94, 95% CI 0.90-0.98) and a 19% increase above this value (OR 1.19, 95% CI, 0.98-1.43). A similar relationship for the composite outcome of death/MI was observed. CONCLUSION: A low baseline haemoglobin level is an independent predictor of the risk of major bleeding in ACS as well as of the risk of death and death and MI. Among other predictors of bleeding risk, baseline haemoglobin should be taken into account in patients presenting with ACS. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number, NCT00139815. http://clinicaltrials.gov/ct2/show/NCT00139815?term=NCT00139815&rank=1.

Differential clinical outcomes associated with hypoglycemia and hyperglycemia in acute myocardial infarction.

BACKGROUND: In patients with acute myocardial infarction (AMI), hyperglycemia predicts death, but the prognostic significance of hypoglycemia is controversial. METHODS AND RESULTS: We evaluated the prognostic significance of hypoglycemia and hyperglycemia in 30 536 AMI patients in a post hoc analysis of 2 large trials of glucose-insulin-potassium therapy in AMI. Glucose levels on admission and at 6 and 24 hours after admission, as well as 30-day mortality, were documented. In separate multivariable Cox models for admission and postadmission glucose, we compared the prognostic value of hypoglycemia (< or =70 mg/dL) and hyperglycemia (> or =140 mg/dL) with normoglycemia (>70 and <140 mg/dL). Analyses were repeated with hypoglycemia defined as glucose < or =60 mg/dL and in key subgroups based on diabetes or insulin (glucose-insulin-potassium) allocation status. Both high and low percentiles of admission glucose predicted increased 30-day mortality. However, for postadmission glucose, this U-shaped relationship was attenuated so that only high and not low glucose levels remained prognostic. Hyperglycemia (> or =140 mg/dL), both on admission (adjusted hazard ratio 1.43, 95% confidence interval 1.32 to 1.56, P<0.0001) and after admission (adjusted hazard ratio 1.47, 95% confidence interval 1.31 to 1.66, P<0.0001), predicted death compared with normoglycemia. In contrast, hypoglycemia (glucose < or =70 mg/dL) on admission was not prognostic (adjusted hazard ratio 1.16, 95% confidence interval 0.84 to 1.62, P=0.37), nor was postadmission hypoglycemia (adjusted hazard ratio 0.96, 95% confidence interval 0.72 to 1.26, P=0.75). Exploratory analyses that redefined hypoglycemia as glucose < or =60 mg/dL showed consistent results, as did analyses restricted to diabetic patients (18% of the study population). Postadmission hypoglycemia was more common in insulin (glucose-insulin-potassium)-treated patients (6.9%) than in untreated patients (3.4%) but did not predict mortality in either subgroup. CONCLUSIONS: Both admission and postadmission hyperglycemia predict 30-day death in AMI patients. In contrast, only hypoglycemia on admission predicted death, and this relationship dissipated after admission. These data suggest hypoglycemia may not be a direct mediator of adverse outcomes in AMI patients.

Can we improve length of hospitalization in ST elevation myocardial infarction patients treated with primary percutaneous coronary intervention?

BACKGROUND: Patients with ST elevation myocardial infarction have traditionally been hospitalized for five to seven days to monitor for serious complications such as heart failure, arrhythmias, reinfarction and death. The Zwolle primary percutaneous coronary intervention (PCI) index is an externally validated risk score that has been used to identify low-risk primary PCI patients who can safely be discharged from the hospital within 48 h to 72 h. METHODS: The Zwolle score was retrospectively applied to all ST elevation myocardial infarction patients treated with primary PCI between April 2004 and February 2006 at a large Canadian teaching hospital. The goal was to characterize length of stay (LOS) in low-risk patients and to identify variables that correlate with patients who were hospitalized longer than expected. RESULTS: Data were collected on 255 patients. The mean LOS was 7.2+/-7.7 days (median 5.0 days [interquartile range 3.5 days]). A total of 179 patients (70%) had a Zwolle score of 3 or lower, identifying them as low risk. There was one death in the low-risk group (0.6% 30-day mortality) and 15 deaths in the higher-risk group (19.7% 30-day mortality), validating the Zwolle score in the population. A contraindication to early discharge was identified in 34 of the low-risk patients. Among the 144 remaining low-risk patients, the mean LOS was 5.1+/-3.3 days (median 4.0 days [interquartile range 3.0 days]). Only 8% were discharged within 48 h and only 28% within 72 h. It was determined that fewer patients were discharged on weekends and Wednesdays (when medical residents were away for teaching) than on other weekdays. LOS was longer among patients who were discharged on warfarin (7.6 days versus 4.6 days, P=0.006), and among patients who were transferred back to their presenting hospital rather than being discharged directly from the hospital where PCI was performed (5.6 days versus 4.0 days, P<0.001). CONCLUSIONS: Seventy-two per cent of low-risk primary PCI patients were hospitalized longer than 72 h. The following three factors were identified as correlating with prolonged LOS in this population: fewer discharges on days when there was less resident staffing; the use of warfarin at discharge; and transfer of patients back to their presenting hospital rather than discharging them directly from the PCI-performing hospital. A programmed approach to the identification and early discharge of low-risk patients could have significant cost savings and should be investigated prospectively.

Efficacy and safety of fondaparinux versus enoxaparin in patients with acute coronary syndromes treated with glycoprotein IIb/IIIa inhibitors or thienopyridines: results from the OASIS 5 (Fifth Organization to Assess Strategies in Ischemic Syndromes) trial.

OBJECTIVES: This study sought to evaluate the relative safety and efficacy of fondaparinux and enoxaparin in patients with acute coronary syndromes (ACS) treated with glycoprotein (GP) IIb/IIIa inhibitors or thienopyridines. BACKGROUND: The OASIS 5 (Fifth Organization to Assess Strategies in Ischemic Syndromes) trial showed that fondaparinux reduced major bleeding by 50% compared with enoxaparin while preserving similar efficacy. Whether this benefit is consistent in the presence or absence of concurrent antiplatelet therapy with clopidogrel and GP IIb/IIIa inhibitors is unknown. METHODS: Patients with ACS (n = 20,078) were randomized as a part of the OASIS 5 trial to receive either fondaparinux or enoxaparin. The use of GP IIb/IIIa inhibitors or thienopyridines was at the discretion of the treating physician. A Cox proportional hazard model was used to compare outcomes. RESULTS: Of the 20,078 patients randomized, 3,630 patients received GP IIb/IIIa and 13,531 received thienopyridines. There was a 40% reduction in major bleeding with fondaparinux compared with enoxaparin in those treated with GP IIb/IIIa (5.2% vs. 8.3%, hazard ratio [HR]: 0.61, p < 0.001). A similar reduction was found in those treated with thienopyridines (3.4% vs. 5.4%, HR: 0.62, p < 0.001). Ischemic events were similar between the groups, resulting in a superior net clinical outcome (death, myocardial infarction, refractory ischemia, or major bleeding) favoring fondaparinux (GP IIb/IIIa subgroup 14.8% vs. 18.9%, HR: 0.77, p = 0.001 and thienopyridines subgroup 11.0% vs. 13.2%, HR: 0.82, p < 0.001). CONCLUSIONS: In patients receiving GP IIb/IIIa inhibitors or thienopyridines, fondaparinux reduces major bleeding and improves net clinical outcome compared with enoxaparin.