Reperfusion in Patients With Renal Dysfunction After Presentation With ST-Segment Elevation or Left Bundle Branch Block: GRACE (Global Registry of Acute Coronary Events) Caroline Medi, Gilles ...Montalescot, Andrzej Budaj, Keith A. A. Fox, José López-Sendón, Gordon FitzGerald, David B. Brieger, on behalf of the GRACE Investigators The relative benefit of reperfusion was assessed in 12,532 patients with renal dysfunction and ST-segment elevation/left bundle branch block. As renal function declined, hospital mortality and morbidity increased (both p < 0.001) and reperfusion rates decreased. Fibrinolysis was not associated with reduced hospital or 6-month mortality in patients with renal dysfunction. Primary percutaneous coronary intervention was not associated with lower hospital mortality in patients with renal dysfunction but was associated with lower 6-month mortality in those with moderate dysfunction. Both strategies of reperfusion were associated with higher mortality for severe dysfunction.
Summary Background Angiotensin receptor blockers (ARB) and angiotensin converting enzyme (ACE) inhibitors are known to reduce proteinuria. Their combination might be more effective than either ...treatment alone, but long-term data for comparative changes in renal function are not available. We investigated the renal effects of ramipril (an ACE inhibitor), telmisartan (an ARB), and their combination in patients aged 55 years or older with established atherosclerotic vascular disease or with diabetes with end-organ damage. Methods The trial ran from 2001 to 2007. After a 3-week run-in period, 25 620 participants were randomly assigned to ramipril 10 mg a day (n=8576), telmisartan 80 mg a day (n=8542), or to a combination of both drugs (n=8502; median follow-up was 56 months), and renal function and proteinuria were measured. The primary renal outcome was a composite of dialysis, doubling of serum creatinine, and death. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov , number NCT00153101. Findings 784 patients permanently discontinued randomised therapy during the trial because of hypotensive symptoms (406 on combination therapy, 149 on ramipril, and 229 on telmisartan). The number of events for the composite primary outcome was similar for telmisartan (n=1147 13·4%) and ramipril (1150 13·5%; hazard ratio HR 1·00, 95% CI 0·92–1·09), but was increased with combination therapy (1233 14.5%; HR 1·09, 1·01–1·18, p=0·037). The secondary renal outcome, dialysis or doubling of serum creatinine, was similar with telmisartan (189 2·21%) and ramipril (174 2·03%; HR 1·09, 0·89–1·34) and more frequent with combination therapy (212 2·49%: HR 1·24, 1·01–1·51, p=0·038). Estimated glomerular filtration rate (eGFR) declined least with ramipril compared with telmisartan (−2·82 SD 17·2 mL/min/1·73 m2 vs −4·12 17·4, p<0·0001) or combination therapy (−6·11 17·9, p<0·0001). The increase in urinary albumin excretion was less with telmisartan (p=0·004) or with combination therapy (p=0·001) than with ramipril. Interpretation In people at high vascular risk, telmisartan's effects on major renal outcomes are similar to ramipril. Although combination therapy reduces proteinuria to a greater extent than monotherapy, overall it worsens major renal outcomes. Funding Boehringer-Ingelheim.
This aim of this study was to assess the clinical utility of quantitative ST-segment depression (STD) for refining the risk stratification of non–ST elevation acute coronary syndromes in the ...prospective, multinational Global Registry of Acute Coronary Events (GRACE). Quantitative measurements of STD on admission electrocardiograms were evaluated independently by a core laboratory, and their predictive value for in-hospital and cumulative 6-month mortality was examined. Although more severe STD is a marker of increased short- and long-term mortality, it is also associated with higher risk clinical features and biomarkers. Thus, after adjustment for these clinically important predictors, quantitative STD does not provide incremental prognostic value beyond simple dichotomous evaluation for the presence of STD. Furthermore, adopting quantitative instead of the prognostically proven qualitative evaluation of STD does not improve risk discrimination afforded by the validated GRACE risk models. In conclusion, the findings do not support the quantification of STD in routine clinical practice beyond simple evaluation for the presence of STD as an integral part of comprehensive risk stratification using the GRACE risk score.
Efficacy and Safety of Fondaparinux Versus Enoxaparin in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention: Results From the OASIS-5 Trial Shamir R. Mehta, ...Christopher B. Granger, John W. Eikelboom, Jean-Pierre Bassand, Lars Wallentin, David P. Faxon, Ron J. G. Peters, Andrzej Budaj, Rizwan Afzal, Susan Chrolavicius, Keith A. A. Fox, Salim Yusuf We report a prospectively planned analysis of 6,238 patients with acute coronary syndrome who underwent early percutaneous coronary intervention in the OASIS-5 (Fifth Organization to Assess Strategies in Ischemic Syndromes) randomized trial. Fondaparinux compared with enoxaparin reduced major bleeding by more than 50% (2.4% vs. 5.1%, hazard ratio HR 0.46, p < 0.00001), with similar rates of ischemic events, resulting in superior net clinical benefit (death, myocardial infarction, stroke, major bleeding: 8.2% vs. 10.4%, HR 0.78, p = 0.004). Catheter thrombus occurred in <1% in both groups, but was prevented by use of standard unfractionated heparin at the time of percutaneous coronary intervention without compromising the benefits of upstream fondaparinux.
Background The OASIS-5 (Organization to Assess Strategies in Ischemic Syndromes-5) trial demonstrated that fondaparinux was noninferior to enoxaparin while reducing the risk of bleeding by 50%. The ...objectives of our study were to assess the effects of fondaparinux compared to enoxaparin in patients stratified by their Global Registry of Acute Coronary Events (GRACE) score and to examine the ability of the GRACE score to predict bleeding in patients with acute coronary syndromes (ACS). Methods We analyzed efficacy and safety according to the GRACE admission risk score. Results The impact of fondaparinux versus enoxaparin on the primary outcome of death, myocardial infarction, and refractory ischemia at 180 days was similar in the low-, intermediate-, and high-risk groups: 7.0% versus 7.7% (hazard ratio HR 0.90, 95% confidence interval CI 0.75-1.08), 10.2% versus 11.3% (HR 0.89, 95% CI 0.77-1.03), and 20.1% versus 21.1% (HR 0.95, 95% CI 0.85-1.06). Major bleeding rates were higher with increasing GRACE risk scores: 2.2%, 3.2%, and 4.1% in the low, intermediate, and high-risk groups. Six-month mortality was 2.2%, 4.2%, and 12.3% in the 3 groups. The risk of major bleeding was substantially lower with fondaparinux in all groups: 1.6% versus 2.9% (HR 0.55, 95% CI 0.39-0.77), 2.2% versus 4.1% (HR 0.53, 95% CI 0.40-0.70), 2.8% versus 5.5% (HR 0.50, 95% CI 0.38-0.64). Conclusion The GRACE score predicted both bleeding and mortality in patients with ACS. The efficacy and safety of fondaparinux were consistent in all risk groups supporting its use in a broad range of ACS patients.
Background Current guidelines advise the use of risk stratification to determine which patients should receive more aggressive antithrombotic and invasive therapies. Our objective was to evaluate the ...relationship between risk stratification and therapeutic decision making in patients with non–ST-segment elevation acute coronary syndromes. Methods We analyzed data from 15 026 patients with acute coronary syndrome who were enrolled into the GRACE registry between 1999 and 2003. We assessed the evidence-based use of antithrombotic therapy and early invasive strategy according to risk profile defined by baseline troponin elevation, presenting ST-segment depression, and GRACE risk score. Patients with possible contraindications were removed to define the use of therapies specifically among clearly eligible patients. Results Patients with elevated troponin were more likely to receive enoxaparin (60% vs 50.4%, respectively), GP IIb/IIIa inhibitors (32.8% vs 17.6%), and to undergo catheterization (66% vs 54%) and percutaneous coronary intervention (37.4% vs 25.6%; all P < .0001). Patients with ST depression received modestly more enoxaparin and GP IIb/IIIa than those without ST depression, but not more catheterization ( P = .8) or percutaneous coronary intervention ( P = .09). Highest risk patients were somewhat less likely to receive enoxaparin ( P < .0001) and cardiac catheterization ( P = .0002) according to GRACE risk deciles. Conclusions In spite of current guidelines recommending the use of selected therapies in high-risk patients, there is no clear correlation of use of effective therapies with overall risk profile even among eligible patients. Thus, there is substantial opportunity to improve use of effective therapies, especially in high-risk populations.
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