Coronary Heart Disease

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1 Coronary Heart Disease Influence of Renal Function on the Effects of Early Revascularization in Non ST-Elevation Myocardial Infarction Data From the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) Karolina Szummer, MD; Pia Lundman, MD, PhD; Stefan H. Jacobson, MD, PhD; Staffan Schön, MD; Johan Lindbäck, MSc; Ulf Stenestrand, MD, PhD; Lars Wallentin, MD, PhD; Tomas Jernberg, MD, PhD; for SWEDEHEART Background It is unknown whether patients with non ST-elevation myocardial infarction derive a similar benefit from an early invasive therapy at different levels of renal function. Methods and Results A total of consecutive non ST-elevation myocardial infarction patients 80 years old were included in a nationwide coronary care unit register between 2003 and Glomerular filtration rate (egfr) was estimated with the Modification of Diet in Renal Disease Study formula. Patients were divided into medically or invasively treated groups if revascularized within 14 days of admission. A propensity score for the likelihood of invasive therapy was calculated. A Cox regression model with adjustment for propensity score and discharge medication was used to assess the association between early revascularization and 1-year mortality across renal function stages. There was a gradient, with significantly fewer patients treated invasively with declining renal function: egfr 90 ml min m 2, 62%; egfr 60 to 89 ml min m 2, 55%; egfr 30 to 59 ml min m 2, 36%; egfr 15 to 29 ml min m 2, 14%; and egfr 15 ml min m 2 /dialysis, 15% (P 0.001). After adjustment, the overall 1-year mortality was 36% lower (hazard ratio 0.64, 95% confidence interval 0.56 to 0.73, P 0.001) with an invasive strategy. The magnitude of survival difference was similar in normal-to-moderate renal function groups. The lower mortality observed with invasive therapy declined with lower renal function, with no difference in mortality in patients with kidney failure (egfr 15 ml min m 2 ) or in those receiving dialysis (hazard ratio 1.61, 95% confidence interval 0.84 to 3.09, P 0.15). Conclusions Early invasive therapy is associated with greater 1-year survival in patients with non ST-elevation myocardial infarction and mild-to-moderate renal insufficiency, but the benefit declines with lower renal function, and is less certain in those with renal failure or on dialysis. (Circulation. 2009;120: ) Key Words: kidney revascularization myocardial infarction prognosis Both the American College of Cardiology/American Heart Association and European Society of Cardiology 2007 guidelines recommend early revascularization for high-risk patients with non ST-elevation myocardial infarction (NSTEMI). 1,2 Patients with renal insufficiency and myocardial infarction (MI) have poor prognosis. 3 5 The risk of adverse events increases with mild renal insufficiency 6,7 and is extremely high in patients on dialysis, of whom only 41% will be alive 1 year after an MI. 8 Therefore, patients with chronic kidney disease and NSTEMI are part of a group in whom an invasive strategy may be reasonable. 1 The evidence supporting this treatment is based on clinical studies that often used renal insufficiency as an exclusion criterion. The benefit of early revascularization has not been examined in patients with different degrees of renal insufficiency, and it is unknown whether this approach alters the outcome. The Continuing medical education (CME) credit is available for this article. Go to to take the quiz. Received November 24, 2008; accepted June 15, From the Department of Medicine (K.S., T.J.), Section of Cardiology, Huddinge, Karolinska Institute, Karolinska University Hospital, Stockholm; Division of Cardiovascular Medicine (P.L.), Division of Nephrology (S.H.J.), Department of Clinical Sciences, Karolinska Institute, Danderyd Hospital; Department of Internal Medicine (S.S.), Ryhov County Hospital, Jönköping; Uppsala Clinical Research Centre (J.L., L.W.), University Hospital, Uppsala; and Department of Cardiology (U.S.), University Hospital, Linköping; all in Sweden. The online-only Data Supplement is available with this article at /DC1. Correspondence to Karolina Szummer, Department of Cardiology, Karolinska University Hospital, Huddinge, Institution of Medicine (H7), Huddinge, Karolinska Institutet, Stockholm, Sweden. karolina.szummer@karolinska.se 2009 American Heart Association, Inc. Circulation is available at DOI: /CIRCULATIONAHA

2 852 Circulation September 8, 2009 Figure 1. Patient selection. aim of the present study, which included a cohort of nearly all consecutive patients with NSTEMI in Sweden between 2003 and 2006, was to describe the distribution of chronic kidney disease and the use of early revascularization, as well as to assess whether an invasive approach is associated with lower mortality at every level of renal function. Editorial see p 828 Clinical Perspective on p 858 Methods Patient Population Patients with NSTEMI admitted to a coronary care unit between 2003 and 2006 were recorded in the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDE- HEART), previously known as the Register of Information and Knowledge about Swedish Heart Intensive care Admission (RIKS- HIA). The analyses are based on NSTEMI patients with available creatinine measurements and age 80 years (Figure 1). Medically treated patients were compared with patients who were revascularized by either a percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG) within the first 14 days of admission. Patients who had coronary angiography but did not have PCI or CABG within 14 days of admission were considered medically treated. All-cause mortality was assessed at 1 year and was available in 99.4% of patients. Glomerular filtration rate (egfr) was estimated with the Modification of Diet in Renal Disease Study formula, 9 which is calculated with creatinine, age, gender, and race. Everyone was assumed to be of white race. The National Kidney Foundation Kidney Disease Outcomes Quality Initiative definition was used for renal function staging 10 : egfr 90 (normal), 60 to 90 (mild), 30 to 59 (moderate), 15 to 29 (severe), and 15 ml min m 2 (renal failure) or receiving dialysis. Physicians were instructed to enter the most relevant in-hospital creatinine measurement that best reflected the patient s underlying renal function. In 2006, SWEDEHEART/RIKS-HIA registered all patients admitted to a coronary care unit at 71 of 74 hospitals admitting patients with acute coronary syndrome in Sweden. Information in SWEDEHEART/RIKS-HIA is collected prospectively for more than 100 variables (see for details) and includes baseline characteristics, ECG changes, biochemical markers, inhospital course, interventions, and discharge medications. NSTEMI was diagnosed with current guidelines. 11 An acute MI was diagnosed if troponin T or troponin I levels or 2 successive creatine kinase MB values were above the 99th percentile for the reference population within 24 hours of the index clinical event or if the creatine kinase MB value was twice the decision limit. Patients were treated as deemed appropriate by the local physician. To ensure the correctness of the data entered into the database, a monitor visits 20 hospitals each year and compares data entered into the register with the information in the patients records in 30 to 40 randomly chosen patients for each hospital. When 586 randomly chosen computer forms containing variables were reviewed in 2006, there was 96.5% agreement ( Data on prior stroke, dementia, congestive heart failure, chronic obstructive pulmonary disease, and cancer were obtained from the National Patient Registry, which collects all discharge diagnosis for patients admitted to a hospital in Sweden. The Swedish Renal Registry provided information on dialysis therapy. All-cause mortality data were obtained from the National Death Registry, which includes information about vital status of all Swedish citizens. All patients were informed about their participation in the registry and the follow-up and had the right to refuse participation. The registry and the merging of registries were approved by the National Board of Health and Welfare, the Swedish Data Inspection Board, and the local ethics committee at Uppsala University. Statistical Analysis Continuous baseline characteristics are reported as means with SDs. Categorical variables were analyzed with 2 test and continuous variables with the Kruskal-Wallis test. A propensity score 12 was created to express the likelihood for revascularization during the first 14 days of admission given the baseline characteristics, medications, and received treatments. A logistic regression model was used to develop the propensity score and included the following 31 clinical characteristics/medications and hospital type: Age (as a second-degree polynomial), gender, diabetes mellitus, hypertension, prior MI, heart failure, PCI, CABG, stroke, chronic obstructive pulmonary disease, dementia, peripheral vascular disease, cancer diagnosis within the last 3 years, medications on admission (aspirin/thienopyridines, warfarin, -blocker, angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker, lipid-lowering drug, diuretic, long-acting nitrate, digoxin, and calcium channel blocker), intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin, in-hospital intravenous therapy ( -blocker, nitrate, inotrope, or diuretic), signs of congestive heart failure during hospital stay (Killip class 1 or use of intravenous diuretic or continuous positive airway pressure), year admitted to hospital, university hospital status, and availability of PCI at admitting hospital. A Cox proportional hazards model was used to assess the adjusted association between revascularization strategy and mortality. In addition to revascularization, propensity score, in-hospital glycoprotein IIb/IIIa receptor inhibitor use, and 10 discharge medications (aspirin/thienopyridines, warfarin, -blocker, calcium channel blocker, angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker, digoxin, diuretic, long-acting nitrate, lipidlowering medication, and antidiabetic medication) were included as covariates in the model. Complete information, including outcome data, in these analyses was available for patients. Analyses were stratified for the 5 renal function groups. To reduce the bias caused by the fact that patients who died early were included in the medically treated group, revascularization status was entered as a time-dependent covariate. Patients who were not yet revascularized provided an event-free time for the medically treated group. The interaction between revascularization as a time-dependent covariate and renal function stage was determined in this model, as was the interaction between gender and revascularization as a timedependent covariate. An additional analysis to evaluate the interaction between renal function class and revascularization in men and women separately was also performed. A separate Cox proportional hazards model was used to assess outcome for 14-day survivors (n ).

3 Szummer et al Renal Function and Revascularization in NSTEMI 853 Table 1. Characteristics and Therapies in Different Treatment Groups Medical Therapy (n 6585) To exclude the possible bias caused by missing values (n 1416; 6.1%), a sensitivity analysis was performed. In this analysis, a new propensity score was calculated in which the independent dichotomous variables were coded as no, yes, or missing. The association between treatment strategy and outcome was then adjusted by this new propensity score and medications at discharge. To assess the influence of missing creatinine values on the overall results, a propensity score that included all patients with missing laboratory values was calculated, and outcome was assessed in a Cox regression model. An additional analysis not limited by patient age was performed. All patients who had creatinine measured (n ) were included to assess the influence of revascularization on mortality regardless of age. A new propensity score for early revascularization that included all of these patients was calculated. The propensity score was then included in the Cox proportional hazards model together with revascularization as a time-dependent covariate to assess the effect on mortality across renal function stages. All analyses were performed with SPSS version 15 (SPSS Inc, Chicago, Ill). The authors had full access to and take full responsibility for the integrity of the data. All authors have read and agree to the manuscript as written. Only Coronary Angiography (n 4647) PCI Within 14 Days (n 10084) CABG Within 14 Days (n 1946) P Age, y Male Known diabetes mellitus Hypertension Current smoker Known COPD Prior MI Prior PCI Prior CABG Prior CHF Prior PVD Prior stroke Known dementia Cancer diagnosis within last 3 y Killip class 1 on admission Medication on admission Aspirin/thienopyridines Warfarin Blocker Calcium antagonist Digoxin ACE/ARB inhibitor Diuretic Lipid-lowering therapy Days to procedure, mean SD COPD indicates chronic obstructive pulmonary disease; CHF, congestive heart failure; PVD, peripheral vascular disease; ACE: angiotensin-converting enzyme; and ARB, angiotensin II receptor blocker. Values are mean SD or percentages. Results Baseline characteristics differed for patients who were treated medically and for those who were revascularized (Table 1). Medically treated patients were older and had more comorbidities, such as prior MI, diabetes mellitus, and heart failure. When baseline characteristics were adjusted for the propensity to be treated with revascularization, no major differences remained between the 2 groups (online-only Data Supplement Table I). Moderate or more advanced renal insufficiency (egfr 60 ml min m 2 ) was present in 5689 patients (24.4%). Of 278 patients with egfr 15 ml min m 2 /dialysis, 125 (45.0%) had been on dialysis for a median of 26 months (interquartile range 12 to 48 months) at the time of admission. The majority (105 patients) had hemodialysis. Patients with renal insufficiency differed significantly with more frequent concomitant diseases across the renal function groups (Table 2). Those with lower egfr were less likely to undergo coronary angiography and to be revascularized within 14 days of admission (P 0.001; Figure 2A). In patients who underwent coronary angiography, declining renal function was associated with more severe coronary artery disease (Figure 2B). Compared with those who were revascularized, patients who only underwent coronary angiography not followed by an intervention had less extensive coronary artery disease. A total of 2321 (20.7%) of the medically treated patients were revascularized between 15 and 365 days after MI.

4 854 Circulation September 8, 2009 Table 2. Baseline Characteristics and Medication on Admission egfr, ml min m 2 Total (n ) 90 (n 6064) (n ) (n 4839) (n 572) 15/ Dialysis (n 278) P Age, y Male Known diabetes mellitus Hypertension Current smoker Known COPD Prior MI Prior PCI Prior CABG Prior CHF Prior PVD Prior stroke Known dementia Cancer diagnosis within last 3 y Killip class 1 on admission Medication on admission Aspirin/thienopyridines Warfarin Blocker Calcium antagonist Digoxin ACE/ARB inhibitor Diuretic Lipid-lowering therapy Days to procedure Only coronary angiography (n) (4261) (1130) (2218) (834) (56) (23) PCI (n) (10084) (3217) (5349) (1415) (69) (34) CABG (n) (1945) (574) (1039) (316) (10) (7) COPD indicates chronic obstructive pulmonary disease; PVD, peripheral vascular disease; CHF, congestive heart failure; ACE, angiotensin-converting enzyme; and ARB, angiotensin II receptor blocker. Values are mean SD or percentages. Overall, 90.3% patients (n ) survived 1 year. Mortality was higher with lower renal function stage (Figure 3). During the first 14 days, there were 619 deaths (5.5%) in the medically treated group and 244 (2.0%) in the group treated with revascularization. In a multivariable Cox regression model with adjustment for propensity score and discharge medication, patients treated with early revascularization had an overall improved survival at 1 year (hazard ratio 0.64, 95% confidence interval 0.56 to 0.73, P 0.001). The magnitude of the difference in mortality was similar in groups with normalto-moderate renal function (Figure 4). There was a gradient toward less of a mortality difference with early revascularization with decreasing renal function, which was most pronounced in those with kidney failure (egfr 15 ml min m 2 ) or who were receiving dialysis. In these patients, there was a trend toward harm with invasive therapy. There was a significant interaction between revascularization and renal function group (P 0.001). There was no interaction between gender and revascularization (P 0.19). Both for men (P 0.001) and for women (P 0.011), there was a significant interaction between renal function and revascularization. To assess the effect of early revascularization without the possible bias of treatment group assignment within the first 14 days, 1-year mortality for 14-day survivors was analyzed. A similarly lower mortality in patients who had undergone early revascularization was seen in those with normal-tomoderate renal dysfunction, less of a mortality difference in those with severe renal insufficiency, and no apparent advantage in those with renal failure or receiving dialysis (onlineonly Data Supplement Figure I). In a sensitivity analysis that also included patients with a missing covariate (n 1416), the point estimate overall (hazard ratio 0.65, 95% confidence interval 0.57 to 0.74, P 0.001) and the stratified analysis were similar to the results obtained with missing covariates (online-only Data Supplement Figure II). When patients with

5 Szummer et al Renal Function and Revascularization in NSTEMI 855 Figure 2. A, Type of revascularization across renal function groups. B, Extent of coronary vascular disease in patients who underwent coronary angiography or revascularization. missing serum creatinine values were included (n ) in a Cox regression analysis, the overall point estimate was similar (hazard ratio 0.64, 95% confidence interval 0.57 to 0.72, P 0.001). When all patients with available creatinine values regardless of age (n ) were included, the point estimates across the renal function stages were comparable to the estimates obtained when the results were limited to Figure 3. Kaplan Meier curve for 1-year survival according to renal function stage (pooled log-rank P 0.001). patients 80 years of age (online-only Data Supplement Figure III). Discussion Approximately 25% to 30% of all patients with NSTEMI have at least moderately reduced renal function, 4,7 but despite the size of this population, evidence-based data supporting recommended therapies such as early revascularization for this patient group are missing. 13 The main finding of the present registry study in a recent, nearly complete, nationwide cohort of NSTEMI patients is that a lower mortality associated with early revascularization is not uniform across the 5 renal function stages. Early revascularization improves 1-year survival in patients with NSTEMI and mild-tomoderate renal insufficiency, but the observed difference in mortality declines with lower renal function, and there is a trend toward harm in those with end-stage renal disease or on dialysis. Randomized clinical trials have shown that early revascularization after NSTEMI reduces mortality by 22% to 32%. 14,15 In high-risk individuals in the VINO study (Value of first-day angiography/angioplasty In evolving NOn-ST segment elevation myocardial infarction), 16 mortality was reduced at 6 months, whereas reductions in mortality were shown at 2 years in FRISC (FRagmin during InStability in Coronary artery disease) II 15 and at 5 years in RITA (Randomized Intervention Trial of unstable Angina) The overall 1-year survival difference with early revascularization

6 856 Circulation September 8, 2009 Figure 4. Estimated hazard ratio for mortality at 1 year for patients treated either medically or with early revascularization(1416 had missing covariate). HR indicates hazard ratio. in the present registry was 36% lower, which is comparable to the results obtained in randomized trials. 14,15 A larger difference in mortality (between 47% and 53%) with early revascularization has been shown in other observational studies. 17,18 The smaller difference in mortality with early revascularization seen in the present study compared with those studies, in which 14- and 30-day survivors were analyzed, is explained by the inclusion of all patients from the first day of admission and the use of revascularization as a time-dependent variable during the first 14 days. The present patient population differs from patients enrolled in clinical trials in several ways. Clinical trials may underestimate the advantage with early revascularization, because between 9% and 40% of patients in the noninvasively treated arm are actually revascularized, which diminishes the observed effect. 16,19 Registries evaluating early revascularization better capture less selected patients with more comorbidities, although they are limited by their nonrandomized nature and a tendency to select healthier patients for intervention. 20,21 In addition, randomized trials evaluate an invasive compared with a noninvasive approach, whereas the present registry analyzed the effect of revascularization. Patients who underwent a coronary angiography not followed by an intervention within 14 days of admission ( 20%) were analyzed in the medical group. In a randomized trial, these patients would have been distributed evenly between the invasively and noninvasively treated patients. Because these patients had less extensive coronary artery disease and a better prognosis, the overall outcome for the medical group was improved. Few trials have examined the effect of an early invasive therapy in patients with mild-to-moderate renal insufficiency and NSTEMI. Although the TACTICS-TIMI 18 trial (Treat Angina with aggrastat and determine Cost of Therapy with Invasive or Conservative Strategy Thrombolysis In Myocardial Infarction 18) 22 excluded patients with a creatinine level 221 mol/l, it found a similar reduction in recurrent MI/death at 6 months in those with mild-to-moderate renal insufficiency and those with normal renal function. 23 In FRISC II, 24 which excluded patients with creatinine 150 mol/l, the absolute reduction in death/mi was larger in those with creatinine clearance 69 ml/min than in those with creatinine clearance 90 ml/min (7.8% versus 0.4%). 25 The results from the present registry support the data that patients with mild-to-moderate renal insufficiency appear to have lower mortality when managed with early revascularization. Fewer patients with moderate than with mild renal insufficiency were revascularized (38% versus 55%, respectively). This underuse of revascularization in patients with moderate renal insufficiency may be explained by awareness of the higher risk of complications. 26,27 The explanation for the lack of survival difference in more advanced renal insufficiency patients is only speculative. These patients probably have more advanced atherosclerosis that is not easily treated with revascularization. 28 Atherosclerosis is caused in part by other mechanisms in patients with severe renal insufficiency. Hyperphosphatemia has been related to atherosclerosis, arterial stiffening, and calcification and may be directly related to mortality. 29,30 Patients with renal insufficiency may have comorbidities that increase their risk, both cardiac (such as more advanced heart failure or arrhythmias) and noncardiac, that are unaffected by treatment choices. As renal function worsens, the frequency of noncardiac adverse events, such as stroke and bleeding, increases in patients with acute coronary syndromes, 4,7 which may ultimately explain their worse prognosis and lack of difference in mortality with revascularization in particular. There are some limitations to the present study. This is a registry study, and therapies were not assigned randomly, which could lead to possible selection bias despite adjustments that were made in the statistical models. Patients who were revascularized within the first 14 days may have been healthier than the patients who were treated medically, which may have led to an overestimation of the potential benefit of intervention. To reduce the bias that either therapeutic strategy could have been associated with a survival benefit or increased mortality, we performed an analysis of 14-day survivors. Although patients who were revascularized early may have had a survival advantage because they lived at least until the intervention, the procedure may have been attempted as a last resort. In comparison, patients in the medical group may not have had the chance to benefit from an intervention.

7 Szummer et al Renal Function and Revascularization in NSTEMI 857 No information regarding whether a procedure was urgent, semiurgent, or more elective was collected in the present register; however, there was no major difference in the results obtained if only 14-day survivors were included. The cut point for revascularization within 14 days was arbitrary; however, any cut point would be arbitrary, and the main results were similar for revascularization within 30 days of index hospitalization (data not shown). It is also possible that the apparent benefit attributed to early revascularization may have been achieved by the use of adjunctive therapies, such as more intense antithrombotic medication. Although we adjusted for all known confounders and entered revascularization as a time-dependent variable, residual bias may remain. The estimated propensity score is only an approximation of the true, unknown treatment assignment. The number of events and the number of patients in the 2 lowest stages of renal function were much smaller than for the other groups. There was a larger uncertainty in the estimates obtained from the models; the power was therefore limited in the present study, and only moderately large differences in mortality between therapies in the 2 lowest renal function groups could have been detected. In the present registry, creatinine measurement was entered by the treating physician. Although physicians were instructed to report the in-hospital measurement that best represented the baseline creatinine value for each individual, the number of measurements obtained may have varied between hospitals, and some patients may only have had a single measurement of creatinine. In the present study, we used the Modification of Diet in Renal Disease Study formula to estimate GFR, but it is unlikely that our results would have differed significantly if a different estimation of GFR had been used. We limited the analysis to patients 80 years old or younger, because in clinical practice, older patients are less frequently considered candidates for an invasive strategy. The decision to revascularize in these patients is often based on characteristics such as cognitive function, more advanced comorbidities, and more unstable in-hospital symptoms that are not captured by a register and for which adjustment therefore cannot be made. In the present registry, only 12% of those older than 80 years were revascularized compared with 52% of those 80 years or younger; however, when all patients regardless of age were included in the analyses, the results were comparable. In conclusion, patients with mild-to-moderate renal function have an associated lower mortality when managed with early revascularization but are less likely to be treated, which may explain part of their worse prognosis. Patients with severe or more advanced renal insufficiency have a remarkably poor prognosis that does not appear to be improved by the use of an invasive therapy. The benefit of early revascularization in those with severe renal insufficiency appears to be lower, and even less certain in those with renal failure or on dialysis. Sources of Funding The SWEDEHEART register is supported by the Swedish National Board of Health and Welfare, the Swedish Association of Local Authorities, and the Swedish Society of Cardiology. This study was supported by grants from the Swedish Heart and Lung Foundation and the National Board of Health and Welfare. None. Disclosures References 1. Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr, Chavey WE II, Fesmire FM, Hochman JS, Levin TN, Lincoff AM, Peterson ED, Theroux P, Wenger NK, Wright RS, Smith SC Jr, Jacobs AK, Halperin JL, Hunt SA, Krumholz HM, Kushner FG, Lytle BW, Nishimura R, Ornato JP, Page RL, Riegel B. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non ST-elevation myocardial infarction: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction): developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons: endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. Circulation. 2007; 116:e148 e Bassand JP, Hamm CW, Ardissino D, Boersma E, Budaj A, Fernandez- Aviles F, Fox KA, Hasdai D, Ohman EM, Wallentin L, Wijns W. Guidelines for the diagnosis and treatment of non-st-segment elevation acute coronary syndromes. Eur Heart J. 2007;28: McCullough PA, Soman SS, Shah SS, Smith ST, Marks KR, Yee J, Borzak S. Risks associated with renal dysfunction in patients in the coronary care unit. J Am Coll Cardiol. 2000;36: Santopinto JJ, Fox KA, Goldberg RJ, Budaj A, Pinero G, Avezum A, Gulba D, Esteban J, Gore JM, Johnson J, Gurfinkel EP. Creatinine clearance and adverse hospital outcomes in patients with acute coronary syndromes: findings from the global registry of acute coronary events (GRACE). Heart. 2003;89: Jernberg T, Lindahl B, James S, Larsson A, Hansson LO, Wallentin L. Cystatin C: a novel predictor of outcome in suspected or confirmed non-st-elevation acute coronary syndrome. Circulation. 2004;110: Gibson CM, Pinto DS, Murphy SA, Morrow DA, Hobbach HP, Wiviott SD, Giugliano RP, Cannon CP, Antman EM, Braunwald E. Association of creatinine and creatinine clearance on presentation in acute myocardial infarction with subsequent mortality. J Am Coll Cardiol. 2003;42: Anavekar NS, McMurray JJ, Velazquez EJ, Solomon SD, Kober L, Rouleau JL, White HD, Nordlander R, Maggioni A, Dickstein K, Zelenkofske S, Leimberger JD, Califf RM, Pfeffer MA. Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction. N Engl J Med. 2004;351: Herzog CA, Ma JZ, Collins AJ. Poor long-term survival after acute myocardial infarction among patients on long-term dialysis. N Engl J Med. 1998;339: Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D; Modification of Diet in Renal Disease Study Group. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med. 1999;130: K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39: S1 S Myocardial infarction redefined: a consensus document of the Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. Eur Heart J. 2000; 21: Joffe MM, Rosenbaum PR. Invited commentary: propensity scores. Am J Epidemiol. 1999;150: Coca SG, Krumholz HM, Garg AX, Parikh CR. Underrepresentation of renal disease in randomized controlled trials of cardiovascular disease. JAMA. 2006;296: Fox KA, Poole-Wilson P, Clayton TC, Henderson RA, Shaw TR, Wheatley DJ, Knight R, Pocock SJ. 5-Year outcome of an interventional strategy in non-st-elevation acute coronary syndrome: the British Heart Foundation RITA 3 randomised trial. Lancet. 2005;366:

8 858 Circulation September 8, Lagerqvist B, Husted S, Kontny F, Naslund U, Stahle E, Swahn E, Wallentin L. A long-term perspective on the protective effects of an early invasive strategy in unstable coronary artery disease: two-year follow-up of the FRISC-II invasive study. J Am Coll Cardiol. 2002;40: Spacek R, Widimsky P, Straka Z, Jiresova E, Dvorak J, Polasek R, Karel I, Jirmar R, Lisa L, Budesinsky T, Malek F, Stanka P. Value of first day angiography/angioplasty in evolving non-st segment elevation myocardial infarction: an open multicenter randomized trial: the VINO Study. Eur Heart J. 2002;23: Ottervanger JP, Armstrong P, Barnathan ES, Boersma E, Cooper JS, Ohman EM, James S, Wallentin L, Simoons ML. Association of revascularisation with low mortality in non-st elevation acute coronary syndrome, a report from GUSTO IV-ACS. Eur Heart J. 2004;25: Stenestrand U, Wallentin L. Early revascularisation and 1-year survival in 14-day survivors of acute myocardial infarction: a prospective cohort study. Lancet. 2002;359: Wallentin L, Lagerqvist B, Husted S, Kontny F, Stahle E, Swahn E. Outcome at 1 year after an invasive compared with a non-invasive strategy in unstable coronary-artery disease: the FRISC II invasive randomised trial: FRISC II Investigators: Fast Revascularisation during Instability in Coronary artery disease. Lancet. 2000;356: Bhatt DL, Roe MT, Peterson ED, Li Y, Chen AY, Harrington RA, Greenbaum AB, Berger PB, Cannon CP, Cohen DJ, Gibson CM, Saucedo JF, Kleiman NS, Hochman JS, Boden WE, Brindis RG, Peacock WF, Smith SC Jr, Pollack CV Jr, Gibler WB, Ohman EM. Utilization of early invasive management strategies for high-risk patients with non-stsegment elevation acute coronary syndromes: results from the CRUSADE Quality Improvement Initiative. JAMA. 2004;292: Fox KA, Anderson FA Jr, Dabbous OH, Steg PG, Lopez-Sendon J, Van de Werf F, Budaj A, Gurfinkel EP, Goodman SG, Brieger D. Intervention in acute coronary syndromes: do patients undergo intervention on the basis of their risk characteristics? The Global Registry of Acute Coronary Events (GRACE). Heart. 2007;93: Cannon CP, Weintraub WS, Demopoulos LA, Vicari R, Frey MJ, Lakkis N, Neumann FJ, Robertson DH, DeLucca PT, DiBattiste PM, Gibson CM, Braunwald E. Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban. N Engl J Med. 2001;344: Januzzi JL, Cannon CP, DiBattiste PM, Murphy S, Weintraub W, Braunwald E. Effects of renal insufficiency on early invasive management in patients with acute coronary syndromes (the TACTICS-TIMI 18 Trial). Am J Cardiol. 2002;90: FRagmin and Fast Revascularisation during InStability in Coronary artery disease Investigators. Invasive compared with non-invasive treatment in unstable coronary-artery disease: FRISC II prospective randomised multicentre study. Lancet. 1999;354: Johnston N, Jernberg T, Lagerqvist B, Wallentin L. Early invasive treatment benefits patients with renal dysfunction in unstable coronary artery disease. Am Heart J. 2006;152: Howell NJ, Keogh BE, Bonser RS, Graham TR, Mascaro J, Rooney SJ, Wilson IC, Pagano D. Mild renal dysfunction predicts in-hospital mortality and post-discharge survival following cardiac surgery. Eur J Cardiothorac Surg. 2008;34: McCullough PA, Wolyn R, Rocher LL, Levin RN, O Neill WW. Acute renal failure after coronary intervention: incidence, risk factors, and relationship to mortality. Am J Med. 1997;103: Bonello L, De Labriolle A, Roy P, Steinberg DH, Okabe T, Pinto Slottow TL, Xue Z, Torguson R, Suddath WO, Satler LF, Kent KM, Pichard AD, Lindsay J, Waksman R. Impact of optimal medical therapy and revascularization on outcome of patients with chronic kidney disease and on dialysis who presented with acute coronary syndrome. Am J Cardiol. 2008;102: Block GA, Hulbert-Shearon TE, Levin NW, Port FK. Association of serum phosphorus and calcium x phosphate product with mortality risk in chronic hemodialysis patients: a national study. Am J Kidney Dis. 1998; 31: Tentori F, Blayney MJ, Albert JM, Gillespie BW, Kerr PG, Bommer J, Young EW, Akizawa T, Akiba T, Pisoni RL, Robinson BM, Port FK. Mortality risk for dialysis patients with different levels of serum calcium, phosphorus, and PTH: the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis. 2008;52: CLINICAL PERSPECTIVE Renal dysfunction affects approximately 25% to 30% of patients admitted with an acute coronary syndrome. Its presence is associated with an exponential increase in mortality. Data to support current guidelines for early revascularization in patients with renal dysfunction admitted with a non ST-elevation myocardial infarction are sparse, because clinical trials have often used elevated creatinine as an exclusion criterion. In this current nationwide registry from Sweden that included patients between 2003 and 2006 who were 80 years old or younger, we evaluated whether early revascularization (by either percutaneous coronary intervention or coronary artery bypass grafting) within 14 days of admission for a non ST-elevation myocardial infarction alters prognosis at all degrees of renal dysfunction. We found that patients with mild-to-moderate renal insufficiency had comparable survival benefit at 1 year with early revascularization. Despite this advantage with treatment, there was a lower use of an early invasive therapy in those with moderate renal insufficiency, among whom only 36% were revascularized compared with 62% of those with normal renal function. More frequent use of an invasive approach in those with mild-to-moderate renal dysfunction could potentially alter their worse outcome. In contrast, the advantage with revascularization in those with more advanced renal impairment is lower and less certain, and its use is questionable in those with renal failure or on dialysis, in whom there was a suggestion of harm with therapy. Further research to find the optimal therapy to improve prognosis for this patient group is needed. Go to to take the CME quiz for this article.