The aim of this study was to compare clinical outcomes among early invasive (EI), deferred invasive (DI), and conservative strategies in patients with acute non–ST-segment elevation myocardial infarction (NSTEMI) and chronic kidney disease (CKD). High-risk patients with NSTEMI are believed to fare better with an EI strategy, but the optimal treatment for patients with NSTEMI and CKD is not known. In total 5,185 patients with acute NSTEMI were enrolled from the Korea Acute Myocardial Infarction Registry and followed for 1 year. Patients were divided into EI, DI, and conservative treatment groups and classified into 4 stages using references from the National Kidney Foundation. The invasive EI and DI groups were compared to the conservative groups, and the EI and DI groups were compared according to each renal function stage. At 1-year follow-up, mortality rates in the conservative group were significantly higher than in the invasive groups except for the severe CKD group. The benefit of the EI over the DI strategy, although there were no significant differences between the 2 groups, tended to decrease as renal function decreased. In conclusion, in the management of NSTEMI, an invasive strategy decreased mortality compared to a conservative strategy except for severe CKD. In the timing of an invasive strategy, the EI strategy was observed to be superior to the DI strategy in patients with mild CKD; however, this tendency reversed as renal function decreased. When patients with NSTEMI have severe CKD, a conservative or DI strategy with prescription of cardioprotective medications and prevention of further deterioration in renal function should be considered.
It is widely accepted that chronic kidney disease (CKD) is 1 of the strongest independent predictors of a high incidence of mortality and adverse events after acute coronary syndrome (ACS). Although several studies have reported that invasive revascularization therapies are beneficial against risk for long-term mortality and improved survival rates in patients with ACS and mild to moderate CKD, the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) data showed that the benefit of revascularization is uncertain in patients with severe CKD or on dialysis. However, there are sparse data regarding optimal treatment including timing of invasive management and conservative medical therapy for patients with non–ST-elevation myocardial infarction (NSTEMI) and CKD. This problem has important implications for the selection of the most effective management in such high-risk patients. To address this important issue, we examined clinical outcomes of patients presenting with NSTEMI according to renal function from a large and prospectively collected database.
Methods
The Korea Acute Myocardial Infarction Registry (KAMIR) is a Korean prospective multicenter on-line registry designed to describe the characteristics and clinical outcomes of Korean patients with acute MI and reflect the current practice of management in Korea. The registry includes 52 community and university hospitals for primary percutaneous coronary intervention, and 13,901 patients were enrolled in this registry. Data were collected at each site by a well-trained study coordinator based on a standardized protocol. The study protocol was approved by the ethics committee at each participating institution and all patients were informed about their participation in this registry.
From November 2005 through January 2008, 5,185 patients were diagnosed with NSTEMI (37.2% with acute MI). Patients who could not be followed for 1 year and whose data could not be confirmed definitely were excluded. Clinical follow-up was performed for 12 months. Because patients with hemodynamic or electrical instability should be treated with an urgent invasive strategy, we excluded patients with shock status (systolic blood pressure <90 mm Hg), ventricular tachycardia or ventricular fibrillation, second- or third-degree atrioventricular block, and cardiopulmonary arrest on admission. In this study patients were divided into 3 groups. (1) The early invasive (EI) group (1,154 patients, 32%) received invasive revascularization therapy including percutaneous coronary intervention and coronary artery bypass grafting within 24 hours after admission. According to some guidelines and some randomized controlled trials, the period for an EI strategy is long (i.e., 6 hours to 7 days). In clinical practice, because the decision of whether an invasive intervention should be performed on the day of admission is crucially important, we defined EI as intervention within 24 hours after admission. (2) The deferred invasive (DI) group (1,663 patients, 46%) received invasive intervention 24 hours after admission. (3) The conservative group (799 patients, 22%) received only medical therapies without invasive revascularization treatment. To indicate differences in renal function, patients were classified into 4 stages using references from the National Kidney Foundation : normal renal function, estimated glomerular filtration rate >90 ml/min/1.73 m 2 ; mild CKD, estimated glomerular filtration rate 60 to 89 ml/min/1.73 m 2 ; moderate CKD, estimated glomerular filtration rate 30 to 59 ml/min/1.73 m 2 ; severe CKD, estimated glomerular filtration rate <30 ml/min/1.73 m 2 . Invasive strategies including EI and DI were compared to conservative strategies, and EI and DI strategies were compared according to each renal function stage. In this study, the new Japanese equation of estimated glomerular filtration rate was used to calculate estimated glomerular filtration rate because Koreans and Japanese have much in common in race and physical constitution and so on. Acute MI was defined by clinical signs or symptoms, increased cardiac biomarkers (creatine kinase-MB, troponin I, or troponin T), and 12-lead electrocardiographic findings. In patients with acute MI, STEMI was defined by the presence of new STE of ≥1 mm (0.1 mV) in continuous leads or new left bundle branch block on index electrocardiogram, and NSTEMI was defined as all other cases of acute MI. Risk scores were calculated using Thrombolysis In Myocardial Infarction risk score and modified Global Registry of Acute Coronary Events score. Left ventricular ejection fraction was checked by 2-dimensional echocardiography. Time to percutaneous coronary intervention was defined as time from first medical contact to the procedure.
All analyses were performed using SPSS 17.0 (SPSS, Inc., Chicago, Illinois). Continuous variables are presented as medians and interquartile ranges and were compared by Kruskal–Wallis nonparametric tests. Categorical variables are expressed as percentages and were compared by chi-square test or Fisher’s exact test. All statistical tests were 2-tailed with statistical significance defined as a p value <0.05. Crude survival rates were compared by chi-square test or Fisher’s exact test to evaluate differences between treatment groups. Propensity scores were created to adjust confounding factors using a logistic regression model. Pretreatment variables that were present before admission were included to create propensity scores; included variables were Thrombolysis In Myocardial Infarction risk score, modified Global Registry of Acute Coronary Events score, age, gender, body mass index, presence of chest symptom, presence of dyspnea, presence of previous angina before MI onset, heart rate, Killip class, ST-T change, atrial fibrillation or atrial flutter, previous ischemic heart disease, history of hypertension, diabetes mellitus, hyperlipidemia, stroke, heart failure, smoker, and family history of heart disease. Predicted accuracy of the logistic model was assessed by an area under the receiver operating characteristic curve (c-statistic). Adjusted survival analyses were calculated using Cox regression models adjusted by propensity score and important risk covariates that showed a p value <0.2 in univariate analysis for end points in each group. Results are presented as adjusted hazard ratios with 95% confidence intervals and as forest plots.
Results
Baseline clinical characteristics are listed in Table 1 . Patients with severe CKD were treated with a conservative strategy. Compared to the invasive groups, patients in the conservative group were older, had higher risk scores, and had a higher prevalence of female gender, previous stroke, coronary artery disease, and heart failure. The conservative group also had a tendency toward heart failure on admission. Compared to the EI group, patients in the DI group were older, had higher risk scores, and had a higher rate of female gender, diabetes mellitus, previous stroke, and heart failure. The DI group was likelier to have heart failure as determined by heart rate, Killip class, presence of dyspnea, and low ejection fraction. Procedural characteristics and in-hospital medications are listed in Table 2 . Prescription rates of all antithrombotic agents were lower in the conservative group compared to the invasive groups, but there were no significant differences in use of cardioprotective drugs such as angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, β blocker, and statin between the conservative and invasive groups. Although prescription rates of antithrombotic agents were similar between the EI and DI groups, use of cardioprotective drugs was greater in the DI group than in the EI group.
| Variable | Renal Function | EI Group | DI Group | Conservative Group | p Value | |
|---|---|---|---|---|---|---|
| Invasive vs Conservative | EI vs DI | |||||
| Overall | 1,154 (32%) | 1,663 (46%) | 799 (22%) | |||
| Normal | 58 (33%) | 74 (43%) | 42 (24%) | |||
| Mild | 464 (36%) | 628 (48%) | 224 (17%) | |||
| Moderate | 562 (33%) | 814 (47%) | 353 (20%) | |||
| Severe | 68 (18%) | 143 (37%) | 174 (45%) | |||
| Age (years) | 63 (53–71) | 65 (56–73) | 69 (59–77) | <0.001 | <0.001 | |
| Men | 826 (72%) | 1,110 (67%) | 459 (58%) | <0.001 | 0.007 | |
| Body mass index (kg/m 2 ) | 24 (22–26) | 24 (22–26) | 23 (21–25) | <0.001 | <0.001 | |
| Hypertension | 601 (52%) | 893 (54%) | 437 (55%) | 0.333 | 0.420 | |
| Diabetes mellitus | 314 (27%) | 565 (34%) | 265 (33%) | 0.262 | <0.001 | |
| Hyperlipidemia | 148 (13%) | 221 (13%) | 97 (12%) | 0.549 | 0.777 | |
| Previous coronary artery disease | 224 (19%) | 331 (20%) | 241 (30%) | <0.001 | 0.736 | |
| Previous stroke | 63 (5.5%) | 146 (8.8%) | 105 (13.1%) | <0.001 | 0.001 | |
| Previous heart failure | 11 (1.0%) | 53 (3.2%) | 72 (9.0%) | <0.001 | <0.001 | |
| Smoker | 677 (59%) | 881 (53%) | 350 (44%) | <0.001 | 0.002 | |
| Heart rate >100 beats/min | 93 (8.1%) | 182 (11%) | 155 (20%) | <0.001 | 0.012 | |
| Killip class >I | 165 (15%) | 383 (24%) | 313 (40%) | <0.001 | <0.001 | |
| Presence of chest symptom on admission | 950 (83%) | 1,323 (81%) | 549 (71%) | <0.001 | 0.070 | |
| Presence of dyspnea on admission | 228 (20%) | 461 (29%) | 312 (41%) | <0.001 | <0.001 | |
| Angina before admission | 660 (57%) | 878 (52%) | 353 (45%) | <0.001 | 0.037 | |
| ST-T change on admission | 645 (56%) | 990 (60%) | 482 (60%) | 0.272 | 0.043 | |
| Atrial fibrillation/atrial flutter | 41 (3.6%) | 63 (3.9%) | 61 (7.8%) | <0.001 | 0.762 | |
| Left ventricular ejection fraction ≤35% | 63 (5.9%) | 156 (9.9%) | 131 (18.4%) | <0.001 | <0.001 | |
| Estimated glomerular filtration rate (ml/min/1.73 m 2 ) | 58 (47–69) | 57 (46–68) | 52 (34–66) | <0.001 | 0.017 | |
| Thrombolysis In Myocardial Infarction risk score ≥5 | 140 (12%) | 236 (14%) | 160 (20%) | <0.001 | 0.114 | |
| Modified Global Registry of Acute Coronary Events score ≥140 | 310 (27%) | 563 (33%) | 434 (54%) | <0.001 | <0.001 | |
| Variable | EI Group | DI Group | Conservative Group | p Value | |
|---|---|---|---|---|---|
| Invasive vs Conservative | EI vs DI | ||||
| Procedural | |||||
| Time to percutaneous coronary intervention, early (hours) or deferred (days) | 8.9 (3.8–17.8) | 2.6 (1.6–4.1) | — | — | — |
| Percutaneous coronary intervention | 1,145 (99.6%) | 1,581 (94.8%) | — | — | <0.001 |
| Coronary artery bypass grafting | 6 (0.5%) | 99 (5.9%) | — | — | <0.001 |
| Medication in hospital | |||||
| Glycoprotein IIb/IIIa inhibitor | 157 (14%) | 189 (11%) | 34 (4%) | <0.001 | 0.090 |
| Low-molecular-weight heparin | 462 (40%) | 632 (38%) | 239 (30%) | <0.001 | 0.238 |
| Medication at discharge | |||||
| Aspirin | 1,139 (99%) | 1,649 (99%) | 773 (97%) | <0.001 | 0.198 |
| Clopidogrel | 1,123 (98%) | 1,617 (98%) | 712 (89%) | <0.001 | 1.000 |
| Cilostazol | 364 (32%) | 528 (32%) | 72 (9%) | <0.001 | 1.000 |
| β Blocker | 821 (71%) | 1,339 (81%) | 598 (75%) | 0.277 | <0.001 |
| Angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker | 882 (77%) | 1,403 (85%) | 649 (81%) | 1.000 | <0.001 |
| Statin | 847 (74%) | 1,248 (75%) | 544 (68%) | <0.001 | 0.378 |
Crude mortality rates are presented in Tables 3 and 4 . Adjusted 12-month survival curves and forest plot using Cox regression models adjusted by propensity score and important risk covariates according to renal function are shown in Figures 1 and 2 . Mortality of the conservative groups was significantly higher than of the invasive groups except for the severe CKD group ( Figure 1 ). Figure 2 presents hazard ratios, 95% confidence intervals, and p values of the EI group for 12-month mortality compared to the DI group according to renal function. Although there were no significant differences between the 2 groups, the benefit of the EI strategy over the DI strategy tended to decrease as renal function decreased.
| Renal Function | Invasive Group (n = 2,817) | Totally Conservative Group (n = 798) | p Value |
|---|---|---|---|
| Overall (n = 3,615) | 146/2,817 (5%) | 178/798 (22%) | <0.001 |
| Normal (n = 174) | 3/132 (2%) | 4/42 (10%) | 0.059 |
| Mild (n = 1,316) | 22/1,092 (2%) | 17/224 (8%) | <0.001 |
| Moderate (n = 1,729) | 77/1,376 (6%) | 85/353 (24%) | <0.001 |
| Severe (n = 385) | 44/211 (20%) | 72/174 (41%) | <0.001 |
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