The appropriate treatment for asymptomatic patients with obstructive coronary stenoses is controversial. The effect of percutaneous coronary intervention (PCI) on the prognosis of such patients is unknown. The present study compared the 1-year outcomes of patients with stable coronary artery disease (CAD) with regard to the presence or absence of symptoms after elective PCI. A total of 1,944 consecutive patients with stable CAD who had undergone elective PCI were studied. They were divided into 2 groups according to symptom status: asymptomatic (n = 1,052) and symptomatic (n = 892). A 1-year follow-up evaluation was conducted by office visit and telephone interview. The end points consisted of all-cause mortality, nonfatal myocardial infarction, and target vessel revascularization. Patients without angina pectoris were older, predominantly men, and more frequently had chronic renal insufficiency, a previous myocardial infarction, a coronary artery bypass graft, and a lower left ventricular ejection fraction. The 1-year mortality rate was greater in the asymptomatic patients (43 [4.1%] vs 16 [1.8%], p = 0.003). The incidence of nonfatal myocardial infarction and target vessel revascularization was similar in the 2 groups (15 [1.5%] vs 12 [1.4%], p = 0.85; and 69 [6.7%] vs 68 [7.7%], p = 0.39, respectively). On multivariate analysis, the absence of symptoms was a strong independent predictor of 1-year mortality (p = 0.017). In conclusion, in patients with stable CAD undergoing elective PCI, the absence of symptoms was associated with an increase in 1-year mortality.
Patients with coronary atherosclerosis might not have symptoms that attract attention to its presence. It has been estimated that in 60% to 70% of patients, sudden death or acute myocardial infarction (MI) is the first clinical manifestation of the disease. Even in the absence of a catastrophic event, recurring or chronic ischemia can produce myocardial changes leading to congestive heart failure, myocardial fibrosis, and cardiac arrhythmia. Thus, it is plausible that asymptomatic patients with obstructive coronary disease who lack warning symptoms would have an even greater risk of a fatal outcome than those with stable symptoms. Asymptomatic coronary artery disease (CAD) poses a therapeutic challenge, and therapy for it is controversial. Freedom from symptoms after percutaneous coronary intervention (PCI) does not ensure that no ischemia is present. Using myocardial perfusion imaging, Zellweger et al demonstrated persistent ischemia in the distribution of the target vessel in 23% of 307 patients. Anginal symptoms were absent in 62% of these patients. The outcome of patients with asymptomatic CAD undergoing PCI is unknown. The present study was undertaken to assess this question in a contemporary, well-studied population undergoing PCI.
Methods
Our prospective registry database included 4,592 consecutive patients with CAD who had undergone elective PCI with a drug-eluting stent from April 2003 to June 2008. All patients underwent their procedure at the Washington Hospital Center. Patients with emergent PCI, MI at admission, or shock were not included. Stable CAD in the present study was defined as no change in the frequency, duration, or intensity of anginal symptom in the 6 weeks before the intervention. The 2,648 patients with progressive, worsening, or changing patterns of anginal symptoms for <6 weeks or with an unstable angina pattern who had severe or prolonged episodes and/or positive troponin I observed were excluded. Furthermore, any patient, regardless of symptoms or lack thereof who had an abnormal troponin I level on admission was excluded. Our analysis included 1,944 patients with stable CAD. Those with no chest discomfort consistent with effort angina (n = 1,052) were compared to the 892 patients with stable angina. All patients gave written informed consent for the PCI procedure, and the institutional review board approved the study.
The primary end point was the 1-year, all-cause mortality. The secondary end points assessed at 1 year included death, repeat revascularization, and nonfatal MI. MI was defined as an elevation in creatine kinase-MB ≥2 times the upper normal value. Q-wave MI was diagnosed when, in association with the biomarker increase, new Q waves had developed on the electrocardiogram in ≥2 contiguous leads. Post-PCI MI was defined as an increase of creatine kinase-MB of ≥3 times the upper normal value, with or without Q waves. Creatine kinase-MB was routinely measured before and after PCI. All repeat revascularization procedures were clinically driven. Target vessel revascularization included either repeat percutaneous or surgical revascularization of the stented epicardial vessel. Target lesion revascularization was defined as a target vessel revascularization for stenosis within a stent or within the 5-mm segments proximal or distal to the stent. Definite stent thrombosis was considered as defined by the Academic Research Consortium. Angiographic success was defined as a residual stenosis of <30% with Thrombolysis In Myocardial Infarction 3 flow.
The demographic, clinical, and procedural data and in-hospital outcomes were collected and entered into a prospective database. The data were obtained from hospital chart review by independent research personnel unaware of the study objectives. All data management and analyses were performed by a dedicated data coordinating center (Data Center, Cardiovascular Research Institute, Washington, DC). Clinical follow-up was performed at 1, 6, and 12 months by trained quality assurance nurses who worked exclusively with the database to determine the post-PCI clinical events. Clinical follow-up data were obtained by telephone interview or office visit. A committee independently adjudicated all clinical events. The 1-year follow-up information was obtained for all patients.
The results are expressed as the mean ± SD or percentages. The differences between groups were assessed using the chi-square test or Fisher’s exact test for categorical variables and Student’s t test for continuous variables. Survival curves were constructed using the Kaplan-Meier method. Differences in survival function were assessed for significance using the log-rank test. The raw and adjusted risks associated with the end points were derived from univariate and multivariate Cox regression models, respectively. The following variables were included in the univariate analysis: absence of symptoms, age, male gender, systemic hypertension, hypercholesterolemia, diabetes mellitus, current smoker, chronic renal insufficiency, previous MI, previous coronary artery bypass graft surgery, previous PCI, number of lesions dilated, left ventricular ejection fraction (%), positive stress test findings, and left anterior descending lesion. Variables with p <0.1 on univariate analysis were entered into the multivariate Cox model to adjust for baseline differences. All variables were entered into the model in their original form without transformation. Statistical analysis was performed using Statistical Analysis Systems, version 9.1 (SAS Institute, Cary, North Carolina). Statistical significance was accepted for all values of p <0.05.
Results
The baseline clinical characteristics are listed in Table 1 . The asymptomatic patients were older (p <0.001) and more often men (p = 0.01). Furthermore, they more often reported chronic renal disease and/or had an admission serum creatine of ≥2.0 mg/dl (p = 0.01). The frequency of diabetes mellitus was similar in both groups. Previous MI (p = 0.001) and previous coronary artery bypass graft surgery (p = 0.009) were also more common in those without symptoms. Asymptomatic patients had, on average, a lower left ventricular ejection fraction than symptomatic patients (p = 0.03). A positive preprocedure stress test was reported in 767 (94.7%) of the 810 patients in the asymptomatic group for whom the results were available. It is likely that positive test results provided the indication for PCI. Symptomatic patients had less often undergone a stress test. In those who did, it was less frequently positive ( Table 1 ). Table 2 lists the baseline angiographic and procedural characteristics according to a by-lesion analysis. The rate of American College of Cardiology/American Heart Association type C lesion (p = 0.04) and the number of stents deployed (p = 0.005) were both greater in the asymptomatic group. Angiographic success was very high in both groups; however, it was slightly, but significantly, greater in the asymptomatic group (p = 0.002).
| Variable | Symptomatic | ||
|---|---|---|---|
| No (n = 1,052) | Yes (n = 892) | p Value | |
| Age (years) | 66.26 ± 10.69 | 64.12 ± 11.79 | <0.001 ⁎ |
| Men | 763 (72.5%) | 599 (67.2%) | 0.010 ⁎ |
| Systemic hypertension | 895 (85.2%) | 731 (82.6%) | 0.114 |
| Hypercholesterolemia | 940 (90.0%) | 775 (87.5%) | 0.085 |
| Diabetes mellitus | 366 (35.1%) | 317 (35.9%) | 0.737 |
| Current smoker | 167 (15.9%) | 117 (13.1%) | 0.086 |
| Family history of coronary artery disease | 558 (54.8%) | 502 (57.7%) | 0.199 |
| Chronic renal insufficiency | 111 (10.6%) | 64 (7.2%) | 0.011 ⁎ |
| Previous myocardial infarction | 232 (23.3%) | 147 (17.1%) | 0.001 ⁎ |
| Previous coronary artery bypass surgery | 207 (19.7%) | 135 (15.2%) | 0.009 ⁎ |
| Previous percutaneous coronary intervention | 302 (29.5%) | 242 (27.7%) | 0.403 |
| No. of diseased vessels | 1.93 ± 0.90 | 1.84 ± 0.86 | 0.144 |
| Left ventricular ejection fraction (%) | 50 ± 14 | 52 ± 13 | 0.033 ⁎ |
| Positive stress test | 767/810 (94.7%) | 492/594 (82.8%) | <0.0001 ⁎ |
| Discharged with aspirin | 1,027 (98.7%) | 871 (98.9%) | 0.680 |
| Discharged with clopidogrel | 1,018 (98.5%) | 859 (98.5%) | 0.920 |
| Discharged with angiotensin-converting enzyme inhibitor | 421 (41.1%) | 383 (44.1%) | 0.194 |
| Discharged with calcium antagonist | 47 (20.2%) | 44 (18.3%) | 0.612 |
| Discharged with β blocker | 766 (74.2%) | 652 (74.9%) | 0.694 |
| Discharged with statin | 935 (96.1%) | 800 (96.2%) | 0.948 |
| Variable | Symptomatic | ||
|---|---|---|---|
| No (n = 1,938) | Yes (n = 1,599) | p Value | |
| Target coronary vessel | |||
| Left main | 30 (1.5%) | 30 (1.9%) | 0.452 |
| Left anterior descending | 741 (38.2%) | 639 (40.0%) | 0.295 |
| Left circumflex | 475 (24.5%) | 356 (22.3%) | 0.117 |
| Right | 592 (30.5%) | 484 (30.3%) | 0.858 |
| Saphenous vein graft | 88 (4.5%) | 83 (5.2%) | 0.370 |
| Restenosis | 71 (3.7%) | 76 (4.8%) | 0.110 |
| Prediameter stenosis (%) | 83 ± 12 | 84 ± 11 | 0.007 ⁎ |
| American College of Cardiology/American Heart Association type C lesion | 363 (19.9%) | 262 (17.1%) | 0.035 ⁎ |
| No. of lesions dilated | 1.86 ± 2.02 | 1.80 ± 2.91 | 0.608 |
| No. of implanted stents | 1.53 ± 0.79 | 1.43 ± 0.72 | 0.005 ⁎ |
| Bare metal stent | 204 (11.3%) | 157 (10.9%) | 0.732 |
| Drug-eluting stent | 1,614 (86.9%) | 1,301 (85.8%) | 0.355 |
| Angiographic success | 1,892 (98.6%) | 1,540 (97.1%) | 0.002 ⁎ |
Table 3 lists the incidence of in-hospital adverse events. They were remarkably similar, other than a substantially greater incidence of acute renal failure in the asymptomatic patients (24 [2.3%] vs 2 [0.2%] in the symptomatic patients; p <0.001). Table 4 lists the adverse cardiac events. The primary end point (1-year, all-cause mortality) occurred in 59 patients (3.0%). Significantly more asymptomatic patients died (43 [4.1%] vs 16 [1.8%] in the symptomatic group, p = 0.003). The incidence of nonfatal MI, target vessel revascularization, and target lesion revascularization was similar between the 2 groups. The relation of the baseline variables with 1-year mortality is listed in Table 5 . Important predictors included an absence of symptoms (p = 0.004), diabetes mellitus (p = 0.006), older age (p = 0.002), and chronic renal insufficiency (p <0.001). A relatively weak association with the end point was found for gender and previous MI. After adjustment using a Cox proportional hazards model, only the absence of symptoms and baseline renal insufficiency remained as independent predictors ( Table 6 ). Kaplan-Meier curves comparing survival between the asymptomatic and symptomatic groups at various points are shown in Figure 1 . The worse survival for the asymptomatic group was significant (log-rank, p = 0.003).
| Outcome | Symptomatic | ||
|---|---|---|---|
| No (n = 1,052) | Yes (n = 892) | p Value | |
| Death | 1 (0.1%) | 1 (0.1%) | 1.000 |
| Q-wave myocardial infarction | 3 (0.3%) | 3 (0.3%) | 1.000 |
| Postprocedure myocardial infarction | 66 (6.4%) | 53 (6.1%) | 0.82 |
| Coronary artery bypass surgery | 0 | 0 | |
| Stent thrombosis | 1 (0.1%) | 1 (0.1%) | 1.000 |
| Creatine kinase-MB maximum ⁎ | 3.04 ± 17.02 | 2.87 ± 11.31 | 0.789 |
| Acute renal failure | 24 (2.3%) | 2 (0.2%) | <0.001 † |
| Major bleeding ‡ | 7 (0.7%) | 3 (0.3%) | 0.359 |
| Transfusion | 19 (2.0%) | 8 (1.1%) | 0.119 |
| Any neurologic event | 1 (0.1%) | 1 (0.1%) | 1.000 |
⁎ With muscle and brain subunits.
‡ Included gastrointestinal bleeding and hematocrit decrease >15%.
| Event | Symptomatic | ||
|---|---|---|---|
| No (n = 1,052) | Yes (n = 892) | p Value | |
| All-cause death | 43 (4.1%) | 16 (1.8%) | 0.003 ⁎ |
| Nonfatal myocardial infarction | 15 (1.5%) | 12 (1.4%) | 0.851 |
| Target vessel revascularization | 69 (6.7%) | 68 (7.7%) | 0.386 |
| Target lesion revascularization | 52 (5.0%) | 45 (5.1%) | 0.944 |
| Cumulative stent thrombosis | 10 (0.9%) | 6 (0.7%) | 0.500 |
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