There are limited data on the prognosis of patients with stable coronary artery disease (CAD) in modern clinical practice. We conducted a multicenter study enrolling 4,184 outpatients with stable CAD defined as previous myocardial infarction (>1 year ago), previous coronary revascularization (>1 year ago), and/or ≥50% coronary stenosis by angiography. Clinical follow-up was performed after 2 years. All cases of death were adjudicated and the mortality rate was compared with expected mortality of persons of the same age and gender in the same geographical area. Mean age was 66.9 ± 11.6 years; 77.7% were men. There was a wide prescription of secondary prevention drugs: antithrombotic drugs, 99.3%; β blockers, 79.4%; statins, 92.2%; and antagonists of the angiotensin system, 81.9%. Two-year follow-up was obtained for 99.2% of the patients. There were 271 deaths (3.3/100 patient-years). The mortality rate was similar to the expected mortality in the general population (p = 0.93). Most deaths were noncardiovascular (1.8/100 patient-years). Among cardiovascular deaths, the leading causes were heart failure death (0.4/100 patient-years) and sudden death (0.4/100 patient-years); in contrast, there were few deaths related to vascular causes (stroke, 0.2/100 patient-years and myocardial infarction, 0.1/100 patient-years). Age, diabetes, multivessel CAD, the absence of previous coronary revascularization, previous hospitalization for decompensated heart failure, a low ejection fraction, a low estimated glomerular filtration rate, and the absence of statin treatment were independent predictors of mortality. In conclusion, the mortality rate of patients with stable CAD in modern clinical practice is similar to that of the general population and is mostly due to noncardiovascular causes.
There has been significant progress over the last decades in the management of patients with coronary artery disease (CAD). Recent international guidelines unanimously recommend the use of secondary prevention drugs that have been shown to improve survival. Moreover, cohort studies have shown that these treatments are nowadays widely prescribed for patients with CAD. Our knowledge on the current prognosis of patients with chronic and stable CAD is however relatively limited; the dominant opinion of a low rate of events in these patients is mainly derived from the data of randomized studies, which may be subjected to selection bias. Indeed, the annual total mortality rates in these trials ranged from 1.1% to 1.7% but patients at high risk or with important co-morbidities were not included. We therefore designed the present study to assess the prognosis of stable CAD in an unselected patient population.
Methods
The Suivi d’une cohorte de patients CORO nariens stables en région NOR d-pas-de-Calais (CORONOR) study was a multicenter study that enrolled 4,184 consecutive patients with stable CAD. The patients were included by 50 cardiologists from the region Nord Pas-de-Calais in France ( Appendix ). The participating physicians were selected on the basis of geographic distribution to provide a representative sample of current cardiology practice in university, nonuniversity, and private centers of the area.
Patients were considered eligible if they had evidence of CAD defined by at least 1 of the following: previous myocardial infarction (MI; >1 year ago), previous coronary revascularization (>1 year ago), and/or obstruction of ≥50% of the luminal diameter of at least 1 native vessel on coronary angiography. The sole exclusion criterion was hospitalization for MI or coronary revascularization within the last year. To present the real-life spectrum of stable CAD, patients with other cardiovascular or noncardiovascular illnesses or co-morbidities were not excluded.
A case record form, which contained information regarding demographic and clinical details of the patients including usual cardiovascular risk factors and treatments, was prospectively completed at the initial visit. Two-year clinical follow-up was performed at outpatient visits or by contacting the general practitioner. We collected data on death, MI, stroke, hospitalization for heart failure, and coronary revascularization. All clinical events were adjudicated blindly by 2 investigators and by 3 investigators in case of disagreement. The cause of death was determined after a detailed review of the circumstances of death and classified as cardiovascular, noncardiovascular, or unknown.
Continuous variables are described as the mean ± SD or as the median (range). Categorical variables are presented as absolute numbers and percentages. Cumulative event rates were estimated with the Kaplan-Meier method. Cox proportional hazards analyses were performed to determine predictors of mortality. Overall mortality rate was compared with expected mortality of persons of the same age and gender in the same geographical area. Control data were obtained from the Region Nord Pas-de-Calais live tables for 2010 provided by the French Institute of Statistics. Sample size calculations were based on a 2-sided alpha error of 0.05 and 80% power. We calculated that including >4,000 patients would provide sufficient power to detect a 1.1% difference between expected and observed mortality rates at 2-year follow-up. Expected and observed mortality rates at 2 years were compared using chi-square analysis. Stata 9.2 (StataCorp, College Station, Texas) was used for statistical analysis.
Results
From February 2010 to April 2011, a total of 4,184 outpatients with stable CAD were included in the CORONOR study. The baseline characteristics of the study population are summarized in Table 1 . The mean age was 66.9 ± 11.6 years (range 26 to 97) and 77.7% of the patients were men. Only 7.3% of the patients were symptomatic (angina) at inclusion. Among all patients, 62.4% had history of MI; the median time interval between the last MI and inclusion was 5 years (range 1 to 34). The majority of the patients underwent at least 1 coronary revascularization procedure before inclusion; the median time interval between the last revascularization and inclusion was 4 years (range 1 to 33). The mean left ventricular ejection fraction (LVEF) was high (57.5 ± 10.8%); 5.8% of the patients had an LVEF of <40%. The mean estimated glomerular filtration rate was 78.9 ± 24.5 ml/min/1.73 m 2 ; 20.4% of the patients had an estimated glomerular filtration rate of <60 ml/min/1.73 m 2 . There was a wide prescription of major secondary prevention drugs, that is, antithrombotic drugs (99.3%), β blockers (79.4%), statins (99.2%), and antagonists of the angiotensin system (81.9%).
| Age (yrs) | 66.9 ± 11.6 |
| Men | 77.7 |
| Body mass index (kg/m 2 ) | 28.2 ± 5.0 |
| Clinical presentation at inclusion: | |
| Stable angina pectoris | 7.3 |
| No symptoms | 92.7 |
| Active smokers | 11.4 |
| Hypertension | 60.2 |
| Diabetes mellitus | 31.0 |
| Previous MI | 62.4 |
| Multivessel CAD | 57.8 |
| Previous myocardial revascularization: | |
| Bare-metal stent | 52.9 |
| Drug-eluting stent | 25.0 |
| Coronary bypass | 21.3 |
| Previous hospitalization for decompensated heart failure | 7.5 |
| LVEF (%) | 57.5 ± 10.8 |
| Estimated glomerular filtration rate (ml/min/1.73 m 2 ) | 78.9 ± 24.5 |
| Treatment at inclusion: | |
| Aspirin | 77.0 |
| Clopidogrel | 40.2 |
| Vitamin K antagonists | 11.1 |
| Any antithrombotic drug | 99.3 |
| ACE inhibitors | 59.3 |
| Angiotensin II receptor antagonists | 24.0 |
| ACE inhibitors or angiotensin II receptor antagonists | 81.9 |
| β Blockers | 79.4 |
| Statins | 92.2 |
Clinical follow-up data were obtained for 4,149 patients (99.2%) at a median of 728 days. There were 271 deaths (3.3/100 patient-years), 91 MIs (1.1/100 patient-years), 48 strokes (0.6/100 patient-years), 146 hospitalizations for heart failure (1.8/100 patient-years), and 230 coronary revascularizations (2.8/100 patient-years). As shown in Figure 1 , the observed mortality rate was indistinguishable from the expected mortality in the general population of the same geographical area (2-year mortality rates: 6.5% and 6.6%, respectively, p = 0.93). The adjudicated causes of death are listed in Table 2 . Most of the deaths were noncardiovascular (1.8/100 patient-years) with almost 1/2 being cancer related. Among cardiovascular deaths, the leading causes were heart failure death (0.4/100 patient-years) and sudden death (0.4/100 patient-years); in contrast, there were few deaths related to vascular causes (stroke, 0.2/100 patient-years and MI, 0.1/100 patient-years). Univariate and multivariate predictors of mortality are listed in Table 3 . Eight variables were independently associated with an increased risk of death during follow-up: age, diabetes mellitus, multivessel CAD, the absence of previous coronary revascularization, previous hospitalization for heart failure, a low LVEF, a low estimated glomerular filtration rate, and the absence of statin treatment.
| Variable | No of Patients | Event Rate ∗ |
|---|---|---|
| Death from cardiovascular causes | 104 | 1.3 |
| Congestive heart failure | 36 | 0.4 |
| Sudden death | 30 | 0.4 |
| Stroke | 13 | 0.2 |
| MI | 10 | 0.1 |
| Limb ischemia | 4 | |
| Mesenteric ischemia | 3 | |
| Aortic aneurysm | 2 | |
| Pulmonary embolism | 2 | |
| Other | 4 | |
| Death from noncardiovascular causes | 152 | 1.8 |
| Cancer | 71 | 0.9 |
| Infection | 34 | 0.4 |
| Suicide or accident | 7 | |
| Respiratory failure | 7 | |
| Renal failure | 6 | |
| Gastrointestinal bleeding | 4 | |
| Liver failure | 3 | |
| Other | 20 | |
| Death from unknown causes | 15 |
∗ The event rate is the number of events per 100 patient-years of follow-up.
| Variable | Univariate Analysis | Multivariate Analysis | ||
|---|---|---|---|---|
| HR (95% CI) | p Value | HR (95% CI) | p Value | |
| Age (per yr) | 1.06 (1.05–1.08) | <0.0001 | 1.05 (1.03–1.06) | <0.0001 |
| Men | 1.18 (0.87–1.59) | NS | — | |
| Body mass index (per kg/m 2 ) | 0.98 (0.96–1.01) | NS | — | |
| Stable angina pectoris | 1.15 (0.74–1.78) | NS | — | |
| Active smokers | 0.81 (0.54–1.21) | NS | — | |
| Hypertension | 1.44 (1.12–1.86) | 0.005 | 0.92 (0.68–1.20) | NS |
| Diabetes | 1.47 (1.15–1.88) | 0.002 | 1.40 (1.07–1.84) | 0.013 |
| Previous MI | 0.85 (0.66–1.08) | NS | — | |
| Multivessel CAD | 1.72 (1.33–2.24) | <0.0001 | 1.37 (1.03–1.83) | 0.028 |
| Previous coronary revascularization | 0.56 (0.42–0.75) | <0.0001 | 0.60 (0.44–0.83) | 0.002 |
| Previous hospitalization for decompensated heart failure | 5.13 (3.92–6.72) | <0.0001 | 2.19 (1.56–3.06) | <0.0001 |
| LVEF (per percent) | 0.95 (0.94–0.96) | <0.0001 | 0.97 (0.96–0.98) | <0.0001 |
| Estimated glomerular filtration rate (per ml/min/1.73 m 2 ) | 0.98 (0.97–0.98) | <0.0001 | 0.99 (0.98–0.99) | 0.003 |
| Antithrombotics | 0.98 (0.24–3.95) | NS | — | |
| ACE inhibitors or angiotensin II receptor antagonists | 0.82 (0.61–1.10) | NS | — | |
| β Blockers | 0.83 (0.63–1.11) | NS | — | |
| Statins | 0.40 (0.29–0.55) | <0.0001 | 0.57 (0.40–0.80) | 0.001 |
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