Clinical Outcomes Utilizing Revascularization and Aggressive Drug Eval
Clinical Outcomes Utilizing Revascularization and Aggressive Drug Eval
The goal of the trial was to evaluate the efficacy of percutaneous coronary intervention (PCI) compared with optimal medical therapy among patients with stable coronary artery disease.
PCI with optimal medical therapy would reduce the risk of death and nonfatal myocardial infarction (MI) in patients with stable coronary artery disease as compared with optimal medical therapy alone.
Patients were randomized to optimal medical therapy alone (n = 1,138) or PCI in addition to optimal medical therapy (n = 1,149). Optimal medical therapy included antiplatelet therapy with aspirin (81-325 mg/day), or clopidogrel (75 mg/day) if aspirin intolerant in the medical therapy group, and aspirin plus clopidogrel in the PCI group. All patients also received aggressive lipid-lowering therapy to a target low-density lipoprotein (LDL) of 60-85 mg/dl. Anti-ischemic therapy included long-acting metoprolol, amlodipine, and isosorbide mononitrate, alone or in combination, and either lisinopril or losartan as secondary prevention.
The large majority of patients (95%) had objective evidence of myocardial ischemia. Multivessel disease was present in 69% of patients, with only 31% having single-vessel disease. One-third of patients had proximal disease of the left anterior descending artery. Canadian Cardiovascular Society (CCS) class II or III angina was present in 58% of patients at study entry. PCI was performed in 94% of the PCI cohort, with successful PCI in 93%. Optimal medication use during the study was high in both treatment groups, with use at 5 years of angiotensin-converting enzyme inhibitors in 64% of patients, statins in 93%, aspirin in 95%, and beta-blockers in 85%. LDL levels were reduced to a median of 71 mg/dl. Diet, exercise, and smoking cessation were also high in both groups. The primary endpoint of death or MI did not differ for the PCI group compared with the medical therapy group (19.0% for PCI vs. 18.5% for medical therapy, hazard ratio [HR] 1.05, 95% confidence interval [CI] 0.87-1.27, p = 0.62). There was also no difference between PCI and medical therapy in the secondary composite endpoint of death, MI, or stroke (20.0% for PCI vs. 19.5% for medical therapy, HR 1.05, 95% CI 0.87-1.27, p = 0.62) or in the secondary endpoint of hospitalization for ACS (12.4% for PCI vs. 11.8% for medical therapy, HR 1.07, 95% CI 0.84-1.37, p = 0.56). Components of the composite endpoints did not differ between groups, including death (7.6% for PCI vs. 8.3% for medical therapy, HR 0.87, p = 0.38), nonfatal MI (13.2% vs. 12.3%, HR 1.13, p = 0.33), or stroke (2.1% for PCI vs. 1.8% for medical therapy, p = 0.19). Angina was significantly reduced in both groups during follow-up, with no difference in the reduction between PCI and medical therapy at 5 years (freedom from angina in 74% of the PCI group and 72% of the medical therapy group, p = 0.35) but slightly higher rates of freedom from angina in the early time frame with PCI (at 1 year: 66% for PCI vs. 58% for medical therapy, p < 0.001; at 3 years: 72% for PCI vs. 67% for medical therapy, p = 0.02). In a cost economic analysis, PCI costs averaged $6,020 higher than medical therapy during the index hospitalization (p < 0.0001), a difference that narrowed slightly over time, but remained at an increased cost of $5,295 by 3 years (p < 0.0001). In a cost-effectiveness analysis, PCI was estimated at $217,000 per quality-adjusted life-year gained. $50,000 is often used as the benchmark for acceptable cost-effective therapies.
Among patients with stable coronary artery disease, treatment with PCI was not associated with a difference in death or MI compared with treatment with medical therapy through 5 years of follow-up. Despite patients in the study having stable angina, disease severity was relatively intensive, with the majority of patients having multivessel disease and objective evidence of ischemia at study entry. There were no differences in any of the clinical endpoints between the PCI and medical therapy groups, nor was there any treatment interaction with the prespecified subgroups. Freedom from angina occurred slightly more frequently with PCI early in the trial but did not differ between the PCI and medical therapy groups by 5 years, with both arms showing marked reductions in angina throughout the trial. Findings from the present study apply to stable angina patients and cannot be extrapolated to the acute coronary syndrome population, which has different pathophysiologic characteristics, although the majority of patients currently undergoing PCI are for stable angina. While the majority of the PCI group did not receive drug-eluting stents since most of the enrollment was completed prior to the introduction of these stents, there is no reason to indicate that use of drug-eluting stents would alter the findings of the trial because drug-eluting stents have never been shown to reduce death or MI compared with bare-metal stents in any trial.
Randomized.
Patients Screened: 35,539
Patients Enrolled: 2,287
Mean Follow-Up: Median, 4.6 years (range 2.5 to 7.0 years)
Mean Patient Age: Mean age, 62 years
% Female: 15
Composite of death from any cause and nonfatal MI
Composite of death, MI, and stroke; hospitalization for unstable angina with negative biomarkers; quality of life; use of resources; and cost-effectiveness
Stable coronary artery disease; initial CCS class IV angina subsequently stabilized medically; either 1) stenosis ≥70% in ≥1 proximal epicardial coronary artery with objective evidence of myocardial ischemia (including either substantial changes in ST-segment depression or T-wave inversion on the resting ECG or inducible ischemia with either exercise or pharmacologic stress test), or 2) ≥1 coronary stenosis of ≥80% and classic angina without provocative testing
Persistent CCS class IV angina; a markedly positive stress; refractory heart failure or cardiogenic shock; an ejection fraction <30%; revascularization within the previous 6 months; and coronary anatomy not suitable for PCI
Description
The goal of the trial was to evaluate the efficacy of percutaneous coronary intervention (PCI) compared with optimal medical therapy among patients with stable coronary artery disease.
Hypothesis
PCI with optimal medical therapy would reduce the risk of death and nonfatal myocardial infarction (MI) in patients with stable coronary artery disease as compared with optimal medical therapy alone.
Drugs/Procedures Used
Patients were randomized to optimal medical therapy alone (n = 1,138) or PCI in addition to optimal medical therapy (n = 1,149). Optimal medical therapy included antiplatelet therapy with aspirin (81-325 mg/day), or clopidogrel (75 mg/day) if aspirin intolerant in the medical therapy group, and aspirin plus clopidogrel in the PCI group. All patients also received aggressive lipid-lowering therapy to a target low-density lipoprotein (LDL) of 60-85 mg/dl. Anti-ischemic therapy included long-acting metoprolol, amlodipine, and isosorbide mononitrate, alone or in combination, and either lisinopril or losartan as secondary prevention.
Principal Findings
The large majority of patients (95%) had objective evidence of myocardial ischemia. Multivessel disease was present in 69% of patients, with only 31% having single-vessel disease. One-third of patients had proximal disease of the left anterior descending artery. Canadian Cardiovascular Society (CCS) class II or III angina was present in 58% of patients at study entry. PCI was performed in 94% of the PCI cohort, with successful PCI in 93%. Optimal medication use during the study was high in both treatment groups, with use at 5 years of angiotensin-converting enzyme inhibitors in 64% of patients, statins in 93%, aspirin in 95%, and beta-blockers in 85%. LDL levels were reduced to a median of 71 mg/dl. Diet, exercise, and smoking cessation were also high in both groups. The primary endpoint of death or MI did not differ for the PCI group compared with the medical therapy group (19.0% for PCI vs. 18.5% for medical therapy, hazard ratio [HR] 1.05, 95% confidence interval [CI] 0.87-1.27, p = 0.62). There was also no difference between PCI and medical therapy in the secondary composite endpoint of death, MI, or stroke (20.0% for PCI vs. 19.5% for medical therapy, HR 1.05, 95% CI 0.87-1.27, p = 0.62) or in the secondary endpoint of hospitalization for ACS (12.4% for PCI vs. 11.8% for medical therapy, HR 1.07, 95% CI 0.84-1.37, p = 0.56). Components of the composite endpoints did not differ between groups, including death (7.6% for PCI vs. 8.3% for medical therapy, HR 0.87, p = 0.38), nonfatal MI (13.2% vs. 12.3%, HR 1.13, p = 0.33), or stroke (2.1% for PCI vs. 1.8% for medical therapy, p = 0.19). Angina was significantly reduced in both groups during follow-up, with no difference in the reduction between PCI and medical therapy at 5 years (freedom from angina in 74% of the PCI group and 72% of the medical therapy group, p = 0.35) but slightly higher rates of freedom from angina in the early time frame with PCI (at 1 year: 66% for PCI vs. 58% for medical therapy, p < 0.001; at 3 years: 72% for PCI vs. 67% for medical therapy, p = 0.02). In a cost economic analysis, PCI costs averaged $6,020 higher than medical therapy during the index hospitalization (p < 0.0001), a difference that narrowed slightly over time, but remained at an increased cost of $5,295 by 3 years (p < 0.0001). In a cost-effectiveness analysis, PCI was estimated at $217,000 per quality-adjusted life-year gained. $50,000 is often used as the benchmark for acceptable cost-effective therapies.
Interpretation
Among patients with stable coronary artery disease, treatment with PCI was not associated with a difference in death or MI compared with treatment with medical therapy through 5 years of follow-up. Despite patients in the study having stable angina, disease severity was relatively intensive, with the majority of patients having multivessel disease and objective evidence of ischemia at study entry. There were no differences in any of the clinical endpoints between the PCI and medical therapy groups, nor was there any treatment interaction with the prespecified subgroups. Freedom from angina occurred slightly more frequently with PCI early in the trial but did not differ between the PCI and medical therapy groups by 5 years, with both arms showing marked reductions in angina throughout the trial. Findings from the present study apply to stable angina patients and cannot be extrapolated to the acute coronary syndrome population, which has different pathophysiologic characteristics, although the majority of patients currently undergoing PCI are for stable angina. While the majority of the PCI group did not receive drug-eluting stents since most of the enrollment was completed prior to the introduction of these stents, there is no reason to indicate that use of drug-eluting stents would alter the findings of the trial because drug-eluting stents have never been shown to reduce death or MI compared with bare-metal stents in any trial.
Conditions
Coronary heart disease
Therapies
Medical
Stent
Study Design
Randomized.
Patients Screened: 35,539
Patients Enrolled: 2,287
Mean Follow-Up: Median, 4.6 years (range 2.5 to 7.0 years)
Mean Patient Age: Mean age, 62 years
% Female: 15
Primary Endpoints
Composite of death from any cause and nonfatal MI
Secondary Endpoints
Composite of death, MI, and stroke; hospitalization for unstable angina with negative biomarkers; quality of life; use of resources; and cost-effectiveness
Patient Population
Stable coronary artery disease; initial CCS class IV angina subsequently stabilized medically; either 1) stenosis ≥70% in ≥1 proximal epicardial coronary artery with objective evidence of myocardial ischemia (including either substantial changes in ST-segment depression or T-wave inversion on the resting ECG or inducible ischemia with either exercise or pharmacologic stress test), or 2) ≥1 coronary stenosis of ≥80% and classic angina without provocative testing
Exclusions
Persistent CCS class IV angina; a markedly positive stress; refractory heart failure or cardiogenic shock; an ejection fraction <30%; revascularization within the previous 6 months; and coronary anatomy not suitable for PCI
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