Effects of intensive versus moderate lipid-lowering therapy on myocardial ischemia in older patients with coronary heart disease: results of the Study Assessing Goals in the Elderly (SAGE).

BACKGROUND: Clinical trials have demonstrated that, compared with placebo, intensive statin therapy reduces ischemia in patients with acute coronary syndromes and in patients with stable coronary artery disease. However, no studies to date have assessed intensive versus moderate statin therapy in older patients with stable coronary syndromes. METHODS AND RESULTS: A total of 893 ambulatory coronary artery disease patients (30% women) 65 to 85 years of age with > or = 1 episode of myocardial ischemia that lasted > or = 3 minutes during 48-hour ambulatory ECG at screening were randomized to atorvastatin 80 mg/d or pravastatin 40 mg/d and followed up for 12 months. The primary efficacy parameter (absolute change from baseline in total duration of ischemia at month 12) was significantly reduced in both groups at month 3 and month 12 (both P<0.001 for each treatment group) with no significant difference between the treatment groups. Atorvastatin-treated patients experienced greater low-density lipoprotein cholesterol reductions than did pravastatin-treated patients, a trend toward fewer major acute cardiovascular events (hazard ratio, 0.71; 95% confidence interval, 0.46, 1.09; P=0.114), and a significantly greater reduction in all-cause death (hazard ratio, 0.33; 95% confidence interval, 0.13, 0.83; P=0.014). CONCLUSIONS: Compared with moderate pravastatin therapy, intensive atorvastatin therapy was associated with reductions in cholesterol, major acute cardiovascular events, and death in addition to the reductions in ischemia observed with both therapies. The contrast between the therapies' differing efficacy for major acute cardiovascular events and death and their nonsignificant difference in efficacy for reduction of ischemia suggests that low-density lipoprotein cholesterol-lowering thresholds for ischemia and major acute cardiovascular events may differ. The Study Assessing Goals in the Elderly (SAGE) demonstrates that older men and women with coronary artery disease benefit from intensive statin therapy.

Factors influencing return to work at one year after coronary bypass graft surgery: results of the PERISCOP study.

PURPOSE: The aim of this study was to evaluate the predictive factors of return to work after coronary bypass graft surgery, for the subgroup of professionally active patients aged less than 60 years included in the PERISCOP study. METHODS: In the principal, prospective, multicentre study, 2065 patients were evaluated 20+/-10 days after surgery by exercise testing, echocardiogram and 24-h ambulatory ECG monitoring. A questionnaire was completed one year after surgery. We studied a subgroup of this population, consisting of 530 patients previously defined (94.5% men; mean age: 50.5+/-5.8 years). RESULTS: One year after surgery, five of these patients had died and 21 were lost to follow-up. Among the remaining patients, 340 patients (67.5%) had returned to work. Forty patients (7.9%) had retired, 45 (8.9%) were on sick leave, 22 (4.4%) were unemployed, 49 (9.7%) returned to work after the deadline of 12 months, eight (1.6%) had given insufficient information on return to work. In multivariate analysis, the independent predictors of a failure to return to work were age >51 years [OR: 0.39 (95% CI: 0.25-0.59)], being a manual worker [OR: 0.49 (95% CI: 0.31-0.79)], being from South East France [(OR: 0.42 (95% CI: 0.23-0.74)], presence of angina [OR: 0.40 (95% CI: 0.20-0.82)], dyspnoea [(OR: 0.46 (95% CI: 0.28-0.77)] and a duration of exercise <420 s [(OR: 0.50 (95% CI: 0.33-0.76)]. CONCLUSIONS: Return to work after coronary bypass graft surgery is observed in 67.5% of cases and depends essentially on socio-professional factors and residual symptoms. A regional effect was also observed, which requires further study.

Use of non-invasive cardiac investigations to predict clinical endpoints after coronary bypass graft surgery in coronary artery disease patients: results from the prognosis and evaluation of risk in the coronary operated patient (PERISCOP) study.

AIMS: Little is known about which patients who have undergone coronary bypass surgery are at risk of future clinical cardiovascular events and may benefit from further medical treatment. We sought to determine if routine non-invasive cardiac investigations performed early after surgery were able to stratify the risk of cardiovascular events in this population. METHODS: Two thousand and sixty-five consecutive patients were enrolled in a prospective multicenter study (PERISCOP). Exercise testing, echocardiography, and 24-h ambulatory ECG monitoring were performed at day 20+/-10 after coronary bypass surgery. Follow-up was performed 1 year after coronary bypass surgery. Causes of all hospitalisation and death occurring within 1 year were documented and classified by an End-point Committee. The principal endpoint was the combination of all-cause deaths and cardiovascular events requiring hospitalisation (myocardial infarction, unstable or severe angina, stroke, congestive heart failure). RESULTS: The 1-year frequency of first events was 155 (8%). In multivariate analysis, exercise duration <420s (RR=1.68; 95% CI: 1.13-2.49), exercise induced ST segment depression >1mm (RR=1.90; 95% CI: 1.18-3.05), and left ventricular (LV) dysfunction (wall motion index <1.15) (RR=1.97; 95% CI: 1.10-3.51) were independent predictors of cardiovascular events and deaths. Ambulatory ECG monitoring had no predictive value. CONCLUSIONS: Exercise testing and echocardiography performed early after coronary bypass surgery are able to identify high-risk patients who may benefit from intensive secondary prevention.

Assessment of anti-ischemic and antianginal effect at trough plasma concentration and safety of trimetazidine MR 35 mg in patients with stable angina pectoris: a multicenter, double-blind, placebo-controlled study.

OBJECTIVE: The study aimed to assess, at trough plasma concentration, the anti-ischemic and antianginal efficacy and tolerability of trimetazidine modified release (MR) 35 mg taken twice daily by patients with stable angina pectoris. DESIGN: This multicenter, randomized, double-blind, placebo-controlled, international study started with a run-in period of 3 weeks with atenolol 50 mg/day and placebo, followed by a 6-month treatment period with once daily atenolol 50 mg and twice daily trimetazidine MR 35 mg or placebo. PATIENTS: The study involved 223 patients with stable angina pectoris (class II or III of the Canadian Cardiovascular Society [CCS] classification). 180 patients were analyzed in the full analysis set (FAS) following the intention to treat principle (ITT) and 167 patients were analyzed in the per protocol set (PPS). The PPS data are presented here. INTERVENTIONS: Two exercise tolerance tests (ETTs) were performed during the run-in period in order to assess the stability of exercise tolerance before angina pectoris and significant ST segment depression. Efficacy was assessed by a third ETT performed after 8 weeks of treatment, at trough, 12 hours after the intake of the drug. Safety was evaluated over the 6-month duration of the study. MAIN OUTCOMES MEASURES: Time to 1 mm ST segment depression. RESULTS: Time to 1 mm ST segment depression was increased by 44 seconds more in the trimetazidine MR 35 mg group than in the placebo group (p = 0.005). A significant difference was also evidenced for the time to onset of angina pectoris (p = 0.049) and for the reason for stopping the exercise (p = 0.02). No difference between groups was found for safety parameters. CONCLUSION: This study demonstrates the anti-ischemic and antianginal efficacy of trimetazidine MR 35 mg twice daily at trough plasma concentrations in patients with stable angina pectoris receiving atenolol 50 mg/day. Furthermore, the drug is well tolerated over 6 months.

Medical treatment of myocardial ischemia in coronary artery disease: effect of drug regime and irregular dosing in the CAPE II trial.

OBJECTIVES: The Circadian Anti-ischemia Program in Europe (CAPE II) compared the efficacy of amlodipine and diltiazem (Adizem XL) and the combination of amlodipine/atenolol and diltiazem (Adizem XL)/isosorbide 5-mononitrate on exercise and ambulatory myocardial ischemia during regular therapy and after omission of medication. BACKGROUND: The optimal medical therapy for ischemia suppression and the impact of irregular dosing using agents with different pharmacologic properties has not been established in patients with coronary disease. METHODS: Patients with > or = 4 ischemic episodes or > or = 20 min of ST segment depression on 72-h electrocardiogram were randomized to amlodipine 10 mg once daily or diltiazem (Adizem XL) 300 mg once daily in a 14-week double-blind randomized multicountry study. In the second phase, atenolol 100 mg was added to amlodipine and isosorbide 5-mononitrate 100 mg to diltiazem (Adizem XL). Ambulatory monitoring (72 h) and exercise testing were repeated after both phases, on treatment and after a 24-h drug-free interval. RESULTS: Both monotherapy with amlodipine and diltiazem (Adizem XL) were effective on symptoms and ambulatory and exercise ischemia. Combination therapy reduced ischemia further, with amlodipine/atenolol superior to diltiazem (Adizem XL)/isosorbide 5-mononitrate. Amlodipine/atenolol was significantly superior during the drug-free interval with maintenance of ischemia reduction. CONCLUSIONS: Amlodipine, with its intrinsically long half-life alone or together with beta-blocker, is likely to produce superior ischemia reduction in clinical practice when patients frequently forget to take medication or dose irregularly.