Intensive multifactorial intervention for stable coronary artery disease: optimal medical therapy in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial.

OBJECTIVES: This paper describes the medical therapy used in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial and its effect on risk factors. BACKGROUND: Most cardiovascular clinical trials test a single intervention. The COURAGE trial tested multiple lifestyle and pharmacologic interventions (optimal medical therapy) with or without percutaneous coronary intervention in patients with stable coronary disease. METHODS: All patients, regardless of treatment assignment, received equivalent lifestyle and pharmacologic interventions for secondary prevention. Most medications were provided at no cost. Therapy was administered by nurse case managers according to protocols designed to achieve predefined lifestyle and risk factor goals. RESULTS: The patients (n = 2,287) were followed for 4.6 years. There were no significant differences between treatment groups in proportion of patients achieving therapeutic goals. The proportion of smokers decreased from 23% to 19% (p = 0.025), those who reported <7% of calories from saturated fat increased from 46% to 80% (p < 0.001), and those who walked >or=150 min/week increased from 58% to 66% (p < 0.001). Body mass index increased from 28.8 +/- 0.13 kg/m(2) to 29.3 +/- 0.23 kg/m(2) (p < 0.001). Appropriate medication use increased from pre-randomization to 5 years as follows: antiplatelets 87% to 96%; beta-blockers 69% to 85%; renin-angiotensin-aldosterone system inhibitors 46% to 72%; and statins 64% to 93%. Systolic blood pressure decreased from a median of 131 +/- 0.49 mm Hg to 123 +/- 0.88 mm Hg. Low-density lipoprotein cholesterol decreased from a median of 101 +/- 0.83 mg/dl to 72 +/- 0.88 mg/dl. CONCLUSIONS: Secondary prevention was applied equally and intensively to both treatment groups in the COURAGE trial by nurse case managers with treatment protocols and resulted in significant improvement in risk factors. Optimal medical therapy in the COURAGE trial provides an effective model for secondary prevention among patients with chronic coronary disease. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; NCT00007657).

Secondary stroke prevention with ximelagatran versus warfarin in patients with atrial fibrillation: pooled analysis of SPORTIF III and V clinical trials.

BACKGROUND AND PURPOSE: Patients with nonvalvular atrial fibrillation and prior stroke or transient ischemic attack (TIA) are at high risk for recurrent stroke. We investigated whether ximelagatran was noninferior to warfarin in patients with prior stroke or TIA. METHODS: We analyzed pooled data from the SPORTIF III and V trials in patients with prior stroke/TIA. The primary outcome was the composite annual rate of both ischemic and hemorrhagic strokes and systemic embolic events. Secondary analyses considered ischemic and hemorrhagic strokes separately, bleeding, and nonrandomized, concomitant therapy with aspirin < or =100 mg/d. RESULTS: Patients from SPORTIF III (n=3407) and SPORTIF V (n=3922) trials were categorized by prior stroke/TIA (21%) versus no prior stroke/TIA (79%) and by treatment group (ximelagatran vs warfarin). The primary event rate in patients with prior stroke/TIA was 2.83%/y with ximelagatran and 3.27%/y with warfarin (absolute difference, -0.44%; 95% CI, -1.88 to1.01; P=0.625). In those without prior stroke/TIA, the primary event rate was 1.31%/y with ximelagatran and 1.26%/y with warfarin (P=NS). Ischemic strokes outnumbered cerebral hemorrhages with both warfarin (31 of 36) and ximelagatran (30 of 32) treatment (difference between treatments was not significant). Combining aspirin with either anticoagulant was associated with higher rates of major bleeding (1.5%/y with warfarin and 4.95%/y with warfarin plus aspirin, P=0.004; 2.35%/y with ximelagatran and 5.09%/y with ximelagatran plus aspirin, P=0.046) but not lower rates of primary events. CONCLUSIONS: Ximelagatran was at least as effective as well-controlled warfarin for the secondary prevention of stroke. The nonrandomized, concomitant treatment with aspirin and anticoagulation was associated with increased bleeding without evidence of a reduction in primary outcome events.

Prediction of the recurrence of atrial fibrillation after cardioversion in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study.

BACKGROUND: The early recurrence of atrial fibrillation (AF) after cardioversion and the need for frequent cardioversions to maintain sinus rhythm are important clinical features of AF management. METHODS: We evaluated patients in the AFFIRM study whose qualifying episode of AF lasted > or = 48 hours and was terminated by cardioversion. Clinical, electrocardiographic, and echocardiographic risk factors associated with AF recurrence within 2 months of cardioversion and > or = 2 cardioversions during the first year were identified using multivariate analysis in 1293 eligible patients. RESULTS: The risk factors for the recurrence of AF within 2 months of cardioversion were no coronary artery disease and an electrocardiographic lead II P-wave duration of > 135 milliseconds. In the subset of patients not taking antiarrhythmic drug therapy, the multivariate risk factors were no coronary artery disease, second or greater episode of AF, left ventricular ejection fraction < 0.50, and mitral valve thickening. Significant risk factors for the need for > 2 cardioversions in the first year in patients taking antiarrhythmic medication were left atrial diameter > 4.5 cm and mitral valve thickening. The overall sensitivity and specificity of these parameters for recurrence and repeated cardioversion are low. CONCLUSION: There are several risk factors for difficulty maintaining sinus rhythm after cardioversion of persistent AF. The clinical predictive value of these factors is low, and they probably should not be used to justify withholding rhythm control efforts in patients who might benefit from sinus rhythm.

Onset of acute myocardial infarction during sleep.

BACKGROUND: Analysis of the chronology of acute cardiovascular events may provide important pathophysiologic information. There is a circadian pattern in the onset of acute myocardial infarction (AMI) with a mid-morning peak, ascribed to the catecholamine surge that accompanies awakening and assuming the upright posture. However, in up to 27% of patients the onset of AMI occurs during sleep (without apparent precipitating factors). The reasons for this finding are unknown. HYPOTHESIS: The aim of the study was to determine why the onset of symptoms of AMI occurs during sleep in some individuals rather than being precipitated by known trigger factors such as physical exertion. METHODS: Using the database from a large multicenter clinical trial, patients were grouped according to whether or not they were awakened from sleep by the symptoms of AMI. RESULTS: In all, 870 of 3,309 patients (26%) were awakened by AMI. In general, these patients were older and sicker, with poorer left ventricular function, lower quality of life indices, more frequent heart failure, lower ejection fractions, higher incidence of angina, and a greater frequency of atrial arrhythmias. On multivariate analysis, only low ejection fraction and older age were independently associated with awakening by the symptoms of AMI. CONCLUSIONS: Patients who are older and sicker are more likely to be awakened from sleep by the onset of symptoms of AMI. Although the reasons are unknown, we speculate that these individuals are less active and therefore less vulnerable to established trigger factors such as vigorous physical exertion.