Effect of amlodipine, atenolol and their combination on myocardial ischemia during treadmill exercise and ambulatory monitoring. Canadian Amlodipine/Atenolol in Silent Ischemia Study (CASIS) Investigators.

OBJECTIVES: This study compared the effects of amlodipine, atenolol and their combination on ischemia during treadmill testing and 48-h ambulatory monitoring. BACKGROUND: It is not known whether anti-ischemic drugs exert similar effects on ischemia during ambulatory monitoring and exercise treadmill testing. METHODS: Patients with stable coronary artery disease and ischemia during treadmill testing and ambulatory monitoring were randomized to receive amlodipine (n = 51) or atenolol (n = 49). Each group underwent a counterbalanced, crossover evaluation of single drug and placebo, followed by evaluation of the combination. RESULTS: Amlodipine and the combination prolonged exercise time to 0.1-mV ST segment depression by 29% and 34%, respectively (p < 0.001) versus 3% for atenolol (p = NS). During ambulatory monitoring, the frequency of ischemic episodes decreased by 28% with amlodipine (p = 0.083 [NS]), by 57% with atenolol (p < 0.001) and by 72% with the combination (p < 0.05 vs. both single drugs; p < 0.001 vs. placebo). Suppression of ischemia during exercise testing and ambulatory monitoring was similar in patients with and without exercise-induced angina. Exercise time to angina improved by 29% with amlodipine (p < 0.01), by 16% with atenolol (p < 0.05) and by 39% with the combination (p < 0.005 vs. placebo, atenolol and amlodipine). In patients with angina, total exercise time improved by 16% with amlodipine (p < 0.001), by 4% with atenolol (p = NS) and by 19% with the combination (p < 0.05 vs. placebo and either single drug). In those patients without angina, no therapy significantly improved total exercise time. CONCLUSIONS: Ischemia during treadmill testing was more effectively suppressed by amlodipine, whereas ischemia during ambulatory monitoring was more effectively suppressed by atenolol. The combination was more effective than either single drug in both settings.

Comparative trial of doxazosin and atenolol on cardiovascular risk reduction in systemic hypertension. The Alpha Beta Canada Trial Group.

The impact of treating hypertension on coronary artery disease has been less than anticipated from epidemiologic studies of cardiovascular risk factors. It has been suggested that adverse effects on lipids of traditional diuretic or beta-blocker regimens may diminish the potential benefits of antihypertensive therapy. Patients with mild to moderate systemic hypertension and normal serum lipids (n = 191) were randomly assigned to doxazosin or atenolol. After dose titration to goal diastolic blood pressure of < or = 90 mm Hg, patients continued treatment for a further 24 weeks. The principal outcome measurement was overall coronary artery disease risk using the Framingham formula. Relative risk of coronary artery disease was reduced to 92.4% of baseline (p = 0.144) for evaluable patients taking atenolol (n = 71), and to 74.6% (p = 0.0001) for patients taking doxazosin (n = 51): atenolol versus doxazosin, p = 0.0074. In patients who met the strict Framingham criteria for age, total cholesterol and high density lipoprotein cholesterol, the relative risk of coronary artery disease for patients taking atenolol (n = 23) was reduced to 86.2% of baseline (p = 0.082), and to 67.4% (p = 0.0004) for patients taking doxazosin (n = 18): atenolol versus doxazosin, p = 0.049. Alpha blockade with doxazosin was more effective than beta blockade with atenolol in reducing the risk of coronary artery disease in hypertensive patients because of the beneficial effects of doxazosin on high-density lipoprotein cholesterol. Overall withdrawal rate was greater in the alpha-blocker group because of a lower response rate and more adverse events.

Relative importance of psychologic traits and severity of ischemia in causing angina during treadmill exercise. Canadian Amlodipine/Atenolol in Silent Ischemia Study (CASIS) Investigators.

OBJECTIVES: This study was conducted to compare the influence of psychologic traits versus ischemia severity on the occurrence of angina during treadmill exercise. BACKGROUND: Some studies suggest that angina is associated with certain psychologic traits, whereas others show an association with more severe ischemia. The relative influence of these two factors and the extent to which they interact are not known. METHODS: Off-drug treadmill exercise testing and a battery of psychologic tests were performed on 122 patients with known coronary artery disease. Psychologic tests measured sensitivity to physical symptoms, denial and deception, type A behavior, anger, hostility, depression, marital adjustment and amount of external stress. Stepwise logistic regression was used to determine the independent association of psychologic traits, ischemic threshold and exercise tolerance with the occurrence of angina. RESULTS: Angina during treadmill exercise was reported by 66 of 122 patients. On univariate testing, angina was positively associated with sensitivity to physical symptoms (p < 0.001), type A behavior (p = 0.021) and depression (p = 0.032) and was negatively associated with exercise tolerance (p < 0.001) and work load threshold for ischemia (p < 0.01). Multivariate analysis revealed independent and additive associations of angina with sensitivity to physical symptoms (p = 0.003), exercise capacity (p = 0.003) and work load threshold for ischemia (p = 0.018). Once these were included in a logistic model, depression and type A behavior were no longer significant. Other psychologic traits showed no association with angina. CONCLUSIONS: Sensitivity to physical symptoms, ischemic threshold and exercise tolerance are independently associated with angina, with sensitivity to physical symptoms having the stronger influence. The physiologic and psychologic mechanisms underlying symptom perception have an influence on angina that is independent of and additive to the severity of underlying ischemia.

Piroxicam suppositories for osteoarthritis and rheumatoid arthritis: an open multicentre study in 116 patients.

Efficacy and toleration of piroxicam suppositories 20 mg, given once daily for 4 weeks were assessed in 96 patients suffering from degenerative joint disease and 20 patients suffering from rheumatoid arthritis. The mean scores of objective parameters measured (tenderness, swelling, limitation of movement) decreased significantly 2 and 4 weeks after initiation of therapy. Patients' self-evaluation of pain and stiffness also significantly improved during the trial. Overall evaluation of efficacy and toleration were excellent or good in more than 80% of patients. Local toleration was excellent in all but two patients.