Summary

Objective: Compare antiischemic response as reviewed by 24-hour Holter monitoring and maximal stress

testing, as well as clinical tolerability with Amlodipine (A) or Isosorbide Dinitrate – prolonged action formulation (N), in oral regimens of respectively 5 to 10 mg (od) or 40 to 80 mg (bid) in patients with history of stable angina pectoris, positive stress test, and recent transitory myocardial ischemia (Holter).

Patients and Methods: Open, prospective, consecutive, parallel, randomized study with 33 patients with angiographycaly proven CHD not referred to revascularization recruited from 2 cardiology centers from those with transient ischemia in recent Holter monitorings. After 2 weeks of wash-out from all antianginal drugs, they were randomized (group A or group N) to the initial dose of both medications, followed by forced uptitration till 12 weeks of study with the possiblity of downtitrating back in case of inadequate tolerance.

Results: Group A 12 patients (4 female) 63 ± 4 years-old. Group N: 12 patients (5 female) 62 ± 9 years-old. Many of the patients have had a previous MI, and risk factors for CHD, but not differently between groups.

Group A experienced significant lowering of DBP. Total ischemic burden (24 hours) at baseline was more present (p<0.05) in group A (316.8 minutes out of 384 hours of recording) in group N (117.0 minutes outof 360 hours).

Significant (p<0.05) changes in group A were: 1) DBP supine at rest (from 82.5 ± 8.4 mmHg to 76.0 ± 6.3 mmHg); 2) Lowering of LDL-cholesterol (from 146 ± 29 mg/dL to 132 ± 28mg/dL); 3) Less silent ischemic events in 24 hours from 3.3 ± 3.2 to 1.6 ± 2.2; 4) Reduction of the total ischemic duration in 65.5% (p=0.07); 5) Improving stress test tolerance from 6.4 + 2.7 minutes to 8.0 ± 2.3 minutes; 6) Increase in the ergometric load from 37 mph% to 50 mph% (33.7% change). As for group N: 1) Improving stress test tolerance from 6.0 + 2.6 minutes to 7.2 + 2.1 minutes; 2) Reduction of the total ischemic duration in 63.1% 3) Less silent ischemic events in 24 hours from 2.9 ± 3.3 to 1.1 ± 2.1.

Conclusion: Due to the lack of comfirmatory transient ischemia in control Holters at baseline (43.7% in group A and 33% in group N) one could once again demonstrate the low reproductibility of this clinical sign of ischemia. DBP lowering only in group A can be explained by Amlodipine’s known mechanism in this disease. Amlodipine and Dinitrate are effective in treating ischemic episodes with very similar effects in lowering total ischemic burden. Both also act by improving stress time tolerance, respectively in 25 and 20%, whereas only group A with 33.7% increase in ergomectric load. Ankle edema in group A (12.5%) and head ache in group N (41.2%) were consistent with reported rates.