[Therapy with nitro derivatives and the development of tolerance: a comparative study with stress ECG and...

The ECG stress test represents the most commonly-used technique to evaluate the occurrence of nitroglycerin tolerance. It acts by increasing cardiac O2 demand with resulting insufficient blood flow through a stenotic coronary artery and development of cardiac ischemia. However, other tests are also potentially suitable, such as the ECG-dipyridamole test. The aim of the present study was to evaluate the acute response of ECG-dipyridamole and ECG-stress tests to nitroglycerin. In particular, the development of nitroglycerin tolerance during chronic therapy was evaluated with both tests in patients with stable angina. Eleven patients (8 men and 3 women) with CAD proven by a previous coronarography, a known history of stable angina within at least six months and a positive response to both the tests were studied. At the end of a seven-day wash-out period, all patients were positive to initial ECG-stress and ECG-dipyridamole tests; after 3 days a new evaluation was carried out (Effort 0 and Dip 0) and this confirmed the previous results. We performed a randomized trial in two phases: acute and chronic therapy. In the acute phase, all patients underwent ECG-stress and ECG-dipyridamole tests (Effort 1 and Dip 1) in a randomized fashion one day apart, four hours after administration of a 10 mg/24 h nitroglycerin patch. The chronic phase consisted of 25 days of continuous treatment with a nitroglycerin patch. The two tests (Effort 2 and Dip 2) were always repeated after four hours of the morning therapy. Nitroglycerin does not modify the hemodynamic response to dipirydamole in either acute or chronic treatment. Lastly, our data confirm the efficacy of nitroglycerin on stress and dipyridamole tests after acute administration. Nitroglycerin tolerance is confirmed by both tests although with different patterns. ECG stress test showed nitroglycerin tolerance because time to ischemia and max ST deteriorated during chronic therapy. Moreover, the ECG-dipyridamole test showed nitroglycerin tolerance because five patients with a negative acute test (Dip 1) became positive during chronic therapy (Dip 2).