Long-Term Nitrate Therapy — A Decade of Changing Concepts

Abstract

Until 1980, the effectiveness of long-term treatment with nitrates was taken for granted even though, in the literature, this had never been documented with certainty. With the intention of confirming their effectiveness, Rudolph and his coworkers began performing controlled studies in 1978, the results of which, however, were suggestive of a development of tolerance and rendered questionable the indication for chronic use of nitrates in the treatment of angina pectoris. This conclusion was based on the finding that during long-term treatment neither 20 mg, 40 mg, nor 60 mg isosorbide dinitrate (ISDN) in sustained-release form three times daily led to a decrease in the amount of exercise-induced ST-segment depression, nor did the rate of anginal attacks or nitrate consumption decrease [1] (Fig. 1). In 1980, Parker added to these findings his report on circulatory tolerance associated with a partial loss of antianginal effects of ISDN. He concluded, however, that maintenance of the beneficial effect would require administration of the drug every 2–3 h.