Nitroglycerin in chronic stable angina pectoris

Abstract

Recent evidence suggests that traditional approaches to the use of nitroglycerin (NTG) in patients with chronic stable angina should be reconsidered. Studies of the time to onset of hemodynamic effects of sublingual NTG suggest that the first detectable effect, on left ventricular end-diastolic pressure, occurs at a mean of 90 seconds after administration. By timing the duration of exertional angina after formal exercise testing, one can show that, on average, chest pain is gone within 2 minutes. Thus, in many patients, it is unlikely that sublingual NTG can further shorten episodes of exertional angina. The value of sublingual NTG is greater when patients exercise beyond the onset of pain, when patients have more protracted episodes of exertional pain and when there is a need to resume immediately the activity that brought on the angina. With respect to angina prophylaxis, the pioneering studies of Parker and co-workers have now been amply confirmed. Continuous nitrate administration by oral, transdermal or intravenous routes results in substantial, albeit incomplete, tolerance. Tolerance occurs even when high plasma concentrations are achieved and persist over time. Tolerance can eliminate responsiveness to sublingual NTG. Preliminary evidence suggests that tolerance to the antianginal effects of NTG at maximal exercise may be more marked than tolerance to the effects of NTG on silent ischemia at submaximal activity levels. The significance of this dissociation in time course and its implications are unclear at this time. Three potential strategies exist for avoiding NTG tolerance in patients with chronic stable angina. Administration of a thiol donor has been shown to reverse some hemodynamic manifestations of tolerance. Whether it can be used effectively for prevention of antianginal tolerance is unclear. Intermittent nitrate administration can, clearly, avoid antianginal tolerance and is quite practical for many patients with chronic stable angina. Finally, increased reliance on short-acting nitrates wherever possible seems appropriate.