What are the long-term safety concerns of nitroglycerin therapy?
Long-term nitrate therapy can offset the beneficial short-term ischemic preconditioning effects. Long-term nitroglycerin therapy is associated with endothelial dysfunction via accumulation of the same oxygen free radicals that seem to be beneficial in short-term administration. Oxygen free radical accumulation increases arterial sensitivity to vasoconstrictors such as angiotensin II, which can be counteracted by concomitant treatment with an ACE inhibitor or hydralazine. Importantly, these physiological changes are independent of dose or the presence or absence of a nitrate-free interval and can result in a decrease in the anginal threshold during the nitrate-free interval. Further research to better understand the balance between the long-term benefits and safety concerns of these compounds is warranted in patients with SIHD.