The Gruppo Italiano per lo Studio della Sopravvivenza nell Infarto Miocardico (GISSI)-3 and International Study of Infarct Survival (ISIS)-4 trials included almost 80000 patients with STEMI and found no difference in mortality with the use of nitrates (7.0% for those treated versus 7.2% who received pla- Thus, the ACC/AHA guidelines for STEMI do not recommend nitroglycerin to reduce events but only to relieve ischemic pain or acute hypertension or to manage pulmonary congestion at a Level of Evidence C. Nitrates should be used with caution in patients with inferior STEMI and are contraindicated if right ventricular infarction is present because of their effects on low- ering preload. The guidelines caution that nitroglycerin should not be used at the expense of agents with proven benefits on outcomes such as -blockers orACE inhibitors (below), particu- larly in the convalescent stage.190 Experience with nitrates in non ST-segment elevationACS is largely extrapolated from STEMI because clinical trials in UA/ NSTEMI have been relatively small. Nitroglycerin should be first administered via the sublingual route in patients with ACS, which can be followed by intravenous or topical administration of nitroglycerin or oral administration of longer-acting nitrate preparations. Patients treated with nitrates need to be monitored for potential adverse effects, in particular profound hypotension, which can exacerbate ischemia. Patients at increased risk include the elderly, individuals who are volume depleted, or those have tolerance is a problem even within the first 24 hours, and attempts should be made to minimize this by reducing intravenous doses and implementing intermittent dosing by nonintravenous routes once the patient is stable from an ischemic standpoint. -Blockers are a cornerstone of ACS treatment because of their ability to reduce both heart rate and BP and thus myo- cardial oxygen demand. These agents were among the first therapies demonstrated to reduce infarct size. 