CCB indicates calcium channel blocker; COR, Class of Recommendation; HF, heart failure; IV, intravenous; LOE, Level of Evidence; LV, left ventricular; MACE, major adverse cardiac event; N/A, not available; NSAIDs, nonsteroidal anti-inflammatory drugs; NSTE-ACS, non ST-elevation acute coronary syndromes; and NTG, nitroglycerin. Amsterdam et al 2014 AHA/ACC NSTE-ACS Guideline e361 to 0.4 mg) every 5 minutes for up to 3 doses, after which an assessment should be made about the need for intravenous nitroglycerin if not contraindicat- (Level of Evidence: C) 2. Intravenous nitroglycerin is indicated for patients with NSTE-ACS for the treatment of persis- tent ischemia, HF, or hypertension.219 224 (Level of Evidence: B) Class III: Harm 1. Nitrates should not be administered to patients with NSTE-ACS who recently received a phosphodiester- ase inhibitor, especially within 24 hours of sildenafil or vardenafil, or within 48 hours of tadalafil.225 227 (Level of Evidence: B) Nitrates are endothelium-independent vasodilators with peripheral and coronary vascular effects. By dilating the capac- itance vessels, nitrates decrease cardiac preload and reduce ventricular wall tension. More modest effects on the arterial circulation result in afterload reduction and further decrease in . This may be partially offset by reflex increases in heart rate and contractility, which counteract the reduction in MVO2 unless a beta blocker is concurrently administered. Nitrates also dilate normal and atherosclerotic coronary arteries and increase coronary collateral flow. Nitrates may also inhibit RCTs have not shown a reduction in MACE with nitrates. The rationale for nitrate use in NSTE-ACS is extrapolated from pathophysiological principles and extensive (although uncontrolled) clinical observations, experimental studies, and clinical experience. The decision to administer nitrates should not preclude therapy with other proven mortality-reducing interventions such as beta blockers. 