(Use should be limited to carvedilol, metoprolol succinate, or bisoprolol, which have been shown to reduce risk of death.)571,760 763 (Level of Evidence: A) Class IIb 1. Beta blockers may be considered as chronic therapy for all other patients with coronary or other vascular disease. (Level of Evidence: C) Beta-receptor activation is associated with increases in heart rate, accelerated AV nodal conduction, and increased con- tractility, which contribute to increased myocardial oxygen demand. Decreases in the rate BP product, AV nodal con- duction, and myocardial contractility from beta blockers reduce myocardial oxygen demand, counteracting beta- receptor activity and contributing to a reduction in angina onset, with improvement in the ischemic threshold during exercise and in symptoms.764 769 These agents significantly reduce deaths and recurrent MIs in patients who have suffered a MI and are especially effective when a STEMI is complicated by persistent or recurrent ischemia or tachyarrhythmias early after the onset of infarction.757 How- ever, no large trials have assessed effects of beta blockers on survival or coronary event rates in patients with SIHD. Many clinically important differences exist between beta blockers. These differences relate to cardioselectivity, pres- ence of intrinsic sympathomimetic activity or vasodilating properties, and relative lipid solubility in the presence of renal or hepatic impairment. Despite these differences, all beta blockers seem to be equally efficacious in SIHD.765 767,770,771 Two large long-term follow-up studies investigating the prognostic importance of heart rate showed that all-cause mortality rate progressively increases with higher resting heart rate after adjustment for exercise capacity, age, diabetes mellitus, systolic arterial pressure, BMI, and level of physical activity.772,773 Therefore, it is recommended that beta-blocker dosing be adjusted to limit the heart rate to 55 to 60 beats per minute at rest. 