CABG indicates coronary artery bypass graft; CAD, coronary artery disease; cTn, cardiac troponin; LBBB, left bundle-branch block; LVH, left ventricular hypertrophy; MI, myocardial infarction; MVO2 , myocardial oxygen consumption; PCI, percutaneous coronary intervention; and URL, upper reference limit. Modified from Thygesen et al.21 Table B. Pharmacological Therapy in Older Patients With NSTE-ACS Age-Related Pharmacological Change Clinical Effect Dose-Adjustment Recommendations Additional Precautions General principles In renal function (CrCl*): drug clearance, water/ electrolyte balance SCr unreliable measure of renal function in older adults Change in body composition Fat, lean body mass/total water GI absorption Levels renally cleared drug Risk high/low electrolyte levels Levels hydrophilic agents Levels lipophilic agents Longer time to reach steady- state lipophilic agents Calculate CrCl in all pts renal- dose accordingly Start at lowest recommended dose, titrate up slowly Avoid interacting drugs Consider doses in women, malnourished, hypovolemic Caution fall risk with BP agents and diuretics Monitor for ADR, especially delirium Frequent monitoring of renal function/electrolytes Minimize polypharmacy watch for drug-drug interactions ASA Hydrophilic; levels with total body water; age-related plasma concentration for similar dose Bleeding risk with age, dehydration, frailty, diuretics Maintenance=81 mg/d (lowest possible dose) Bleeding with NSAIDs, other AP, AC, AT; risk peptic ulcer with NSAIDs Nitrates Sensitivity Hypotensive response with baroreceptor response Lowest dose possible, especially if hypovolemic Risk OH, syncope, falls ACE inhibitors First-pass metabolism (some) with effect; enalapril effect May have effect May need dose Risk AKI and K+ and effect with NSAIDs; avoid K-sparing diuretics ARBs No significant age-related changes No age-related clinical changes None Risk AKI and K+ and effect with NSAIDs; avoid K-sparing diuretics Alpha blockers Sensitivity; BP with baroreceptor response BP; OH Avoid when possible Risk OH, falls, syncope, especially with loop diuretics Beta blockers Myocardial sensitivity ( postreceptor signaling), conduction system sensitivity Bradycardia/heart block; BP effect vs. younger pts May need dose with age Caution conduction system blocks (Continued) CCBs DHPs (amlodipine; nifedipine) Lipophilic; hepatic and overall clearance; fat storage; sinus node sensitivity; baroreceptor response to BP BP more than non DHP and with age; edema hypotension, bradycardia Initiate low dose, titrate cautiously Inhibits clopidogrel; risk OH, falls, syncope; most potent BP first 3 mo, then less Non-DHP (verapamil; diltiazem) Hepatic and overall clearance; less PR prolongation than DHP and with age; negative inotropy; SA node sensitivity and HR than DHP and with age; AV conduction with age; baroreceptor response to BP BP more with tage; edema; heart block; hypotension; bradycardia and bradyarrhythmias with age Initiate low dose, titrate cautiously Risk OH, falls, syncope; consider rhythm monitoring Diuretics Diuretic/natriuretic response, EC space, drug concentration if GFR; baroreceptor response to volume shifts Sensitivity; hypotension; risk hypokalemia/hypomagnesemia/ hyponatremia; diuretic effect with GFR; risk hypovolemia- thirst May need doses if GFR; may need dose if cotreating with NSAIDs Monitor Na+ , K+ levels; risk OH/falls; With NSAIDs: natriuretic and diuretic effect, K+ Heparins UFH Hydrophilic; concentration, especially if lean body mass or plasma proteins; levels with age Bleeding risk with age; more potent anticoagulation per dose with age; weight-based dosing but with precautions for shift in body composition Weight-based 60 U/kg loading dose + 12 U/kg/h INF. 