Rx:PREVENTION SCREENING AND RX (Natl Choles Educ Program—JAMA 2001;285:2486). Use diet and exercise 1st, meds after 3+ mo

1st: LDL rx of all pts 160 mg % (4.1 mM/I)

• if >130 mg % (3.4 mM/L), rx pts w 2+ risk factors (smoking, HT, low HDL, Fm h/o ASCVD before age 55 yr in men or 65 yr in women, age >45 yr men or 55 yr women);
• if >100 mg % rx pts w h/o ASHD, periph artery disease, carotid disease, or AAA, hence secondary prevention; or if 10-yr ASHD risk >20% by Framingham tables (see NCEP charts)

2nd: After above accomplished, rx triglycerides >200 mg % and/or low HDL (Nejm 2005;353:1252) w nicotinic acid 1st, and/or fibrates 2nd, and/or statins 3rd. But unclear that rx of fasting triglyceride levels alone helps unless over 1000 mg % where rx indicated to prevent pancreatitis (Nejm 2007;357:1009); studies skewed by elevations in diabetes (Jama 2007;298:299, 309, 336)

Primary prevention drug rx w pravastatin 40 mg po hs in asx men over age 40 yr w LDL 150 mg % had improved survival, NNT-5 = 40 (Nejm 1995;333:1301); while lovistatin 20-40 mg po qd in pts w avg LDL and total cholesterols but low HDL, men and women up to age 75 yr decr ASHD events, NNT-5 = 50 (Jama 1998;279:1615, 1679) but significant limitations (ACP J Club 1998;129[3]:58). Decrements in attention and psychomotor speed are induced by dietary or statin cholesterol lowering (Am J Med 2000;108:538:547).

Disputed:

• in women (clearly not, or barely helpful even in those w CAD—Jama 2004;291:2243), young and old, has been disputed unless h/o ASCVD (Ann IM 2000;132:769, 780, 833; 1996;124:518 vs 505; Jama 1995;274:1152)
• in children who may be harmed by rx (Jama 1995;273:1429, 1461 vs Peds 1991;87:943) although statins experimentally used in adolescent boys w heterozygous familial hypercholesterolemia (Jama 1999;282:137)
• in elderly, esp women, and in men and women over 65-70 yr (Jags 2005;53:219; Jama 1994;272:1335, 1372) vs yes for elderly men (Ann IM 1990;113:916) though risk curve is U-shaped (Jags 2004;52:1975, 1981). Marginally helpful for LDL >160 in men, not women (Jags 2005;53:2159)
• Need to rx triglyceridemia to less than pancreatitis causing levels unclear (Jama 2009;302:1993)

Secondary prevention, is data supported (Nejm 1997;336:332; Ann IM 1996;124:518 vs 505; Jama 1995;274:1152), by decreasing cholesterol in patients with known CAD, eg, Scandinavian simvastatin study of CAD pts showed a 9% absolute risk reduction = NNT-5 = 11 (Lancet 1994;344:1383). In women, MI incidence but not overall death rate reduced (Jama 2004;291:2243)

Exercise, at least walk 2 mi qd or run up to 40 mi q wk helps HDL and ASHD risk in men and women (Nejm 1996;334:1298)

Diet: helps decr LDL only if combined w exercise (Nejm 1998;339:12)

• Lose weight.
• Low cholesterol <300 mg qd (Nejm 1993;328:1213)
• Polyunsaturated and monounsaturated fats like olive oil (Nejm 1986;314:745) or canola or soy oil, any of which reduce death in post-MI pts from 5% to 1%/yr (Lancet 1994;343:1454); phyto-estrogens like sitosterol or sitostanol-ester margarine reduce LDL by 10-15% and may improve ASHD (Med Let 1999;41:56; Nejm 1995;333:1308); stearic and oleic, but not palmitic saturated fats are ok (Nejm 1988;318:1244); but transoleic fatty acids just as bad, so margarine no good (Nejm 1990;323:439); partially hydrogenated (trans) fatty acid worsen LDL (Nejm 1999;340:1933, 1994), so liquid oils better than semiliquid, better than soft, better than stick margerines, and because of better total/HDL ratios, butter not as bad as stick margarine
• Fish or fish oil pills decrease triglycerides, but elevate LDL (Ann IM 1989;111:900); slows or reverses ASHD progression (Ann IM 1999;130:554), and also help BP (Nejm 1990;322:795)
• Oleic and -linolenic acid in walnuts (Ann IM 2000;132:538; Nejm 1993;328:603)
• Soy protein 20-40 gm qd (Nejm 1995;333:276)
• Alcoholic drinks 2-4 qd (Nejm 2001;344:549; BMJ 1996;312:731, 736)
• Garlic 1/2 to 1 clove qd (decreases cholesterol by 9%—Ann IM 1993;119:545) vs no help by double-blind RCT (Arch IM 1998;158:1189; Jama 1998;279:1900)
• Soluble fiber (Nejm 1993;329:21) like psyllium (Metamucil) 4.3-gm pkt in water bid-tid (5% cholesterol reduction—Ann IM 1993;119:545; Arch IM 1989;151:1597; 1988;148:292) or oat bran 56 gm qd (Jama 1991;265:1833) or beans 100 gm/d (Med Let 1988;30:111)

MEDICATIONS (Nejm 1999;341:498; Med Let 2001;43:43): all have a nearly 50% 1-yr cessation rate by pts in practice except HMG-CoA reductase drugs (25%) (Nejm 1995;332:1125)

HMG-CoA reductase inhibitors (statins) (Med Let 2003;45:17; 2004;46:93); po hs because cholesterol synthesis occurs mostly at night, all may also stabilize plaques, retard thrombosis (Jama 1998;279:1643), and decr vascular inflammation (CRP levels—Jama 2001;286:64); and all may slow osteoporosis and fracture rates (Jama 2000;283:3205, 3211, 3255 vs Ann IM 2003;139:97; Jama 2001;285:1850), also appear to decr cataracts (Jama 2006;295:2752) and macular degeneration (BMJ 2001;323:375); cmplc: mild asx hepatitis (1-2%), check LFTs q6-12mos but allow to go up to 3× upper limit of normal; dose-dependent severe rhabdomyolysis/myopathy (Jama 2004;292:2585) heralded by myalgias and increased CPK, more frequently seen w concomitant grapefruit juice (inhibits 3A4 only), verapamil, erythromycin, ketoconazole, itraconazole, niacin or gemfibrozil use, can allow asx CPK incr up to 3× upper normal; also rare perhipheral neuropathy, memory loss, sleep disturbance, impotence, gynecomastia, and debatable incr cancer risk; all cost $60-120/mo for standard dose, cheaper generics coming

• Atorvastatin (Lipitor) (Med Let 1997;39:29; Jama 1995;275:128) 10-80 mg po qd and cheaper 40-mg extended release, being pushed to the 80 mg end by studies showing lower MI rates but no incr survival! (Nejm 2005;352:1425, 1483); lowers choles more than others (Nejm 2004;350:1495), also decr TGs by 40%, long half-life, no CNS effect; CYP3A4 metabolism; $70/mo
• Fluvastatin (Lescol) qd (Arch IM 1991;151:43; Nejm 1988;319:24) 20 (10-40) mg po qd, no CNS effect, CYP2C9 metabolism; $52/mo at 20 mg
• Lovastatin (Mevacor) (primary prevention—Jama 1997;278:313) 20-40 mg po hs; CYP3A4 metab; $52/mo
• Pravastatin (Pravachol) 40 mg po hs, worked as primary prevention in Scottish trials of LDLs >175 mg % up to 15 yr later even though only 30% still took drug (NNT-15 = 30) (Nejm 2007;357:1477) but cost was $35 000/yr life saved (BMJ 1997;315:1577); no CNS effect; good alternative if intolerant of other statins; sulfation metabolism; $132/mo
• Rosuvastatin (Crestor) (Med Let 2003;45:81) 10+ mg po qd; helps decr TGs and incr HDL like atorvastatin; slow metabolism in some causes myopathy incidence incr × 10 to 5/10 000 pt/yr; sulfation metabolism
• Simvastatin (Zocor) (primary prevention—Jama 1998;279:1615; 1997;278:313) 10-40, occasionally 80 mg po hs; raises HDL and lowers triglycerides as well as atorvastatin; CYP3A4 metabolism; $132/mo

Cholesterol binders; all can incr TGs (L. Keilson):

• Cholestyramine 24 gm qd divided (Ann IM 1990;150:1822)
• Colesevelam (Welchol) (Med Let 2000;42:102) 625-mg tabs, 3-6 po qd or divided; fewer gi side effects and drug interactions, can take w statins; $150/mo
• Cholestipol 5-10 gm bid-tid (Nejm 1990;323:1290), alone or w
• Psyllium 2.5 gm po tid decr lipids more than cholestipol alone, is better tolerated, and costs 1/2 as much ($500/yr) (Ann IM 1995;123:493); or

Cholesterol absorption inhibitors

• Ezetimibe (Zetia) 10 mg po qd, or combined w simvastatin as Vytorin but efficacy now in serious question (Nejm 2008;358:1431); adv effects: rare (<2%) hepatitis, incr myopathy risk when used w statins

Nicotinic acid (niacin) 100 mg po hs, or 125 mg bid increased gradually over 2 mo to 1 gm qid; or slow-release forms like Niaspan up to 2 gm po hs; or combination w lovastatin (Advicor) 500/10-2 gm/40. Raises HDL the most of all the drugs, helps triglycerides too, so often used as complement w statins; adverse effects: flushing, which is helped by 300 mg ASA half hour before each dose; aggravation of glucose intolerance; hepatotoxicity; rhabdomyolysis sometimes when give w statins

Fibrates: used esp for triglyceride elevations; can also cause rhabdomyolysis w statins; overall benefit questionable (Jama 2011;305:1217)

• Gemfibrozil (Lopid) 600 mg bid, similar to discontinued clofibrate (Atromid); decreases triglycerides and raises HDL, can decr recurrent MIs in pts w LDL <130 but HDL <40 (Jama 2001;285:1585; Nejm 1999;341:410); decreased all-cause mortality, esp in pts with metabolic syndrome (Arch IM 2006;166:743); adverse effects: gallstones (Am J Med 2000;108:418), rhabdomyolysis when give w statins though still done cautiously
• Fenofibrate (Tricor) (Med Let 1998;40:68) 67-220 mg po qd

Cholesterol ester tranfer protein inhibitors: anacetrapid, perhap; HDL increases of 138%, LDL decreases up to 40%, danger of LDL dropping too low (Nejm 2010;363:2406)

Herbal: red yeast rice (Hongqu) extract of Monascus purpureus(Xuezhikang) 0.6 mg po bid; contains statins et al, prevents 2nd MIs, death, and PCTA. NNTs all 18-30 over and 25-50 under 65 (Jags 2007;55:1015)