Drug update: lipid modification for secondary prevention of coronary events.
Current consensus is that virtually everyone with known coronary disease ought to be on an HMG-CoA reductase inhibitor, regardless of LDL cholesterol level. These well-studied drugs, commonly known as statins, cut risk by lowering LDL cholesterol and through anti-inflammatory and plaque-stabilizing effects.
The Adult Treatment Panel III Report guidelines of the National Cholesterol Education Program (NCEP) also recommend statins for all patients who have diabetes, peripheral artery disease, and other conditions placing an individual at very high risk for coronary events. The LDL cholesterol treatment goal is in flux. The existing NCEP recommendation is that drug therapy be reserved for patients with an LDL level above 100 mg/dL. But some experts are now comfortable driving LDL levels to 70 mg/dL or less, especially in a patient who's had a coronary event despite a modest LDL level.
Experts frequently use combination drug therapy for secondary coronary event prevention, mainly in patients who have a mixed hyperlipidemia featuring a low HDL level and elevated triglycerides, those with a modest LDL response to statins, and patients with familial hypercholesterolemia and very high cholesterol levels. Combinations consisting of a statin and niacin are the most popular, but combinations of a statin and a fibrate or a statin and a bile acid sequestrant are also used. The lipidmodifying effects of combination therapy are additive, with evidence of markedly enhanced risk reduction. Triple-drug and occasionally quadruple-drug therapy is warranted in patients with familial hypercholesterolemia and very high LDL levels.
Marketing approval is anticipated soon for two new agents: rosuvastatin (Crestor), a drug that, like atorvastatin, lies at the high end of the LDL-lowering potency spectrum, and ezetimibe (Zeria). Ezetimibe is drawing considerable interest because of its unique mechanism of action--it affects cholesterol transport in the gut--and because in combination with a statin, it results in a further 18%-20% LDL level reduction, equivalent to a threefold boost in a patient's statin dose.
Ali lipid-modifying drugs are safe in the elderly without the need for dosage reductions. Because of insufficient safety data in pregnant and breast-feeding women, prudence dictates a 1- to 2-year drug holiday in what is otherwise lifelong therapy.
HMG-COA REDUCTASE INHIBITORS (STATINS) Most physicians believe that the roughly 30% risk reduction in coronary events obtained with statin therapy is a class effect. They select a statin based upon what the patient's insurance plan covers, provided the drug's potency is sufficient to get close to the LDL goal. Experts like to begin a regimen during hospitalization for an acute coronary event to effects as soon as possible and because doing so promotes long-term compliance. They pick a low- or midrange does; muscle soreness and other tolerability issues generally become a problem only at the highest does of each statin. A useful dosage rule of thumb is that, on average, a 27% reduction in LDL level results from a daily dosage of 5 mg atorvastatin, 10 mg simvastatin, 20 mg lovastatin, 20 mg pravastatin, and 40 mg fluvastatin. Every doubling of statin dosage thereafter results in about a further 6% drop in LDL level. By increasing from 40 mg/day to 80 mg/day atorvastatin, for example, a patient's LDL level will drop by only another 6%. All statins cause elevated liver enzymes in about 1% of patients; these drugs shouldn't be used in patients with active liver disease or unexplained transaminase elevations. Drug Dosage Cost/Day * atorvastatin 5-80 mg/day $1.16 (5 mg) (Lipitor) fluvastatin 20-80 mg/day $1.48 (Lescol) (40 mg) lovastatin 20-80 mg/day $2.39 (20 mg) pravastatin 10-40 mg/day $2.78 (20 mg) (Pravachol) simvastatin 5-80 mg/day $2.53 (Zocor) (10 mg) NIACIN niacin, extended- 1-2.5 g/day $1.41 (1 g) release (Niaspan) BILE ACID SEQUESTRANTS cholestyramine 4-16 g/day $2.96 (8 g) colesevelam 2.5-3.75 $4.74 (WelChol) g/day (3.75 g) colestipol 5-20 g/day $2.40 (5 g) (Colestid) FIBRATES gemfibrozil 600 mg b.i.d $1.98 fenofibrate 200 mg/day $2.58 (Tricor) Drug Comment ** atorvastatin Most widely prescribed statin, most (Lipitor) potent LDL reducer, and the sole statin not backed by a larger clinical trial demonstrating reductions in acute Ml, mortality, and other key end points. Such studies are ongoing. Exports reach for atorvastatin preferentially only for patients with LDL levels in excess of 160 mg/dL. Smallest pill size is 10 mg; 5-mg dosage listed in cost column is achieved by cutting pill in half, which also lowers the cost. fluvastatin Well-used option despite its lower (Lescol) potency, compared with others in class. Attractive price and presence on many formularies make it a reasonable choice for patients who need only a modest drop in LDL level. lovastatin The first approved statin has generic. Also available combined with extended-release niacin (Advicor). pravastatin Starred in 11-year, 4,200-patient (Pravachol) Cholesterol and Recurrent Events (CARE) trial that helped usher in the era of statins for secondary coronary prevention. simvastatin Some partisans of the nearly (Zocor) 21,000-patient Heart Protection Study (HPS) now recommend giving everyone with known coronary disease 40 mg/day simvastatin and not bothering to measure LDL level. It's their blanket treatment of choice for secondary prevention based upon convincing clinical benefits across a broad spectrum of HPS patients, including diabetics, the elderly, women, those with a history of stroke, and patients with peripheral vascular disease. NIACIN niacin, extended- The unsung hero of cardiovascular release risk reduction. Other niacin (Niaspan) preparations are available, but experts say Niaspan is easiest to use and safer than OTC products. A user-friendly niacin, tolerated by up to 90% of patients. Start with 500 mg at bedtime following a small, nonfatty snack and increase by 500 mg/month until side effects become limiting. Taking an aspirin 30 minutes beforehand reduces flushing. BILE ACID SEQUESTRANTS cholestyramine Resin powder. Shunned by some as messy and inconvenient; others say the lowest maintenance dose, 8 g, is very well tolerated and provides a further 10%-15% reduction in LDL. That's about equivalent to quadrupling a patient's statin dose. A bile acid sequestrant should not be used by patients with high triglycerides; it will worsen the problem. Must be taken at least 1 hour after or 4 hours before any other medication. colesevelam More convenient than other bile (WelChol) acid sequestrants; can be taken with other medications. Fewer Gl side effects, too. colestipol Micronized tablets avoid mess. (Colestid) But even using the lowest dosage to minimize Gl distress and constipation means swallowing five large tablets per day. Must be taken at least 1 hour after or 4 hours before any other medication. FIBRATES gemfibrozil Impressive triglyceride-lowering and HDL cholesterol-boosting effects make fibric acid derivatives especially attractive in diabetic patients. In class, gemfibrozil is preferred by some for its longer track record. Some lingering concern over increase in Gl cancers seen with gemfibrozil at 9-year follow-up in Helsinki Heart Study. Class requires monitoring of liver function when used with a statin. fenofibrate Micronized formulation allows (Tricor) once-daily dosing for most patients. * Cost/day is based in the average wholesale price for a 100-unit container or closest available size of the generic formumation, unless otherwise indicated, in the 2002 Red Book. ** Comments reflect the viewpoints and expertise of the following sources: Dr. Louis Kuritzky, a family physician at the University of Florida, Gainesville. Dr. C. Noel Bairey Merz, director of the preventive and rehabilitative cardiac center at Cedars-Sinai Medical Center, Los Angeles, and a member of the NCEP Coordinating Committee. Dr. Richard Pasternak, director of preventive cardiology and cardiac rehabilitation at Massachusetts General Hospital, Boston, and a member of the NCEP Coordinating Committee.
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|Author:||Zoler, Mitchel L.|
|Publication:||OB GYN News|
|Date:||Nov 1, 2002|
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