Drug update: lipid modification for secondary prevention of coronary events.

Mitchel L. Zoler, editor Bruce Jancin, writer

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 ...