Cholesterol-reduction intervention study (CRIS): a randomized trial to assess effectiveness and costs in clinical practice.

BACKGROUND

The 1988 US National Cholesterol Education Program Expert Panel Report recommended initial treatment with niacin or bile acid sequestrants, followed by other agents if needed, to lower low-density lipoprotein cholesterol (LDL-C) levels in hypercholesterolemic patients who require drug therapy. It is unknown how the effectiveness and costs of such an approach ("stepped care") compare in typical clinical practice to those of initial therapy with lovastatin.

PATIENTS AND METHODS

We randomly assigned 612 patients, aged 20 to 70 years, who met 1988 National Cholesterol Education Program guidelines for drug treatment of elevated LDL-C level and had not previously used cholesterol-lowering medication, to either a stepped-care regimen or initial therapy with lovastatin (both n=306). The study, conducted at Southern California Kaiser Permanente, was designed to approximate typical practice: provider compliance with treatment plans was encouraged but not enforced, and patients paid for medication as they customarily would.

RESULTS

At 1 year, the decline in mean LDL-C level was significantly greater among patients assigned to initial treatment with lovastatin (22% vs 15% for stepped care; P<.001), as was the number who attained goal LDL-C level (</= 4.14 mmol/L [</= 160 mg/dL], or </= 3.36 mmol/L [</= 130 mg/dL] if coronary heart disease or two or more risk factors were present) (40% vs 24%; P<.001). The increase in mean high-density lipoprotein cholesterol levels was significantly greater in the stepped-care group, however (8% vs 1% for lovastatin; P<.001). Patients who were randomized to stepped care were more likely to report substantial bother caused by side effects (30% vs 16% for lovastatin; P<.001) and discontinuation of therapy at 1 year (28% vs 18%, respectively; P<.01). Costs of care were $333 higher per patient in the lovastatin group ($786 vs $453; P<.001).

CONCLUSIONS

A stepped-care regimen beginning with niacin is less costly than initial therapy with lovastatin, but also less effective in lowering LDL-C level. While it is more effective in increasing high-density lipoprotein cholesterol levels, the tolerability of such a regimen may be a problem.