Therapy with HMG CoA reductase inhibitors: characteristics of the long-term permanence of hypocholesterolemic activity.

Treatment with hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors has gained considerable success in the management of hypercholesterolemia. A large number of studies have shown the efficacy of these drugs in lowering plasma total and low density lipoprotein (LDL) cholesterol levels, but there have been less studies evaluating their effectiveness in standard clinical practice, particularly relating to the maintenance of hypocholesterolemic activity. In the present study, the long-term effectiveness of HMG CoA reductase inhibitors has been tested in 177 patients with familial hypercholesterolemia (FH) who had been on statin therapy (simvastatin or pravastatin) for at least 12 months and up to 5 years or longer. The mean 'dose normalized' LDL cholesterol reduction in the whole group was around 20%. However, in spite of a generally good efficacy of both statins in lowering total and LDL cholesterol, a wide variety of responses, either after short- or long-term treatment, was noted. Individual responses were calculated and patients classified into three different groups: (a) responders, (b) non-responders, and (c) response losers. Of the 177 patients, 4% did not respond to treatment and a further 10% showed an initial unsatisfactory response (LDL cholesterol reduction < or = 10%). Another 10% experienced a progressive loss of response over time. There appeared to be little difference between the two treatments in the long-term efficacy and no predictive index could be established. Treatment with HMG CoA reductase inhibitors is generally effective and well tolerated, but a non-negligible number of patients may show a primary non-response or a progressive loss of response.