Efficacy and safety of simvastatin in current clinical practice: The Italian Family Physician Simvastatin Study

The a availability of modern hypocholesterolemic drugs that are easy to handle may give any physician the ability to treat patients with elevated levels of total serum cholesterol and low-density lipoprotein (LDL) cholesterol, The Italian Family Physician Simvastatin Study was an open-label, noncomparative, diet-controlled, multicenter, postmarketing surveillance study carried out by nonspecialist physicians to evaluate the efficacy and safety of simvastatin in the current clinical practice, The study evaluated 5348 patients (2887 men [mean age, 61 +/- 7 years]) and 2461 women [mean age, 55 +/- 11 years]) with primary hypercholesterolemia. After a 10-week washout period, the selected patients were actively treated for 24 weeks with simvastatin 10 mg administered once a day in the evening. The dose was increased, if necessary, at the 12- and 18-week visits, to 20 or 40 mg/d, A total of 5081 patients (95%) completed the study; 195 patients (3.6%) were lost at follow-up and the other 72 (1.3%) discontinued the study because of the occurrence of adverse effects. Of the 5081 patients, 3691 (72.6%) received 10 mg/d simvastatin, 1159 (22.8%) 20 mg/d, and 202 (4.0%) 40 mg/d; in the others a personalized dose of the drug (range, 5 to 30 mg/d) was given. Simvastatin produced significant decreases in total serum cholesterol of 30%, LDL cholesterol of 41%, and triglyceride levels of 14%, and significant increases in high-density lipoprotein (HDL) cholesterol of 13%. The efficacy goal of total serum cholesterol level (<5.2 mmol/L) was achieved in 44.8% (n = 2276) of the patients with a mean dose of 13 mg/d of simvastatin (32.2%, n = 1638 for 10 mg/d; 9.8%, n = 500 for 20 mg/d; 2.7% 90 to 40 mg/d), At 24 weeks a significant increase in aminotransferase levels was observed in comparison with baseline values (aspartate aminotransferase: baseline 21 +/- 8 Un vs week 24 23 +/- 9 U/L; alanine aminotransferase: baseline 21 +/- 9 Un vs week 24 23 +/- 10 Un) but on a per-patient basis, abnormal elevations (>3 times the upper limit of normal) were recorded only in 0.7% of all control visits. Serum creatine kinase (CII) did not significantly change and serum elevations >10 times the upper limit of normal without muscle symptoms was observed in 0.4% of all patients, whereas myalgia without concomitant increase of CK was reported by 0.6% of the 5081 patients. On the whole, 267 clinical adverse effects occurred in 235 patients (4.4%), in a dose-dependent manner. Simvastatin, when studied in the current clinical practice of general practitioners, produced a marked decrease in LDL cholesterol and improved the global lipoprotein profile with infrequent, minor, dose-dependent side effects.