EFFICACY AND SAFETY OF SIMVASTATIN IN CURRENT CLINICAL-PRACTICE - THEITALIAN FAMILY PHYSICIAN SIMVASTATIN STUDY

The a availability of modern hypocholesterolemic drugs that are easy t o handle may give any physician the ability to treat patients with ele vated levels of total serum cholesterol and low-density lipoprotein (L DL) cholesterol, The Italian Family Physician Simvastatin Study was an open-label, noncomparative, diet-controlled, multicenter, postmarketi ng surveillance study carried out by nonspecialist physicians to evalu ate the efficacy and safety of simvastatin in the current clinical pra ctice, The study evaluated 5348 patients (2887 men [mean age, 61 +/- 7 years]) and 2461 women [mean age, 55 +/- 11 years]) with primary hype rcholesterolemia. After a 10-week washout period, the selected patient s were actively treated for 24 weeks with simvastatin 10 mg administer ed 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 patient s (95%) completed the study; 195 patients (3.6%) were lost at follow-u p and the other 72 (1.3%) discontinued the study because of the occurr ence of adverse effects. Of the 5081 patients, 3691 (72.6%) received 1 0 mg/d simvastatin, 1159 (22.8%) 20 mg/d, and 202 (4.0%) 40 mg/d; in t he others a personalized dose of the drug (range, 5 to 30 mg/d) was gi ven. Simvastatin produced significant decreases in total serum cholest erol of 30%, LDL cholesterol of 41%, and triglyceride levels of 14%, a nd 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 i n aminotransferase levels was observed in comparison with baseline val ues (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 t he upper limit of normal) were recorded only in 0.7% of all control vi sits. Serum creatine kinase (CII) did not significantly change and ser um elevations >10 times the upper limit of normal without muscle sympt oms was observed in 0.4% of all patients, whereas myalgia without conc omitant increase of CK was reported by 0.6% of the 5081 patients. On t he 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 decreas e in LDL cholesterol and improved the global lipoprotein profile with infrequent, minor, dose-dependent side effects.