SAFETY AND TOLERABILITY OF FLUVASTATIN WITH CONCOMITANT USE OF ANTIHYPERTENSIVE AGENTS - AN ANALYSIS OF A CLINICAL-TRIAL DATABASE

The coexistence of hypercholesterolemia and hypertension often require s concomitant drug treatments. Thus, it is interesting to evaluate the efficacy, safety, and tolerability of the new lipid-lowering agent fl uvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA)-reductase inhibitor, in patients receiving concomitant antihypertensive/cardiov ascular drug treatments. A retrospective analysis was based on data fr om controlled clinical trials in which 1815 patients were treated with fluvastatin and 783 patients received placebo. The daily dose of fluv astatin was greater-than-or-equal-to 20 mg. At least one of the follow ing drug treatments was taken by 445 of the fluvastatin-treated patien ts (24.5%) and 181 of those receiving placebo (23.1%): beta-adrenergic receptor blockers (fluvastatin: n = 182; placebo: n = 84); diuretics ( fluvastatin: n = 168; placebo: n = 72); calcium antagonists (fluvastat in: n = 161; placebo: n = 69); and angiotensin-converting enzyme (ACE) inhibitors (fluvastatin: n = 101; placebo: n = 30). The majority of p atients received monotherapy with one of the above-mentioned antihyper tensive agents (fluvastatin: 69%; placebo: 65%). The efficacy of fluva statin in modifying low-density lipoprotein (LDL)- and high-density li poprotein (HDL)-cholesterol and triglyceride levels was not consistent ly different in patients taking a given antihypertensive compared with the overall group and the patients not taking the antihypertensive ag ent. In patients taking fluvastatin and antihypertensives, confirmed ( measured at two consecutive occasions) increases more than three times the upper limit of normal in aspartate aminotransferase (ASAT) and al anine aminotransferase (ALAT) occurred in only two patients. One case involved the concomitant use of a beta-blocker (ASAT and ALAT) and the other a diuretic (ALAT). Notable increases in creatine kinase (CK) of more than 10 times the upper limit of normal were not more frequent w ith fluvastatin than with placebo (the incidence with both was 0.3%) a nd were not observed in patients taking antihypertensives as monothera py. The tolerability of fluvastatin, as assessed by an analysis of adv erse events, was not consistently influenced by concomitant antihypert ensive therapy. In conclusion, an exploratory analysis of fluvastatin in patients using concomitant antihypertensive drug treatment suggests that the efficacy and safety profile of this new HMG-CoA-reductase in hibitor is not affected by concomitant drug treatment with beta-blocke rs, diuretics, calcium antagonists, or ACE inhibitors.