title: Safety and tolerability of fluvastatin with concomitant use of antihypertensive agents. An analysis of a clinical trial database.
abstract: The coexistence of hypercholesterolemia and hypertension often requires concomitant drug treatments. Thus, it is interesting to evaluate the efficacy, safety, and tolerability of the new lipid-lowering agent fluvastatin, a 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA)-reductase inhibitor, in patients receiving concomitant antihypertensive/cardiovascular drug treatments. A retrospective analysis was based on data from controlled clinical trials in which 1815 patients were treated with fluvastatin and 783 patients received placebo. The daily dose of fluvastatin was > or = 20 mg. At least one of the following drug treatments was taken by 445 of the fluvastatin-treated patients (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 (fluvastatin: n = 161; placebo: n = 69); and angiotensin-converting enzyme (ACE) inhibitors (fluvastatin: n = 101; placebo: n = 30). The majority of patients received monotherapy with one of the above-mentioned antihypertensive agents (fluvastatin: 69%; placebo: 65%). The efficacy of fluvastatin in modifying low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol and triglyceride levels was not consistently different in patients taking a given antihypertensive compared with the overall group and the patients not taking the antihypertensive agent. 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 alanine 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).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Clinical Research and Development, Sandoz Pharma Ltd., Basel, Switzerland.
authors.forename: T K
authors.initials: TK
authors.lastname: Peters
authors.forename: J
authors.initials: J
authors.lastname: Jewitt-Harris
authors.forename: M
authors.initials: M
authors.lastname: Mehra
authors.forename: E N
authors.initials: EN
authors.lastname: Muratti
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000592:standards / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000592:standards / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000009:adverse effects* / Q000592:standards* / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000592:standards / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003402:Creatine Kinase / Q000097:blood; D004232:Diuretics / Q000009:adverse effects / Q000592:standards / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005229:Fatty Acids, Monounsaturated / Q000009:adverse effects* / Q000592:standards* / Q000627:therapeutic use; D005260:Female; D000077340:Fluvastatin; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology; D006973:Hypertension / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology; D007211:Indoles / Q000009:adverse effects* / Q000592:standards* / Q000627:therapeutic use; D007256:Information Systems; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies
chemical_list: D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004232:Diuretics; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D008055:Lipids; D008074:Lipoproteins; D000077340:Fluvastatin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003402:Creatine Kinase