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 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)

Determination of the optimal dose of the antihypertensive drug cicletanine hydrochloride in man.

The optimal antihypertensive dose of cicletanine (BN 1270) was investigated in 3 short-term and 3 long-term therapeutic trials using doses of 12.5 to 200 mg. There was a dose-response effect such that in double-blind studies of 1 month's duration, 50 mg/d was the minimum effective dose in mild to moderate hypertensive patients, while a higher dose, 200 mg/d, was more effective in patients with severe hypertension. Despite a quicker reduction in blood pressure by 100 mg cicletanine compared with 50 mg, a similar antihypertensive effect resulted after 3 months' treatment. In patients with mild to moderate hypertension the average decrease in blood pressure over this period was 43.7/38.0 mmHg. A daily dose of 50 mg, which may be increased, particularly at the beginning of treatment, is therefore the optimal recommended dose for these patients. Furthermore, the similar efficacy of the 50 mg and 100 mg doses was confirmed in the long-term trial in the elderly. In all studies, at all doses, cicletanine had a gradual antihypertensive effect, avoiding the risks associated with a sudden fall in blood pressure. The different rates of effect of the 50 mg and 100 mg doses are thought to be due to different mechanisms of action: since 50 mg has no natriuretic effect and 100 mg has a slight natriuretic effect, which is even more pronounced at higher doses.