Comparison of the AT1-receptor blocker, candesartan cilexetil, and the ACE inhibitor, lisinopril, in fixed combination with low dose hydrochlorothiazide in hypertensive patients.

AIM: To compare candesartan cilexetil and lisinopril in fixed combination with hydrochlorothiazide with respect to antihypertensive efficacy and tolerability. METHODS: This was a double-blind (double-dummy), randomised, parallel group comparison in patients with a mean sitting diastolic blood pressure 95-115 mm Hg on prior antihypertensive monotherapy. Treatments were candesartan cilexetil/hydrochlorothiazide 8/12.5 mg once daily (n = 237) and lisinopril/hydrochlorothiazide 10/12.5 mg once daily (n = 116) for 26 weeks. The primary efficacy variable was change in trough sitting diastolic blood pressure. RESULTS: Changes in mean sitting diastolic blood pressure did not differ significantly between the groups (mean difference 0.5 mm Hg; 95% confidence interval -1.6, 2.7, P = 0.20). No significant differences between the groups was found for other haemodynamic variables (sitting systolic blood pressure, standing blood pressure, sitting/erect heart rate, and proportion of responders and controlled patients). Both drugs were well tolerated but the proportion of patients with at least one adverse event was significantly greater in the lisinopril group (80% vs 69%, P = 0.020). The proportion of patients spontaneously reporting cough (23.1% vs 4.6%) and discontinuing therapy due to adverse events (12.0% vs 5.9%) was also higher in the lisinopril group compared with the candesartan cilexetil group. CONCLUSIONS: The fixed combinations of candesartan cilexetil and hydrochlorothiazide 8/12.5 mg and lisinopril and hydrochlorothiazide 10/12.5 mg once daily are equally effective as antihypertensive agents. The fixed combination containing candesartan cilexetil is better tolerated than that containing lisinopril.

A Combination of Candesartan Cilexetil/hydrochlorothiazide (HCTZ), 8/12.5 mg, has a Similar Antihypertensive Efficacy and is Better Tolerated than Lisinopril/HCTZ, 10/12.5 mg.

Monotherapy with an antihypertensive agent is likely to achieve a desirable lowering of blood pressure in about 50% of patients. The remaining proportion of patients are likely to be only partially responsive or unresponsive, even if appropriate dose adjustments are made. For these patients, combination therapy usually leads to better control of hypertension. The aim of this study was to compare the antihypertensive effect and tolerability of a once-daily combination of the angiotensin II type 1 (AT 1 ) receptor blocker candesartan cilexetil, 8 mg, and the diuretic hydrochlorothiazide (HCTZ), 12.5 mg, with a combination of the angiotensin-converting enzyme inhibitor, lisinopril, 10 mg, and HCTZ, 12.5 mg, in patients with primary hypertension. The study included men and women, 20-80 years of age, with sitting diastolic blood pressure (DBP) of 95-114 mm Hg. After a run-in period of 2 weeks on any antihypertensive monotherapy, 355 patients were randomized to double-blind treatment with either a combination of candesartan cilexetil/HCTZ, 8/12.5 mg, or a combination of lisinopril/HCTZ, 10/12.5 mg, for 26 weeks. Blood pressure was measured 24 h after dose intake, the primary efficacy variable being the change in sitting DBP at trough between baseline and 26 weeks of treatment. Reductions in mean sitting DBP after 26 weeks were similar for both combination treatments. In addition, no differences were found between the two treatment groups regarding standing DBP, sitting and standing systolic blood pressure, heart rate, and the proportion of responders and controlled patients. Significantly fewer patients reported at least one adverse event with candesartan cilexetil/HCTZ than with lisinopril/HCTZ (68.9% vs 79.5%, p = 0.02; see Table). Furthermore, the proportion of patients spontaneously reporting cough was markedly higher in the lisinopril/HCTZ group (23.9%) than in the candesartan cilexetil/HCTZ group (5.0%). Thus, although the combinations of candesartan cilexetil/HCTZ, 8/12.5 mg once daily, and lisinopril/HCTZ, 10/12.5 mg once daily, had similar antihypertensive efficacy in patients with mild to moderate hypertension during the 26-week treatment period, candesartan cilexetil/HCTZ was significantly better tolerated than lisinopril/HCTZ.

Treatment of hypertensive and hypercholesterolaemic patients in general practice. The effect of captopril, atenolol and pravastatin combined with life style intervention.

OBJECTIVE: To elucidate the effect on blood pressure and blood lipids of an angiotensin converting enzyme inhibitor (captopril), and a beta-receptor blocking agent (atenolol), given alone or in combination with a cholesterol reducing drug, the beta-hydroxy-methylglutaryl-coenzyme A reductase inhibitor pravastatin, in patients who were also encouraged to improve their lifestyle. DESIGN: A longitudinal study consisting of three phases. I: Lifestyle intervention alone. II: Continued lifestyle intervention combined with captopril or atenolol. III: Continued lifestyle intervention combined with the same drugs as in phase II and in addition pravastatin or placebo. SETTING: Fifty-four general practice surgeries in Norway. PARTICIPANTS: Hypertensive patients, 210 females and 160 males, treated or untreated with antihypertensive drugs with a sitting diastolic blood pressure between 95 and 115 mmHg and a serum total cholesterol between 6.5 mmol/l (7.0 for those age 60-67 years) and 9.0 mmol/l. RESULTS: The antihypertensive effect of captopril and atenolol was not influenced by concurrent administration of pravastatin. The effect of pravastatin was not limited by concurrent medication with captopril or atenolol. Improvement in lifestyle seemed to reduce the need for supplementary treatment with diuretics. CONCLUSION: Pravastatin can be used in combination with captopril or atenolol in the treatment of hypertensive and hypercholesterolaemic patients.

Fosinopril versus enalapril in the treatment of hypertension: a double-blind study in 195 patients.

The new angiotensin-converting enzyme (ACE) inhibitor fosinopril was compared with the ACE inhibitor enalapril in a multicenter (n = 11), multinational (Denmark, Finland, Iceland, Norway, and Sweden), double-blind, randomized, parallel-group 24-week study in 195 patients with mild to moderate essential hypertension [supine diastolic blood pressure, (SDBP) > or = 95 to < or = 110 mm Hg]. After discontinuing all previous antihypertensive medication, patients were entered into a placebo lead-in period of 4-6 weeks, followed by 24 weeks of randomized treatment with the active compounds administered with a double-dummy technique. The dose of fosinopril was 20 mg, which could be increased to 40 mg after 8 weeks (average 25.6 mg); that of enalapril was 10 mg, which could be increased to 20 mg after 8 weeks (average 12.9 mg). Hydrochlorothiazide 12.5 mg could be added after 16 weeks and was administered to 27% of the patients in the fosinopril group and to 30% in the enalapril group. All drugs were administered once daily. Supine systolic BP (SSBP) decreased from 157 to 143 mm Hg in the fosinopril group (p < 0.01), and from 159 to 147 mm Hg in the enalapril group (p < 0.01). SSDP decreased from 100 to 89 mm Hg in the fosinopril group (p < 0.01) and from 100 to 92 mm Hg in the enalapril group (p < 0.01). Throughout the study period, fosinopril reduced SSBP and SDBP numerically more than did enalapril, by 0-3 mm Hg. Adverse events (AE) caused withdrawal of study medication in 8 patients in the fosinopril group and in 14 patients in the enalapril group (NS). The number of reported AE was not statistically different in the two groups. Inhibition of the ACE was assessed in a subgroup of patients (n = 26, 13 in each group). Fosinopril caused a greater inhibition of ACE at the doses used in the present study, which was statistically significant. Both fosinopril and enalapril caused statistically significant reductions in BP of a similar magnitude, and both agents were well tolerated. However, fosinopril was consistently numerically slightly more effective than enalapril in reducing BP. There were fewer withdrawals due to AE (NS) in the fosinopril group, and the overall recorded AE were fewer in the fosinopril group (NS).

Fluvastatin efficacy and tolerability in comparison and in combination with cholestyramine.

The aim of this study was to investigate the new synthetic HMG-CoA reductase inhibitor, fluvastatin, for efficacy, safety and tolerability in comparison to cholestyramine. One hundred fifty one primary hypercholesterolaemic patients participated in this double-blind, parallel-group, randomized study. During the first 12 weeks of the study, fluvastatin (20 mg and 40 mg daily) was compared with cholestyramine (16 g per day). In the subsequent, 6-week part of the study, the comparative efficacy, safety and tolerability of 20 mg fluvastatin, combined with cholestyramine (4 g, 8 g, or 16 g) were assessed. Fluvastatin (40 mg) reduced LDL cholesterol by 28.0%, triglycerides by 10.5% and increased HDL cholesterol by 3.7%. Cholestyramine (16 g) reduced LDL cholesterol by 35.0%, but raised triglycerides and HDL cholesterol by 12.3% (p < 0.01) and 3.7% respectively. The combination of fluvastatin 20 mg and cholestyramine (4 g, 8 g and 16 g) induced the following reductions in LDL cholesterol: 30.4%, 35.6% and 46.6% respectively. There was no significant change in triglycerides in either group although HDL cholesterol was raised by 4.9%, 8.3% and 7.2% respectively. One patient treated with fluvastatin and two treated with cholestyramine were withdrawn from the study due to elevation of liver transaminases. The most frequent subjective adverse effects in both treatment groups were mild, transient gastrointestinal complaints. Thus, fluvastatin was effective as a lipid-lowering agent; the effect was further enhanced when fluvastatin was combined with cholestyramine.

[Treatment of hypercholesterolemia in adults. A treatment program 1991]. / Behandling av hyperkolesterolemi hos voksne. Handlingsprogram 1991.

A Norwegian programme for treatment of hypercholesterolemia in adults was published in 1988. In 1990 the Norwegian Medical Association appointed a group to modify this programme in the light of current knowledge, and taking into consideration the recommendations of the Consensus Conference on Cholesterol of October 1989. The present article presents this modified programme. When evaluating the risk of developing coronary heart disease a combined risk score should be calculated which also takes into account important risk factors other than cholesterol, such as family history, sex, age, smoking, hypertension, presence of diabetes etc. For those considered to be at high risk of developing coronary heart disease, the programme gives guidelines on how to intervene. With regard to treatment, special emphasis is placed on changing the diet.

Emphysema and occupational exposure to industrial pollutants.

In a case-referent study, the possible association between the development of emphysema and occupational exposure to industrial pollutants has been studied. Based on complete work histories from the participants, the number of years of employment in a polluted workplace was assessed for 36 patients with emphysema and 72 referents, matched for age (+/- 2 a) and smoking habits. Analyzed as matched triplets, the estimated risk ratio for the exposed (greater than or equal to 10 a in polluted workplaces) subjects developing emphysema in comparison to the nonexposed (less than 10 a in polluted workplaces) was 3.0, a value statistically significant. Estimated risk ratios according to the number of years employed in a polluted workplace did not show any significant trend towards a dose-response relationship. Only one of the emphysema patients had never smoked. In the further study of the relationship between emphysema and occupational exposure, the interaction between cigarette smoke and different occupational exposures seems to be of particular interest.