Efficacy and safety of calcipotriol (MC 903) ointment in psoriasis vulgaris. A randomized, double-blind, right/left comparative, vehicle-controlled study.

BACKGROUND: The biologically active form of vitamin D3, calcitriol, may offer a new therapeutic approach to psoriasis. Calcipotriol, a new vitamin D3 analogue, is at least 100 times less calcemic than calcitriol. OBJECTIVE: Our purpose was to study the efficacy and safety of calcipotriol in the treatment of psoriasis vulgaris. METHODS: In a right/left comparative, double-blind study, treatment with calcipotriol ointment (50 micrograms/gm) twice daily and placebo was given for 4 weeks. The preferred treatment was continued, without opening the code, for another 4 weeks. Efficacy, as measured by the Psoriasis Area and Severity Index and by the investigator's and patient's global assessment, and safety were assessed every 2 weeks. RESULTS: The mean Psoriasis Area and Severity Index fell in 4 weeks from 14.2 to 6.3 with calcipotriol and from 14.1 to 9.2 with placebo (p < 0.001; 95% confidence interval for difference: 1.78-->3.94). Local side effects were equally common with calcipotriol and placebo. The mean serum calcium remained unchanged. CONCLUSION: Topical application of up to 50 gm of calcipotriol ointment per week was found to be an effective and safe treatment of psoriasis vulgaris.

A multicentre, parallel-group comparison of calcipotriol ointment and short-contact dithranol therapy in chronic plaque psoriasis.

Short-contact treatment with dithranol (anthralin) is a widely used treatment for chronic plaque psoriasis. Although effective, it causes staining and irritation, and is therefore inconvenient. Calcipotriol is a recently developed vitamin D analogue which is effective and easy to use. To evaluate the relative efficacy, safety and acceptability of these treatments a multicentre, open, randomized, parallel-group comparison was performed. Four hundred and seventy-eight patients with chronic plaque psoriasis were randomized to use one of the two treatments for 8 weeks. One group applied calcipotriol ointment (50 micrograms/g) twice daily. The other used a single application for 30 min each day of Dithrocream in the highest concentration tolerated. Severity of psoriasis was assessed by modified PASI score at baseline, and after 2, 4, and 8 weeks of treatment. A five-point scale was used by subjects and by investigators as an additional assessment of overall response, and a similar scale was used by subjects to grade acceptability. Total serum calcium was monitored at baseline and after 2 and 8 weeks on treatment. The mean PASI score fell from 9.1 to 4.7 after 8 weeks on dithranol (P < 0.001), and from 9.4 to 3.4 on calcipotriol (P < 0.001). The difference between the two treatments was significant in favour of calcipotriol at 2 weeks (P < 0.001), and remained so at subsequent assessments. At 8 weeks the difference between mean improvements in scores for the two groups was 1.6 (95% confidence interval 0.5-2.7). Efficacy grading by subjects and investigators, and acceptability grading by subjects, were all significantly better for calcipotriol.(ABSTRACT TRUNCATED AT 250 WORDS)

Quality of life on antihypertensive therapy: a double-blind trial comparing quality of life on pinacidil and nifedipine in combination with a thiazide diuretic. European Pinacidil Study Group.

The quality of life (QL) was evaluated in a 6 month double-blind trial in six European countries. Patients with a sustained supine diastolic blood pressure (SDBP), phase V, of 95 mm Hg or more on bendrofluazide, 5 mg daily (or an equivalent dose of a thiazide diuretic) were randomised to additional pinacidil (n = 127), 25 mg up to 100 mg daily, or nifedipine (n = 130), 20 mg up to 80 mg daily. The treatment groups were similar at entry for QL scores, average DBP of 103 +/- 6 (SD) mm Hg, and average age of 56 +/- 10 (SD) years. Eighteen patients on pinacidil and 12 on nifedipine withdrew due to side effects, such as oedema (both drugs) and flushing (nifedipine). The maximum antihypertensive effect was achieved within 6 weeks and maintained, resulting in a significant fall in SDBP of 13.7 mm Hg on pinacidil and 15.5 mm Hg on nifedipine at the end of the trial. There was no significant difference in the antihypertensive effect. The target SDBP was achieved in 57% of pinacidil-and 63% of nifedipine-treated patients. The average number of symptomatic complaints fell in both groups, with significant decreases in the reporting of blurred vision and headaches on nifedipine. Complaints of growth of body and facial hair increased on pinacidil but there were no significant between-drug comparisons with respect to side effects. In measures of psychological well being, patients on pinacidil showed a significant (p less than 0.05) improvement in total and cognitive function scores compared to nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)

The long-term effect of alprenolol on plasma apolipoproteins A-I and B.

The concentration of lipids, lipoproteins and apolipoprotein A-I and B was measured in the plasma of 33 patients, enrolled in a double-blind, controlled trial of alprenolol in myocardial infarction, after one year on the study medication and again after 6 months off the medication. Sixteen patients received 200 mg alprenolol twice daily and 17 received placebo. There were no statistically significant differences between the parameters in the two groups after one year on medication. However, when medication was stopped, the ratio of apolipoprotein B to apolipoprotein A-I fell by 9% in the alprenolol group and increased by 2% in the placebo group. This difference was statistically significant. Our results suggest that alprenolol, a beta-blocker with weak intrinsic sympathomimetic effect, has slight effects on plasma lipoproteins. These effects were apparent only by measurements of apolipoproteins.

Long-term alprenolol treatment affects serum T4, T3 and rT3 in euthyroid patients with ischaemic heart disease.

After treatment with alprenolol for 1 year, serum 3,3',5'-triiodothyronine (rT3) was significantly increased (P less than 0.01) in a group (n = 20) of euthyroid subjects compared to a control group (n = 20) given placebo. All subjects had definite or suspected myocardial infarction one year previously. Serum thyroxine (T4), free T3 index (FT4I), serum 3,5,3'-triiodothyronine, (T3) and free T3 index (FT3I) were not significantly different in the two groups. Alprenolol and placebo were gradually withdrawn over 14 days. On the first day after withdrawal a significant decrease in serum rT3 in the alprenolol treated group was the only change observed. Fourteen days after withdrawal a significant fall in serum T4, FT4I, rT3 and a rise in serum T3 and FT3I was found in the alprenolol treated group. Six months after withdrawal the only further change observed in the alprenolol treated group was an increase in T3 and FT3I. No changes occurred in the placebo treated group in any of the hormones studied. The results are consistent with a direct effect of long-term alprenolol treatment on the peripheral levels of serum T4, T3 and rT3 in euthyroid subjects. The changes in the thyroid hormones after withdrawal further indicate withdrawal of a permanent inhibition of 5'deiodinase during long-term treatment with alprenolol in euthyroid subjects.

Oxyhaemoglobin equilibrium and chronic beta-adrenoceptor blockade in coronary heart disease.

In 20 patients with coronary heart disease the effect of long-term beta-adrenergic receptor blockade on the haemoglobin oxygen equilibrium was investigated. Study patients received alprenolol 200 mg twice daily for 12-41 months (mean: 24 months) as a secondary preventive measure following a myocardial infarction. While on and again following gradual withdrawal of alprenolol, the patients performed a maximum bicycle ergometer test. Haemoglobin oxygen affinity as expressed by the P50 value, 2,3-diphosphoglycerate (2,3-DPG) and carbon monoxide haemoglobin were measured before and following exercise. Pre-exercise P50 decreased from 25.2 +/- 0.3 mm Hg (mean +/- s.e. mean) while on beta-adrenoceptor blocker to 24.6 +/- 0.4 mm Hg in the off-treatment state (P less than 0.05). Five minutes after stopping exercise P50 was 25.1 +/- 0.3 in patients taking alprenolol as compared to 24.7 +/- 0.3 after withdrawal of the drug (P less than 0.01). It is concluded that the slight decrease in haemoglobin oxygen affinity in long-term treatment with alprenolol, which is observed in the present study probably is without clinical bearing. The question should be further elucidated by analysis of coronary sinus blood samples.

Effect of long-term beta-blockade with alprenolol on platelet function and fibrinolytic activity in patients with coronary heart disease.

In 14 patients with coronary heart disease the effect of long-term treatment (mean 16 months, range 12-33) with alprenolol on platelet function and fibrinolytic activity was studied. While on the beta-blocker and two weeks after gradual withdrawal of it, the patients performed a bicycle-ergometer test and blood samples were obtained before and following exercise. Pre-exercise fibrinolytic activity, assessed by the euglobulin clot lysis time, was 183 +/- 27 min (mean +/- SEM) while on alprenolol as compared to 111 +/- 18 min (p less than 0.01) after its withdrawal. Activation of fibrinolysis following exercise was not significantly influenced by alprenolol. In patients treated with alprenolol, the pre-exercise threshold level of ADP, producing platelet aggregation was 3.3 muM (geometric mean) and 5.1 muM after stopping treatment (p less than or equal to 0.05). In patients receiving the beta-blocker, the ADP- threshold value dropped from 3.3 muM before exercise to 2.3 muM immediately after exercise (not significant). The corresponding values after withdrawal of alprenolol were 5.1 muM and 2.7 muM (p less than or equal to 0.02). Adrenaline - stimulated aggregation was not significantly influenced by alprenolol. Serotonin release from platelets following maximal ADP- and adrenaline stimuli was not significantly changed by exercise in patients on beta-blockade. After stopping treatment, ADP-induced serotonin release was 22 +/- 4.1% before and 15 +/- 4.7% after exercise (p less than 0.02). the corresponding values using the adrenaline stimulus were 29 +/- 5.7% and 17 +/- 4.7% (p less than 0.05). It is suggested that during physical stress alprenolol may protect platelets against aggregatory stimuli.