Blood pressure levels in treated hypertensive patients in general practice in Norway.

The aim of this study was to examine the blood pressure (BP) levels in patients treated for essential hypertension in 1816 patients in general practice in Norway. The study was based on an optical readable questionnaire filled out by the physician including information about systolic (S) and diastolic (D) BP, gender, age, body weight, smoking habits and all pharmaceutical treatment given. Sixty-four per cent of the patients were treated with one antihypertensive drug. Only 22.3% of the women and 30.7% of the men (p < 0.05) had BP < or = 140/90 mmHg. When BP < 160/95 was used as criterion for BP control, the fraction of patients was 50%. The fraction of patients with DBP < or = 80 mmHg was 26% in the whole group of patients. DBP < or = 90 mmHg was achieved in 74% and SBP < or = 140 mmHg in 30% of the patients. The BP control was less in women and in patients above 60 years of age. Patients on combination therapy were no better controlled than those on monotherapy. Based on our results, the proportion of hypertensive patients on drug treatment with insufficient BP control is too high. Efforts should be made to improve the medical treatment of hypertension in general practice in Norway.

[Prescription patterns of antihypertensive agents in general practice in 1995]. / Forskrivningsmønster av blodtrykksmedisiner i allmennpraksis i 1995.

BACKGROUND: Hypertension represents a risk factor in the development of cardiovascular disease. MATERIAL AND METHODS: The prescription of antihypertensive drugs and the daily doses used were examined in a questionnaire-based survey among 2,586 drug-treated hypertensive patients who attended a general practitioner for clinical control in November 1995. RESULTS: The proportion of patients treated with one antihypertensive drug only was 63%. ACE inhibitors, alpha blockers and angiotensin-II antagonists constituted 22.7%, 6.6% and 4.4%, and betablockers, calcium channel blockers and diuretics 21.7%, 23.7% and 16.3% of the prescriptions respectively. Women were more often prescribed diuretics than men, and older individuals more often than younger persons. No striking difference in the prescription of antihypertensive drugs were observed between the five health regions of Norway. There was no reduction in the prescribed daily doses of antihypertensives used in combination therapy compared with monotherapy. In approximately one quarter of the prescriptions there was a positive correlation between the prescribed daily dose and the patient's weight. The number of antihypertensives prescribed did positively correlate with the patient's weight. INTERPRETATION: This survey shows that antihypertensives without any documented effect on morbidity and mortality were frequently prescribed for hypertension in general practice. Except for the low proportion of diuretic users among elderly patients, our results is in accordance with the Guidelines from the Norwegian Society of General Practitioners.

Doxazosin GITS compared with doxazosin standard and placebo in patients with mild hypertension.

Doxazosin, an effective treatment for mild-to-moderate hypertension and benign prostatic hyperplasia, in its standard formulation requires a multiple-step titration regimen to minimize the potential for first-dose effects. A new controlled-release gastrointestinal therapeutic system (GITS) formulation of doxazosin was developed to enhance the pharmacokinetic profile, significantly reducing serum peak-to-trough ratios, thereby minimizing the need for titration. We assessed the efficacy and tolerability of doxazosin GITS compared with doxazosin standard and placebo in a prospective, randomized, double-blind, parallel-group, dose-titration, multicenter study of 392 patients with mild hypertension (blood pressure [BP] < or = 180/95-105 mmHg). Patients were randomized to doxazosin GITS, doxazosin standard, or placebo in 2:2:1 manner. The primary outcome measure was the proportion of patients in the per-protocol analysis (PPA) who achieved goal BP response (sitting BP < or = 90 mmg or 10 mmHg decrease from baseline at 24 h postdose at the final evaluable visit). Goal BP response in the intention-to-treat (ITT) population and prespecified BP and/or heart rate changes in the PPA and/or ITT population were also analyzed. Tolerability was assessed throughout the study. Doxazosin GITS and doxazosin standard produced comparable goal BP responses superior to that of placebo, with 92 of 156 patients (59.0%) on doxazosin GITS and 86 of 152 patients (56.6%) on doxazosin standard in the PPA population achieving goal BP response 24 hours postdose on the final visit, compared with 25 of 70 patients (35.7%) on placebo. Both active treatments produced mean significant BP reductions compared with baseline and placebo (p < 0.001). The most commonly reported side effects were headache, dizziness, and asthenia. No syncope was reported in the doxazosin GITS group; two cases were observed in the doxazosin standard group and one case in the placebo group. Doxazosin GITS was well tolerated and as effective as doxazosin standard in patients with mild hypertension, producing well-tolerated, comparable BP reductions with minimal need for titration. Both active treatments were clinically and statistically superior to placebo.

Adverse drug reactions in current antihypertensive therapy: a general practice survey of 2586 patients in Norway.

The objective of this study was to determine the frequency and profile of adverse reactions to antihypertensive drugs in an unselected group of drug-treated hypertensive patients. A questionnaire-based survey was carried out among 2586 drug-treated hypertensive patients who attended a general practitioner for clinical control. Adverse drug reactions reported spontaneously, upon general inquiry, upon specific questioning and as evaluated by a physician were used as the main outcome measures. The study shows that the percentage of patients who reported adverse drug reactions spontaneously, upon general inquiry and upon specific questioning were 16%, 24% and 62% respectively. Users of diuretics reported the lowest frequency of adverse reactions, whereas users of beta-blockers reported the highest frequency. In 7% of the patients, the adverse drug reactions were of such a nature that the physicians considered discontinuing the treatment. As a conclusion, the reported frequency of adverse drug reactions in antihypertensive treatment is high, but with significant differences between the various drug groups. Monotherapy is connected with far fewer adverse drug reactions than combination therapy.

Effects of doxazosin in the gastrointestinal therapeutic system formulation versus doxazosin standard and placebo in mild-to-moderate hypertension. Doxazosin Investigators' Study Group.

The alpha 1-blocker doxazosin is a well-established therapy for hypertension and benign prostatic hyperplasia; however, in its standard form, a multiple-step titration regimen is usually required. The new gastrointestinal therapeutic system (GITS) formulation of doxazosin greatly minimizes the need for titration by changing drug-delivery rate and the pharmaco-kinetic profile. To demonstrate this in hypertensive patients, we assessed the effects of doxazosin GITS 4 or 8 mg once daily versus doxazosin standard 1-8 mg once daily, and placebo, in an integrated analysis of two multicenter, double-blind, randomized, parallel-group trials. Each trial included a 2-week washout period and 12 weeks of therapy. One study compared doxazosin GITS, doxazosin standard, and placebo in 392 patients with mild hypertension [blood pressure (BP) 95-105/ < or = 180 mm Hg]; the other study compared doxazosin GITS with doxazosin standard in 315 patients with mild-to-moderate hypertension (BP 95-115/ < or = 220 mm Hg). The primary outcome measure was the proportion of responders (sitting diastolic BP < 90 mm Hg or 10-mm Hg decrease from baseline 24 h after the dose) at the final visit for the per-protocol population. Mean baseline BP and heart rate were well matched in each group. Approximately 64% of patients with doxazosin GITS (198 of 309 patients) and 68% with doxazosin standard (207 of 304 patients) achieved goal BP response at the final visit versus 36% with placebo (25 of 70 patients; p < 0.05). The majority with doxazosin GITS (60%) remained at the initial 4-mg starting dose. Doxazosin GITS was as effective as doxazosin standard, and both were more effective than placebo in controlling BP in mild-to-moderate hypertension. Doxazosin GITS was well tolerated, and fewer patients with the GITS formulation discontinued therapy because of side effects compared with doxazosin standard or placebo. Syncope was not reported with doxazosin GITS. Whereas the efficacy of doxazosin GITS at 4 or 8 mg is equivalent to that of the standard regimen in this combined analysis, the GITS formulation appears to eliminate the need for titration in most patients.

[How to combine antihypertensive drugs?]. / Hvordan kombinere blodtrykkssenkende medikamenter?

Many hypertensive patients do not respond adequately to single-drug therapy and may therefore require two or more drugs to reach the treatment goal. The drugs used in combination therapy should have additive or synergistic effects on blood pressure. A potential benefit of combinations is to use lower doses of each drug, which may attenuate or abolish the occurrence of side effects. Different combinations are discussed, as well as the inhibition of compensatory mechanisms that may otherwise counteract the antihypertensive effect.

[Doxazosin (Carduran)--a research survey]. / Doxazosin (Carduran)--overvåkingsundersøkelse.

4,260 patients were included in an open surveillance study simultaneously with the introduction of doxazosin for treatment of essential hypertension in Norway. The main aim of the study was to systematically collect information on side effects and events in patients being treated with a new drug. The effect on blood pressure, heart rate and lipids was also recorded. The study lasted for one year. 21 deaths were reported. 53% of the patients reported side effects and/or events. The frequency of side effects was particularly high during the first month of treatment. No new types of side effects were found. The initial higher frequency of reported side effects referred to all organ systems, and was also of the same magnitude in the different systems. A relation was found between certain cardiac side effects and/or events and cessation of previous medication upon starting treatment with doxazosin. The study shows that certain safety precautions should be observed in patients with coronary heart disease and heart failure. In three patients, doxazosin should be used only in combination with more specific treatment. Special caution should be observed when changing the specific basic treatment. Doxazosin had a very favourable antihypertensive effect. A drop in cholesterol and triglycerides was observed, as expected. The HDL-cholesterol value declined, which was unexpected. The results are difficult to interpret, owing to lack of a control group. On the other hand, the study shows how high blood pressure is being treated with drugs in ordinary practice. The authors discuss the methodology of surveillance studies.

Preliminary results of the Norwegian doxazosin postmarketing surveillance study: a twelve-week experience.

The study was designed to investigate the safety and efficacy of doxazosin in the control of blood pressure in general medical practice; the results presented concern the first 748 patients evaluated over a 12-week period. Blood pressure was significantly reduced after treatment with doxazosin (-13/-9 mm Hg), and heart rate was not significantly altered. In addition, doxazosin significantly reduced total cholesterol levels (-6.7%), reduced triglyceride levels (-19.8%), increased high-density lipoprotein cholesterol levels (+2.5%), and the high-density lipoprotein:total cholesterol ratio (+9.7%). The calculated risk of coronary heart disease was reduced by 20.5% over a 12-week period. Thirty-five percent of patients reported at least one side effect, and the number of patients experiencing severe adverse reactions was small. Twenty patients (2.7%) discontinued treatment because of adverse events, and 2.7% had the dose of doxazosin reduced.