Expertise: no longer a sine qua non for guideline authors?

: Several sets of guidelines have been published recently and more are in the works. The very recent American College of Physicians/American Academy of Family Practitioners guidelines were put together by a set of authors and consultants without any expertise in the topic under discussion, that is, hypertension. Although we are not maintaining that all guidelines should be written exclusively by experts, complete lack of expertise among guideline authors is not acceptable.

[Why not always diuretics?]. / Hvorfor ikke alltid diuretika?

BACKGROUND: New guidelines adopted in Norway for antihypertensive medication implies prescription of a thiazide diuretic as the drug of first choice. The background for the change in the rules for prescription drugs paid for by the National Insurance system with a capped co-payment is a resolution of the Norwegian parliament as part of a budget compromise for 2004. The resolution was supported by results from the ALLHAT study (antihypertensive and lipid-lowering treatment to prevent heart attack trial). METHODS: ALLHAT was carried out in a group of elderly, high-risk patients with a large proportion of Afro-Americans. RESULTS AND INTERPRETATION: ALLHAT has important shortcomings with regard to design, results, analysis and interpretation. The trial is considered unfit as a basis for general guidelines on antihypertensive treatment in Norway.

Effect of doxazosin GITS on blood pressure in hypertensive and normotensive patients: a review of hypertension and BPH studies.

Doxazosin is an effective treatment for patients with hypertension, benign prostatic hyperplasia (BPH) and the two comorbidly. In its standard formulation, doxazosin requires a multistep titration regimen to minimize a possible first-dose effect. A new extended-release gastrointestinal therapeutic system (GITS) formulation of doxazosin was developed to improve the pharmacokinetic profile of the parent compound and to reduce or eliminate the need for dose titration and the potential risk of overdosing. This review presents an analysis of the effect of doxazosin GITS monotherapy on blood pressure (BP) and tolerability, as evaluated in four clinical trials, two conducted in patients with stage 1 to stage 2 hypertension and two in patients with BPH with different levels of BP. Doxazosin GITS was as effective as doxazosin standard and more effective than placebo was in reducing and controlling BP in patients with hypertension. Among normotensive patients with BPH, no clinically significant effect on BP was observed and no episodes of syncope were recorded. Doxazosin GITS was generally better tolerated than doxazosin standard, based on the proportion of patients with adverse events and those withdrawing due to adverse events. Moreover, the GITS formulation eliminated the need for titration in most patients. Doxazosin GITS is an effective and well-tolerated treatment in patients with hypertension and/or BPH and without heart failure or clinical coronary heart disease and has advantages over doxazosin standard in terms of a simpler dosing regimen and improved tolerability.

Quantification of leg oedema in postmenopausal hypertensive patients treated with lercanidipine or amlodipine.

OBJECTIVE: Of the study was to compare the leg oedema-forming potential of two different dihydropyridine calcium channel blockers in postmenopausal women. DESIGN: A total of 92 postmenopausal hypertensive patients [systolic blood pressure (SBP) 150-179 mmHg or diastolic blood pressure (DBP) 95-109 mmHg were randomized to receive a 4-week treatment with either 10 mg/day lercanidipine (n = 48) or 5 mg/day amlodipine (n = 44), with force-titration to 20 and 10 mg/day, respectively for an additional 4 weeks. METHODS: Leg volume was measured by water displacement volumetry, patients were questioned for symptoms and a physical examination was performed to detect the presence of oedema. RESULTS: A total of 77 patients completed the study, without a major protocol violation and were included in the primary analysis. Leg volume increase from baseline was significantly higher in the amlodipine than in the lercanidipine group (60.4 +/- 8.6 versus 5.3 +/- 8.1 ml; P < 0.001). The percentage of patients with evidence of oedema on physical examination (33.3 versus 9.8%, P = 0.011) and with symptoms of leg swelling (63.9 versus 22%, P < 0.001) and leg heaviness (47.2 versus 12.2%, P < 0.001) was also greater with amlodipine compared with lercanidipine. A positive correlation was found between leg volume and sign or symptoms of oedema (P < 0.001). Both drugs reduced SBP and DBP, with no significant differences between treatments. No correlation was found between leg volume changes from baseline and the antihypertensive effect of either drug. CONCLUSIONS: In postmenopausal females with mild to moderate hypertension the oedema formation of Lercanidipine was significantly less than that of Amlodipine, despite no significant differences in the antihypertensive effect.

Influence of age, sex and blood pressure on the principal endpoints of the Nordic Diltiazem (NORDIL) Study.

BACKGROUND: The aim of the Nordic Diltiazem (NORDIL) Study was to compare patients with essential hypertension receiving calcium-antagonist-based treatment with diltiazem and similar patients receiving conventional diuretic/beta-blocker-based treatment, with respect to cardiovascular morbidity and mortality. OBJECTIVE: To assess the influence of age, sex, severity of hypertension and heart rate on treatment effects, in a sub-analysis. METHODS: The NORDIL study was prospective, randomized, open and endpoint-blinded. It enrolled, at health centres in Norway and Sweden, 10 881 patients aged 50-74 years who had diastolic blood pressure (DBP) of 100 mmHg or more. Systolic blood pressure (SBP) and DBP were decreased by 20.3/18.7 mmHg in the diltiazem group and by 23.3/18.7 mmHg in the diuretic/beta-blocker group - a significant difference in SBP (P < 0.001). RESULTS: The incidence of the primary endpoint - a composite of cardiovascular death, cerebral stroke and myocardial infarction - was similar for the two treatments. Fatal and non-fatal stroke occurred in 159 patients in the diltiazem group and in 196 patients in the conventional treatment group [relative risk (RR) 0.80, 95% confidence interval (CI) 0.65 to 0.99; P = 0.040], whereas there was a non-significant inverse tendency with respect to all myocardial infarction. There were significantly fewer cerebral strokes in patients receiving diltiazem in the subgroups with baseline SBP > 170 mmHg (n = 5420, RR 0.75, 95% CI 0.58 to 0.98; P = 0.032), DBP >/= 105 mmHg (n = 5881, RR 0.74, 95% CI 0.57 to 0.97; P = 0.030) and pulse pressure >/= 66 mmHg (n = 5461, RR 0.76, 95% CI 0.58 to 0.99, P = 0.041), and more myocardial infarctions in those with heart rate less than 74 beats/min (n = 5303, RR 1.13, 95% CI 1.01 to 1.87; P = 0.040). However, the tendencies for fewer strokes and greater incidence of myocardial infarction were present across subgroups when results were analysed for age, sex, severity of hypertension and heart rate, and treatment-subgroup interaction analyses were not statistically significant. CONCLUSIONS: Compared with a conventional diuretic/beta-blocker-based antihypertensive regimen, there were additional 25% reductions in stroke in the diltiazem-treated patients with blood pressure or pulse pressure greater than the medians, and an increase in myocardial infarction in those with heart rate less than the median. Such findings may be attributable to chance, but the consistency of, in particular, the stroke findings may also suggest an ability of diltiazem, beyond conventional treatment, to prevent cerebral stroke in hypertensive patients with the greatest cardiovascular risk.

Comparison of home and office blood pressure in treated hypertensives in the Nordic Diltiazem (NORDIL) Study.

The aim of the Nordic Diltiazem (NORDIL) Study was to compare cardiovascular morbidity and mortality in calcium-antagonist-based treatment with diltiazem and conventional diuretic/beta-blocker-based treatment in essential hypertension. The objective of the present sub-study was to compare self-measured home blood pressure with office blood pressure at a time-point in the study when the patients' blood pressures had been treated to the level that the investigators conceived to be the blood pressure target. The NORDIL study was prospective, randomized, open and endpoint-blinded. It enrolled 10881 patients aged 50-74 years at health centers in Norway and Sweden who had diastolic blood pressure (BP) of 100 mmHg or more. The present sub-study group (n = 87) was small but fairly representative for the entire study population regarding baseline characteristics. Both systolic (4.0 mmHg, p = 0.01) and diastolic blood pressures (3.1 mmHg, p < 0.001) were significantly lower at home than in the office. Pearson correlation coefficients between the respective office and home readings were statistically highly significant (p < 0.001), but of moderate strength ranging from r = 0.41 for heart rate to r = 0.46 and r = 0.58 for diastolic and systolic blood pressures, respectively. Altman plots also gave statistical support to some inconsistency between the two methods of measurements. Pearson correlation coefficients between afternoon and morning measurements showed strong relationships with r-values >0.9 for both blood pressures and heart rate. The Altman plots also suggested excellent consistency between afternoon and morning measurements. Thus, motivated and trained hypertensive patients can perform home recordings of blood pressure and heart rate with precision; however, there are differences between recordings at home and in the investigators' offices that suggest some degree of "white coat effect" in these treated hypertensives.

Efeitos hemodinâmicos da nifedipina na hipertensäo essencial em repouso e durante o exercício / Hemodynamic effects of nifedipine in essential hypertension at rest and during exercise

Quinze homens com hipertensäo essencial previamente näo tratada no estágio I da WHO, com idades de 20-64 anos, foram estudados em regime de pacientes ambulatoriais. O consumo de oxigênio, a taxa de batimentos cardíacos, o débito cardíaco (Cardiogreen) e a pressäo braquial intra-arterial foram registradas em repouso, nas posiçöes supina e sentada e durante esforço em estado constante a 50, 100 e 150 W. Após o estudo hemodinâmico, nifedipina (formulaçäo de açäo prolongada) na posologia de 40-80 mg diárias foi administrada como droga única durante 3-12 meses (média 11 meses), quando se repetiu o estudo hemodinâmico. As pressöes sistólica, diastólica e pressäo arterial média caíram cerca de 17% em repouso nas posiçöes supina e sentada e de 15% a 10% nas três diferentes cargas de trabalho (p <0,001). Todos, com exeçäo de um paciente, demonstraram uma queda na pressäo arterial média de 100 mm de Hg ou mais. A queda de pressäo estava associada a uma reduçäo estatisticamente significativa (p <0,05) na resistência periférica total (17% durante o repouso e 16% durante o exercício). Näo houve variaçöes estatisticamente significativas em relaçäo ao consumo de oxigênio, taxa de batimentos cardíacos, índice cardíaco ou índice de pulsaçäo

Long-Term Haemodynamic Effects of Enalapril at Rest and During Exercise in Essential Hypertension.

Twelve males with moderately severe essential hypertension (mean arterial pressure [MAP] ranging 113-162 mmHg) were studied at rest supine and sitting and during bicycle exercise (50, 100 and 150 W). Intraarterial blood pressure (BP), and heart rate (HR) were recorded continuously. Cardiac output (CO) was measured by dye dilution (Cardiogreen). After 6-8 months (enalapril dose 10-40 mg daily) patients were restudied. BP fell in all patients, at rest sitting from 184/107 mmHg to 150/87 (-19%) and during 100 W from 223/117 to 194/98 mmHg (p < 0.001). Pretreatment total peripheral resistance index (TPRI) was greatly increased in all patients and fell from 4137 to 3651 dyn s cm-5 m2 (-16%) (p < 0.05). No significant changes were seen in CO, HR or stroke volume. No side effects were seen. It is concluded that enalapril reduces BP in patients with moderately severe hypertension at rest and during exercise due to reduction in TPRI without significant changes in CO or HR.