[Short and long-term clinical tolerance of hypertensive treatment during the HOT study (Hypertension Optimal Treatment)]. / Tolérance clinique à court et long terme du traitement antihypertenseur au cours de l'étude HOT.

International, prospective, randomized HOT study aims to determine the optimal BP level under treatment in order to reduce at the most the cardiovascular morbidity/mortality. Defined by randomization, the level to obtain is DBP < or = 80, 85, 90 mmHg. The treatment is started by felodipine 5 mg/day then, if necessary, a bitherapy is prescribed and then, if necessary, a tritherapy. 19,193 patients have been included (BP at randomization 170 +/- 15/105 +/- 4 mmHg). After 1 year treatment, it is possible to search for the influence on the clinical tolerance of sex, age, BP goal, geographic area, time and treatment. The percentage of patients with side effects by BP goals and by treatment type are, during the time and in different geographic areas, the following (NE/Northern Europe = Norway, Switzerland, Belgium, Hungary, Sweden, Denmark, Finland, The Netherlands, UK, Germany, Austria; SE/Southern Europe = Italy, Spain, Greece): [table: see text] The target BP and age don't nearly influence the clinical tolerance. The side effects reported by the physicians are more numerous at the treatment start than at longeur terme. That is due to the therapeutic modifications of the physicians or to a better acceptation of the drugs by the patients or to a real disappearance of the side effects. Reported side effects are more frequent in Southern Europe, France than Northern Europe and more frequent among women that men. The incidence of side effects is proportional to the number of prescribed drugs. Time and the number of antihypertensive drugs appear as the most important factors.

[Quality of blood pressure control in general practice and in the HOT study. French Research Group HOT (Hypertension Optimal Treatment)]. / Qualité du contrôle tensionnel en pratique courante et dans l'étude HOT. Groupe de recherche français de l'étude HOT.

A previous investigation of the French League against Hypertension has shown that only 27% of the hypertensives aged below 64 years and 19% of those aged above 64 years have their BP controlled under treatment (BP < 140/90 mmHg). The international, prospective, randomised HOT study aims at assessing the optimal diastolic BP (DBP) level during active antihypertensive treatment to reduce at the best the cardiovascular morbidity and mortality. The study is on-going, with a completion of inclusions. The BP measurements are performed by oscillometric method with the D2 international BP device, HESTIA. At enrollment, only 52% of the hypertensives were treated, their mean BP level being 161/99 mmHg +/- 18/9 mmHg (n = 10,005). On randomisation, two weeks after the treatment withdrawal, BP was 170/106 +/- 15/4 mmHg. Six months later, under treatment, BP was 150/84 +/- 10/7 mmHg with a mean decrease of 11/15 mmHg compared to values under previous treatment. Depending on the randomisation groups which are defined by different DBP objectives, 87.5 to 92.2% of the patients have a BP normalisation (DBP < or = 90 mmHg) after one year of treatment. Five explanations may be proposed for the better BP control observed in the study compared to the results at inclusion, reflecting the general practice: (1) the fact that the patient is free to participate and has been informed may have improved the compliance, (2) the patient's follow-up was reinforced during the first weeks, (3) the protocol is based on the treatment initiation by a dihydropyridine with a long duration of action: felodipine, (4) the BP objectives are rigorously defined by a DBP between 80 and 90 mmHg depending on the randomisation group whereas in general practice, the physician may have a smoother objective mainly aiming at improving tolerability, (5) the larger use of a bi-therapy. CONCLUSION. The more ambitious aims of BP control (DBP < or = 90, 85, 80 mmHg) in this study have induced a treatment intensification with a better BP control.

Comparison of effects of felodipine versus hydrochlorothiazide on arterial diameter and pulse-wave velocity in essential hypertension.

In a double-blind cross-over study, the arterial changes produced by hydrochlorothiazide were compared with those observed after the calcium antagonist felodipine in 16 patients with mild to moderate systemic hypertension. Diameter changes at the site of the common carotid and brachial arteries were investigated using pulsed Doppler velocimetry, and pulse-wave velocities of the aortic, brachial and femorotibial areas were measured using standard noninvasive techniques. Whereas hydrochlorothiazide and felodipine similarly decreased blood pressure, hydrochlorothiazide did not change pulse-wave velocity, and the diameters of the brachial and common carotid arteries. Felodipine significantly decreased pulse-wave velocity, and increased brachial arterial diameter and compliance, with no change in carotid arterial diameter. Evidence was found that although felodipine had specific effects on the arterial system of hypertensive subjects, hydrochlorothiazide did not produce any sizable arterial change. These differential effects may influence specifically the heart afterload, with important consequences for diuretics that are known to cause minimal changes in cardiac structure and function.

[Felodipine in arterial hypertension. Double-blind comparison with atenolol]. / La félodipine dans l'hypertension artérielle. Comparaison en double aveugle avec l'aténolol.

Felodipine is a new dihydropyridine calcium antagonist which selectively relaxes vascular smooth muscle. It lovers dose-dependently blood pressure in hypertensives patients. In this multicentre double-blind study, 113 patients (mean age 50 +/- 14 years) whose diastolic blood pressure was higher than 95 mmHg after withdrawal of an eventual antihypertensive therapy and a week of placebo administration. The patients received randomly either felodipine (5 mg x 2/j during two weeks and then 10 mg x 2/day) either atenolol (100 mg/day) during two months. Antihypertensive effects of these two drug regimens were not significantly different. Supine blood pressure decreased from 177 +/- 22/107 +/- 8 mmHg to 152 +/- 27/91 +/- 13 mmHg with felodipine and from 176 +/- 19/107 +/- 8 to 152 +/- 24/91 +/- 12 with atenolol. Side effects recorded by means of active questioning were ankle oedemas and headache with felodipine and fatigue and headache with atenolol.

[Treatment of essential hypertension with felodipine or atenolol as first line therapy. Comparative double-blind randomized study]. / Traitement de l'hypertension artérielle essentielle par la félodipine ou par l'aténolol en première intention. Etude comparative randomisée à double insu.

This study involved 113 patients (mean age 50 +/- 14 years) with diastolic blood pressure above 95 mmHg. The patients abstained from taking any antihypertensive drug and received a placebo for one week before entering felodipine, a new calcium antagonist (5 mg x2/day for 2 weeks, then 10 mg x2/day) or atenolol (100 mg/day). There was no significant difference between the two treatment groups. Atenolol tended to be more effective in young subjects and felodipine in subjects aged 60 years or more. Heart rate was more reduced by atenolol than by felodipine (P less than 0.01). Undesirable side-effects were recorded by means of an open questionnaire. Their incidence was 23 per cent during the week under placebo and 84 per cent and 80 per cent respectively during treatment with felodipine or atenolol. The most frequent side-effects were oedema of the ankles and headache under felodipine, fatigue and headache under atenolol. Alkaline phosphatase levels were higher in the felodipine group (P less than 0.05), and a slight rise in blood potassium level (0.2 mmol/l) was noted in the atenolol group (P = 0.001), but these values remained within normal limits.

[Metoprolol, a new effective antimigraine agent]. / Le métoprolol, nouvel antimigraineux de fond.

The effectiveness of metoprolol as a prophylactic treatment of migraine was investigated in double-blind comparative trials involving more than 500 patients. In two trials using a slow-release preparation and a dose of 200 mg per day, metoprolol proved significantly better than a placebo and as effective as propranolol 160 mg/day or flunarizine 10 mg/day. At the dose of 100 mg per day metoprolol was significantly more effective than clonidine and clomipramine and not different from a placebo, propranolol 80 mg/day or pizotifen 1.5 mg/day. It is concluded that metoprolol is useful as prophylactic treatment of migraine and ranks among the main drugs used for the same purpose, such as propranolol and pizotifen.