Clinical experience with guanfacine in long-term treatment of hypertension.

Of 662 hypertensive patients originally selected for long-term treatment, 580 were evaluated after one year and 169 continued for a second year of treatment with guanfacine. There were 257 women (mean age 52.1 yr) and 323 men (mean age 51.7 yr) in the trial: 499 (86%) suffered from essential, 55 (9%) from renal, 22 (4%) from renovascular and 4 (1%) from other forms of hypertension; 200 (34%) were classified as having mild, 275 (47.5%) moderate and 101 (17.5%) severe hypertension. In four patients the degree of severity was not specified. Nearly 40% of all patients had signs of left ventricular hypertrophy, and in 71% a pathological ocular fundus was found; 72% had been pretreated with antihypertensive drugs, 56% suffered from a concomitant disease and 18% had signs of heart failure; 224 patients were classified as having a sedentary mode of life, 316 were moderate and 27 heavy physical workers. In 13 no classification was given. Whenever possible, a wash-out period of 3 weeks with a placebo identical in appearance with the active drug was carried out at the beginning and at the end of the 12-month treatment period to establish the pretreatment blood pressure and the possible withdrawal phenomena after therapy discontinuation. At the beginning, two doses of guanfacine 1 mg were administered daily and the dose was successively increased. A diuretic was added if necessary. To non-responders, a β-adrenoceptor-blocker or a vasodilator was given. In all trial groups a statistically significant decrease in blood pressure was found. The average reduction in mean arterial pressure was 16% at the end of the first year and 17% at the end of the second year. Normalization of blood pressure was achieved in 54% of the patients at the end of the first year and in 66% after the second year of treatment. In patients with hypertension of a higher degree of severity, combined treatment was used more often and higher doses of guanfacine were administered; monotherapy was used predominantly in patients with mild to moderate hypertension. The mean daily dose of guanfacine at the end of the first year was 3.4 mg for monotherapy and 6 mg for combined treatment. After 2 yr, these values were 3.2 mg and 5 mg, respectively. With the once-daily and twice-daily dosage schedules the same antihypertensive effect as with the three times daily dose regimen was observed, with a higher normalization rate and fewer side-effects. Moreover, the normalization rate was higher with doses up to 3 mg than with doses in the range 4-25 mg. This applied to both monotherapy and combined treatment. It is suggested that low doses of guanfacine are more suitable for the treatment of patients with established but uncomplicated hypertension, because of the lack of peripheral α-mimetic effects is the lower dose range. In view of the relatively long half-life of guanfacine, it is recommended that the drug be given only once daily or at the most twice daily. The ECG analysis after one year of treatment revealed signs of regression in left-ventricular size. Ophthalmological examinations showed no deterioration, and there were no pathological changes in laboratory values. No untoward reactions were seen when guanfacine was combined with cardiac glycosides, antidiabetic agents, anticoagulants or psychotropic drugs.