METABOLIC EFFECTS OF ISRADIPINE AS MONOTHERAPY OR IN COMBINATION WITH PINDOLOL DURING LONG-TERM ANTIHYPERTENSIVE TREATMENT

Objectives. To evaluate the effects of isradipine alone and in combination with pindolol on glucose and lipid metabolism during long-term antihypertensive therapy. Design. Open long-term study with parallel groups. Setting. Kungsgardet Geriatric Hospital, Uppsala, a tertiary referral hospital. Subjects. Twenty-six untreated hypertensive subjects. Interventions. After 4 weeks on placebo, isradipine was titrated up to 10 mg daily to achieve appropriate blood pressure control (n = 11). If this failed, 5-10 mg pindolol was added. The treatments were continued for 2 years. Main outcome measures. Blood pressure, lipoprotein measurements, intravenous glucose tolerance test, hyperinsulinaemic euglycaemic clamp, HbA(1c), body weight. Results. Treatment with isradipine alone caused a sustained reduction in blood pressure (-22/-10 mm Hg, P < 0.01), but an increase in body weight(+2.2 kg, P < 0.05) and HbA(1c) (+1.5%; P < 0.001) were also noted. Addition of pindolol resulted in a similar degree of blood pressure reduction and weight gain, whilst HbA(1c) was less affected (+1.0%; P < 0.05, compared to isradipine alone). Insulin sensitivity became impaired in both groups (-1.2 to -1.5 mg kg(-1)min(-1); P < 0.01 for M-value at hyperinsulinaemic clamp) but after adjustment for the change in body weight the impairment was only significant (P < 0.01) in the group with combined treatment. The combined treatment also resulted in an increase in very-low-density-lipoprotein (VLDL) triglyderides (+0.37 mmol L(-1); P < 0.05). Conclusions. The hypotensive effect of isradipine was sustained during long-term use but was associated with weight gain and an impaired glucose control. When isradipine was combined with pindolol there was also a reduction in insulin sensitivity and an increase in VLDL triglycerides, possibly as effects of the beta-adrenergic blockade.