Addition of urapidil or metoprolol to the treatment of hypertensive non-responders to nifedipine monotherapy: efficacy and metabolic effects. Italian Urapidil Study Group.
This study compared the effects on blood pressure and some metabolic variables of a 3-month period addition therapy of urapidil or metoprolol in 273 hypertensive non-responders to nifedipine sustained release (SR) monotherapy. This was a randomised, open-label, controlled, parallel-group comparative study, followed by another 3-month period during which all patients received the combination nifedipine SR-urapidil independently of the treatment they were previously randomized to. Both treatments caused significant falls in systolic (SBP) and diastolic blood pressure (DBP) when compared with the nifedipine SR monotherapy phase. The addition of urapidil to nifedipine SR caused a significant blood pressure reduction of 16.6/13.6 mmHg (p < 0.001), whereas after metoprolol the decrease was of 15.1/14 mmHg (p < 0.001). While in the overall population there was no statistically significant difference between the reduction caused by the two antihypertensive agents added to nifedipine SR, significant differences (DBP, p < 0.05; SBP, p < 0.01) were observed in the group of 51 patients aged at least 60 years. Total cholesterol and LDL-cholesterol were significantly reduced (p < 0.001) after the addition of urapidil to nifedipine SR, while, on the contrary, the addition of metoprolol to nifedipine SR was followed by a significant rise (p = 0.001). The changes caused by the two agents were statistically different among them (p < 0.01). The non-atherogenic HDL-cholesterol did not change during the addition of urapidil or metoprolol to nifedipine SR, while, the HDL/total cholesterol ratio was significantly increased after the addition of urapidil (p < 0.01) and unmodified after the addition of metoprolol. Between-group analysis showed a significant difference (p = 0.005). Serum triglycerides did not change in the urapidil plus nifedipine SR group but significantly increased in the metoprolol plus nifedipine SR group (p < 0.001); between-group difference was not statistically significant. Plasma glucose was unchanged after the addition of urapidil whereas it was significantly (p < 0.001) increased in the metoprolol-added group with a between-group difference statistically significant (p < 0.05). When metoprolol was substituted by urapidil during the second 3-month period, the negative effects on glucose, total cholesterol, LDL cholesterol and triglycerides were abolished while in the group already treated with urapidil plus nifedipine SR the favourable effects of urapidil plus nifedipine SR on total cholesterol, LDL-cholesterol and HDL/total cholesterol ratio were significantly increased compared with the end of the first 3-month treatment. The results of this study show that when urapidil and metoprolol are added to non-responders to nifedipine SR therapy there is a clinically and statistically relevant blood pressure reduction with both agents, with a therapeutic advantage for the combination urapidil + nifedipine SR in patients more than 60 years old. Moreover, the addition of urapidil was associated with a more favourable effect on serum lipids and glucose than that produced by the addition of metoprolol.
Centro di Fisiologia Clinica e Ipertensione, Ospedale Maggiore, Milano.
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Zanchetti
D000328:Adult; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008790:Metoprolol / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009543:Nifedipine / Q000009:adverse effects / Q000627:therapeutic use*; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D010879:Piperazines; C015568:urapidil; D008790:Metoprolol; D009543:Nifedipine