Comparative effects of mibefradil and nifedipine gastrointestinal transport system on autonomic function in patients with mild to moderate essential hypertension

Background L-type dihydropyridine calcium channel blockers (CCBs) have been implicated in increased cardiovascular events in patients with hypertensio n, perhaps due to adverse effects on autonomic nervous system (ANS) functio n. Blockade of T-type calcium channels may limit ANS dysfunction by inhibit ion of T channel-mediated neuroendocrine effects. Objective and design This double-blind, parallel group study compared the e ffect of nifedipine gastrointestinal transport system (GITS) (L-type CCB) v ersus mibefradil (T-type CCB) on ANS function in patients with mild-moderat e essential hypertension. Methods Sixteen patients (10 male, 6 female; age 51.2 +/- 2.3 years), diast olic blood pressure (DBP) < 95 mmHg were randomized to nifedipine 30 mg dai ly or mibefradil 50 mg daily (2 weeks), then nifedipine 60 mg daily or mibe fradil 100 mg daily (4 weeks). Sympathetic nervous system activity (SNSA) w as assessed using norepinephrine kinetics. Parasympathetic nervous system a ctivity (PSNA) was assessed from 24 h Holter recordings of heart rate varia bility (HRV). Non-invasive baroreflex sensitivity (BRS) provided integrated assessment of ANS, Results Patient groups were well matched at baseline. Achieved DBP was lowe r in patients treated with mibefradil compared with nifedipine, (83.4 +/- 1 ,7 versus 95.25 +/- 3.3 mmHg). There were no significant differences in SNS A and BRS between groups, however the root mean square of successive differ ences and high frequency power (HFP) were increased in mibefradil compared with nifedipine-treated patients [(+ 1.07 +/- 1.6 versus -3.36 +/- 1.2 ms, P < 0.05) and (+ 0.28 +/- 0.1 versus -0.23 +/- 0.1 ms(2), P < 0.01), respec tively]. Furthermore, Ln HFP/Ln total power was increased from week 0 to we ek 6 in the mibefradil-treated group, (0.71 +/- 0.02 versus 0.74 +/- 0.03, P = 0.046). Conclusion No differences existed between effect of Land T-type CCBs on SNS A and BRS. However, T-type CCBs increased PSNA, independent of achieved cha nges in heart rate. (C) 2001 Lippincott Williams & Wilkins.