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(Hypertension. 1999;33:713-718.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Irbesartan Reduces QT Dispersion in Hypertensive Individuals

Pitt O. Lim; Marleen Nys; Abdul A. O. Naas; Allan D. Struthers; Mary Osbakken; Thomas M. MacDonald

From the Hypertension Research Centre (P.O.L., A.A.O.N., A.D.S., T.M.M.), Department of Clinical Pharmacology and Therapeutics, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK; Bristol-Myers Squibb (M.N.), Waterloo, Belgium; Bristol-Myers Squibb (M.O.), Princeton NJ.

Correspondence to Dr Pitt Lim, Hypertension Research Centre, Department of Clinical Pharmacology and Therapeutics, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK. E-mail pitt{at}clinpharm.dundee.ac.uk

Abstract—Angiotensin type 1 receptor antagonists have direct effects on the autonomic nervous system and myocardium. Because of this, we hypothesized that irbesartan would reduce QT dispersion to a greater degree than amlodipine, a highly selective vasodilator. To test this, we gathered electrocardiographic (ECG) data from a multinational, multicenter, randomized, double-blind parallel group study that compared the antihypertensive efficacy of irbesartan and amlodipine in elderly subjects with mild to moderate hypertension. Subjects were treated for 6 months with either drug. Hydrochlorothiazide and atenolol were added after 12 weeks if blood pressure (BP) remained uncontrolled. ECGs were obtained before randomization and at 6 months. A total of 188 subjects (118 with baseline ECGs) were randomized. We analyzed 104 subjects who had complete ECGs at baseline and after 6 months of treatment. Baseline characteristics between treatments were similar, apart from a slight imbalance in diastolic BP (irbesartan [n=53] versus amlodipine [n=51], 99.2 [SD 3.6] versus 100.8 [3.8] mm Hg; P=0.03). There were no significant differences in BP normalization (diastolic BP <90 mm Hg) between treatments at 6 months (irbesartan versus amlodipine, 80% versus 88%; P=0.378). We found a significant reduction in QT indexes in the irbesartan group (QTc dispersion mean, –11.4 [34.5] milliseconds, P=0.02; QTc max, –12.8 [35.5] milliseconds, P=0.01), and QTc dispersion did not correlate with the change in BP. The reduction in QT indexes with amlodipine (QTc dispersion, –9.7 [35.4] milliseconds, P=0.06; QTc max, –8.6 [33.2] milliseconds, P=0.07) did not quite reach statistical significance, but there was a correlation between the change in QT indexes and changes in systolic BP. In conclusion, irbesartan improved QT dispersion, and this effect may be important in preventing sudden cardiac death in at-risk hypertensive subjects.

Key Words: irbesartan • amlodipine • electrocardiography • QT dispersion • aged • hypertension, essential

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