This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Staessen, J. A. Articles by Yodfat, Y. Search for Related Content PubMed PubMed Citation Articles by Staessen, J. A. Articles by Yodfat, Y.

(Hypertension. 1998;32:410-416.)
© 1998 American Heart Association, Inc.

Scientific Contributions

Calcium Channel Blockade and Cardiovascular Prognosis in the European Trial on Isolated Systolic Hypertension

Jan A. Staessen; Lutgarde Thijs; Robert H. Fagard; Willem H. Birkenhäger; Guramy Arabidze; Speranta Babeanu; Blas Gil-Extremera; Christopher J. Bulpitt; Christopher Davidson; Peter W. de Leeuw; Aris D. Efstratopoulos; Astrid E. Fletcher; Roberto Fogari; Matti Jääskivi; Kalina Kawecka-Jaszcz; Choudomir Nachev; James C. Petrie; Marie-Laure Seux; Jaakko Tuomilehto; John Webster; Yair Yodfat; ; for the Systolic Hypertension in Europe (Syst-Eur) Trial Investigators¹

Correspondence to Jan A. Staessen, MD, PhD, Klinisch Laboratorium Hypertensie, Inwendige Geneeskunde-Cardiologie, UZ Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. E-mail jan.staessen{at}med.kuleuven.ac.be

Abstract—In the double-blind Systolic Hypertension in Europe (Syst-Eur) Trial, active treatment was initiated with nitrendipine (10 to 40 mg/d) with the possible addition of enalapril (5 to 20 mg/d) and/or hydrochlorothiazide (12.5 to 25 mg/d) titrated or combined to reduce sitting systolic blood pressure by at least 20 mm Hg to <150 mm Hg. In the control group, matching placebos were used similarly. In view of persistent concerns about the use of calcium channel blockers as first-line antihypertensive drugs, this report explored to what extent nitrendipine, administered alone, prevented cardiovascular complications. Age at randomization averaged 70.2 years and systolic/diastolic blood pressure 173.8/85.5 mm Hg. Of 2398 actively treated patients, 1327 took only nitrendipine (average dose, 23.4 mg/d), and 1042 progressed to other treatments including nitrendipine (n=757; 35.7 mg/d), enalapril (n=783; 13.4 mg/d), and/or hydrochlorothiazide (n=294; 21.0 mg/d). Compared with the whole placebo group (n=2297), patients receiving monotherapy with nitrendipine had 25% (P=0.05) fewer cardiovascular end points, and those progressing to other active treatments showed decreases (P0.01) in total mortality (40%), stroke (59%), and all cardiovascular end points (39%). Among the control patients, 863 used only the first-line placebo. Compared with this subgroup, patients receiving monotherapy with nitrendipine showed a nearly 50% (P0.004) reduction of all types of end points, including total and cardiovascular mortality. The full relative benefit from nitrendipine was seen as early as 6 months after randomization. To ascertain that the benefit conferred by the dihydropyridine was not due to selection bias, the 1327 patients remaining on monotherapy with nitrendipine were matched by gender, age, previous cardiovascular complications, and systolic blood pressure at entry with an equal number of placebo patients. In this analysis, nitrendipine reduced (P0.05) cardiovascular mortality by 41%, all cardiovascular end points by 33%, and fatal and nonfatal cardiac end points by 33%. Despite the limitations inherent in post hoc analyses, the present findings suggest that the calcium channel blocker nitrendipine, given as a single antihypertensive medication, prevents cardiovascular complications in older patients with isolated systolic hypertension.

Key Words: calcium channel blockers • hypertension, isolated systolic • prognosis

This article has been cited by other articles:

				P. S. Sever, N. R. Poulter, W. J. Elliott, M. C. Jonsson, H. R. Black, P. S. Sever, N. R. Poulter, W. J. Elliott, M. C. Jonsson, and H. R. Black Blood Pressure Reduction Is Not the Only Determinant of Outcome Circulation, June 13, 2006; 113(23): 2754 - 2774. [Full Text] [PDF]

				R. C. Brown and T. P. Davis Calcium Modulation of Adherens and Tight Junction Function: A Potential Mechanism for Blood-Brain Barrier Disruption After Stroke Stroke, June 1, 2002; 33(6): 1706 - 1711. [Abstract] [Full Text] [PDF]

				P. A Meredith and P. Trenkwalder Therapy in the elderly hypertensive Journal of Renin-Angiotensin-Aldosterone System, March 1, 2002; 3(1_suppl): S49 - S56. [Abstract] [PDF]

				D. R. Abernethy and J. B. Schwartz Calcium-Antagonist Drugs N. Engl. J. Med., November 4, 1999; 341(19): 1447 - 1457. [Full Text] [PDF]

				Randomized Double-Blind Comparison of a Calcium Antagonist and a Diuretic in Elderly Hypertensives Hypertension, November 1, 1999; 34(5): 1129 - 1133. [Abstract] [Full Text] [PDF]

				S. Salpeter, J. Tuomilehto, J. A. Staessen, and W. H. Birkenhager Calcium-Channel Blockade and Hypertension N. Engl. J. Med., July 29, 1999; 341(5): 372 - 373. [Full Text]

				T. C. Fagan and J. Sowers Type 2 Diabetes Mellitus: Greater Cardiovascular Risks and Greater Benefits of Therapy Arch Intern Med, May 24, 1999; 159(10): 1033 - 1034. [Full Text] [PDF]

				J. Tuomilehto, D. Rastenyte, W. H. Birkenhager, L. Thijs, R. Antikainen, C. J. Bulpitt, A. E. Fletcher, F. Forette, A. Goldhaber, P. Palatini, et al. Effects of Calcium-Channel Blockade in Older Patients with Diabetes and Systolic Hypertension N. Engl. J. Med., March 4, 1999; 340(9): 677 - 684. [Abstract] [Full Text] [PDF]