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(Hypertension. 2000;35:1038.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Influence of Diabetes and Type of Hypertension on Response to Antihypertensive Treatment

Morris J. Brown; Alain Castaigne; Peter W. de Leeuw; Giuseppe Mancia; Christopher R. Palmer; Talma Rosenthal; Luis M. Ruilope

From the Clinical Pharmacology Unit (M.J.B.) and Centre for Applied Medical Statistics (C.R.P.), University of Cambridge, United Kingdom; Service de Cardiologie (A.C.), Hopital Henri Mondor, University of Paris, France; University of Maastricht (P.W.D.), The Netherlands; Cattedra di Medicina Interna (G.M.), University of Milan, Italy; Hypertension Unit (T.R.), Chaim Sheba Medical Center, University of Tel Aviv, Israel; and Nephrology Department (L.M.R.), Hospital 12 de Octobre, University of Madrid, Spain.

Correspondence to Prof M.J. Brown, Clinical Pharmacology Unit, University of Cambridge, Addenbrooke’s Centre for Clinical Investigation, Level 6, Addenbrooke’s Hospital, Box 110, Cambridge CB2 2QQ, UK. E-mail morris.brown{at}cai.cam.ac.uk

Abstract—The aim of our investigation was to determine whether the presence of additional risk factors or type of hypertension (diastolic or isolated systolic) influences blood pressure (BP) response to treatment. The International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) study is a double-blinded outcome comparison of calcium channel blockade with diuretics in high-risk patients aged 55 to 80 years. Dynamic randomization between nifedipine once daily and hydrochlorothiazide/amiloride was performed to ensure that approximately equal numbers of patients in the 2 groups had each of the major cardiovascular risk factors. Patients with isolated systolic hypertension were also separately randomized. Atenolol or enalapril was the mandatory second-line drug. In 5669 patients who completed the 18-week titration, BP fell from 172±15/99±9 mm Hg (mean±SD) while receiving placebo to 139±12/82±7 mm Hg. Twenty-six percent of patients required 2 drugs, and 4% required 3 drugs. Patients with diabetes were the most resistant to treatment, requiring second and third drugs 40% and 100% more frequently than patients without diabetes and achieving marginally the highest final BP, for any risk group, of 141±13/82±8 mm Hg. Age, smoking, gender, hypercholesterolemia, left ventricular hypertrophy, and existing atherosclerosis had little (<1 mm Hg) or no influence on BP at the end of titration, but all except smoking slightly reduced the initial response of either systolic or diastolic BP. Patients with isolated systolic hypertension were slightly more responsive than average to treatment. Our findings suggest that in patients at high absolute risk of cardiovascular complications from hypertension, the risk factors themselves do not prevent the recommended BP targets from being achieved.

Key Words: cardiovascular diseases • diabetes mellitus • random allocation • antihypertensive therapy • calcium channel blockers • diuretics

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