The current literature supports the immediate use of combinations of antihypertensive drugs in terms of ease of use and adherence, but the key issue whether combination therapy is more effective than monotherapy in the prevention of cardiovascular complications remains unproven.
We analysed the double-blind (median follow-up 2.0 years) and open follow-up (6.0 years) phases of the Systolic Hypertension in Europe trial. Patients were 60 years or more with an entry systolic/diastolic blood pressure (BP) of 160–219/less than 95 mmHg. Antihypertensive treatment started immediately after randomization in the active-treatment group, but only after completion of the double-blind trial in control patients. Treatment consisted of nitrendipine (10–40 mg/day) with the possible addition of enalapril (5–20 mg/day). We adjusted our analyses for sex, age, history of cardiovascular complications, baseline systolic BP and previous antihypertensive treatment.
During the double-blind trial, adding enalapril to nitrendipine (n = 515), compared with the equivalent combination of placebos (n = 559), decreased systolic BP by a further 9.5 mmHg and reduced all cardiovascular events by 51% (P = 0.0035) and heart failure by 66% (P = 0.032), with similar trends for stroke (–51%; P = 0.066) and cardiac events (−44%; P = 0.075). Over the whole duration of follow-up, combination therapy (n = 871), compared with nitrendipine monotherapy (n = 1552), decreased systolic BP by 3.1 mmHg and reduced total mortality (−32%; P = 0.023), with similar trends for all cardiovascular events (−23%; P = 0.081) and stroke (−42%; P = 0.054).
Despite the limitations of a posthoc analysis, but congruent with the stronger BP reduction, our results suggest that combination therapy with nitrendipine plus enalapril might improve outcome over and beyond the benefits seen with nitrendipine monotherapy.
aThe Studies Coordinating Centre, Division of Hypertension and Cardiovascular Rehabilitation, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium
bDepartment of Epidemiology, The Netherlands
cCardiovascular Research Institute, The Netherlands
dDepartment of Internal Medicine, Maastricht University, Maastricht, The Netherlands
eDepartment of Internal Medicine and Gerontology, Poland
fFirst Department of Cardiology and Hypertension, Jagiellonian University Medical College, Kraków, Poland
gConway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland
hFundacion de Investigacion Hospital Clinico Valencia, University of Valencia, Valencia, Spain
iErasmus University, Rotterdam, The Netherlands
Received 23 September, 2009
Revised 1 December, 2009
Accepted 4 December, 2009
Correspondence to Jan A. Staessen, MD, PhD, FESC, FAHA, Studies Coordinating Centre, Laboratory of Hypertension, University of Leuven, Campus Sint Rafaël, Kapucijnenvoer 35, Block d Level 00, B-3000 Leuven, Belgium Tel: +32 16 34 7104; fax: +32 16 34 7106; e-mail: email@example.com and firstname.lastname@example.org