Usual versus tight control of systolic blood pressure in non-diabetic patients with hypertension (Cardio-Sis): an open-label randomised trial

Lancet. 2009 Aug 15;374(9689):525-33. doi: 10.1016/S0140-6736(09)61340-4.


Background: The level to which systolic blood pressure should be controlled in hypertensive patients without diabetes remains unknown. We tested the hypothesis that tight control compared with usual control of systolic blood pressure would be beneficial in such patients.

Methods: In this randomised open-label trial undertaken in 44 centres in Italy, 1111 non-diabetic patients with systolic blood pressure 150 mm Hg or greater were randomly assigned to a target systolic blood pressure of less than 140 mm Hg (usual control; n=553) or less than 130 mm Hg (tight control; n=558). After stratification by centre, we used a computerised random function to allocate patients to either group. Observers who were unaware of randomisation read electrocardiograms and adjudicated events. Open-label agents were used to reach the randomised targets. The primary endpoint was the rate of electrocardiographic left ventricular hypertrophy 2 years after randomisation. Analysis was by intention to treat. This study is registered with, number NCT00421863.

Results: Over a median follow-up of 2.0 years (IQR 1.93-2.03), systolic and diastolic blood pressure were reduced by a mean of 23.5/8.9 mm Hg (SD 10.6/7.0) in the usual-control group and by 27.3/10.4 mm Hg (11.0/7.5) in the tight-control group (between-group difference 3.8 mm Hg systolic [95% CI 2.4-5.2], p<0.0001; and 1.5 mm Hg diastolic [0.6-2.4]; p=0.041). The primary endpoint occurred in 82 of 483 patients (17.0%) in the usual-control group and in 55 of 484 patients (11.4%) of the tight-control group (odds ratio 0.63; 95% CI 0.43-0.91; p=0.013). A composite cardiovascular endpoint occurred in 52 (9.4%) patients in the usual-control group and in 27 (4.8%) in the tight-control group (hazard ratio 0.50, 95% CI 0.31-0.79; p=0.003). Side-effects were rare and did not differ significantly between the two groups.

Interpretation: Our findings lend support to a lower blood pressure goal than is recommended at present in non-diabetic patients with hypertension.

Funding: Boehringer-Ingelheim, Sanofi-Aventis, Pfizer.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antihypertensive Agents / therapeutic use
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / prevention & control
  • Cause of Death
  • Drug Therapy, Combination
  • Electrocardiography
  • Female
  • Follow-Up Studies
  • Humans
  • Hypertension / complications
  • Hypertension / drug therapy
  • Hypertension / prevention & control*
  • Hypertrophy, Left Ventricular / diagnosis
  • Hypertrophy, Left Ventricular / epidemiology
  • Hypertrophy, Left Ventricular / etiology*
  • Hypertrophy, Left Ventricular / prevention & control
  • Incidence
  • Italy / epidemiology
  • Kaplan-Meier Estimate
  • Linear Models
  • Logistic Models
  • Male
  • Prevalence
  • Proportional Hazards Models
  • Risk Reduction Behavior
  • Systole
  • Treatment Outcome


  • Antihypertensive Agents

Associated data