Published Online
on December 6, 2004

A more recent version of this article appeared on January 1, 2005

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Submitted on April 19, 2004
Revised on May 13, 2004

Stroke Reduction in Hypertensive Adults with Cardiac Hypertrophy Randomized to Losartan Versus Atenolol. The Losartan Intervention For Endpoint Reduction in Hypertension Study

Jorge R. Kizer^*; Björn Dahlöf; Sverre E. Kjeldsen; Stevo Julius; Gareth Beevers; Ulf de Faire; Frej Fyhrquist; Hans Ibsen; Krister Kristianson; Ole Lederballe-Pedersen; Lars H. Lindholm; Markku S. Nieminen; Per Omvik; Suzanne Oparil; Hans Wedel; Kristian Wachtell; Jonathan M. Edelman; Steven M. Snapinn; Katherine E. Harris; and Richard B. Devereux

From the Weill Medical College of Cornell University (J.R.K., R.B.D.), New York, NY; Sahlgrenska/Östra University Hospital (B.D.), Gothenburg, Sweden; Ullevaal University Hospital (S.E.K.), Oslo, Norway; University of Michigan (S.J.), Ann Arbor; City Hospital (G.B.), Birmingham, UK; Karolinska University Hospital (U.d.F.), Stockholm, Sweden; Helsinki University Central Hospital (F.F., M.S.N.), Finland; Glostrup University Hospital (H.I., K.H.), Copenhagen, Denmark; Merck Research Laboratories Scandinavia (K.K.), Stockholm, Sweden; Viborg Hospital (O.L.-P.), Denmark; Umeå University (L.H.L.), Sweden; Haukeland University Hospital (P.O.), Bergen, Norway; University of Alabama (S.O.), Birmingham; The Nordic School of Public Health (H.W.), Gothenburg, Sweden; and Merck & Co, Inc (J.M.O., S.M.S., K.E.H.), Whitehouse Station, NJ.

^* To whom correspondence should be addressed. E-mail: jok2007{at}med.cornell.edu.

Abstract--The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study showed that treatment with the angiotensin II type-1 receptor antagonist losartan reduces overall stroke risk compared with conventional therapy with the -blocker atenolol. We conducted secondary analyses in LIFE to determine the extent to which the cerebrovascular benefits of losartan apply to different clinical subgroups and stroke subtypes and to assess the dependence of these benefits on baseline and time-varying covariates. Among 9193 hypertensive patients with electrocardiographic evidence of left ventricular hypertrophy, random allocation to losartan-based treatment lowered the risk of fatal (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.43 to 0.96; P=0.032) and atherothrombotic stroke (HR, 0.72; 95% CI, 0.59 to 0.88; P=0.001) compared with atenolol-based therapy. Although comparable risk reductions occurred for hemorrhagic and embolic stroke, these were not statistically significant. The number of neurological deficits per stroke was similar, but there were fewer strokes in the losartan group for nearly every level of stroke severity. Effects were consistent in all clinical subgroups except for those defined by age and ethnicity. The benefits of losartan on all strokes were independent of baseline and time-varying risk factors, including blood pressure. The number needed to treat for 5 years to prevent 1 stroke was 54 for the average participant, declining to 25, 24, and 9 for patients with cerebrovascular disease, isolated systolic hypertension, and atrial fibrillation, respectively. In conclusion, substantial cerebrovascular benefit could be realized with the institution of losartan-based therapy over conventional therapy among hypertensive patients with left ventricular hypertrophy across the spectrum of cardiovascular risk.

Key words: population • drug therapy • clinical trials • angiotensin antagonists • hypertrophy • stroke

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