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CLINICAL RESEARCH: HYPERTENSION

Baseline Heart Rate, Antihypertensive Treatment, and Prevention of Cardiovascular Outcomes in ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial)

Neil R. Poulter, MB, MSc^_*,_*, Joanna E. Dobson, MSc^_*, Peter S. Sever, PhD^_*, Björn Dahlöf, MD, PhD, Hans Wedel, PhD, Norm R.C. Campbell, MD on behalf of the ASCOT Investigators

^_* Imperial College London, London, United Kingdom
Sahlgrenska University Hospital, Göteborg, Sweden
Nordic School of Public Health, Göteborg, Sweden
University of Calgary, Calgary, Alberta, Canada

Manuscript received February 16, 2009; revised manuscript received April 22, 2009, accepted April 26, 2009.

^_* Reprint requests and correspondence: Prof. Neil R. Poulter, International Centre for Circulatory Health, Imperial College London, 59 North Wharf Road, London W2 1PG, United Kingdom (Email: n.poulter{at}imperial.ac.uk).

Objectives: The aim of this study was to evaluate the effect of baseline heart rate on the efficacy of atenolol-based compared with amlodipine-based therapy in patients with hypertension uncomplicated by coronary heart disease in the ASCOT-BPLA (Anglo-Scandinavian Cardiac Outcomes Trial–Blood Pressure Lowering Arm).

Background: Heart rate is an established risk factor for cardiovascular events. Consequently, it is a widely held belief that beta-blockers should be prescribed for management of hypertension in patients with higher heart rates.

Methods: Patients with atrial fibrillation or taking rate-limiting antihypertensive drugs at baseline were excluded. Primary analyses used Cox models to investigate the potential attenuation of the treatment effect with higher baseline heart rate on total cardiovascular events and procedures (TCVP) via introduction of an interaction term. Secondary analyses assessed coronary and total stroke outcomes.

Results: Primary unadjusted analyses included 12,759 patients and 1,966 TCVP. At the final visit, mean heart rate reduction from baseline was 12.0 (SD 13.7) and 1.3 (SD 12.1) beats/min in atenolol- and amlodipine-based groups, respectively. There was a reduction in TCVP in those allocated amlodipine-based therapy compared with atenolol-based therapy (unadjusted hazard ratio: 0.81, p < 0.001). This benefit was unattenuated at higher heart rates (interaction p value = 0.81). Similar results were obtained for coronary and total stroke outcomes.

Conclusions: There was no evidence that the superiority of amlodipine-based over atenolol-based therapy for patients with hypertension uncomplicated by coronary heart disease was attenuated with higher baseline heart rate. These data suggest that, in similar hypertensive populations without previous or current coronary artery disease, higher baseline heart rate is not an indication for preferential use of beta-blocker–based therapy.

Key Words: beta-blockers • cardiovascular risk • heart rate • hypertension

Abbreviations and Acronyms   BP = blood pressure   CHD = coronary heart disease   MI = myocardial infarction   TCVP = total cardiovascular events and procedures

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