New ASCOT Analysis: Beta Blockers Not Beneficial in Hypertensives With Tachycardia
News Author: Lisa Nainggolan
September 24, 2009 — A new analysis of the Anglo-Scandinavian Cardiac Outcomes Trial--Blood Pressure Lowering Arm (ASCOT-BPLA) shows that the amlodipine (Norvasc, Pfizer)-based arm of the study remained superior to the beta-blocker arm, even when resting heart rate was taken into account [1].
The study was published in the September 22, 2009 issue of the Journal of the American College of Cardiology.
The findings mean that "there is no reason to believe that beta blockers should be used earlier on in the treatment of hypertension on the basis of heart rate," lead author Dr Neil R Poulter (Imperial College London, UK) told heartwire . He said many cardiologists have had "a hindbrain belief" that "if there is a touch of tachycardia, beta blockers are the right drugs to use in hypertension management." But prior to this analysis, there had been no data from randomized controlled trials available to assess the impact of this advice on patient outcomes, he noted.
No Attenuation of Amlodipine Superiority on Basis of Heart Rate
The ASCOT trial enrolled 19 257 hypertensive patients with at least three other cardiovascular risk factors from 650 general practices in the UK, Ireland, and the Nordic countries. The results showed that an antihypertensive strategy based on amlodipine, with perindopril added as required, significantly reduced all-cause mortality and other cardiovascular end points, including stroke, compared with an atenolol-based strategy, with the diuretic bendroflumethiazide added as required.
In this new subgroup analysis, patients with atrial fibrillation or taking rate-limiting antihypertensive drugs at baseline were excluded. The potential attenuation of the treatment effect with higher baseline heart rate on total cardiovascular events and procedures (TCVP) was assessed via an interaction term. Secondary analyses evaluated coronary and stroke outcomes.
There were 12 759 of the ASCOT patients included and 1966 total cardiovascular events and procedures. At the final visit, mean heart-rate reduction from baseline was 12.0 and 1.3 beats per minute in the atenolol- and amlodipine-based groups, respectively. There was a reduction in total cardiovascular events and procedures in those allocated to amlodipine-based therapy compared with those on atenolol-based therapy (unadjusted hazard ratio 0.81; p<0.001).
Until further notice, beta blockers should not come up the pecking order on the basis of pulse rate.
This benefit was unattenuated at higher heart rates (interaction p value=0.82). Similar results were obtained for coronary and total stroke outcomes.
Poulter has served as a consultant to and received travel expenses, payment for speaking at meetings, or funding for research from one or more pharmaceutical companies marketing BP-lowering or lipid-lowering drugs. Poulter has also previously received financial support from Pfizer to cover administrative and staffing costs of the ASCOT study and travel or accommodation expenses or both incurred by attending relevant meetings. Disclosures for the coauthors are listed in the paper.
References
Poulter NR, Dobson JE, Sever PS, et al. Baseline heart rate, antihypertensive treatment, and prevention of cardiovascular outcomes in ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial). J Am Coll Cardiol 2009; 54:1154-1161.
Clinical Context
Resting heart rate has been shown to be a significant predictor of all-cause and CV mortality among men and women, including patients with hypertension, and heart rate reduction has been one of the important mechanisms for beta-blockers to exert their beneficial effects. However, it is not certain if superior effects of amlodipine on CV outcomes in patients with hypertension are attenuated by higher resting heart rate and whether beta-blockers should be a first-line treatment in patients with hypertension and a higher baseline heart rate.
This is an examination of data from the ASCOT trial, a 2 x 2-factorial design trial comparing CV outcomes in patients with hypertension treated with atenolol vs amlodipine with or without lipid-lowering therapy.
Study Highlights
ASCOT recruited 19,257 patients between 1998 and 2000 from family practices in the United Kingdom, Ireland, and the Nordic countries and randomly assigned them to atenolol (with or without bendroflumethiazide) or amlodipine (with or without perindopril).
Included were patients aged 40 to 79 years with untreated hypertension (systolic BP ≥ 160 mm Hg and diastolic BP ≥ 100 mm Hg) who had at least 3 CV risk factors.
The CV risk factors included male sex, age 55 years or older, microalbuminuria or proteinuria, smoking, total to high-density lipoprotein cholesterol ratio of 6 or higher, premature coronary disease in the family, left ventricular hypertrophy, and comorbidities that increase CV risk.
Excluded were patients with a previous history of myocardial infarction, current angina, cerebrovascular event within 3 months, fasting triglyceride level of more than 4.5 mmol/L, heart failure, arrhythmias including atrial fibrillation, or beta-blocker at screening.
Heart rate and BP were measured at screening, baseline, and at every follow-up visit (6 weeks, 3 months, 6 months, and then every 6 months).
Heart rate and BP were measured 3 times at each visit, and the mean of the last 2 readings was used for analysis.
Baseline heart rate was analyzed as a continuous variable and also at intervals of 10 beats per minute.
The primary outcome was the effect of baseline heart rate on the effect of either atenolol or amlodipine on TCVP.
Secondary analyses examined stroke and coronary outcomes.
Mean age of the patients was 63 years, one quarter had diabetes, one third were smokers, and one quarter were taking antihypertensive medications at baseline.
Mean systolic BP was 165 mm Hg and mean diastolic BP was 95 mm Hg, with a mean baseline heart rate of 74 beats per minute.
Baseline heart rates were higher among women, smokers, and diabetic patients.
Heart rate decreased with increasing age and increased with increasing body mass index, BP, alcohol intake, triglyceride levels, and glucose levels.
There were 12,759 patients with 1966 TCVP.
Allocation to atenolol was associated with a decrease in heart rate regardless of baseline heart rate, with a mean heart rate reduction of 12 beats per minute.
Allocation to amlodipine was associated with increased heart rate in the lowest tertile of baseline heart rate, no change in the middle tertile, and reduced heart rate in the highest baseline tertile, with an average decrease in heart rate of 1.3 beats per minute overall.
Baseline heart rate did not affect TCVP, nonfatal myocardial infarction, or total stroke outcomes.
Allocation to amlodipine was associated with significantly better CV outcomes vs allocation to atenolol, and this was not attenuated by higher baseline heart rate in either group.
The heart rate for TCVP reduction in the amlodipine group vs the atenolol group was 0.81 (P < .0001).
The effect on the 3 CV outcomes was not affected by baseline heart rate in the amlodipine group.
The authors concluded that baseline heart rate in patients with hypertension did not attenuate the CV benefits of amlodipine treatment and that this does not support use of beta-blockers in patients with hypertension and a higher baseline heart rate.
Clinical Implications
Use of atenolol vs amlodipine in patients with hypertension is associated with a greater reduction in heart rate vs baseline heart rate.
The CV benefits of amlodipine are not attenuated by baseline heart rate in patients with hypertension.