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.
"We thought, if it's true that a touch of tachycardia should push you toward beta blockers, we'd be able to see that in ASCOT," Poulter added. Noting that the ASCOT-BPLA study–-reported in 2005--confirmed the superiority of an amlodipine-based regimen over an atenolol-based regimen, "we looked to see whether, if you started with tachycardia, was that still the case?" he noted. "The bottom line is, yes, it is. Pulse rate should not be the determinant of what drugs you use in hypertension."
These findings "reinforce the UK guidelines that state that, in primary prevention, beta blockers should be kept to a much later stage of intervention," Poulter says.
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.
"These analyses provide no evidence that atenolol-based therapy is superior to amlodipine-based therapy for patients with hypertension uncomplicated by coronary heart disease across the wide range of baseline heart rates observed in the ASCOT database," say Poulter et al.
"Pending further information--which could perhaps be gleaned from other studies such as [Losartan Intervention for Endpoint Reduction in Hypertension] LIFE--beta-blocker–based therapies are not appropriate to select as initial therapy for hypertension on the basis of a higher heart rate unless congestive heart failure and/or symptomatic ischemic heart disease coexist," they conclude.
Results Apply to All Beta Blockers, Until Further Notice
Poulter added to heartwire that "some cardiologists will say that if we hadn’t used atenolol the results would have been different: 'If you'd used my favorite "olol," ' for example, and I say, 'Prove it!' "
He believes that beta blockers "are not all the same, they do have different effects on all sorts of things," but "there is no evidence of heterogeneity in terms of cardiovascular outcomes," he maintains.
"Until further notice, beta blockers should not come up the pecking order on the basis of pulse rate."
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.
