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Amlodipine-Based vs. Atenolol-Based Treatment for Hypertension

Results are in from the ASCOT trial’s BP-lowering arm.

In ASCOT, an industry-sponsored randomized trial conducted at 650 general practices across northern Europe, researchers compared the effectiveness of two antihypertensive regimens in 19,257 patients (mean age, 63; 77% men) with hypertension and at least three other cardiovascular risk factors. Baseline hypertension was defined as untreated systolic BP 160 mm Hg or diastolic BP 100 mm Hg, or treated SBP 140 mm Hg or DBP 90 mm Hg.

One regimen consisted of daily treatment with the calcium-channel blocker amlodipine (5–10 mg), with the ACE inhibitor perindopril (4–8 mg) added as needed; the other consisted of the beta-blocker atenolol (50–100 mg), with the thiazide diuretic bendroflumethiazide (1.25–2.5 mg) added as needed. Doses for each drug were given (and tertiary therapy added if necessary) according to a treatment algorithm. Mean baseline BP was 164/95 mm Hg in both groups; target BPs were <140/90 mm Hg for diabetic patients and <130/80 mm Hg for nondiabetic patients. (Results from ASCOT’s lipid-lowering arm, involving a subgroup of 10,305 subjects with total-cholesterol levels 250 mg/dL [6.5 mmol/L] randomized to atorvastatin or placebo, were published in 2003 [Journal Watch Cardiology May 30 2003].)

The BP-lowering arm was stopped early (median follow-up, 5.5 years) because the all-cause mortality rate was significantly lower with the amlodipine-based regimen than with the atenolol-based regimen (7.8% vs. 8.9%); by this point, mean BPs had dropped to 136/77 mm Hg and 138/79 mm Hg, respectively — a significant difference. Amlodipine-based therapy also was associated with a nonsignificantly lower rate of the primary endpoint (nonfatal MI or fatal coronary heart disease; 4.5% vs. 4.9%; P=0.105), as well as significantly lower rates of stroke, cardiovascular death, and new-onset diabetes (prespecified endpoints) and of total cardiovascular events and procedures (a non-prespecified endpoint). Cessation of therapy due to serious adverse events was significantly less common with amlodipine-based treatment than with atenolol-based treatment (2% vs. 3%).

Comment: In ASCOT, an amlodipine-based antihypertensive treatment strategy prevented more cardiovascular events and had fewer side effects than did an atenolol-based strategy. However, as the editorialists note, although the majority of ASCOT subjects used two or more antihypertensive medications, only 32% of subjects with diabetes and 60% of those without diabetes had reached BP goals by the time the trial was stopped. They also emphasize that the weight of published evidence suggests that BP lowering accounts for the bulk of the benefit of antihypertensive-drug treatment, regardless of the agent used. The ASCOT data support a particular drug-treatment approach to BP lowering, but the lowering itself (to target levels) is of greatest importance, along with appropriate screening and follow-up.

— JoAnne M. Foody, MD

Published in Journal Watch Cardiology September 30, 2005

Citation(s):

Dahlöf B et al. for the ASCOT Investigators. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): A multicentre randomised controlled trial. Lancet 2005 Sep 10; 366:895-906.

• Medline abstract (Free)

Staessen JA and Birkenhäger WH. Evidence that new antihypertensives are superior to older drugs. Lancet 2005 Sep 10; 366:869-71.

• Medline abstract (Free)