ASCOT-BPLA: Newer agents proved better than older agents

A regimen of newer antihypertensive agents was found superior to older agents in reducing outcomes associated with high blood pressure in the ASCOT-BPLA trial.

Researchers presented the results of the blood pressure-lowering arm of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT-BPLA) at the European Society of Cardiology Congress 2005. Results of the lipid-lowering arm were presented two years ago.

In this part of the trial, investigators compared the efficacy of the standard antihypertensive regimen of the beta-blocker atenolol and/or the diuretic thiazide vs. a new regimen of the calcium antagonist amlodipine and/or the ACE inhibitor perindopril (Aceon, Solvay) on nonfatal MI and fatal CHD.

ASCOT was stopped early due to a high mortality benefit in the treatment arm. Because of that, the 10% reduction in favor of the amlodipine (Norvasc, Pfizer) and/or perindopril regimen was not statistically significant.

Guidelines should be amended

Franz H. Messerli, MD, director of the hypertension program at St. Luke’s-Roosevelt Hospital in New York and section editor of Cardiology Today’s Hypertension and Vascular Disease section, said that ASCOT “is unique in that both arms in the 2x2 design [including the lipid-lowering arms] were stopped prematurely because of positive results.”

Messerli said the ASCOT trial “provides ammunition” to the argument that beta-blockers and diuretics may hamper the metabolic status of some patients despite their documented beneficial effects on BP.

“However, we should also consider that in ASCOT, systolic BP was lowered significantly better in the amlodipine/perindopril arm than in the beta-blocker/diuretic arm. This may simply indicate that newer drugs are more efficacious and better tolerated,” he said.

Whether there are blood pressure benefits or other independent benefits, the active therapy in ASCOT is clearly better than the comparator group, he said. “The current guidelines should be amended accordingly,” Messerli said.

ASCOT design

The ASCOT trial enrolled 19,257 patients from five European countries who had untreated BP ≥160 mm Hg/100 mm Hg or treated BP ≥140 mm Hg/90 mm Hg. These patients had to have three or more cardiovascular disease risk factors, but they could not have had any previous MI or current clinical CHD.

Patients were randomized to one of two arms with a BP target of <140 mm Hg/90 mm Hg or, if diabetic, <130 mm Hg/80 mm Hg. The active treatment arm began with amlodipine at 5 mg, titrated to 10 mg as needed, and followed by perindopril at 4 mg titrated to 8 mg. The comparator arm began with atenolol at 50 mg, titrated to 100 mg, followed by bendroflumethiazide-K (Corzide, King Pharmaceuticals) 1.25 mg titrated to 2.5 mg.

After five years of follow-up, the active treatment had lowered systolic BP from 164.1 mm Hg to 137.7 mm Hg while the comparator group had a reduction from 165.9 mm Hg to 136.1 mm Hg, for a mean difference of 2.7 mm Hg in favor of the active group. Similarly, with diastolic pressure the difference was 1.9 mm Hg in favor of the treatment arm.

Outcome differences

Bjorn Dahlof, MD, associate professor of medicine at Sahlgrenska University Hospital in Sweden, presented the main outcome results of the trial. He said that even though the primary outcome of nonfatal MI and fatal CHD was not statistically significant, the active treatment group had a 13% reduction in nonfatal MI and fatal CHD once silent MIs were excluded.

When coronary revascularization procedures were added to the mix, the reduction in the primary outcome in favor of the active treatment group was 14% (P=.0058). – by Jeremy Moore

For more information:

• Sever PS, Dahlof B, Poulter NR. ASCOT-BPLA: The Anglo-Scandinavian cardiac outcomes trial: blood pressure-lowering arm. Presented at the European Society of Cardiology Congress 2005. Sept. 3-7, 2005. Stockholm.