Impaired results of a randomised double blinded clinical trial of propranolol versus placebo on the expansion rate of small abdominal aortic aneurysms

Abstract

Background: To study the propranolol treatment of small abdominal aortic aneurysms (AAA) concerning intention to treat, side effects, and inhibition of expansion.

Design: Two-year lasting prospective randomised double-blinded intervention trial.

Setting: Hospital-based mass screening for AAA with annual ambulatory control of small AAA.

Participants: Of 122 screening-diagnosed small AAA, 51 (42%) were excluded because of contraindications or present beta-blockage, and 17 refused participation. Thus, 54 (44.3%) were included.

Intervention: Participants were randomised to 40 mg propranolol twice a day or placebo.

Measures: The same observed was used to follow-up AAA-expansion, side effects, quality of life (QL), branchial and ankle blood pressure (ABI), and pulmonary function (FEV1 and FVC).

Results: Sixty percent in the propranolol group, and 25% in the placebo group dropped out, mainly caused by dyspnoea in the propranolol group (RR=1.74, 95% C.I.: 1.06-2.86). Five (16.7%) died in the propranolol group, while 1 (4.2%) died in the placebo group (RR=1.6 (1.02-2.51)). Furthermore, decreased pulmonary function, ABI, and QL was noticed in the propranolol group. Consequently, the trial was stopped after two years. Ninety-five percent of the measurements of the AAA were measured within 2 mm variation. If expansion was defined as above 2 mm annually, the relative risk of expansion in the placebo group was 1.17 (0.74-1.85), and 2.44 (0.88-6.77) among the non-drop-outs.

Conclusions: Only 22% of small screenings-diagnosed AAA were treatable with propranolol for two years. Consequently, only large scale studies are capable of showing potential minor inhibition of expansion by propranolol. However, whether such treatment ever becomes ethically acceptable is debatable.