An angiotensin-receptor blocker wasn’t better than standard beta-blockers for slowing the aortic-root enlargement that often leads to dissection and death in Marfan syndrome, a trial showed.

Aortic root size standardized for body surface area and adjusted for baseline improved similarly with treatment in both groups, Ronald V. Lacro, MD, of Boston Children’s Hospital, and colleagues found.

The z-score slopes were negative with both losartan (Cozaar) and atenolol (Tenormin, -0.107 versus -0.139 standard-deviation units per year, P=0.08), they reported here at the American Heart Association meeting.

“The 3-year rates of aortic-root surgery, aortic dissection, death, and a composite of these events did not differ significantly between the two treatment groups,” they wrote in a simultaneous publication online in the New England Journal of Medicine.

A press release from the National Heart, Lung and Blood Institute, which largely funded the study as part of its Pediatric Heart Network research, enthusiastically heralded the study as having found another good treatment option for the connective tissue disease.

“These study results are very valuable for clinical practice,” NHLBI director Gary H. Gibbons, MD, said in the statement. “Both drugs were well-tolerated by study participants, and losartan may be another treatment option for patients with Marfan syndrome.”

However, it’s just as likely that the trial found another equally ineffective treatment, study discussant John A. Elefteriades, MD, of director of the Aortic Institute at Yale, said at a press conference.

The trial included no placebo arm.

The evidence for a positive effect of beta-blockers on aortic root aneurysms is weak, he explained, citing limitations of the classic study and equivocal findings, at best, from other subsequent studies.

“If [the trial] was really comparing against a ‘straw man’ placebo, then the thrust of the trial is that losartan is of no benefit at all,” he said.

The answer may be “wait and see,” Juan M. Bowen, MD, and Heidi M. Connolly, MD, both of the Mayo Clinic in Rochester, Minn., suggested in an editorial accompanying the NEJMpaper.

Meanwhile, “clinicians should continue to consider beta-blockers to be the primary medical therapy for aortic protection in Marfan’s syndrome,” they wrote. “Losartan appears to be a reasonable treatment option, especially in patients who cannot take beta-blockers. The risk of harm from losartan appears to be very low, but its efficacy needs to be firmly established before it becomes a first-line therapy.”

There is hope, though, that other effective medications will be found, Elefteriades said. His group recently showed some benefit from statins.

Lacro’s group had carefully lined up over the years a molecular basis for why an ARB should be better in this population with animal models and small studies.

However, the negative findings were unlikely to be false negative because the trial was well-powered, of adequate duration, and generously dosed for losartan, Elefteriades noted.

The trial included 608 Marfan syndrome patients ages 6 months to 25 years with an aortic-root z score greater than 3.0 seen at 21 clinical centers.

They were randomized to atenolol at a maximum dose of 4 mg/kg per day, titrated to reduce heart rate by at least 20%, or to losartan at a maximum dose of 1.4 mg/kg per day for 3 years.

Other findings for atenolol versus losartan included:

• No difference in estimated rate of change in aortic-root absolute diameter (0.069 versus 0.075,P=0.20)
• No difference in dissection or surgery (P=0.10)
• No difference in freedom from dissection, surgery, or death (P=0.10)

While there were no significant interactions by subgroup, the change in aortic-root diameter z-score from both treatments progressively declined across the age groups.

Adverse events and serious adverse events were similar between groups, although possibly or probably related mild or moderate events were significantly more common with atenolol (P=0.03).