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Treatment with losartan instead of more conventional atenolol yielded no significant difference in aortic-root dilation in children and young adults with Marfan’s syndrome over 3 years, according to a new study published in the New England Journal of Medicine and presented simultaneously at the American Heart Association’s Scientific Sessions.
In a randomized trial, researchers identified 608 children and young adults with Marfan’s syndrome and randomized them to treatment with either losartan (267) or atenolol (268) for 3 years. The participants were between the ages of 6 months and 25 years, had been diagnosed with Marfan’s syndrome according to the original Ghent criteria, and possessed a z score of 3.0 for maximum aortic-root diameter indexed to body surface area. The baseline subgroups were predefined as aortic-root z score being less than 4.5 vs. at or greater than 4.5, young adult vs. child, and previous use of beta-blocker (yes vs. no).
The results indicate that the baseline-adjusted annual rate of change in the aortic-root z score did not differ substantially between the losartan and atenolol groups: –0.107 ± 0.013 and –0.139 ± 0.013 standard deviation units, respectively (P = .08). Both data groups were significantly less than 0, however, indicating that both treatments were effective in decreasing aortic-root z scores. Younger patients in both groups experienced greater decreases in aortic-root z scores, but one was not significantly more than the other (P = .002 and P < .001 for losartan and atenolol, respectively).
“We did not find the expected advantage of angiotensin-receptor blockade therapy over beta-blocker therapy,” wrote the authors, led by Dr. Ronald V. Lacro of Boston Children’s Hospital’s Department of Cardiology (N. Engl. J. Med. 2014 [doi:10.1056/NEJMoa1404731]).
There were “small but significant differences favoring atenolol in the average annual change in the absolute diameter and z score for the aortic annulus, but there were no significant differences in the diameter or z score for the ascending aorta,” according to the investigators.
“This finding was unexpected, without a clear physiological explanation,” wrote Dr. Lacro and his associates.
The study was supported by a grant from the National Institute of Health’s National Heart, Lung, and Blood Institute. The authors reported no other financial conflicts of interest.
The study by Dr. Lacro and his colleagues is a large trial evaluating angiotensin-receptor blockade in patients with Marfan’s syndrome. Many expected the trial to confirm the superiority of losartan over atenolol in reducing rates of aortic growth. However, the trial showed no benefit in the rate of aortic dilatation when losartan was compared with atenolol over a 3-year period. The critical question is whether this finding argues for the rejection of losartan as a therapeutic option, or whether the study design masked its true benefit. “We believe the answer is, ‘Let’s wait and see,’ ” noted Dr. Juan M. Bowen and Dr. Heidi M. Connolly in an editorial accompanying the research report (N. Engl. J. Med. 2014 [doi:10.1056/NEJMe1412950]).
The results will stimulate healthy discussion about future directions in research and treatment. These findings indicate that clinicians should continue to consider beta-blockers to be the primary medical therapy for aortic protection in Marfan’s syndrome. 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, they noted.
Dr. Bowen and Dr. Connolly are both affiliated with the divisions of primary care internal medicine and cardiovascular diseases at the Mayo Clinic in Rochester, Minn. They did not report any relevant financial conflicts of interest.
The study by Dr. Lacro and his colleagues is a large trial evaluating angiotensin-receptor blockade in patients with Marfan’s syndrome. Many expected the trial to confirm the superiority of losartan over atenolol in reducing rates of aortic growth. However, the trial showed no benefit in the rate of aortic dilatation when losartan was compared with atenolol over a 3-year period. The critical question is whether this finding argues for the rejection of losartan as a therapeutic option, or whether the study design masked its true benefit. “We believe the answer is, ‘Let’s wait and see,’ ” noted Dr. Juan M. Bowen and Dr. Heidi M. Connolly in an editorial accompanying the research report (N. Engl. J. Med. 2014 [doi:10.1056/NEJMe1412950]).
The results will stimulate healthy discussion about future directions in research and treatment. These findings indicate that clinicians should continue to consider beta-blockers to be the primary medical therapy for aortic protection in Marfan’s syndrome. 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, they noted.
Dr. Bowen and Dr. Connolly are both affiliated with the divisions of primary care internal medicine and cardiovascular diseases at the Mayo Clinic in Rochester, Minn. They did not report any relevant financial conflicts of interest.
The study by Dr. Lacro and his colleagues is a large trial evaluating angiotensin-receptor blockade in patients with Marfan’s syndrome. Many expected the trial to confirm the superiority of losartan over atenolol in reducing rates of aortic growth. However, the trial showed no benefit in the rate of aortic dilatation when losartan was compared with atenolol over a 3-year period. The critical question is whether this finding argues for the rejection of losartan as a therapeutic option, or whether the study design masked its true benefit. “We believe the answer is, ‘Let’s wait and see,’ ” noted Dr. Juan M. Bowen and Dr. Heidi M. Connolly in an editorial accompanying the research report (N. Engl. J. Med. 2014 [doi:10.1056/NEJMe1412950]).
The results will stimulate healthy discussion about future directions in research and treatment. These findings indicate that clinicians should continue to consider beta-blockers to be the primary medical therapy for aortic protection in Marfan’s syndrome. 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, they noted.
Dr. Bowen and Dr. Connolly are both affiliated with the divisions of primary care internal medicine and cardiovascular diseases at the Mayo Clinic in Rochester, Minn. They did not report any relevant financial conflicts of interest.
Treatment with losartan instead of more conventional atenolol yielded no significant difference in aortic-root dilation in children and young adults with Marfan’s syndrome over 3 years, according to a new study published in the New England Journal of Medicine and presented simultaneously at the American Heart Association’s Scientific Sessions.
In a randomized trial, researchers identified 608 children and young adults with Marfan’s syndrome and randomized them to treatment with either losartan (267) or atenolol (268) for 3 years. The participants were between the ages of 6 months and 25 years, had been diagnosed with Marfan’s syndrome according to the original Ghent criteria, and possessed a z score of 3.0 for maximum aortic-root diameter indexed to body surface area. The baseline subgroups were predefined as aortic-root z score being less than 4.5 vs. at or greater than 4.5, young adult vs. child, and previous use of beta-blocker (yes vs. no).
The results indicate that the baseline-adjusted annual rate of change in the aortic-root z score did not differ substantially between the losartan and atenolol groups: –0.107 ± 0.013 and –0.139 ± 0.013 standard deviation units, respectively (P = .08). Both data groups were significantly less than 0, however, indicating that both treatments were effective in decreasing aortic-root z scores. Younger patients in both groups experienced greater decreases in aortic-root z scores, but one was not significantly more than the other (P = .002 and P < .001 for losartan and atenolol, respectively).
“We did not find the expected advantage of angiotensin-receptor blockade therapy over beta-blocker therapy,” wrote the authors, led by Dr. Ronald V. Lacro of Boston Children’s Hospital’s Department of Cardiology (N. Engl. J. Med. 2014 [doi:10.1056/NEJMoa1404731]).
There were “small but significant differences favoring atenolol in the average annual change in the absolute diameter and z score for the aortic annulus, but there were no significant differences in the diameter or z score for the ascending aorta,” according to the investigators.
“This finding was unexpected, without a clear physiological explanation,” wrote Dr. Lacro and his associates.
The study was supported by a grant from the National Institute of Health’s National Heart, Lung, and Blood Institute. The authors reported no other financial conflicts of interest.
Treatment with losartan instead of more conventional atenolol yielded no significant difference in aortic-root dilation in children and young adults with Marfan’s syndrome over 3 years, according to a new study published in the New England Journal of Medicine and presented simultaneously at the American Heart Association’s Scientific Sessions.
In a randomized trial, researchers identified 608 children and young adults with Marfan’s syndrome and randomized them to treatment with either losartan (267) or atenolol (268) for 3 years. The participants were between the ages of 6 months and 25 years, had been diagnosed with Marfan’s syndrome according to the original Ghent criteria, and possessed a z score of 3.0 for maximum aortic-root diameter indexed to body surface area. The baseline subgroups were predefined as aortic-root z score being less than 4.5 vs. at or greater than 4.5, young adult vs. child, and previous use of beta-blocker (yes vs. no).
The results indicate that the baseline-adjusted annual rate of change in the aortic-root z score did not differ substantially between the losartan and atenolol groups: –0.107 ± 0.013 and –0.139 ± 0.013 standard deviation units, respectively (P = .08). Both data groups were significantly less than 0, however, indicating that both treatments were effective in decreasing aortic-root z scores. Younger patients in both groups experienced greater decreases in aortic-root z scores, but one was not significantly more than the other (P = .002 and P < .001 for losartan and atenolol, respectively).
“We did not find the expected advantage of angiotensin-receptor blockade therapy over beta-blocker therapy,” wrote the authors, led by Dr. Ronald V. Lacro of Boston Children’s Hospital’s Department of Cardiology (N. Engl. J. Med. 2014 [doi:10.1056/NEJMoa1404731]).
There were “small but significant differences favoring atenolol in the average annual change in the absolute diameter and z score for the aortic annulus, but there were no significant differences in the diameter or z score for the ascending aorta,” according to the investigators.
“This finding was unexpected, without a clear physiological explanation,” wrote Dr. Lacro and his associates.
The study was supported by a grant from the National Institute of Health’s National Heart, Lung, and Blood Institute. The authors reported no other financial conflicts of interest.
FROM THE AHA SCIENTIFIC SESSIONS
Key clinical point: No significant difference in aortic-root dilation was found in children and young adults with Marfan’s syndrome treated with losartan or atenolol over a 3-year period.
Major finding: Annual rate of change in aortic-root z score did not differ significantly between losartan and atenolol groups: –0.107 ± 0.013 and –0.139 ± 0.013 standard deviation units, respectively (P = .08).
Data source: Randomized trial of 608 people with Marfan’s syndrome.
Disclosures: The study was supported by a grant from the National Institute of Health’s National Heart, Lung, and Blood Institute. The authors reported no other financial conflicts of interest.