Angiotensin receptor blockers, beta-blockers have separate, joint benefits in Marfan syndrome
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Angiotensin receptor blockers and beta-blockers slow down the expansion of the aorta in patients with Marfan syndrome and no previous aortic surgery, according to data reported at the European Society of Cardiology Congress.
Marfan syndrome, a genetic condition, “causes a swelling of the main blood vessel, the aorta, in the heart. These aneurysms can cause a risk of death from tearing of the aorta, and that risk is at least 100 times greater than the normal population — it can be as high as 1,000 times higher for some kinds of patients,” Alex Pitcher, BMBCh, MRCP, DPhil, consultant cardiologist at Oxford University Hospitals NHS Foundation Trust, said during a press conference. “Heart surgery is often needed, usually between the ages of 20 and 40 years, when the aortic enlargement becomes too large and is at great risk of tearing.”
While several trials of angiotensin receptor blockers in patients with Marfan syndrome have been conducted in recent years, none were large enough to definitively establish benefit, so the Marfan Treatment Trialists’ Collaboration performed an individual patient data meta-analysis in 1,442 patients from seven trials, Pitcher said.
Four trials compared angiotensin receptor blockers with placebo or an open-label control and three trials compared angiotensin receptor blockers with beta-blockers, he said.
“This allowed us to estimate the effects of angiotensin receptor blockers in certain circumstances, and to indirectly estimate the effects of beta-blockers,” he said.
The primary outcome was change in body surface area-adjusted aortic root Z score.
At a median follow-up of 3 years, compared with placebo/control, angiotensin receptor blockers were associated with a reduction in the rate of change of aortic root Z score (median annual increase in angiotensin receptor blocker group, 0.07; standard error [SE], 0.02; median annual increase in placebo/control group, 0.13; SE, 0.02; absolute difference, –0.07; 95% CI, –0.12 to –0.01; P = .012), according to the researchers.
The greatest treatment effect was in patients with pathogenic variants in fibrillin-1 (P for heterogeneity vs. patients without variants = .005) and the results did not vary based on beta-blocker use (P for heterogeneity = .54), the researchers found.
The beta-blocker finding “makes us think these two treatments are probably working independently of each other,” Pitcher said.
At a median follow-up of 3 years, there was no difference between angiotensin receptor blockers and beta-blockers in the rate of change of aortic root Z score (median annual change in angiotensin receptor blocker group, –0.08; SE, 0.03; median annual change in beta-blocker group, –0.11; SE, 0.02; absolute difference, 0.03; 95% CI, –0.05 to 0.1; P = .48), they found.
Pitcher said the researchers were able to determine indirectly that beta-blockers were associated with a reduction in the rate of increase of aortic root Z score compared with placebo (absolute difference, –0.09; 95% CI, –0.18 to 0.0; P = .042).
He said there has only been one trial comparing beta-blockers with placebo in this population, and it was small.
“Doctors are usually wary of drawing conclusions based on the findings of a single small trial, and we believe this study provides important corroborative evidence from a much larger set of trials,” Pitcher told Healio.
“Two treatments have now been shown to benefit patients with Marfan syndrome,” Pitcher said at the press conference. “They work separately or together, they are widely available at low cost, and they would be expected to delay the time to surgery or the tearing of the aorta if taken for a number of years. The effects may be greater if the treatments are taken in combination.”
Reference:
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Gregg C. Fonarow, MD, FACC, FAHA, FHFSA
Individuals with Marfan syndrome are at increased risk for progressive dilation of the aortic root and aortic dissection, which is life threatening.
Beta-blockers are commonly utilized in individuals with Marfan syndrome to delay aortic root dilation. Angiotensin receptor blockers have been shown to slow aortic root dilation. However, these two agents have not been specifically compared in combination.
This individual patient level meta-analysis of prior randomized trials (seven trials, 1,442 persons with Marfan syndrome) found that beta-blockers and angiotensin receptor blockers appear to have comparable benefits, but that the two taken together provided incremental benefits. Further, both therapies appeared to be safely and generally well tolerated.
This study suggests that combination therapy with beta-blockers and angiotensin receptor blockers provides greater benefit than either one alone, and together could decrease the rate of progression in aortic root dilation by half. This combination therapy should be considered the current standard of care for individuals with Marfan syndrome.
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Pitcher A, et al. Hot Line 9. Presented at: European Society of Cardiology Congress; Aug. 26-29, 2022; Barcelona, Spain (hybrid meeting).
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