Study of the effects of celiprolol on 53 patients
The Beta-Blockers in Ehlers-Danlos Syndrome Treatment (BBEST) Trial
The BBEST Trial was published in 2010 in The Lancet, a medical journal from the United Kingdom. The study took patients with vascular EDS and split them into two groups:
Group 1: The ‘No Treatment’ group. This is known as a control group. These patients received no treatment during the study, including the use of any other beta-blockers(2).
Group 2: The ‘Celiprolol’ group. This is known as an experimental group. These patients all received celiprolol as a treatment.
The researchers then followed all of these patients for several years. All the while, they were keeping track of adverse events. This included events such as artery rupture, artery dissection (artery tears), intestinal perforations and death. In the end, the study was stopped early after 64 months because of the benefit they saw with Celiprolol treatment(2). Only 5 of 25 patients in the celiprolol group had a ‘primary endpoint’ recorded, compared to 14 of 28 patients in the No Treatment group(2). Primary endpoints were the above mentioned adverse events (dissection, artery rupture etc.). In the end, this study suggests that treatment of vascular EDS with celiprolol ‘extends the time to vascular complications compared to those not treated’(1). It is because of this study that celiprolol is being used as the standard treatment for all patients with vEDS in France, as well as many other parts of Europe and the United Kingdom.
Challenges to the BBEST Trial:
While this is an exciting study, it’s important to recognize that it does have some issues. The selection of patients to place on the study was based on clinical features. This means that not all patients on the study had a genetic diagnosis of vascular EDS. It was determined part way through that ~1/3 of all patients on the study did not have a COL3A1 gene mutation(1). Remember, COL3A1 mutations are the cause of vascular EDS. In total, 12 of the 25 patients on the ‘Celiprolol’ group did NOT have proven COL3A1 mutations and 8 out of 28 in the ‘No Treatment’ group did NOT have proven COL3A1 mutations(2).
Some researchers in the vascular EDS community feel that these facts muddy the results of the study. They argue that with so many patients not having a proven genetic diagnosis of vEDS, it makes it more difficult to interpret if celiprolol really delays or prevents vascular events in patients with vEDS. Other researchers (who support celiprolol) still point to the fact that patients with a COL3A1 mutation (and therefore vascular EDS) who were treated with celiprolol still appeared to benefit from a reduction in vascular events.
Byers PH, Belmont J, Black J, De Backer J, Frank M, Jeunemaitre X, Johnson D, Pepin MG, Robert L, Sanders L, Wheeldon N. 2017. Diagnosis, natural history and management in vascular Ehlers-Danlos syndrome. American Journal of Medical Genetics Part C (Seminars in Medical Genetics). 175C:40-47.
Ong KT, Perdu J, De Backer J, Bozec E, Collignon P, Emmerich J, Fauret AL, Fiessinger JN, Germain DP, Georgesco G, Hulot JS, De Paepe A, Plauchu H, Jeunemaitre X, Laurent S, Boutouyrie P. 2010. Effect of celiprolol on prevention of cardiovascular events in vascular Ehlers-Danlos syndrome: A prospective randomized, open, blinded-endpoints trial. Lancet 376: 1476-1484.