Atorvastatin Effect on Aortic Dilatation and Valvular Calcification Progression in Bicuspid Aortic Valve (BICATOR): A Randomized Clinical Trial

Circulation. 2024 Jun 18;149(25):1938-1948. doi: 10.1161/CIRCULATIONAHA.123.067537. Epub 2024 May 28.

Abstract

Background: Ascending aorta dilation and aortic valve degeneration are common complications in patients with bicuspid aortic valve. Several retrospective studies have suggested the benefit of statins in reducing these complications. This study aimed to determine whether atorvastatin treatment is effective in reducing the growth of aortic diameters in bicuspid aortic valve and if it slows the progression of valve calcification.

Methods: In a randomized clinical trial, 220 patients with bicuspid aortic valve (43 women; 46±13 years of age) were included and treated with either 20 mg of atorvastatin per day or placebo for 3 years. Inclusion criteria were ≥18 years of age, nonsevere valvular dysfunction, nonsevere valve calcification, and ascending aorta diameter ≤50 mm. Computed tomography and echocardiography studies were performed at baseline and after 3 years of treatment.

Results: During follow-up, 28 patients (12.7%) discontinued medical treatment (15 on atorvastatin and 13 taking placebo). Thus, 192 patients completed the 36 months of treatment. Low-density lipoprotein cholesterol levels decreased significantly in the atorvastatin group (median [interquartile range], -30 mg/dL [-51.65 to -1.75 mg/dL] versus 6 mg/dL [-4, 22.5 mg/dL]; P<0.001). The maximum ascending aorta diameter increased with no differences between groups: 0.65 mm (95% CI, 0.45-0.85) in the atorvastatin group and 0.74 mm (95% CI, 0.45-1.04) in the placebo group (P=0.613). Similarly, no significant differences were found for the progression of the aortic valve calcium score (P=0.167) or valvular dysfunction.

Conclusions: Among patients with bicuspid aortic valve without severe valvular dysfunction, atorvastatin treatment was not effective in reducing the progression of ascending aorta dilation and aortic valve calcification during 3 years of treatment despite a significant reduction in low-density lipoprotein cholesterol levels.

Registration: URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2015-001808-57. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02679261.

Keywords: aortic valve; aortic valve insufficiency; aortic valve stenosis; atorvastatin; bicuspid aortic valve disease; dilatation.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aorta / diagnostic imaging
  • Aorta / drug effects
  • Aorta / pathology
  • Aortic Valve Disease / drug therapy
  • Aortic Valve Stenosis
  • Aortic Valve* / abnormalities
  • Aortic Valve* / diagnostic imaging
  • Aortic Valve* / drug effects
  • Aortic Valve* / pathology
  • Atorvastatin* / therapeutic use
  • Bicuspid Aortic Valve Disease* / diagnostic imaging
  • Bicuspid Aortic Valve Disease* / drug therapy
  • Calcinosis* / diagnostic imaging
  • Calcinosis* / drug therapy
  • Calcinosis* / pathology
  • Dilatation, Pathologic / drug therapy
  • Disease Progression*
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Heart Valve Diseases* / diagnostic imaging
  • Heart Valve Diseases* / drug therapy
  • Heart Valve Diseases* / pathology
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
  • Male
  • Middle Aged
  • Treatment Outcome

Substances

  • Atorvastatin
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors

Supplementary concepts

  • Aortic Valve, Calcification of

Associated data

  • ClinicalTrials.gov/2015-001808-57
  • ClinicalTrials.gov/NCT02679261