Marfan's syndrome: propranolol slowed the rate of aortic dilatation.

Clinical bottom line (level 1b)

  1. Patients with Marfan's syndrome who took propranolol had a slower rate of aortic dilatation compared with controls.
  2. Side effects were more common in patients who took propranolol (NNH = 3 at 10 years) .
Shores et al: New England Journal of Medicine 1994; 330 (19): 1335-1341
Expires December 2004

The study

Unblinded concealed randomised trial without intention-to-treat
Setting: teaching hospital, USA

70 patients (aged mean 15 years, 56% male) Marfan's syndrome

Excluded if
  • <12 or >50 years old
  • ongoing treatment with propranolol
  • aortic dissection
  • aortic regurgitation on auscultation
  • moderate or severe mitral regurgitation
  • previous cardiothoracic surgery
  • dyspnoea on moderate exercise
  • orthopnoea
  • peripheral oedema
  • LV function <50%
  • atrioventricular conduction delay of any degree
  • diabetes mellitus
  • recurrent bronchospasm requiring medication


    • Control Group: (n = 38, 38 analysed): nothing
    Experimental Group: (n = 32, 32 analysed): propranolol initially 10 mg qds, and after 2-4 weeks titred so that heart rate was <100 bpm during exercise, or systolic interval increased by <30%

    100% followed for 10 years
    Outcome notes:
    • clinical endpoint : death, heart failure, aortic regurgitation, aortic dissection or cardiovascular surgery
    • side effects : heart block, lethargy, insomnia

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    clinical endpoint 10 years 9
    (23.7%)    		 5
    (15.6%)    		 34%
    (-77% to 75%)    		 8.06%
    (-10.4% to 26.5%)    		 12
    (NNT = 10 to infinity;
    NNH = 4 to infinity)
    side effects 10 years 0
    (0.00%)    		 10
    (31.3%)    		 %
    (% to %)    		 -31.3%
    (-47.3% to -15.2%)    		 -3
    (-7 to -2)

    Outcome Control Group
    (SD)    		 Experimental Group
    (SD)    		 Mean Difference
    (95% CI)
    rate of aortic dilatation per year 0.084
    ()     		0.023
    ()     		p=0.001
    ( to )

  • Two patients with clinical endpoints in the experimental group did not take their propranolol.
  • mean propranolol dose 212 mg +/- 68 mg, in four divided doses per day
  • aortic ratio: aortic diameter on echocardiogram/ aortic diameter predicted by patient's height/ weight/ age. Slope of regression line equivalent to the rate of dilatation.

    • Comments

    1. The study was not large enough to demonstrate benefit in terms of clinical outcome, despite showing delay in dilatation of aorta.

    Citation

    1. Shores J, Berger KR, Murphy EA, et al: Progression of aortic dilatation and the benefit of long-term beta-adrenergic blockade in Marfan's syndrome. New England Journal of Medicine 1994; 330 (19): 1335-1341
    Contributor: Chris Ball and Clare Wotton, December 2000
    Reviewer:

    Clinical Question.
    Patient Marfan's syndrome
    Intervention or Exposure propranolol
    Comparison nothing
    Outcome clinical endpoint, side effects