Unstable angina: adding a beta-blocker to standard medical therapy and calcium blocker shortened length and recurrence of angina.

Clinical bottom line (level 1b)

  1. Adding propranolol to medical treatment with a calcium channel blocker, reduced the number of ischaemic episodes (~2 less a day) and shortened the length of recurrent angina attacks (by 17 minutes).
  2. The effect on subsequent MI or revascularisation procedures was unclear.
Gottlieb et al: Circulation 1986; 73 (2): 331-337
Expires July 2003

The study

Single-blinded concealed randomised trial with intention-to-treat
Setting: acute hospital, USA

81 patients (aged range 37 to 82 years; mean 62, 51% female) hospitalised with unstable angina (chest pain >10 minutes with ECG changes)

Excluded if
  • chest pain within 30 days of MI (CK> twice normal level)
  • systolic blood pressure <90 mmHg
  • resting heart rate <50 beats/min
  • PR interval >0.24 secs or higher degree of AV block with no pacemaker
  • bronchospastic pulmonary disease
  • congestive heart failure
  • prior CABG
  • significant valvular/ congenital heart disease
  • symptomatic cerebrovascular accident


    • Control Group: (n = 39, 39 analysed): placebo every 6 hours po
    Experimental Group: (n = 42, 42 analysed): propranolol 40 mg every 6 hours po
    All patients had iv or long-acting oral or topical nitrates and nifedipine 20 mg every 6 hours po.
    95% followed for 30 days
    Outcome notes:
    • MI : prolonged chest pain with persistent ECG changes and elevation of CK to >twice normal

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    MI 30 days 3
    (7.69%)    		 6
    (14.3%)    		 -86%
    (-592% to 50%)    		 -6.59%
    (-20.1% to 6.90%)    		 -15
    (NNT = 15 to infinity;
    NNH = 5 to infinity)
    CABG or angioplasty 30 days 17
    (43.6%)    		 14
    (33.3%)    		 24%
    (-33% to 56%)    		 10.3%
    (-10.9% to 31.4%)    		 10
    (NNT = 3 to infinity;
    NNH = 9 to infinity)

    Outcome Control Group
    (SD)    		 Experimental Group
    (SD)    		 Mean Difference
    (95% CI)
    duration of angina (mins) 24.3
    (6.30)     		7.60
    (2.80)     		16.7
    (14.6 to 18.8)
    ischaemic events (days) 3.80
    (0.70)     		2.00
    (0.50)     		1.80
    (1.53 to 2.07)

    Comments

    1. Low number of patients makes the study less certain.
    2. Very low number of patients on aspirin at study entry and low number on heparin reduce the applicability.
    3. No details on mortality.
    4. Outcomes unrealistic in follow-up period and power of study.

    Citation

    1. Gottlieb SO, Weisfeldt ML, Ouyang P, et al: Effect of the addition of propranolol to therapy with nifedipine for unstable angina pectoris: a randomized, double-blind, placebo-controlled trial. Circulation 1986; 73 (2): 331-337
    Contributor: Nick Shenker and Clare Wotton, July 2000
    Reviewer:

    Clinical Question.
    Patient unstable angina, angina
    Intervention or Exposure beta-blocker
    Comparison standard therapy
    Outcome pain, death, MI, recurrent angina