Unstable angina: for <48 hours before admission (Braunwald class III) predicts a worse outcome.

Clinical bottom line (level 1b)

  1. Patients with unstable angina <48 hours (Braunwald class III) are at increased risk of death, MI or coronary revascularisation in the next 6 months (NNF = 4 for 6 months) (level 1a).
  2. Patients with unstable angina within two weeks of a myocardial infarction are probably at increased risk of death, MI or coronary revascularisation in the next 6 months (NNF = 10 for 6 months) (level 1a).
  3. Other risk factors include (level 1b):
    • male (NNF = 4 for 6 months)
    • on iv nitrates (NNF = 6 for 6 months)
    • ECG changes present (NNF = 8 for 6 months)
van Miltenburg-van Zijl et al: Journal of the American College of Cardiology 1995; 25 (6): 1286-1292
Expires July 2003

The study

Inception cohort study with unblinded, unobjective outcomes, adjusted for confounding factors, validated in an independent set of patients.

Setting: two acute hospitals, Holland

417 patients (aged mean 62 years, 64% male) clinically suspected unstable angina, defined as:
  • history of chest pain at rest or on minimal exertion, probably of ischaemic origin
  • without ECG signs of acute infarction or signs of other causes of chest pain (e.g. dissecting aneurysm or arrhythmia)


Excluded if
  • secondary referrals from other hospitals
  • angina secondary to extracardiac condition


    • Patients had antianginal drugs, nitrates, beta-adrenergic and calcium-channel blockers as required.

    Multivariate regression analysis was performed on risk factors.

    97% followed for 6 months
    Outcomes studied:
  • final diagnosis unstable angina
  • final diagnosis MI
  • final diagnosis noncardiac/nonspecific disease
  • final diagnosis extracoronary cause (GI problems, hypertension, heart failure, pericarditis)
  • final diagnosis IB new onset of severe/accelerated angina; no rest pain
  • final diagnosis IC new onset of severe/accelerated angina; no rest pain; within 2 weeks of MI
  • final diagnosis IIB angina at rest but not within last 48 hours
  • final diagnosis IIC angina at rest but not within last 48 hours; within 2 weeks of MI
  • final diagnosis IIIB angina at rest within 48 hours
  • final diagnosis IIIC angina at rest within 48 hours; within 2 weeks of MI
  • death, infarction or intervention

    • Validation of a clinical prediction rule.
    • Final diagnosis was established during admission and grouped accordingly:
      • MI: CK levels more than twice upper limit of normal
      • definite unstable angina: based on evaluation of symptoms, ECG and exercise test
      • noncardiac/nonspecific disease
    • Patients with unstable angina were classified according to Braunwald criteria. New onset of severe/accelerated angina; no chest pain:
      • in presence of extracardiac condition that intensifies MI- IA
      • no exacerbating extracardiac condition- IB
      • within two weeks of MI- IC
      angina at rest but not within last 48 hours:
      • in presence of extracardiac condition that intensifies MI- IIA
      • no exacerbating extracardiac condition- IIB
      • within two weeks of MI- IIC
      angina at rest within 48 hours:
      • extracardiac condition- IIIA
      • no extracardiac condition- IIIB
      • within two weeks of MI- IIIC

    The evidence

    outcome time to outcome number of patients/total number %
    (95% CI)
    final diagnosis unstable angina 6 months 282/417 68%
    (63% to 72%)
    final diagnosis MI 6 months 26/417 6.2%
    (3.9% to 8.6%)
    final diagnosis noncardiac/nonspecific disease 6 months 109/417 26%
    (22% to 30%)
    final diagnosis extracoronary cause 6 months 25/417 6.0%
    (3.7% to 8.3%)
    final diagnosis IB 6 months 50/417 18%
    (13% to 22%)
    final diagnosis IC 6 months 5/417 1.8%
    (0.2% to 3.3%)
    final diagnosis IIB 6 months 84/417 30%
    (24% to 35%)
    final diagnosis IIC 6 months 16/417 5.7%
    (3.0% to 8.4%)
    final diagnosis IIIB 6 months 102/417 36%
    (31% to 42%)
    final diagnosis IIIC 6 months 25/417 8.9%
    (5.5% to 12%)
    death, infarction or intervention 6 months 120/417 28.8%
    (24.4% to 33.1%)

    prognostic factor for
    death, infarction or intervention     		time to outcome control rate (%) adjusted OR
    (95% CI)    		 NNF+
    (95% CI)
    class III 6 months /
    (28.8%)     		3.0
    (2.1 to 4.3)     		4
    (3 to 6)
    male 6 months /
    (28.8%)     		2.7
    (1.8 to 4.1)     		4
    (3 to 8)
    maximal antianginal therapy (iv nitrate) 6 months /
    (28.8%)     		2.1
    (1.5 to 3.1)     		6
    (4 to 11)
    ECG changes present 6 months /
    (28.8%)     		1.8
    (1.2 to 2.8)     		8
    (4 to 26)
    class C 6 months /
    (%)     		1.6
    (1.0 to 2.4)     		10
    (5 to inf)

    Comments

    1. Significant increased risk noted for patients in class III (angina at rest within 48 hours).
    2. New risk factors identified need to be prospectively validated in another set of patients.
    3. Difficult to know how to use these prediction rules in clinical practice- no studies have been done to address whether early intervention in high-risk patients improves long-term outcome.
    4. Actual expected event rates may now be much smaller with use of newer acute interventions

    Citation

    1. van Miltenburg-van Zijl AJM, Simoons ML, Veerhoek RJ, et al: Incidence and follow-up of Braunwald subgroups in unstable angina pectoris. Journal of the American College of Cardiology 1995; 25 (6): 1286-1292
    Contributor: Nick Shenker and Chris Ball, July 2000
    Reviewer: Mary Ross Southworth

    Clinical Question.
    Patient unstable angina
    Intervention or Exposure risk factors
    Outcome death, MI or revascularisation