CASS

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CASS Writers. "Coronary artery surgery study (CASS): a randomized trial of coronary artery bypass surgery. Survival data". Circulation. 1983. 68(5):939-950.
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Clinical Question

In patients with stable ischemic heart disease, does coronary artery bypass surgery reduce mortality as compared to medical management?

Bottom Line

In patients with stable ischemic heart disease, CABG did not improve survival as compared to medical therapy. However, the 10-year follow-up results showed a significant long term mortality benefit of CABG in patients with initial LVEF<0.5.

Major Points

The Coronary Artery Surgery Study (CASS) consists of a patient registry and randomized trial. The registry includes a total of 24,959 patients of which 780 entered the randomized trial. The trial evaluated the effects of CABG on mortality as compared to medical therapy in patients with stable IHD.

The 5- and 10-year follow-up results did not observe any significant differences in survival between surgically and medically treated patients. However, the 10-year follow-up results showed a significant long term survival benefit of CABG in patients with initial LVEF<0.5 (79% vs 51%; P=0.01). It is important to consider the differences in current medical and surgical therapy for IHD as compared to that in the trial.

Other studies with a similar focus are the European Coronary Surgery Study (ECSS) [1] and the Veterans Administration (VA) Randomized Trial of Coronary Bypass Surgery for Stable Angina.[2] The 5-year follow-up result of ECSS showed a significant advantage of CABG over medical therapy, however the beneficial effect attenuated at 12-year follow-up. The 7-year follow-up result of the VA trial showed a significant advantage of CABG over medical therapy, however the beneficial effect was not seen after follow-up for 11 years.

Guidelines

2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery[3]

2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease[4]

  • CABG or PCI to improve symptoms is beneficial in patients with 1 or more significant (≥70% diameter) coronary artery stenoses amenable to revascularization and unacceptable angina despite guideline-directed medical therapy  (GDMT). (Class I, Level of Evidence: A)
  • CABG or PCI to improve symptoms is reasonable in patients with 1 or more significant (≥70% diameter) coronary artery stenoses and unacceptable angina for whom GDMT cannot be implemented because of medication contraindications, adverse effects, or patient preferences. (Class IIa, Level of Evidence: C)
  • CABG to improve symptoms might be reasonable for patients with previous CABG, 1 or more significant (≥70% diameter) coronary artery stenoses not amenable to PCI, and unacceptable angina despite GDMT. (Class IIb,Level of Evidence: C)
  • CABG or PCI to improve symptoms should not be performed in patients who do not meet anatomic (≥50% left main or ≥70% non–left main stenosis) or physiological (eg, abnormal fractional flow reserve) criteria for revascularization. (Class III, Level of Evidence: C)

Design

The CASS consists of a patient registry and randomized trial.[5] The registry includes a total of 24,959 patients who had coronary angiography during July 1974 to May 1979 at 15 CASS registry sites. However, only 2,099 patients met criteria for randomization. Among these patients, only 780 agreed to enter the randomized trial.

  • Group A (n=31490) mild angina with LVEF≥0.5
  • Group B (n=106) mild angina with LVEF between 0.35-0.50
  • Group C (n=160) asymptomatic after previous MI

The characteristics below describe the trial specifically.

  • Randomized, controlled trial
  • N=780
    • Surgical management (n=390)
    • Medical management (n=390)
  • Setting: 10 centers in the United States and 1 in Canada
  • Enrollment: August 1975 to May 1979
  • Follow-up: 5 years (initially planned)
  • Analysis:
  • Primary outcome: mortality

Population

Inclusion Criteria[5]

  • age ≤65 years
  • stable angina that was Canadian Cardiovascular Society (CCS)class I or II
  • documented MI more than 3 weeks before randomization
  • angiographic criteria:
    • significant coronary artery disease, defined as ≥70% stenosis in one or more major operable coronary arteries or
    • 50% or more stenosis of the left main coronary artery (LMCA)
  • LVEF>35%

Exclusion Criteria

  • prior CABG
  • progressive or unstable angina
  • angina more than Canadian Cardiovascular class II
  • congestive heart failure (NYHA class III or IV)
  • coexisting illness that would Increase the likelihood of death within 5 years
  • ejection fraction (EF)<35%
  • LMCA stenosis of ≥70% luminal diameter
  • valvular heart disease likely to require valve replacement
  • ventricular aneurysm likely to require surgical resection

Baseline Characteristics[6]

This describes the patients randomized to receive surgical management

  • Mean age: 51.5±7.3 years
  • Male: 90.5
  • Ethnic origin (white): 98%
  • Angina of CCS class I: 16.9%
  • Angina of CCS class II: 55.6%
  • Prior MI: 57.2%
  • Hypertension: 32.7%
  • Diabetes mellitus: 9.3%
  • Current smoker: 38.7%
  • Three-vessel disease: 31.5%
  • LAD stenosis of ≥70% in 1 or more segments: 72.1%
  • LVEF<5.50%: 20%

Interventions

For all randomized patients

  • Non-pharmacological and pharmacological management, if required, were recommended for modification of CV risk factors including smoking, obesity, hypertension, diabetes mellitus and anxiety.
  • β-blockers and nitrates were prescribed for treatment of angina

Surgical management:

  • CABG within 4 weeks of coronary angiography
  • 96% had vein grafts ahereasnd 16% had internal mammary artery grafts[7]

Outcomes[6]

Comparisons are surgical vs medical therapy

Primary Outcomes

5-year average annual mortality rate

1.1% vs. 1.6% (P=NS)

Secondary Outcomes

6-year cumulative survival rate

92% vs. 90% (P=0.34)

10-year cumulative survival survival rate[7]

82% vs. 79% (P=NS)

Probability of non-fatal Q-wave MI[8]

14% vs. 11% (P=NS)

5-year probability of remaining alive and without MI

83% vs. 82% (P=NS)

10-year percentage remaining alive and without nonfatal MI

66% vs. 69% (P=NS)

Subgroup Analysis

At 5-year follow up, there were no significant differences in survival according to the subgroups: number of diseased vessels, clinical subgroup (A, B or C), ejection fraction.

  • In patients with initial LVEF<0.5 (group B and some from group C), the survival rates were 59% vs. 54% (P=0.085)
  • In patients with initial LVEF<0.5 and triple-vessel disease, the survival rates were 32% vs 25% (P=0.063)

At 10-year follow up:[7]

  • In patients with initial LVEF≥5.50% (group A), the probability of remaining alive and without MI was 68% vs. 75% (P=0.04)
  • In patients with initial LVEF<0.5 (group B), the survival rates were 80% vs. 59% (P=0.01)
  • In patients with initial LVEF<0.5 (group B and some from group C), the survival rates were 79% vs. 51% (P=0.01)

Adverse Events

Criticisms

  • There has been substantial advancements in surgical techniques and medical therapy. Therefore the relative benefits of CABG on survival and symptom relief may not be evident if compared to current medical therapy.[4]
  • Medical therapy of angina during the trial consists of β-blocker and nitrates only which is markedly different from current therapies.[9]
  • Surgical management has also improved. There is increasing use of internal mammary artery (IMA) grafts whereas only 16% of patients had IMA grafts during the trial.[9]
  • PTCA is also available now as a management option for stable IHD.[9]
  • Many patients who entered the trial have a relatively low risk profile. Hence the results of the trial may not be applicable to high-risk patients.[10]

Funding

National Heart, Lung, and Blood Institute (NHLBI)

Further Reading

  1. Varnauskas E. Twelve-Year Follow-up of Survival in the Randomized European Coronary Surgery Study. New England Journal of Medicine. 1988 Aug 11;319(6):332–7.
  2. Eleven-Year Survival in the Veterans Administration Randomized Trial of Coronary Bypass Surgery for Stable Angina. New England Journal of Medicine. 1984 Nov 22;311(21):1333–9.
  3. Writing Committee Members, Hillis LD, Smith PK, Anderson JL, Bittl JA, Bridges CR, et al. 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011 Dec 6;124(23):e652–735.
  4. 4.0 4.1 Fihn SD, Gardin JM, Abrams J, Berra K, Blankenship JC, Dallas AP, et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart DiseaseA Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2012 Dec 18;60(24):e44–164.
  5. 5.0 5.1 Principal Investigators of CASS and Their Associates, Killip  T, Fisher  LD, Mock  MB; The National Heart, Lung, and Blood Institute Coronary Artery Surgery Study (CASS). Circulation 63 1981:I-1-I-81. (suppl I). 
  6. 6.0 6.1 Coronary artery surgery study (CASS): a randomized trial of coronary artery bypass surgery. Survival data. Circulation. 1983 Nov 1;68(5):939–50.
  7. 7.0 7.1 7.2 Alderman EL, Bourassa MG, Cohen LS, Davis KB, Kaiser GG, Killip T, et al. Ten-year follow-up of survival and myocardial infarction in the randomized Coronary Artery Surgery Study. Circulation. 1990;82(5):1629–46.
  8. Myocardial Infarction and Mortality in the Coronary Artery Surgery Study (CASS) Randomized Trial. New England Journal of Medicine. 1984 Mar 22;310(12):750–8.
  9. 9.0 9.1 9.2 Kannel WB. Coronary artery surgery study revisited. Limitation of the intent-to-treat principle. Circulation. 1990;82(5):1859–62.
  10. Rahimtoola SH. Some unexpected lessons from large multicenter randomized clinical trials. Circulation. 1985 Sep;72(3):449–55.