In patients with stable chest pain, does coronary computed tomographic angiography (CCTA) in addition to standard care compared to standard care alone decrease the composite endpoint of death from coronary heart disease or nonfatal myocardial infarction?
Patients with stable angina evaluated with CCTA in addition to standard care compared to standard care alone were found in this trial to have lower rates of the composite end point of death from coronary heart disease or nonfatal myocardial infarction at 5 years, driven primarily by a lower rate of nonfatal myocardial infarction.
Coronary CT Angiography is a promising tool in anatomically detecting coronary heart disease underlying stable angina. There are still unanswered questions about the physiologic significance of anatomically detected lesions, as evidenced by the FAME-2 trial. There are also questions about how the lesions identified by this technology affect management. Previous trials concerning CCTA in the evaluation of angina include the ROMICAT-II and PROMISE trials. ROMICAT-II found that patients seen in the emergency department for symptoms suggestive of acute coronary syndrome had reduced length of stay and were admitted less frequently when evaluated with CCTA compared to standard of care. PROMISE found no difference in clinical outcomes in an outpatient population evaluated using CCTA vs functional testing over 2 years.
This trial added additional information on how CCTA can inform clinical decision-making with the goal of better targeting which patients would benefit from preventive care. The authors found that CCTA in addition to standard care, with subsequent changes in management, resulted in a statistically significant reduction in a composite endpoint of death from coronary heart disease or nonfatal myocardial infarction, driven by nonfatal myocardial infarction events, than standard care alone at 5 years. They did not find that CCTA increased use of angiography or coronary revascularization. It is possible that CCTA detects patients with non-obstructive lesions to target with preventative therapy that would be otherwise missed by standard evaluations. The accompanying editorial notes that the PROMISE trial, which found no difference in clinical outcomes, had an increase in preventive therapy use in both groupings unlike this trial. It is not clear if this intervention has an effect on mortality. The authors also note that thresholds for initiating preventative therapies in this population has lowered since the trial completed, so it is possible that the benefit observed would no longer be evident.
The 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guidelines were written before the results of this trial were published.
- Open-label, parallel group, prospective, randomized trial
- Standard Care plus CCTA (n=2073)
- Standard Care (n=2073)
- Setting: 12 centers in Scotland
- Enrollment: November 2010 to September 2014
- Median follow-up: 4.8 years (3-7 years of follow-up)
- Analysis: Intention-to-treat
- Primary outcome: composite of death from coronary heart disease or nonfatal myocardial infarction
- Age 18-75 years
- Inability or unwillingness to undergo computed tomography scanning, including exceeding weight limit of scanner
- Known severe renal failure (serum creatinine > 200 umol/L or estimated GFR < 30 mL/min)
- Major allergy to iodinated contrast agent
- Unable to give informed consent
- Known pregnancy
- Acute coronary syndrome within 3 months
- Mean age: 57.1 years
- Mean BMI: 29.7 +/- 5.9
- Cardiovascular risk factor
- Current or former smoker: 53%
- Hypertension 34%
- Diabetes mellitus: 11%
- Hypercholesterolemia: 53%
- Family history of CHD: 42%
- Atrial Fibrillation: 2%
- History of CHD: 9%
- Relevant medications
- Antiplatelet agent: 48%
- Statin: 43%
- Beta-blocker: 33%
- ACE inhibitor or ARB: 17%
- Calcium-channel blocker: 9%
- Nitrates: 28%
- Other antianginal agent: 5%
- Anginal symptoms
- Typical angina: 35%
- Atypical angina: 24%
- Nonanginal chest pain: 41%
- Diagnosis at baseline
- CHD: 47%
- Angina due to CHD: 36%
- Randomized to CCTA plus standard care vs. standard care groups
- management was left to discretion of attending clinician
- CCTA group was prompted to consider the results of the CCTA in management decision
- when there was evidence of non obstructive (10-70% cross-sectional luminal stenosis) or obstructive coronary artery disease, prescription of preventive therapies was prompted.
- Standard care group was prompted to consider the ASSIGN cardiovascular disease risk score
- when ASSIGN score >/= 20, prompted to prescribe preventive therapies.
Comparisons are CCTA plus standard care vs. standard care alone.
- Death from coronary heart disease or nonfatal myocardial infarction
- 2.3% vs. 3.9% (HR 0.59; 95% CI 0.41-0.84; P=0.004)
- Nonfatal myocardial infarction
- 2.1% vs. 3.5% (HR 0.60; 95% CI 0.41-0.87)
- Death from CHD
- 0.2% vs. 0.4% (HR 0.46; 95% CI 0.14-1.48)
- Death from any cause
- 2.1% vs 2.1% (HR 1.02; 95% CI 0.67-1.55)
- Invasive coronary angiography
- 23.7% vs 24.2% (HR 1.00; 95% CI 0.88-1.13)
- 13.5% vs 12.9% (HR 1.07; 95% CI 0.91-1.27)
- Started on preventive therapies
- 19.4% vs 14.7% (OR 1.40; 95% CI 1.19-1.65)
- Started on antianginal therapies
- 13.2% vs 10.7% (OR 1.27; 95% CI 1.05-1.54)
- Clinical importance is unclear given that there was no observed mortality difference despite a significant difference in nonfatal MI which drove the difference in primary end point.
- The accompanying editorial brought up the point that the differences in subsequent medical management between groups were modest and would not explain the difference in nonfatal myocardial infarction.
- Endpoints were classified using diagnostic coding, without a formal event adjudication. This could introduce some diagnostic error, and there is general controversy over the clinical significance of the endpoint of nonfatal myocardial infarction given advances in cardiac biomarker sensitivity. If clinically meaningful MIs were being prevented, then there would be an expected mortality benefit. Being non-blinded, there is potential for introduction of biases in the coding of clinical events.
Study funded by the Scottish Government Chief Scientist Office. Supplementary funding from British Heart Foundation, Edinburgh and Lothians Health Foundation Trust and the Heart Diseases Research Fund.
- Hoffmann U et al. Coronary CT angiography versus standard evaluation in acute chest pain. N. Engl. J. Med. 2012. 367:299-308.
- Douglas PS et al. Outcomes of anatomical versus functional testing for coronary artery disease. N. Engl. J. Med. 2015. 372:1291-300.
- Hoffmann U & Udelson JE Imaging Coronary Anatomy and Reducing Myocardial Infarction. N. Engl. J. Med. 2018. 379:977-978.
- Fihn SD et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a 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. Circulation 2012. 126:e354-471.