In our previous report from the SCOT-HEART trial, we found that the use of CTA had a significant effect on the diagnosis and treatment of patients who had been referred for evaluation of stable chest pain, in that it influenced both the certainty and the frequency of the diagnosis of coronary heart disease and led to alterations in management.9 Here, we report the 5-year clinical outcomes.13 We found that the use of CTA, with consequent changes in treatment, resulted in a significantly lower rate of death from coronary heart disease or nonfatal myocardial infarction than standard care alone. Although the rates of invasive coronary angiography and coronary revascularization were higher in the CTA group than in the standard-care group in the first few months of follow-up, we did not find any differences in the overall use of invasive coronary angiography and coronary revascularization at 5 years. Our findings suggest that the use of CTA resulted in more correct diagnoses of coronary heart disease than standard care alone, which, in turn, led to the use of appropriate therapies, and this change in management resulted in fewer clinical events in the CTA group than in the standard-care group.

In the SCOT-HEART9 and PROMISE11 trials, the use of CTA resulted in a higher rate of detection of obstructive coronary heart disease, as confirmed by invasive coronary angiography, than standard care alone (SCOT-HEART trial) or functional testing (PROMISE trial). Invasive coronary angiography and coronary revascularization are more likely to be used appropriately in patients who receive a correct diagnosis of coronary heart disease9,11; patients who receive a correct diagnosis are also more likely to receive appropriate preventive therapies10 and may have greater motivation to implement healthy lifestyle modifications. In addition, the SCOT-HEART trial encouraged initiation of secondary prevention strategies in patients with nonobstructive coronary artery disease. Among patients in the CTA group, approximately half the subsequent myocardial infarctions occurred among patients who had nonobstructive disease at baseline. This proportion was probably higher among patients who received standard care alone, since nonobstructive disease may have been unrecognized and untreated in some of the patients in that group. In the PROMISE trial, in which preventive therapies were not mandated, two thirds of subsequent cardiac events occurred in patients with nonobstructive disease.21 Finally, event rates in the two groups in the current trial were similar until diagnoses were confirmed and alterations in treatment were made after approximately 7 weeks,10 which suggests that the groups were similar at baseline and changes in outcomes occurred only once treatment interventions directed by CTA findings were initiated. We hypothesize that the immediate reductions in events were mediated through the use of aspirin22,23 and coronary revascularization procedures,24,25 and that longer-term benefits are attributable to lifestyle modification26 and statin therapy.27

Previous studies have suggested that the use of CTA is associated with higher early rates of both invasive coronary angiography and coronary revascularization.9,11,28 Over the 5-year follow-up, we found that these higher procedure rates were no longer apparent. We performed landmark analyses at 12 months to distinguish the immediate effects of CTA from the longer-term consequences. We found that beyond 12 months, rates of invasive coronary angiography and coronary revascularization were higher in the standard-care group than in the CTA group. This would be consistent with both the emergence of unrecognized disease and nonfatal myocardial infarction in the standard-care group and the reduction in disease progression in the CTA group owing to the implementation of lifestyle modifications and preventive therapies.27

Some observers have highlighted the low cardiovascular event rates in trials of CTA involving patients with stable chest pain, which has prompted others to suggest that such patients should not undergo cardiovascular testing at all. In the SCOT-HEART trial, we enrolled patients with a broad range of cardiovascular risks. Overall, we observed event rates of approximately 4% over 5 years, which equates to 8% over 10 years. However, half the trial population had normal or near-normal coronary arteries, which implies that patients with nonobstructive or obstructive coronary heart disease would have 10-year event rates of approximately 16%. This highlights the importance of promptly and accurately identifying the presence of coronary heart disease.

Strategies to stratify patients before testing have been proposed and are included in current guidelines.4-6 However, these strategies still lead to overtesting, owing to the poor predictive accuracy of the current scoring systems.20,29 Recently, NICE has recommended a simple symptom-based approach that would classify patients into one of two categories: those with nonanginal chest pain and those with possible angina.19 We found that patients with possible angina were at higher risk than those with nonanginal chest pain, especially in the first 3 to 6 months after the onset of symptoms, which perhaps reflects the fact that patients with recent onset of angina pectoris constitute a particularly high-risk group.30,31 However, overall, all patients appeared to derive similar benefits from CTA, which raises the question of whether more widespread testing may be helpful, irrespective of symptoms. Our data suggest that 63 patients with stable chest pain would need to be referred for CTA to prevent 1 fatal or nonfatal myocardial infarction over the course of 5 years.

We acknowledge that there are some limitations of the trial. First, this was an open-label trial, and ascertainment bias is inherent to the trial design. Because event adjudication was not blinded and clinical diagnoses were coded with knowledge of the assigned trial group, the risk of ascertainment bias is probably higher. This risk may have been mitigated, however, by the fact that the primary long-term end point was composed of hard clinical events. Second, we do not have data on lifestyle alterations during follow-up and can only speculate that these may have been greater in the CTA group than in the standard-care group. Third, cardiovascular-risk thresholds for the initiation of preventive therapies have fallen since the trial was completed, and it is unclear whether the benefits of CTA will be maintained with these lower thresholds. Finally, the benefit of CTA with respect to the rate of death from coronary heart disease and nonfatal myocardial infarction (1.6 percentage points lower than the rate with standard therapy) may be considered modest, but this absolute benefit is similar to, if not greater than, the benefits achieved in recent pharmaceutical interventional trials involving patients with established coronary heart disease.32-34

In conclusion, in the SCOT-HEART trial, we found that the use of CTA in patients who had been referred to a cardiology clinic for assessment of stable chest pain resulted in a lower subsequent risk of death from coronary heart disease or nonfatal myocardial infarction than standard care alone. This benefit was achieved without greater long-term use of invasive coronary angiography or coronary revascularization in the CTA group.