5-year outcome of an interventional strategy in non-ST-elevation acute coronary syndrome: the British Heart Foundation RITA 3 randomised trial

Summary

Background

The long-term outcome of an interventional strategy in patients with non-ST-elevation acute coronary syndrome is unknown. We tested whether an interventional strategy (routine angiography followed by revascularisation) was better than a conservative strategy (ischaemia-driven or symptom-driven angiography) over 5 years' follow-up.

Methods

In a multicentre randomised trial, 1810 patients (from 45 hospitals in England and Scotland, UK) with non-ST-elevation acute coronary syndrome were randomly assigned to receive an early intervention (n=895) or a conservative strategy (n=915) within 48 h of the index episode of cardiac pain. In each group, the aim was to provide the best medical treatment, and also to undertake coronary arteriography within 72 h in the interventional strategy with subsequent management guided by the angiographic findings. Analysis was by intention to treat and the primary outcome (composite of death or non-fatal myocardial infarction) had masked independent adjudication. RITA 3 has been assigned the International Standard Randomised Control Trial Number ISRCTN07752711.

Findings

At 1-year follow-up, rates of death or non-fatal myocardial infarction were similar. However, at a median of 5 years' follow-up (IQR 4·6–5·0), 142 (16·6%) patients with intervention treatment and 178 (20·0%) with conservative treatment died or had non-fatal myocardial infarction (odds ratio 0·78, 95% CI 0·61–0·99, p=0·044), with a similar benefit for cardiovascular death or myocardial infarction (0·74, 0·56–0·97, p=0·030). 234 (102 [12%] intervention, 132 [15%] conservative) patients died during follow-up (0·76, 0·58–1·00, p=0·054). The benefits of an intervention strategy were mainly seen in patients at high risk of death or myocardial infarction (p=0·004), and for the highest risk group, the odds ratio of death or non-fatal myocardial infarction was 0·44 (0·25–0·76).

Interpretation

In patients with non-ST-elevation acute coronary syndrome, a routine invasive strategy leads to long-term reduction in risk of death or non-fatal myocardial infarction, and this benefit is mainly in high-risk patients. The findings provide support for national and international guidelines in the need for more robust risk stratification in acute coronary syndrome.

Introduction

In patients that present with acute coronary syndrome without ST-segment elevation, the pathophysiological mechanisms include plaque disruption, thrombus formation, and microembolisation.¹ Antiplatelet and antithrombin therapy affect acute and subsequent outcome, but the long-term effect of an interventional strategy is currently unknown. The rationale for an interventional strategy, in addition to a pharmacological approach for non-ST-elevation acute coronary syndrome, is based on evidence indicating that disrupted architecture of the plaque contributes to ischaemia and progression of coronary disease. Revascularisation procedures (percutaneous coronary intervention [PCI] and coronary artery bypass grafting surgery [CABG]) improve coronary perfusion, reduce ischaemia, and could reduce the likelihood of presentation with a further coronary event.

Meta-analysis of all the published trials of a selective strategy versus a routine invasive strategy in acute coronary syndrome suggests a net reduction in risk of death or myocardial infarction with a routine interventional strategy (odds ratio 0·82, 95% CI 0·72–0·93).² However, there was an early net increase in the risk of death during the index hospital admission (1·60, 1·14–2·25, p=0·007). The defining of long-term outcomes in patients with acute coronary syndrome is of critical importance. Experience from trials of surgical revascularisation in patients with stable coronary heart disease shows that the early hazards of surgery are outweighed by benefits that emerge after 2 to 5 years of follow-up.³

The RITA 3 study was designed to investigate whether a strategy of early angiography and revascularisation (as clinically indicated) is more effective than a conservative strategy in patients with non-ST-elevation acute coronary syndrome.⁴ At 4 months, 10% of patients in the intervention group had died, had a myocardial infarction, or had an episode of refractory angina compared with 15% in the conservative group (risk ratio 0·66, 95% CI 0·51–0·85, p=0·001). This difference was mainly due to a halving of the frequency of refractory angina in the intervention group. Rates of death or non-fatal myocardial infarction were similar in both treatment groups at 1 year (7·6% [intervention] vs 8·3% [conservative]; 0·91, 0·67–1·25). Thus, the 1-year results of RITA 3 showed clear evidence that a systematic strategy of angiography and (where angiographically indicated) revascularisation mainly reduced refractory angina.4, 5 We designed RITA 3 to analyse the long-term effect of this interventional strategy on the basis that the benefits of revascularisation may accrue over time.³ We report the first long-term outcome results (at a median of follow-up 5·0 years [IQR 4·6–5·0]) for a trial of an interventional strategy in non-ST-elevation acute coronary syndrome patients.