Elsevier

The Lancet

Volume 386, Issue 9994, 15–21 August 2015, Pages 665-671
The Lancet

Articles
Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease (DANAMI-3—PRIMULTI): an open-label, randomised controlled trial

https://doi.org/10.1016/S0140-6736(15)60648-1Get rights and content

Summary

Background

Patients with acute ST-segment elevation myocardial infarction (STEMI) and multivessel coronary disease have a worse prognosis compared with individuals with single-vessel disease. We aimed to study the clinical outcome of patients with STEMI treated with fractional flow reserve (FFR)-guided complete revascularisation versus treatment of the infarct-related artery only.

Methods

We undertook an open-label, randomised controlled trial at two university hospitals in Denmark. Patients presenting with STEMI who had one or more clinically significant coronary stenosis in addition to the lesion in the infarct-related artery were included. After successful percutaneous coronary intervention (PCI) of the infarct-related artery, patients were randomly allocated (in a 1:1 ratio) either no further invasive treatment or complete FFR-guided revascularisation before discharge. Randomisation was done electronically via a web-based system in permuted blocks of varying size by the clinician who did the primary PCI. All patients received best medical treatment. The primary endpoint was a composite of all-cause mortality, non-fatal reinfarction, and ischaemia-driven revascularisation of lesions in non-infarct-related arteries and was assessed when the last enrolled patient had been followed up for 1 year. Analysis was on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01960933.

Findings

From March, 2011, to February, 2014, we enrolled 627 patients to the trial; 313 were allocated no further invasive treatment after primary PCI of the infarct-related artery only and 314 were assigned complete revascularisation guided by FFR values. Median follow-up was 27 months (range 12–44 months). Events comprising the primary endpoint were recorded in 68 (22%) patients who had PCI of the infarct-related artery only and in 40 (13%) patients who had complete revascularisation (hazard ratio 0·56, 95% CI 0·38–0·83; p=0·004).

Interpretation

In patients with STEMI and multivessel disease, complete revascularisation guided by FFR measurements significantly reduces the risk of future events compared with no further invasive intervention after primary PCI. This effect is driven by significantly fewer repeat revascularisations, because all-cause mortality and non-fatal reinfarction did not differ between groups. Thus, to avoid repeat revascularisation, patients can safely have all their lesions treated during the index admission. Future studies should clarify whether complete revascularisation should be done acutely during the index procedure or at later time and whether it has an effect on hard endpoints.

Funding

Danish Agency for Science, Technology and Innovation and Danish Council for Strategic Research.

Introduction

In patients with acute ST-elevation myocardial infarction (STEMI), the recommended treatment is primary percutaneous coronary intervention (PCI), provided this procedure can be accomplished within a reasonable time from first medical contact.1, 2 About 40–50% of people presenting with STEMI have multivessel disease,3, 4 although most individuals are asymptomatic until the acute presentation.5 Compared with patients with single-vessel disease, individuals with STEMI and multivessel disease have higher mortality rates and a greater incidence of non-fatal reinfarction.6, 7, 8 It is, however, unclear whether this poorer prognosis is attributable to an increased disease burden or because relevant lesions in other areas are left untreated

Any benefits of revascularisation of lesions in non-infarct-related arteries should be counterbalanced by potential disadvantages connected with additional PCI. Meta-analyses of registry studies in the acute setting of primary PCI9, 10, 11 have not demonstrated any clear benefit when PCI was done in arteries other than the infarct-related artery. In two large meta-analyses, including more than 40 000 patients in each,12, 13 acute multivessel PCI (done during the index procedure) was associated with the highest mortality whereas staged multivessel PCI (done at a later stage during the index admission or within 1 month) was associated with the lowest mortality. However, small randomised trials show either no difference in clinical outcome or an improved prognosis in patients treated with acute complete revascularisation.14, 15, 16 Furthermore, in the somewhat larger PRAMI and CVLPRIT trials,17, 18 a benefit in clinical outcome was reported when patients with STEMI and multivessel disease had complete revascularisation guided by angiography, rather than treatment of the infarct-related artery only.

Research in context

Evidence before this study

We searched PubMed and Medline for any studies published in English, and ClinicalTrials.gov for studies ongoing or completed, in which revascularisation of the culprit vessel alone was compared with complete revascularisation in a primary percutaneous coronary intervention (PCI) setting. Our search terms were: “infarct related artery”, “complete revascularisation”, “culprit vessel”, “primary PCI”, “primary percutaneous coronary intervention”, “primary angioplasty”, and “ST-segment elevation myocardial infarction” or “STEMI”. We identified five randomised trials. In a trial in a small cohort (di Mario), complete revascularisation at the time of primary angioplasty was compared with PCI of the infarct-related artery only, and reduced need for subsequent repeat revascularisation was noted. In the second trial, Politi compared culprit revascularisation, staged treatment of non-infarct-related arteries, and concomitant treatment of non-infarct-related arteries and showed that rates of all-cause mortality, reinfarction, readmission for acute coronary syndrome, and repeat coronary revascularisation were halved in the complete revascularisation groups, driven by readmission and the need for repeat revascularisation. In a small study (Dambrink), measurement of fractional flow reserve (FFR) to guide PCI of lesions in non-infarct-related arteries did not alter clinical outcome. In the largest study to date (PRAMI), a surprising 65% reduction in the composite endpoint of death, myocardial infarction, and refractory angina was recorded in favour of full revascularisation at the time of treatment of the index artery. Finally, in the CVLPRIT trial (Kelly), immediate or delayed complete revascularisation reduced the composite endpoint of all-cause mortality, recurrent myocardial infarction, heart failure, and repeat revascularisation, although individual components of the primary endpoint were indifferent when compared with index-vessel PCI alone.

Added value of this study

The results of the PRIMULTI trial showed that complete revascularisation guided by FFR measurement of lesions in non-culprit lesions and done 2 days after primary PCI is safe and reduces the primary endpoint. However, the effect of this staged strategy is driven by the need for repeat revascularisation.

Implications of all the available evidence

Although findings of most previous randomised trials suggest a complete revascularisation strategy is beneficial, these studies raise three questions. Does angiographic assessment of stenoses in non-infarct-related arteries offer sufficient information to select lesions for additional treatment? What is the best timing for a complete revascularisation strategy? Are reductions in endpoints sufficiently robust to mandate complete revascularisation in all patients? The findings of our trial shed light on the efficacy and safety of doing revascularisation of additional coronary lesions in a substantial population of patients. Although complete revascularisation should probably be recommended, reinterventions are mainly done on the basis of stable angina.

PCI guided by measurement of the fractional flow reserve (FFR) has proven superior to PCI guided by angiography alone in patients with stable coronary disease.19 Therefore, in a population of patients with multivessel disease who had already had primary PCI of the infarct-related artery, we aimed to investigate the effect of complete revascularisation guided by FFR measurements before discharge compared with no further invasive treatment.

Section snippets

Study design

The DANAMI-3–PRIMULTI trial is a part of the DANAMI-3 trial programme,20 done at four large primary PCI centres in Denmark. The programme encompasses three randomised trials investigating the effect of deferred stenting (DANAMI-3–DEFER), ischaemic postconditioning (DANAMI-3–POSTCON), and complete revascularisation (DANAMI-3–PRIMULTI). The study protocol, approved in Copenhagen by a central ethics committee, has been described in detail elsewhere.20 The DANAMI-3 trial programme was undertaken in

Results

Between March, 2011, and February, 2014, 627 patients met inclusion criteria and were enrolled in the PRIMULTI trial (figure 1). 314 patients were randomly allocated complete revascularisation and 313 individuals were assigned no further invasive treatment. Baseline characteristics were well balanced between groups (table 1; appendix p 2).

Complete revascularisation guided by FFR measurements was done a median of 2 days after the initial PCI procedure (IQR 2–4). Median follow-up of all

Discussion

The results of the PRIMULTI trial show that patients with STEMI and multivessel disease, who have timely primary PCI, benefit from supplementary FFR-guided complete revascularisation of lesions in non-infarct-related arteries when the second procedure is done during the index admission. We reported a significant reduction in the combination of all-cause mortality, non-fatal reinfarction, and ischaemia-driven revascularisation of coronary artery lesions located remote from the culprit artery.

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