Immediate multivessel revascularization after myocardial infarction: change of strategy? (2024)

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Abstract

Multivessel coronary artery disease (MVD) is a frequently encountered condition in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) of the culprit vessel. Several studies have demonstrated the benefit of complete coronary revascularization compared with the treatment of the culprit lesion only in patients with STEMI. Based on this evidence, the current European guidelines recommend that in haemodynamically stable patients with STEMI and MVD, routine complete revascularization should be achieved either during the same procedure in concomitance with the treatment of the culprit lesion (immediate multivessel PCI) or with a subsequent intervention within 45 days from the index PCI of the culprit lesion (deferred multivessel PCI). However, the guidelines do not express a preference for immediate vs. delayed multivessel PCI. Therefore, the optimal timing of the treatment of non-culprit lesions in patients with STEMI and haemodynamic stability is still debated and has been evaluated in recent studies that showed the non-inferiority of immediate vs. delayed multivessel PCI. The article discusses the results and clinical implications of these studies on the timing of complete revascularization of non-culprit lesions in haemodynamically stable patients with STEMI.

Keywords: ST-segment elevation myocardial infarction, Multivessel disease, Complete revascularization, Multivessel percutaneous coronary intervention, Immediate revascularization

The standard treatment of ST-segment elevation myocardial infarction (STEMI) consists of mechanical reperfusion of the culprit coronary artery using primary percutaneous coronary intervention (PCI).¹ However, multivessel coronary artery disease is commonly found in ∼50% of patients presenting with STEMI and is associated with an increased risk of re-infarction and mortality,^2,3 suggesting the need to define the optimal treatment of concomitants coronary lesions that are not responsible for the acute myocardial infarction. Several randomized studies have shown that in the setting of STEMI with multivessel disease, complete coronary revascularization using multivessel PCI is superior to PCI of the culprit lesion only in reducing the risk of ischaemic events.^4–8 In particular, the COMPLETE (Complete vs. Culprit-only Revascularization Strategies to Treat Multivessel Disease after Early PCI for STEMI) trial, which was the largest study and the only one with adequate statistical power to evaluate the most relevant clinical endpoints, showed that among patients with STEMI and multivessel coronary disease (n = 4000) complete revascularization of non-culprit coronary lesions compared with PCI of the culprit lesion only significantly reduced the incidence of the composite endpoint of cardiovascular death and myocardial infarction during a median follow-up of 36 months [7.8 vs. 10.5%; HR (hazard ratio) 0.74, 95% CI (confidence interval) 0.60–0.91, P = 0.004]. The consistency of the favourable results observed across studies and confirmed in the COMPLETE trial has led recent European guidelines to recommend the strategy of complete revascularization as Class IA in haemodynamically stable patients with STEMI.⁹ However, in the latter clinical setting, the timing to obtain complete revascularization of non-culprit lesions remains still undetermined. Indeed, studies have implemented different timings for multivessel PCI in STEMI, achieving complete coronary revascularization through immediate intervention during the same procedure of primary PCI (immediate multivessel PCI) or through subsequent planned PCI procedure during the same index hospitalization or in a subsequent hospitalization scheduled within 45 days from primary PCI (deferred multivessel PCI).^5–8 Therefore, the optimal timing of multivessel PCI in STEMI is currently debated and has been evaluated in recent dedicated trials.^10–12 This article discusses the design, populations, results, and clinical implications of studies on the timing of revascularization of non-culprit lesions in haemodynamically stable patients with STEMI.

Summary of evidence on the timing of complete revascularization in ST-segment elevation myocardial infarction

Two randomized trials, BIOVASC (Percutaneous Complete Revascularization Strategies Using Sirolimus-eluting Biodegradable Polymer-coated Stents in Patients Presenting with Acute Coronary Syndrome and Multivessel Disease) and MULTISTARS AMI (MULTivessel Immediate vs. STAged RevaScularization in Acute Myocardial Infarction), compared immediate multivessel PCI vs. deferred multivessel PCI in haemodynamically stable patients with acute coronary syndromes.^10–12

BIOVASC was the first randomized study to evaluate the issue of the timing of complete revascularization in myocardial infarction.¹⁰ It is a prospective, multi-centre (29 European centres), open-label, non-inferiority trial, which randomized 1525 patients with acute coronary syndrome (∼40% with STEMI) to immediate multivessel PCI or deferred PCI of non-culprit lesions. In the latter group of patients, the second PCI procedure could be performed during the same hospitalization or in a subsequent hospitalization scheduled within 6 weeks, at the investigator’s discretion. The main exclusion criteria included cardiogenic shock, previous coronary artery bypass surgery, and the concomitant presence of chronic total occlusion. The trial showed that complete revascularization using immediate multivessel PCI was non-inferior to delayed PCI in reducing the composite primary endpoint of all-cause death, non-fatal myocardial infarction, ischaemia-driven unplanned revascularization, or cerebrovascular disease at one year after the index procedure (7.6 vs. 9.4%; HR 0.78, 95% CI 0.55–1.11; non-inferiority P = 0.0011). The complete revascularization approach using immediate multivessel PCI was associated with lower incidences of ischaemia-driven unplanned revascularization and myocardial infarction, attributable to a reduction in early events occurring between the primary PCI and the second PCI procedure planned to complete the revascularization of non-culprit lesions. One-year all-cause mortality was similar to the two treatment groups.

In the subgroup of patients with STEMI (n = 608) included in the BIOVASC trial, no significant differences were observed in the composite primary endpoint at one year between immediate vs. deferred complete revascularization (7.0 vs. 8.3%; HR 0.84, 95% CI 0.47–1.50; P = 0.55).¹¹ Furthermore, at one-year follow-up, no statistically significant differences were observed between immediate and deferred multivessel PCI in total mortality (2.3 vs. 1.3%; HR 1.77, 95% CI 0.52–6.04; P = 0.36), myocardial infarction (1.7 vs. 3.3%; HR 0.50, 95% CI 0.17–1.47; P = 0.21), unplanned ischaemia-driven revascularization (4.1 vs. 5.0%; HR 0.80, 95% CI 0.38–1.71; P = 0.57), and cerebrovascular events (1.4 vs. 1.3%; HR 1.01, 95% CI 0.25–4.03; P = 0.99), respectively. Since peri-procedural infarction may have been underdiagnosed in the group of patients undergoing immediate complete revascularization, an analysis was performed excluding all procedural infarctions. This latter showed similar incidences of spontaneous infarction in the two PCI groups (1.3% in the immediate multivessel PCI vs. 1.7% in the deferred multivessel PCI). Therefore, although with limited statistical power, the STEMI subgroup analysis of the BIOVASC trial showed that the two approaches of complete revascularization, that is immediate or deferred multivessel PCI of non-culprit lesions, were associated with similar clinical outcomes.

The MULTISTARS AMI trial is a randomized, prospective, multi-centre (37 European centres involved), open-label trial, designed to evaluate whether in haemodynamically stable patients with STEMI and multivessel coronary disease (N = 840) complete revascularization by immediate multivessel PCI of non-culprit lesions is not inferior to the deferred multivessel PCI scheduled between 19 and 45 days after culprit lesion treatment.¹² The main exclusion criteria included significant disease of the left main or left anterior descending coronary artery or circumflex at the ostial segment, concomitant chronic total occlusion, in-stent restenosis/thrombosis, previous coronary artery bypass grafting, planned cardiac and non-cardiac surgery, and severe mechanical complications of STEMI. Immediate vs. delayed multivessel PCI was non-inferior and apparently even better in reducing the one-year incidence of the composite primary endpoint of all-cause mortality, non-fatal myocardial infarction, stroke, and ischaemia-driven unplanned revascularization and hospitalization for heart failure (Table 1). The difference in the primary endpoint, which also reached statistical superiority, was primarily driven by a significant reduction in rates of myocardial infarction and urgent revascularizations with immediate vs. delayed multivessel PCI, with similar incidences of death, stroke, and hospitalization for heart failure between the two groups (Table 1). The excess risk of myocardial infarction observed in the group undergoing complete revascularization by deferred PCI was mainly due to an increase in procedural myocardial infarction, while the one-year incidence of spontaneous infarction was similar between the two treatment groups. However, in most cases, spontaneous infarctions (seven of eight) occurred before scheduled PCI in the group undergoing deferred complete revascularization. Furthermore, in the latter group, in 23 of 39 cases, the event of unplanned revascularization driven by ischaemia occurred before carrying out the planned PCI. However, 13 of these 23 early unplanned revascularization events were due to isolated symptoms of angina and were not driven by an acute coronary syndrome. Therefore, excluding procedural infarction, the difference in events with deferred vs. immediate multivessel revascularization can be attributed primarily to an excess of 10 events (∼2%) of unplanned revascularization events that can be defined as urgent. The doubt remains whether these events could have been avoided with a complete revascularization through a deferred multivessel PCI carried out during the same hospitalization, a timing that was not applied in the MULTISTARS AMI trial. In this regard, in the group of patients undergoing deferred multivessel PCI, the median time from randomization to the procedure scheduled after discharge to treat non-culprit lesions was 37 days (interquartile range from 30 to 43 days). It cannot be excluded that this time window introduced a bias in favour of the non-inferiority and superiority of the immediate multivessel PCI strategy. Finally, immediate multivessel PCI was associated with no increase in renal failure and bleeding, and with similar procedural success.

Therefore, the MULTISTARS AMI trial confirmed that in patients with STEMI and haemodynamic stability, immediate vs. delayed multivessel PCI is associated with similar efficacy and safety outcomes. However, these results must be interpreted in light of the predominantly low risk of the populations enrolled in the described trials. It is, in fact, important to note that the majority of patients (∼80%) in the MULTISTISTARS MI trial had only one vessel involved by a non-culprit lesion. In general, one can logically expect that the complexity of the non-culprit lesions could have influenced the operator’s choice to include or exclude a patient from randomization to immediate or deferred multivessel PCI.

Practical implications of studies on the timing of complete revascularization in ST-segment elevation myocardial infarction

In haemodynamically stable patients with STEMI and multivessel coronary disease, routine complete revascularization to be performed during the index procedure or within 45 days is recommended in Class IA by the most recent European guidelines.⁹ This recommendation is based on data from several randomized trials which have shown that complete revascularization of non-culprit STEMI lesions, achieved either during the same procedure of primary PCI of the culprit vessel or through a further planned intervention during the same hospitalization or in a subsequent elective hospitalization, is safe and reduces the risk of re-infarction or future revascularization compared with the treatment of the culprit lesion only.^4–8 However, the guidelines do not provide a recommendation in favour of immediate vs. deferred PCI of coronary lesions not causing the STEMI, since at the time of their release no adequate studies were available to evaluate the optimal timing of complete revascularization in STEMI. This lack of evidence in association with observational studies that showed signs of increased risk of mortality with immediate multivessel PCI in STEMI,^13,14 have contributed to the current common interventional practice of treating only the culprit lesion and deferring treatment of non-culprit lesions. The results of the BIOVASC and MULTISTARS AMI trials have given a new impetus to immediate multivessel revascularization in STEMI, showing that this strategy compared with deferred multivessel PCI appears to be non-inferior in terms of clinical outcomes, equally safe and associated with possible advantages related to a reduction in urgent revascularizations, which can occur during the time window while waiting for the planned PCI, and to a lower use of healthcare resources. These data are reassuring and support the concept that immediate PCI of all angiographically significant coronary lesions during the index procedure is not associated with harmful effects, suggesting the opportunity to implement this approach in the treatment of patients with STEMI and haemodynamic stability. However, it is important to underline that the MULTISTRAS AMI study was designed to compare two multivessel PCI strategies in STEMI only in terms of non-inferiority which is what it demonstrated in a population of patients predominantly at lower risk, suggesting that immediate multivessel PCI in STEMI should not be the preferred strategy in all patients but should be considered in selected patients and in safe clinical and logistical conditions.

The decision on the optimal timing to achieve revascularization of non-culprit coronary lesions in haemodynamically stable patients with STEMI and multivessel disease should consider the following factors: (i) the complexity, duration, and outcome of PCI of the culprit lesion; (ii) the characteristics (number, location, severity, and complexity) of non-culprit coronary lesions; (iii) the risk of procedural complications; (iv) the risk of kidney injury or bleeding complications; and (v) logistical conditions. In the absence of haemodynamic instability, immediate multivessel PCI is preferable in cases of uncomplicated PCI of the culprit lesion and coexistence of other coronary lesions with non-complex anatomy, at low risk of procedural complications and whose treatment does not require a high volume of contrast or a long procedural time, in patients with known normal renal function or in those at lower risk of developing acute kidney injury. The PCI treatment of coronary lesions not responsible for STEMI could be preferentially deferred in the presence of at least one of the following conditions: complex or complicated PCI of the culprit vessel; the presence of complex lesions or lesions requiring further clinical or functional evaluation; patients with renal failure; high risk of developing acute kidney injury; and unfavourable logistics. Planned complete revascularization of non-STEMI lesions is more commonly performed during the index hospitalization rather than in a subsequent elective hospitalization. A pre-specified analysis of the COMPLETE trial showed that in STEMI the benefit of complete revascularization compared with PCI of the culprit lesion only is maintained regardless of the timing in which the deferred PCI procedures of the non-culprit lesions are performed, i.e. if during the same hospitalization or in a subsequent scheduled hospitalization which in the trial was carried out at a median of 23 days from the index procedure.¹⁵ However, in this analysis, the two deferred multivessel PCI approaches were not directly compared, and by inspecting the event curves, the benefit of complete revascularization compared with the culprit lesion only PCI would appear to start earlier when the PCI of non-culprit lesions was performed during the same hospitalization. This latter approach could have potentially prevented the urgent revascularizations that were observed before the next scheduled elective hospitalization in the deferred multivessel PCI group of the MULTISTARS AMI trial. The deferred treatment of non-culprit coronary lesions in STEMI patients should preferably be carried out during the index hospitalization in cases of haemodynamic instability, in the presence of angiographic aspects of high risk or instability, in critical stenoses of the left main or proximal vessels, in severe stenosis, or in patients with left ventricular impairment or significant valvular disease, especially mitral insufficiency. On the contrary, complete revascularization could be achieved later during a second planned hospitalization in case of intermediate lesions which should be functionally evaluated, in the absence of angiographic characteristics of plaque instability; or in the case of unfavourable logistics.

Conclusions

Recent clinical evidence shows that in patients with STEMI in conditions of haemodynamic stability, complete revascularization through immediate multivessel PCI compared with deferred PCI is an equally safe and effective strategy, supporting its practical implementation in selected patients. The strategy of immediate multivessel PCI in STEMI could be particularly useful in patients with two-vessel coronary disease, with a low risk of developing acute kidney injury, and with reasonably simple non-culprit lesions not requiring a prolonged procedure time or the use of complex techniques and associated with a high probability of procedural success. In general, the decision to perform immediate complete revascularization should be individualized based on the patient's clinical risk and logistic considerations.

Contributor Information

Piera Capranzano, Cardiovascular Department, Policlinico Hospital, University of Catania, Catania.

Luca Lombardo, Cardiovascular Department, Policlinico Hospital, University of Catania, Catania.

Funding

No funding provided.

Data availability

No new data were generated or analysed in support of this research.

References