Introduction

ST-elevation myocardial infarction (STEMI) is one of the highest-risk subsets of patients who undergo percutaneous coronary intervention (PCI), and it is important to have comprehensive guidelines to aid physicians in the management and clinical decision making process. The 2015 American College of Cardiology (ACC)/American Heart Association (AHA)/ Society for Cardiovascular Angiography and Interventions (SCAI) focused update on primary PCI for patients with STEMI addresses the management of multivessel disease and the use of aspiration thrombectomy.¹ As new data have emerged since the 2011 ACCF/AHA/SCAI guidelines for PCI and the 2013 ACCF/AHA guidelines for the management of STEMI, this update is necessary and an excellent resource. However, it is also important to critically analyze these recommendations so that health care providers can use them appropriately in individualized patient care.

Infarct Artery-Only Versus Multivessel PCI

Approximately 40% of patients with STEMI undergoing primary PCI may have severe coronary artery disease in one or more non-infarct arteries.² The 2013 STEMI guidelines recommended against treatment of a non-infarct artery during primary PCI in otherwise hemodynamically stable patients (Class III, Level of Evidence [LOE] B) but did give consideration to staged PCI of a non-infract artery in patients with signs or symptoms of recurrent ischemia (Class I, LOE C) or high-risk features on noninvasive studies (Class IIa, LOE B).³ The previous Class III recommendation against treatment of a non-infarct artery was largely based on data from retrospective/observational studies, which demonstrated little or no benefit to multivessel revascularization during primary PCI.^4-10 These studies also raised safety concerns related to longer procedural times, contrast-induced nephropathy, radiation safety, and possible trend towards higher mortality.

However, more recent randomized trials (Preventive Angioplasty in Acute Myocardial Infarction [PRAMI], Complete versus Lesion-only PRimary PCI Trial [CvLPRIT] and The Third DANish Study of Optimal Acute Treatment of Patients With STEMI: PRImary PCI in MULTIvessel Disease [DANAMI 3 PRIMULTI]) demonstrated safety and benefit with multivessel PCI in STEMI either during the primary procedure or as a staged procedure (Table 1).^11-13 The primary outcome in these trials was a composite of death, non-fatal MI, or refractory angina/ischemia-driven revascularization. While these studies showed significant benefit with complete revascularization, reduction in refractory angina/need for ischemia-driven revascularization drove this. Therefore, the Class III recommendation for PCI of a non-infarct artery in stable patients with STEMI was appropriately changed to Class IIB (LOE B) with the caveat that physicians individualize the decision for non-infarct artery revascularization based on each patient's risk-benefit profile. This is a reasonable recommendation given that the benefit on hard clinical outcomes, such as death and non-fatal MI, is yet to be demonstrated and the subject of the on-going prospective, randomized, multicenter, open-label Complete vs Culprit-only Revascularization to Treat Multi-vessel Disease After Primary PCI for STEMI (COMPLETE) trial with blinded assessment of outcomes (primary endpoint: composite of cardiovascular death and new MI) (ClinicalTrials.gov identifier NCT01740479).

Table 1: Randomized Trials of Infarct Artery Only PCI vs. Complete Revascularization in Patients With STEMI and Multivessel Coronary Artery Disease

Trial	Trial Design	Population	Intervention	Control	Crossover	Primary Endpoint	Results (Intervention vs. Control)
PRAMI11	Multicenter, United Kingdom, 1:1 randomization, single-blind	465	Complete revascularization of >50% angiographic stenoses during index procedure	Infarct artery only PCI	None	Composite of cardiac death, nonfatal MI, or refractory angina (mean follow-up 23 months)	9 per 100 vs. 23 per 100, (HR 0.35 [95% CI 0.21 to 0.58]; p <0.001)
CvLRIT12	Multicenter, United Kingdom, 1:1 randomization, open-label	296	In-hospital complete revascularization (70% during index procedure, 30% staged procedure)	Infarct artery only PCI	Intervention to control group 7%; Control to intervention group 5%	Composite of death, recurrent MI, heart failure, or ischemia-driven revascularization (12 months)	10.0% vs. 21.2% (HR 0.45 [95% CI 0.24 to 0.84]; p = 0.009).
DANAMI-3-PRIMULTI13	2 centers, Denmark, 1:1 randomization, open-label	627	Complete revascularization guided by fractional flow reserve assessment (2 days after index procedure)	Infarct artery only PCI	Intervention to control group 6%; Control to intervention group 3%	Composite of death, non-fatal MI, or ischemia-driven revascularization of lesions in non-infarct arteries (1 year)	13% vs. 22% (HR 0.56 [95% CI 0.38-0.83]; p = 0.004)

The focused update does not, however, give a recommendation on when to perform PCI of the non-infract artery. The COMPLETE trial will evaluate the strategy of culprit lesion only revascularization versus complete revascularization using a staged PCI approach (within 45 days of the index procedure).

Aspiration Thrombectomy

Routine manual aspiration thrombectomy was common practice to prevent "no reflow" or "slow flow" in patients with STEMI and angiographic evidence of intracoronary thrombus and given a Class IIa (LOE B) recommendation in the prior guidelines. This recommendation was largely driven by the single-center Thrombus Aspiration During Percutaneous Coronary Intervention in Acute Myocardial Infarction (TAPAS) trial, which demonstrated a significant improvement in myocardial blush grade and a greater degree of resolution in ST-segment changes in patients randomized to aspiration thrombectomy versus direct stent technique (Table 2).¹⁴ This early benefit translated to lower rates of major adverse cardiac events and cardiac mortality at one-year follow-up, although the study was not powered for mortality and may simply have been a play of chance.¹⁵ The subsequent Thrombectomy With Export Catheter in Infarct-Related Artery During Primary Percutaneous Coronary Intervention (EXPIRA) trial also demonstrated improvement in myocardial blush grade and rate of ST-segment resolution.¹⁶

Table 2: Randomized Trials of Routine Aspiration Thrombectomy During Primary PCI in Patients With STEMI

Trial	Trial Design	Population	Intervention	Control	Crossover	Primary Endpoint	Results (Intervention vs. Control)
TAPAS14	Single-center, Netherlands, 1:1 randomization, open-label with blinded adjudication of endpoints	1,071	Routine aspiration thrombectomy	PCI alone	Intervention to control group 10%; Control to intervention group 1%	Myocardial blush grade of 0 or 1	17.1% vs 26.3%, p<0.001
INFUSE-AMI17	Multicenter, 6 countries, 2 × 2 factorial design, 1:1 randomization, open-label	452	Intracoronary abciximab and/or aspiration thrombectomy	PCI alone	1.7% for abciximab and 2.6% for aspiration	Infarct size (percentage of total left ventricular mass) using cardiac MRI (30 days)	1) Abciximab (median [IQR]): 15.1% [6.8%-22.7%] vs 17.9% [10.3%-25.4%]; p=0.03 2) Aspiration (median [IQR]): 17.0% [9.0%-22.8%] vs 17.3% [7.1%-25.5%]; p=0.51
TASTE18	Multicenter, Sweden, 1:1 randomization, open-label with registry-based follow-up	7,244	Routine aspiration thrombectomy	PCI alone	Intervention to control group 6%; Control to intervention group 5%	Death (30 days)	2.8% vs 3.0% (HR 0.94 [95% CI 0.72 to 1.22; p=0.63).
TOTAL20	Multicenter, 20 countries, 1:1 randomization, open-label with blinded adjudication of endpoints	10,732	Routine aspiration thrombectomy	PCI alone	Intervention to control group 4.6%; Control to intervention group 1.4%. Bailout thrombectomy 7.1%	Composite of cardiac death, recurrent MI, cardiogenic shock, or NYHA class IV heart failure (180 days)	6.9% vs 7.0% (HR 0.99 [95% CI 0.85 to 1.15; p=0.86).

More recent, larger trials have demonstrated contrary results (Table 2).^17-19 The Infuse–Acute Myocardial Infarction (INFUSE-AMI) study demonstrated no difference in infarct size at 30 days as measured by cardiac magnetic resonance imaging with versus without routine aspiration thrombectomy.¹⁷ However, this study was performed in the setting of a 2x2 design, and the additional examination of with versus without intracoronary abciximab pooled across strata of thrombus aspiration was designated as the study's primary endpoint. The comparison between aspiration thrombectomy and no thrombectomy pooled across strata of intracoronary abciximab was a secondary endpoint, and although median infarct size was lowest in the intracoronary abciximab plus thrombectomy group, there was no significant interaction between the two randomization groups. The subsequent Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia (TASTE) trial demonstrated no difference in all-cause mortality at 30 days and one year.^18-19 However, this study used the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) to evaluate the endpoints rather than central adjudication. The most recent and largest study to evaluate aspiration thrombectomy in the setting of primary PCI was the Total Occlusion Trial with Angioplasty by using Laser guidewire (TOTAL) trial.²⁰ The primary composite outcome of cardiovascular death, recurrent MI, cardiogenic shock, and New York Heart Association Class IV heart failure within 180 days was not different between patients randomized to aspiration thrombectomy versus PCI alone. The key safety outcome of stroke within 30 days, on the other hand, occurred more often in the thrombectomy group, and one-year follow-up showed similar results.²¹

Based on these studies, the recommendation to perform routine aspiration thrombectomy was appropriately changed from a Class IIA to Class III (LOE A) recommendation. However, the guidelines do still allow a provision to perform bailout thrombectomy in cases in which reperfusion is not successfully established (Class IIB, LOE C).

Radial Access

While this update to the guidelines does an excellent job incorporating new data related to the issues of multivessel PCI and aspiration thrombectomy in the setting of STEMI, it does not address the growing body of evidence for radial artery access in this population.

The RadIal Vs femorAL access for coronary intervention (RIVAL) study demonstrated that radial artery access for PCI in patients with acute coronary syndrome (ACS) was equally as safe and effective as femoral artery access with respect to the primary composite outcome of death, MI, stroke, and non-coronary artery bypass graft (CABG)-related bleeding at 30 days.²² In subgroup analysis, the study demonstrated a significant benefit of radial access in high-volume radial centers and patients with STEMI. There was also a lower rate of vascular complications. A subsequent analysis of the RIVAL data more clearly defined the benefit of radial access in STEMI patients.²³ This analysis not only demonstrated a significant benefit associated with radial access with respect to the primary outcome but also the secondary outcomes of death, MI, and stroke, as well as all-cause mortality. The authors concluded that radial access may be preferred in STEMI patients when the operator has considerable radial experience. The Radial Versus Femoral Randomized Investigation in ST Elevation Acute Coronary Syndrome (RIFLE-STEACS) study focused on radial versus femoral artery access for primary PCI performed by high-volume radial operators in STEMI patients and demonstrated significant reductions in the primary composite outcome of cardiovascular death, recurrent MI, stroke, target lesion revascularization, and non-CABG bleeding.²⁴ The secondary endpoint of cardiovascular death was also less common in the radial versus the femoral group (5.2% vs. 9.2%, p = 0.02), as was non-CABG bleeding (7.8% vs. 12.2%, p = 0.026). There was no significant difference in recurrent MI, stroke, target lesion revascularization, thrombolysis in MI major bleeding, or fatal bleeding (Table 3).

Table 3: Randomized Trials of Radial vs. Femoral Artery Access in Patients With ACS

Trial	Trial Design	Population	Intervention	Control	Crossover	Primary Endpoint	Results (Intervention vs. Control)
RIVAL22	Multicenter, 32 countries, 1:1 randomization, open label	7,021 ACS	Radial access	Femoral access	7.6% (radial) vs. 2.0% (femoral)	Composite of death, MI, stroke, or non-CABG bleeding (30 days)	3.7% vs. 4.0%, p = 0.50
RIVAL (STEMI subgroup analysis)23	Multicenter, 32 countries, 1:1 randomization, open label	1,958 STEMI	Radial access	Femoral access	Data not available	Composite of death, MI, stroke, or non-CABG bleeding (30 days)	3.1% vs. 5.2%, p = 0.026
RIFLE-STEACS24	Multicenter, European centers, 1:1 randomization, open label	1,001 STEMI	Radial access	Femoral access	6% (radial) vs. 1% (femoral)	Composite of cardiac death, recurrent MI, stroke, TLR, or non-CABG bleeding (30 days)	13.6% vs. 21.0%, p = 0.003
MATRIX26	Multicenter, European centers, 1:1 randomization, open label	8,404 ACS	Radial access	Femoral access	Data not available	Co-primary composite endpoints of 1) death, MI, or stroke and 2) death, MI, stroke, or BARC non-CABG major bleed (30 days)	1) 8.8% vs. 10.3%, p = 0.0307; 2) 9.8% vs. 11.7%, p = 0.0092 (pre-specified significance level of 0.025)

Based on these data, the 2014 European Society of Cardiology and the European Association for Cardio-Thoracic Surgery guidelines recommended that radial artery access be preferred over femoral artery access for PCI, especially in patients with ACS, provided that the PCI is performed by an experienced radial operator (Class IIa, LOE A).²⁵ Since then, the Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX (MATRIX) trial demonstrated a significant reduction in net adverse clinical events, defined as death, MI, stroke or BARC major bleeding not related to CABG, with radial versus femoral artery access in patients with ACS (Table 3).²⁶ This difference in adverse outcomes was driven by bleeding (1.6% vs. 2.3%, p = 0.013), though all-cause mortality was also numerically lower in the radial artery group (1.6% vs. 2.2%, p = 0.045). There was not, however, a statistical difference in the second co-primary outcome of major cardiovascular events (death, MI, or stroke). The most recent 2015 European Society of Cardiology guidelines for the management of ACS in patients presenting without persistent ST-segment elevation took this additional data into consideration and changed the recommendation to Class I (LOE A) for use of radial artery as the preferred method of access in patients with ACS.²⁷

In conclusion, while the most recent update on the ACC/AHA/SCAI guidelines for primary PCI in STEMI is an excellent resource for the new data on multivessel PCI and routine aspiration thrombectomy, I believe that the evidence supports an additional recommendation for radial artery access in STEMI patients when performed by experienced operators to improve rates of bleeding, vascular complications, and possibly mortality.

References

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22. Jolly SS, Yusuf S, Cairns J, et al. Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL): a randomized, parallel group, multicentre trial. Lancet 2011;377:1409-20.
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Keywords: Acute Coronary Syndrome, American Heart Association, Antibodies, Monoclonal, Constriction, Pathologic, Control Groups, Coronary Angiography, Coronary Artery Bypass, Coronary Artery Disease, Decision Making, Femoral Artery, Follow-Up Studies, Health Personnel, Heart Failure, Immunoglobulin Fab Fragments, Magnetic Resonance Imaging, Myocardial Infarction, Patient Care, Percutaneous Coronary Intervention, Prospective Studies, Radial Artery, Random Allocation, Randomized Controlled Trials as Topic, Registries, Retrospective Studies, Shock, Cardiogenic, Single-Blind Method, Stents, Stroke, Thoracic Surgery, Thrombectomy, Thrombosis, Angiography

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