An Analysis of the 2015 ACC/AHA/SCAI Focused Update on Primary PCI for Patients With STEMI

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)

CI = confidence interval; HR = hazard ratio; MI = myocardial infarction; PCI = percutaneous coronary intervention; STEMI = ST-elevation myocardial infarction.

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).

CI = confidence interval; HR = hazard ratio; IQR = interquartile range; MI = myocardial infarction; MRI = magnetic resonance imaging; NYHA = New York Heart Association; PCI = percutaneous coronary intervention; STEMI = ST-elevation myocardial infarction.

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)

ACS = acute coronary syndrome; BARC = bleeding academic research consortium; CABG = coronary artery bypass graft; MI = myocardial infarction; TLR = target lesion revascularization; STEMI = ST-elevation myocardial infarction.

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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  13. Engstrøm T, Kelbæk H, Helqvist S, et al. 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. Lancet 2015;386:665–71.
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  20. Jolly SS, Cairns JA, Yusuf S, et al. Randomized trial of primary PCI with or without routine manual thrombectomy. N Engl J Med 2015;372:1389-98.
  21. Jolly SS, Cairns JA, Yusuf S, et al. Outcomes after thrombus aspiration for ST elevation myocardial infarction: 1-year follow-up of the prospective randomized TOTAL trial. Lancet 2015 Oct 12. [Epub ahead of print]
  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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  24. Romagnoli E, Biondi-Zoccai G, Sciahbasi A, et al. Radial versus femoral randomized investigation in ST elevation acute coronary syndromes: the RIFLE STEACS study. J Am Coll Cardiol 2012;60:2481-9.
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  26. Valgimigli M, Gagnor A, Calabro P, et al. Radial versus femoral access in patients with acute coronary syndromes undergoing invasive management: a randomized multicentre trial. Lancet 2015;385:2465-76.
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Clinical Topics: Acute Coronary Syndromes, Arrhythmias and Clinical EP, Cardiac Surgery, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Aortic Surgery, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Novel Agents, Acute Heart Failure, Interventions and ACS, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Magnetic Resonance Imaging, Nuclear Imaging

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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