J Thromb Thrombolysis DOI 10.1007/s11239-014-1133-y
Comparison of radial to femoral PCI in acute myocardial infarction and cardiogenic shock: a systematic review Sumeet Gandhi • Ron Kakar Christopher B. Overgaard
•
Ó Springer Science+Business Media New York 2014
Abstract In randomized control trials and meta-analyses in patients with acute MI undergoing PCI, the radial artery (RA) approach compared to the femoral artery (FA) approach has shown to safely reduce access site related bleeding, length of hospitalization, and major adverse cardiac event (MACE) rates. However, these studies have excluded patients with cardiogenic shock. A systematic search was conducted to retrieve studies that investigated the safety of RA to FA PCI in patients with AMI and cardiogenic shock. Primary outcomes of interest was the pooled relative risk ratio (RR) of access site related bleeding. Secondary outcomes included (i) 30-day all cause mortality, (ii) major bleeding, (iii) final TIMI 3 flow, (iv) fluoroscopy time, and (v) amount of contrast volume administered. 6 observational studies with 7,753 patients met inclusion; 5,347 (69 %) with STEMI, 2,406 (31 %) with non-STEMI. In comparison of RA to FA PCI, there was less access site related bleeding (relative risk (RR) 0.11, p = 0.001), less 30-day mortality (RR 0.65, p = 0.0 \ 0.001), and less major bleeding (RR of 0.46 p \ 0.0001). There was no significant difference in final TIMI 3 flow
S. Gandhi (&) Division of Cardiology, McMaster University, Hamilton, ON, Canada e-mail: [email protected] S. Gandhi 6 Eaton North Room 232, 200 Elizabeth Street, Toronto, ON M5G 2C4, Canada R. Kakar Royal College of Surgeons in Ireland, Dublin, Ireland C. B. Overgaard Peter Munk Cardiac Centre, University Health Network, University of Toronto, Toronto, ON, Canada
(p = 0.27), fluoroscopy time (p = 0.95), and contrast volume administered (p = 0.59). In conclution, despite its limitations, our analysis demonstrates an association towards lower adverse events in the RA PCI group. Although we believe that the choice of access site in a high-risk setting should be at the operator discretion, if technically feasible, the RA appears to be a reasonable vascular access approach in high-risk patients in cardiogenic shock. Keywords Radial Femoral Shock Bleeding PCI Cardiogenic shock
Introduction The incidence of cardiogenic shock in acute ST-elevation myocardial infarction (STEMI) is estimated between 5–10 %, with overall high mortality [1]. The SHOCK trial demonstrated that in patients with STEMI and cardiogenic shock, emergent revascularization reduces long-term mortality [2]. Despite advances in antiplatelet and antithrombotic therapies in acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI), access site related bleeding and complications remains a significant contributor to patient morbidity and mortality. In randomized control trials and meta-analyses in patients with acute MI undergoing PCI, the radial artery (RA) approach compared to the femoral artery (FA) approach has shown to safely reduce access site related bleeding, length of hospitalization, and major adverse cardiac event (MACE) rates [3–6]. However, these studies have excluded patients with cardiogenic shock. We performed a systematic review and meta-analysis of observational studies of patients with AMI and cardiogenic
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shock. Our study objectives were to compare clinical outcomes and procedure characteristics in shock patients that underwent PCI via the RA versus FA approach.
Methods Study selection This meta-analysis was performed in accordance with the PRISMA (Preferred Reporting Items for Systemic Reviews and Meta-Analyses) checklist [7]. A systematic search was conducted to retrieve studies that investigated the safety of RA to FA PCI in patients with AMI and cardiogenic shock. We identified potential English-language sources from the Pubmed, Medline, EMBASE, and Cochrane databases from 1950 to June 2014. Keywords used were (radial, femoral, transradial, transfemoral) and [AMI, acute coronary syndrome (ACS), STEMI, non-STEMI] and (shock, cardiogenic shock). In addition, reference lists of any studies meeting inclusion criteria were reviewed to identify additional relevant publications by manual search. Electronic search of abstracts available online were also reviewed from the annual congresses of the Canadian Cardiovascular Congress, European Society of Cardiology, American College of Cardiology, and the American Heart Association. Inclusion/exclusion criteria Studies were included if they met the following criteria: (i) subjects included patients with STEMI undergoing primary PCI or non-STEMI undergoing emergent PCI, (ii) subjects included patients with cardiogenic shock defined as systolic blood pressure B90 mmHg for [30 min or vasopressors/inotropes required to maintain systolic blood pressure [90 mmHg; clinical signs of hypoperfusion (coldness and/or pallor in the extremities, oliguria, decreased level of consciousness), (iii) the choice of RA or FA access site was chosen by the operator, and (iv) published in the English language. Eligibility assessment and data extraction were carried out independently by two investigators (SG and RK) with discrepancies resolved by consensus. Study outcomes Primary outcomes of interest was the pooled relative risk ratio (RR) of access site related bleeding. Secondary outcomes included (i) 30-day all cause mortality, (ii) major bleeding, (iii) final TIMI 3 flow, (iv) fluoroscopy time, and (v) amount of contrast volume administered.
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Study quality and data extraction Quality assessment was carried out independently by two investigators (SG and RK) using the Newcastle–Ottawa quality assessment scale. We assessed eligibility by three criteria: (1) the selection of the study groups (0–4 points), (2) the comparability of the groups (0–2 points), and (3) the ascertainment of either the exposure or outcome of interest (0–3 points), with a total score of 9. A score C5 was adequate for inclusion in this meta-analysis. Discrepancies in interpretation of data and inclusion of studies were resolved by consensus. Statistical analysis Meta-analysis was conducted by combining the risk ratios of individual studies into a pooled RR using a randomeffects model [8]. Relative risk ratios are reported with 95 % confidence intervals and a p value \0.05 was found to be statistically significant. We tested for heterogeneity using the v2 test and the I2 test. The I2 test describes the percentage of variability in effect estimates that is due to heterogeneity rather than chance. A value of 25 % suggests low variability, 50 % suggests moderate variability, and 75 % suggests high variability between studies [9]. Mean difference was calculated for continuous variables using a random-effects model, reported with 95 % confidence intervals. Funnel plots were constructed to assess for publication bias. Analyses were performed with RevMan 5.1 [Review Manager (RevMan) (Computer program) Version 5.1. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2011].
Results Search results Figure 1 outlines the search strategy. Our search strategy yielded 251 studies, of which 238 were excluded on review of the title and abstract. A further 7 studies [3, 10] were excluded after careful review of the full text. Where only partial information on the outcomes of interest was reported, the authors were contacted and asked to provide additional information. The RADIAL PUMP UP registry (Radial versus Femoral Approach PCI in Patients with IABP support) is a retrospective analysis of 321 consecutive patients receiving intra-aortic balloon pump support during RA or FA PCI [15]. 69 % of patients included in this study had a diagnosis of cardiogenic shock. The RIFLE-STEACS trial (Radial Versus Femoral Randomized Investigation in ST-Elevation Acute Coronary Study) was a
Comparison of radial to femoral PCI
platelet transfusion, or an arterial access site complication requiring surgery [21], TIMI major bleeding [16], intracranial, respiratory, gastrointestinal, genitourinary bleeding that was life threatening or required blood transfusion [18], bleeding requiring transfusion [19], and bleeding requiring transfusion, delaying hospital discharging or resulting in death [20]. We assessed the quality of included studies using the Newcastle–Ottawa quality assessment scales (Table 1). A score C5 was considered adequate quality for inclusion. Overall, the quality of included studies was high. Three studies scored 8 points [16, 20, 21], two studies score 7 points [18, 19], and one study scored 6 points [17]. There was no publication bias detected in comparing access site related bleeding, 30-day mortality, major bleeding, and final TIMI 3 flow between both groups based on the symmetry of the funnel plots. Fig. 1 Study flow diagram: flow chart showing literature search strategy, and selection process for inclusion in systematic review
Results randomized comparison of RA to FA PCI in patients admitted with STEMI [3]. Unfortunately, the authors of these studies could not provide specific outcomes and characteristics exclusively to patients with cardiogenic shock, and therefore were excluded from our analysis. Overall 6 studies [16–21] were eligible for inclusion in the systematic review. Among these, 4 studies allowed calculation of RR for access site related bleeding, 6 studies allowed calculation of RR for 30-day mortality, 5 studies allow for calculation of major bleeding, 4 studies allowed for calculation of final TIMI 3 flow, 3 studies allowed for calculation of weighted mean difference (WMD) for fluoroscopy time, and 5 studies allowed for calculation of WMD for amount of contrast volume administered.
Access site related bleeding Four observational studies [16, 18–20] that assessed access site related bleeding met inclusion criteria, with 286 patients who underwent RA PCI, and 199 patients who underwent FA PCI (Fig. 2). Overall, access site related bleeding occurred in 16 of the 485 patients (3.3 %); 1 of the 286 in the RA PCI group (0.3 %), and 15 of the 199 in the FA PCI group (7.5 %). There was a significant pooled RR of 0.11 [(95 % CI 0.03–0.41), p = 0.001, I2 = 0 %]. Sensitivity analysis demonstrated similar results when each individualized study was removed. 30-day all cause mortality
Characteristics of included studies Characteristics of all eligible studies, and patient and procedure characteristics are outlined in Table 1 and Table 2. 7,753 patients met inclusion; 5,347 (69 %) with STEMI, 2,406 (31 %) with non-STEMI. The mean age of subjects was 67.8 years, 25 % were female. Study specific outcomes are outlined in Table 3. All studies included patients with a diagnosis of STEMI, and three studies [18, 20, 21] included patients with non-STEMI. Two studies [16, 17] defined access site related bleeding as TIMI major bleeding [22], one study [18] defined it as severe life threatening bleeding requiring transfusion, and one study [19] defined it as bleeding requiring transfusion, one study defined it as bleeding requiring transfusion, delaying hospital discharge, or resulting in death. Major bleeding was defined as gastrointestinal bleed, intra-cerebral bleed, retroperitoneal hematoma, blood or
Six observational studies [16–21] that assessed 30-day all cause mortality met inclusion criteria, with 2,185 patients having underwent RA PCI, and 5,568 patients who underwent FA PCI (Fig. 3). Overall, 30-day all cause mortality occurred in 2,512 of the 7,753 patients (32.4 %); 471 of the 2,185 in the RA PCI group (21.6 %), and 2,041 of the 5,568 in the FA PCI group (36.7 %). There was a significant pooled RR of 0.65 [(95 % CI 0.52–0.80), p \ 0.0001, I2 = 56 %]. Sensitivity analysis demonstrated similar results when each individualized study was removed. Major bleeding Five observational studies [16, 18–21] that assessed major bleeding met inclusion criteria, with 2,163 patients having underwent RA PCI, and 5,553 patients who underwent FA
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S. Gandhi et al. Table 1 Study characteristics Study, year
Study design
Inclusion
Quality assessmenta
Mamas, 2014
Retrospective analysis of prospectively collected data, January 2006–December 2012, United Kingdom
1. STEMI or non-STEMI undergoing PCI
8
Iga, 2014
Retrospective study, 2006–20012, Japan
2. Cardiogenic Shock: SBP \100 mmHg with pulse [100 bpm combined with signs of peripheral hypoperfusion (cold, clammy, pallor, etc.), or a requirement for inotropes or intraaortic balloon pump to support the circulation and maintain a blood pressure 1. STEMI undergoing primary PCI
8
2. Non-STEMI undergoing emergent PCI 3. Cardiogenic shock: SBP persistently B90 mmHg in the presence of systemic hypoperfusion and adequate left ventricular filling pressure Bernat, 2013
RodriguezLeor, 2013
Retrospective analysis of prospectively collected data, 2006–2010, Czech Republic
1. STEMI undergoing primary PCI
Prospective study, enrollment February 2007– January 2012, Spain
1. STEMI undergoing primary PCI or rescue angioplasty
8
2. Cardiogenic shock: SBP B90 mmHg for at least 30 min, heart rate C60 bpm, signs of systemic hypoperfusion or required inotropes to maintain a SBP C90 mmHg 7
2. Non-STEMI 3. Cardiogenic shock: SBP \90 mmHg or the need for or vasopressors to maintain SBP [90 mmHg combined with signs of peripheral hypoperfusion (coldness and/or pallor in the extremities, oliguria, or a decrease in level of consciousness)
Fujii, 2013
Retrospective study, 2005–2011, Japan
1. STEMI
7
2. Cardiogenic shock: SBP \90 mmHg on arrival Fernandez Diaz, 2011 (abstract)
a
Retrospective study, 2005–2010
1. Acute myocardial infarction (Kilip class IV)
6
2. Cardiogenic shock: SBP \90 mmHg for 30 min or vasopressors required to maintain SBP [90 mmHg, evidence of end organ hypoperfusion (urine output \30 mL or cold/ diaphoretic extremities, or altered mental status) and evidence of elevated left ventricle filling pressures (pulmonary congestion on examination or chest X-ray)
Newcastle–Ottawa quality assessment scale
bpm beats per minute, PCI percutaneous coronary intervention, SBP systolic blood pressure, STEMI ST elevation myocardial infarction
PCI (Fig. 4). Overall, major bleeding occurred in 258 of the 7,716 patients (3.3 %); 53 of the 2,163 in the RA PCI group (2.5 %), and 205 of the 5,553 in the FA PCI group (3.7 %). There was a significant pooled RR of 0.46 [(95 % CI 0.34–0.62), p \ 0.0001, I2 = 0 %]. Sensitivity analysis demonstrated similar results when each individualized study was removed. Final TIMI 3 flow Four observational studies [16, 18–20] that assessed final TIMI 3 flow met inclusion criteria with 286 patients who underwent RA PCI, and 199 patients that underwent FA PCI (Fig. 5). Overall, final TIMI 3 flow was achieved in 373 of the 485 patients (77 %); 230 of the 286 in the RA PCI group (80.4 %), and 143 of the 199 in the FA PCI group (71.9 %). There was a non-significant pooled RR of
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1.08 [(95 % CI 0.94–1.24), p = 0.27, I2 = 58 %] demonstrating no significant difference in final TIMI 3 flow between groups. Fluoroscopy time Three observational studies [16–18] that assessed fluoroscopy time met inclusion criteria with 210 patients who underwent RA PCI, and 146 patients who underwent FA PCI (Fig. 6). WMD in fluoroscopy time was 0.12 min (p = 0.95) demonstrating no significant difference in total fluoroscopy time between groups. Amount of contrast volume administered Five observational studies [16–20] that assessed amount of contrast volume administered met inclusion criteria with
Comparison of radial to femoral PCI Table 2 Patient and procedure characteristics Study
Bernat, 2013
RodriguezLeor, 2013
Fujii, 2013
Fernandez Diaz, 2011
Iga, 2014
Mamas, 2014
RA
FA
RA
FA
RA
FA
RA
FA
RA
FA
RA
FA
Subjects
108
90
90
42
Mean age (years)
69
64
65
68
38
43
22
5
60
25
1,877
5,354
71
72.7
70.36
70.35
68.2
70.3
67.2
Female (%)
29
29
11
26
18
39
31
29
17
28
74
Smoking (%)
38
44
36.2
26.2
65.8
51.2
36 %
35 %
58.3
40
30
69 31
Diabetes (%)
13
26
66.2
45.2
63.2
48.8
–
–
31.7
44
17
21
Dyslipidemia (%) Hypertension (%)
38 47
46 54
51.2 57.5
61.9 57.1
52.6 84.2
55.8 90.7
– –
– –
51.7 53.3
32 64
42 44
42 47
Previous MI (%)
14
18
27.5
45.2
7.9
18.6
–
–
10
8
21
25
Crossover (%)
n/a
n/a
7.5
2.4
n/a
n/a
5
0
1.7
0
–
–
IABP (%)
36
55
37.5
52.4
34.2
58.1
40.9
52.9
61.7
84
29
38
Mechanical ventilation before PCI (%)
42
66
41.2
66.7
–
–
–
–
–
–
19
34
Cardiac arrest (%)
16 %
15 %
38.1
32.5
42.1
51.2
–
–
31.7
28
–
–
Mean SBP on admission (mmHg)
n/a
n/a
69
79
72.7 (±34.5) 72.7
–
–
46.2
48.2
–
–
GP IIb/IIIa inhibitor (%)
41
40
56.7
35.7
83.1 (±45.4) 83
–
–
0
0
56
58
Procedure duration (min)
46
47
–
–
126.6
123.7
–
–
–
–
–
–
Circumflex
12
12
–
–
–
–
–
–
5
8
14
14
LAD
57
56
–
–
–
–
–
–
38.3
40
54
52
RCA
29
28
–
–
–
–
–
–
48.3
40
27
27
Left main
1.9
3.4
–
–
–
–
–
–
6.7
12
4
5
Initial TIMI 0 flow (%)
61
65
–
–
76.3
55.8
–
–
63.3
76
–
–
Culprit lesion (%)
– Data not available FA femoral artery group, IABP intra-aortic balloon pump, LAD left anterior descending, RA radial artery group, RCA right coronary artery, SBP systolic blood pressure
308 patients that underwent RA PCI, and 214 patients that underwent FA PCI (Fig. 7). WMD in amount of contrast volume administered was 5.33 mL (p = 0.59) demonstrating no significant difference in total amount of contrast volume administered between groups.
Discussion The results of this systematic review of observational studies show an overall high 30-day all cause mortality in patients with AMI and cardiogenic shock. There was lower observed access site related bleeding, major bleeding, and 30-day all cause mortality in the RA PCI group, with no significant difference in final TIMI 3 flow, fluoroscopy time, and amount of contrast volume administered between both groups. Over the past decade, there has been an increase in uptake of RA approach PCI in high-risk patients, with gaining operator and centre wide experience. The superficial course of the RA allows for early recognition of access
site bleeding and easy compressibility with the ability to provide safe and rapid achievement of hemostasis [5]. In patients with ACS, procedural related bleeding has been independently associated with increased mortality with access site related bleeding as a large contributor [23]. For this reason, strategies have been adopted to decrease major bleeding through augmentation of peri-procedural antithrombotic agents as well as the transition to RA approach PCI. A large Canadian database study of 32,822 patients demonstrated in patients undergoing PCI, RA approach was independently associated with a significant reduction in transfusion rate, 30-day and one-year mortality [24]. The RIVAL (Radial vs. Femoral Access for Coronary Intervention) trial was a parallel group, multicenter, randomized trial which assigned 7,021 patients with ACS to undergo cardiac catheterization via the RA or FA approach [25]. In patients with STEMI, there was significant decrease in the primary composite outcome of death, MI, stroke, or noncoronary artery bypass graft (CABG) related bleeding in the RA PCI group (HR 0.60, p = 0.026). However, there was no major difference in access site related bleeding
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S. Gandhi et al. Table 3 Study outcomes Outcomes assessed: RA vs. FA PCI Mamas, 2014
30-day mortality Propensity score-matched cohort: 30-day mortality In-hospital MACCE Major bleeding
Independent predictors of mortality overall 24.7 vs. 39.8 % (p \ 0.001) 22.8 vs. 29.9 % (p \ 0.001) HR 0.64 (p \ 0.0001) 1.5 vs. 3.5 % (p \ 0.0001)
Radial PCI Glycoprotein IIb/IIIa inhibitor use Primary PCI Poor LV function Inotrope use
HR 0.56 (p \ 0.0001) HR 0.75 (p \ 0.0001) HR 1.11 (p \ 0.0001) HR 2.59 (p \ 0.0001) HR 1.55 (p \ 0.0001)
Iga, 2014
PCI access-site related bleeding Non-PCI access site related bleeding 30-day mortality 30-day stroke Hospitalization (days)
0 vs 12 % (p \ 0.05) 6.7 vs. 16 % (p = 0.23)
n/a
n/a
Radial artery approach
HR 0.65 (p = 0.41)
26.7 vs. 40 % (p = 0.30) 0 vs. 8 % (p = 0.08) 32.5 vs. 43.1 (p = 0.40)
Bernat, 2013
Non-CABG major bleeding Access site-related bleeding Non-access site bleeding 30-day mortality 1-year mortality
13 % vs 25 % (p = 0.42) 0.9 vs. 9.0 % (p = 0.12) 4.6 vs. 5.6 % (p = 0.76) 41 vs. 53 % (p = 0.11)
GP IIb-IIIa receptor inhibitors Baseline creatinine [110 umol/L Initial glycemia [200 mg/ dL Age [65 years
In-hospital mortality Access site complications Requiring transfusion MACE
32.5 vs. 64.3 % (p = 0.001)
C75 years
2.5 vs. 11.9 % (p = 0.03)
Use of IABP
54.1 vs. 42.8 % (p = 0.001)
HR 3.34 (p \ 0.0001) HR 2.02 (p = 0.0008) HR 1.80 (p = 0.006)
44 vs. 64 % (p = 0.0044) Rodriguez-Leor, 2013
HR 0.63 (p = 0.032)
Diuretics before PCI Radial artery PCI Procedure success
OR 3.47 (p = 0.007) OR 3.01 (p = 0.02) OR 2.10 (p = 0,05) OR 0.39 (p \ 0.0001) OR 0.07 (p \ 0.0001)
Fujii, 2013
30-day mortality Stent thrombosis Stroke Hospitalization (days)
28.9 vs. 25.6 % (p \ 0.001)
n/a
n/a
n/a
n/a
0 vs. 2.3 % (p = 0.0495) 2.6 vs. 4.7 % (p = 0.0478) 21.1 vs. 32.7 (p = 0.1253)
Fernandez Diaz, 2011 [abstract]
All cause mortality at 30 days LVEF at discharge
61.9 vs. 79.5 % (p = ns) 29.1 vs. 27.8 % (p = ns)
n/a Not available CABG coronary artery bypass graft, FA femoral artery, RA radial artery, IABP intra-aortic balloon pump, MACE major adverse cardiac event, OR odds ratio; PCI percutaneous coronary intervention
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Comparison of radial to femoral PCI
Fig. 2 Access site related bleeding: forrest plot of pooled data from studies showing the relative risk ratio of access site related bleeding in the RA group compared to the FA group
Fig. 3 30-day all cause mortality: forrest plot of pooled data from studies showing the relative risk ratio of 30-day all cause mortality in the RA group compared to the FA group
Fig. 4 Major Bleeding: forrest plot of pooled data from studies showing relative risk ratio of major bleeding in the RA group compared to the FA group
found between the RA and FA group (0.1 vs. 0.2 %, p = 0.604). The RIFLE-STEACS was a multicenter, randomized parallel-group study that assigned 1,001 patients with STEMI to undergo primary/rescue PCI via the RA or FA approach [3]. The primary composite end point of cardiac death, stroke, MI, target lesion revascularization, and bleeding at 30 days occurred less frequently in the RA group (13.6 vs. 21.0 %, p = 0.003). There was also a significant reduction in access site related bleeding in the RA
PCI group (2.6 vs. 6.8 %, p = 0.002). The STEMIRADIAL Trial was a randomized, multicenter trial of 707 patients with STEMI, assigned to the RA or FA approach PCI. The primary composite endpoint of 30-day major bleeding and MACE was lower in the RA PCI group (11.0 vs. 4.6 %, p = 0.0028) with a reduction in 30-day major bleeding (7.2 vs. 1.4 %, p = 0.0001) [26]. These results were supported by a recent meta-analysis of 12 randomized controlled trials that showed RA approach PCI was
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Fig. 5 Final TIMI 3 flow: forrest plot of pooled data from studies showing no difference in TIMI 3 flow in the RA group compared to the FA group
Fig. 6 Fluoroscopy time (minutes): forrest plot of pooled data from studies showing no difference in fluoroscopy time in the RA group compared to the FA group
Fig. 7 Amount of contrast volume administered (mL): forrest plot of pooled data from studies showing no difference in amount of contrast volume administered in the RA group compared to the FA group
associated with decreased risk of mortality (OR 0.55, p \ 0.001) and access site related bleeding (OR 0.35, p \ 0.001) [5] in STEMI patients. There are several limitations to this analysis. Our analysis included observational studies with two retrospective studies, and therefore our results do not imply causation or a treatment effect. For the primary outcome measures of access site related bleeding and 30-day all cause mortality, only four and five studies were included respectively, limiting study power and the ability to detect statistically significant findings. The absence of a radial pulse in the FA PCI group may represent vasoconstriction and increased illness severity, and therefore these may be sicker patients at increased risk of bleeding complications and higher mortality. The results of our analysis does not account for IABP access, in which FA access is preferred
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or may require double FA access site puncture in the FA group, increasing the risk of access site related bleeding. Although the number of patients that crossed over from each group was low, our analysis cannot incorporate this variable. The pooled analysis cannot control for patient characteristics, clinical variables, procedural outcomes, and anticoagulant/antithrombotic therapy that may account for increased bleeding and mortality. The metaanalysis cannot attest to operator discretion and choice for FA approach PCI. Due to the limited data available, we cannot provide a more robust analysis with a variety of clinical endpoints such as door-to-balloon time, total procedure duration, length of hospitalization, stroke, and other further systemic complications. Individuals with acute myocardial infarction and cardiogenic shock represent the highest risk patients, which
Comparison of radial to femoral PCI
adds to the challenge of radial access. The radial artery is a small caliber vessel, prone to spasm, with further anatomical variance of the often torturous and calcified subclavian artery. In patients with cardiogenic shock, the lack or absence of a palpable pulse may be due to systemic vasoconstriction in which a delay in obtaining arterial access and subsequent revascularization and reperfusion may lead to poor outcomes. Furthermore, operators must also evaluate for preferred bilateral femoral artery access for advanced support devices and guiding catheter sheaths in critically ill patients. Current research has been focused on optimizing and improving radial access with vasodilator and spasmolytic agents, hydrophilic introducer sheaths, and ultrasound guided radial artery puncture. Our analysis is consistent with previous studies assessing outcomes comparing RA to FA PCI in high-risk STEMI patients. Future prospective studies with larger sample size are needed to validate these findings and assess the potential advantage of radial PCI in AMI and cardiogenic shock. A randomized comparison of access site in patients with cardiogenic shock may not be feasible due to issues of patient consent in this complex high acuity setting. Although we believe that the choice of access site in a high-risk setting should be at the operator discretion, if technically feasible, the RA appears to be a reasonable vascular access approach in high-risk patients in cardiogenic shock. Disclosures The authors do not believe that they have any conflicts of interest with regards to this research paper. This article represents original work and is not under consideration for publication elsewhere. All authors meet criteria for authorship.
References 1. Babaev A, Frederick PD, Pasta DJ, Every N, Sichrovsky T, Hochman JS (2005) Trends in management and outcomes of patients with acute myocardial infarction complicated by cardiogenic shock. JAMA 294(4):448–454 2. Hochman JS, Sleeper LA, Webb JG et al (1999) Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investigators. Should we emergently revascularize occluded coronaries for cardiogenic shock. N Engl J Med 341(9):625–634 3. Romagnoli E, Biondi-Zoccai G, Sciahbasi A et al (2012) Radial versus femoral randomized investigation in ST-segment elevation acute coronary syndrome: the RIFLE-STEACS (radial versus femoral randomized investigation in ST-Elevation Acute Coronary Syndrome) study. J Am Coll Cardiol 60(24):2481–2489 4. Jolly SS, Yusuf S, Cairns J et al (2011) Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL): a randomised, parallel group, multicentre trial. Lancet 377(9775):1409–1420 5. Karrowni W, Vyas A, Giacomino B et al (2013) Radial versus femoral access for primary percutaneous interventions in STsegment elevation myocardial infarction patients: a meta-analysis of randomized controlled trials. JACC Cardiovasc Interv 6(8):814–823
6. Vorobcsuk A, Konyi A, Aradi D et al (2009) Transradial versus transfemoral percutaneous coronary intervention in acute myocardial infarction systematic overview and meta-analysis. Am Heart J 158(5):814–821 7. Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6(7):e1000097 8. Riley RD, Higgins JP, Deeks JJ (2011) Interpretation of random effects meta-analyses. BMJ 342:d549 9. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560 10. Johnman C, Pell JP, Mackay DF et al (2012) Clinical outcomes following radial versus femoral artery access in primary or rescue percutaneous coronary intervention in Scotland: retrospective cohort study of 4534 patients. Heart 98(7):552–557 11. Cafri C, Zahger D, Merkin M, Weinstein JM, Kobal S, Ilia R (2013) Efficacy of the radial approach for the performance of primary PCI for STEMI. J Invasive Cardiol 25(3):150–153 12. Kedev S, Kalpak O, Antov S, Kostov J, Pejkov H, Spiroski I, Boshev M (2011) Single centre registry of trasradial versus transfeomral access for primary PCI. J Am Coll Cardiol 57(14s1):E1803 13. Marinucci L, Uguccioni L, Parisi R et al (2012) TCT-428 Radial access does not affect door to balloon time in patients undergoing primary PCI. J Am Coll Cardiol. doi:10.1016/j.jacc.2012.08.1013 14. Ratib K, Mamas M, Large A et al (2012) TCT-424 Trends in access site choice for PCI and influence on mortality—Observational data from the British Cardiovascular Intervention Society PCI database. J Am Coll Cardiol. doi:10.1016/j.jacc.2012.08. 453 15. Romagnoli E, De Vita M, Burzotta F et al (2013) Radial versus femoral approach comparison in percutaneous coronary intervention with intraaortic balloon pump support: the RADIAL PUMP UP registry. Am Heart J 166(6):1019–1026 16. Bernat I, Abdelaal E, Plourde G et al (2013) Early and late outcomes after primary percutaneous coronary intervention by radial or femoral approach in patients presenting in acute STelevation myocardial infarction and cardiogenic shock. Am Heart J 165(3):338–343 17. Diaz JF, Mitroi D, Ruigomez JG et al (2011) OP-020: safety and feasibility of radial approach for primary angioplasty in cardiogenic shock. Int J Cardiol 147:S43–S43 18. Rodriguez-Leor O, Fernandez-Nofrerias E, Carrillo X et al (2013) Transradial percutaneous coronary intervention in cardiogenic shock: a single-center experience. Am Heart J 165(3):280–285 19. Fujii T, Masuda N, Ijichi T et al (2014) Transradial intervention for patients with ST elevation myocardial infarction with or without cardiogenic shock. Catheter Cardiovasc Interv 83(1):E1– E7 20. Iga A, Wagatsuma K, Yamazaki J, Ikeda T (2014) Transradial versus transfemoral coronary intervention for acute myocardial infarction complicated by cardiogenic shock: is transradial coronary intervention suitable for emergency PCI in high-risk acute myocardial infarction? J invasive cardiol 26(5):196–202 21. Mamas MA, Anderson SG, Ratib K et al (2014) Arterial access site utilization in cardiogenic shock in the United Kingdom: is radial access feasible? Am heart j 167(6):900–908 e901 22. Mehran R, Rao SV, Bhatt DL et al (2011) Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation 123(23):2736–2747 23. Eikelboom JW, Mehta SR, Anand SS, Xie C, Fox KA, Yusuf S (2006) Adverse impact of bleeding on prognosis in patients with acute coronary syndromes. Circulation 114(8):774–782 24. Chase AJ, Fretz EB, Warburton WP et al (2008) Association of the arterial access site at angioplasty with transfusion and
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S. Gandhi et al. mortality: the M.O.R.T.A.L study (mortality benefit of reduced transfusion after percutaneous coronary intervention via the arm or leg). Heart 94(8):1019–1025 25. Mehta SR, Jolly SS, Cairns J et al (2012) Effects of radial versus femoral artery access in patients with acute coronary syndromes with or without ST-segment elevation. J Am Coll Cardiol 60(24):2490–2499
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26. Bernat I, Horak D, Stasek J et al (2014) ST elevation myocardial infarction treated by RADIAL or femoral approach in a multicenter randomized clinical trial : the STEMI-RADIAL Trial. J Am Coll Cardiol 63(10):964–972
Comparison of radial to femoral PCI in acute myocardial infarction and cardiogenic shock: a systematic review Sumeet Gandhi • Ron Kakar Christopher B. Overgaard
•
Ó Springer Science+Business Media New York 2014
Abstract In randomized control trials and meta-analyses in patients with acute MI undergoing PCI, the radial artery (RA) approach compared to the femoral artery (FA) approach has shown to safely reduce access site related bleeding, length of hospitalization, and major adverse cardiac event (MACE) rates. However, these studies have excluded patients with cardiogenic shock. A systematic search was conducted to retrieve studies that investigated the safety of RA to FA PCI in patients with AMI and cardiogenic shock. Primary outcomes of interest was the pooled relative risk ratio (RR) of access site related bleeding. Secondary outcomes included (i) 30-day all cause mortality, (ii) major bleeding, (iii) final TIMI 3 flow, (iv) fluoroscopy time, and (v) amount of contrast volume administered. 6 observational studies with 7,753 patients met inclusion; 5,347 (69 %) with STEMI, 2,406 (31 %) with non-STEMI. In comparison of RA to FA PCI, there was less access site related bleeding (relative risk (RR) 0.11, p = 0.001), less 30-day mortality (RR 0.65, p = 0.0 \ 0.001), and less major bleeding (RR of 0.46 p \ 0.0001). There was no significant difference in final TIMI 3 flow
S. Gandhi (&) Division of Cardiology, McMaster University, Hamilton, ON, Canada e-mail: [email protected] S. Gandhi 6 Eaton North Room 232, 200 Elizabeth Street, Toronto, ON M5G 2C4, Canada R. Kakar Royal College of Surgeons in Ireland, Dublin, Ireland C. B. Overgaard Peter Munk Cardiac Centre, University Health Network, University of Toronto, Toronto, ON, Canada
(p = 0.27), fluoroscopy time (p = 0.95), and contrast volume administered (p = 0.59). In conclution, despite its limitations, our analysis demonstrates an association towards lower adverse events in the RA PCI group. Although we believe that the choice of access site in a high-risk setting should be at the operator discretion, if technically feasible, the RA appears to be a reasonable vascular access approach in high-risk patients in cardiogenic shock. Keywords Radial Femoral Shock Bleeding PCI Cardiogenic shock
Introduction The incidence of cardiogenic shock in acute ST-elevation myocardial infarction (STEMI) is estimated between 5–10 %, with overall high mortality [1]. The SHOCK trial demonstrated that in patients with STEMI and cardiogenic shock, emergent revascularization reduces long-term mortality [2]. Despite advances in antiplatelet and antithrombotic therapies in acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI), access site related bleeding and complications remains a significant contributor to patient morbidity and mortality. In randomized control trials and meta-analyses in patients with acute MI undergoing PCI, the radial artery (RA) approach compared to the femoral artery (FA) approach has shown to safely reduce access site related bleeding, length of hospitalization, and major adverse cardiac event (MACE) rates [3–6]. However, these studies have excluded patients with cardiogenic shock. We performed a systematic review and meta-analysis of observational studies of patients with AMI and cardiogenic
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shock. Our study objectives were to compare clinical outcomes and procedure characteristics in shock patients that underwent PCI via the RA versus FA approach.
Methods Study selection This meta-analysis was performed in accordance with the PRISMA (Preferred Reporting Items for Systemic Reviews and Meta-Analyses) checklist [7]. A systematic search was conducted to retrieve studies that investigated the safety of RA to FA PCI in patients with AMI and cardiogenic shock. We identified potential English-language sources from the Pubmed, Medline, EMBASE, and Cochrane databases from 1950 to June 2014. Keywords used were (radial, femoral, transradial, transfemoral) and [AMI, acute coronary syndrome (ACS), STEMI, non-STEMI] and (shock, cardiogenic shock). In addition, reference lists of any studies meeting inclusion criteria were reviewed to identify additional relevant publications by manual search. Electronic search of abstracts available online were also reviewed from the annual congresses of the Canadian Cardiovascular Congress, European Society of Cardiology, American College of Cardiology, and the American Heart Association. Inclusion/exclusion criteria Studies were included if they met the following criteria: (i) subjects included patients with STEMI undergoing primary PCI or non-STEMI undergoing emergent PCI, (ii) subjects included patients with cardiogenic shock defined as systolic blood pressure B90 mmHg for [30 min or vasopressors/inotropes required to maintain systolic blood pressure [90 mmHg; clinical signs of hypoperfusion (coldness and/or pallor in the extremities, oliguria, decreased level of consciousness), (iii) the choice of RA or FA access site was chosen by the operator, and (iv) published in the English language. Eligibility assessment and data extraction were carried out independently by two investigators (SG and RK) with discrepancies resolved by consensus. Study outcomes Primary outcomes of interest was the pooled relative risk ratio (RR) of access site related bleeding. Secondary outcomes included (i) 30-day all cause mortality, (ii) major bleeding, (iii) final TIMI 3 flow, (iv) fluoroscopy time, and (v) amount of contrast volume administered.
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Study quality and data extraction Quality assessment was carried out independently by two investigators (SG and RK) using the Newcastle–Ottawa quality assessment scale. We assessed eligibility by three criteria: (1) the selection of the study groups (0–4 points), (2) the comparability of the groups (0–2 points), and (3) the ascertainment of either the exposure or outcome of interest (0–3 points), with a total score of 9. A score C5 was adequate for inclusion in this meta-analysis. Discrepancies in interpretation of data and inclusion of studies were resolved by consensus. Statistical analysis Meta-analysis was conducted by combining the risk ratios of individual studies into a pooled RR using a randomeffects model [8]. Relative risk ratios are reported with 95 % confidence intervals and a p value \0.05 was found to be statistically significant. We tested for heterogeneity using the v2 test and the I2 test. The I2 test describes the percentage of variability in effect estimates that is due to heterogeneity rather than chance. A value of 25 % suggests low variability, 50 % suggests moderate variability, and 75 % suggests high variability between studies [9]. Mean difference was calculated for continuous variables using a random-effects model, reported with 95 % confidence intervals. Funnel plots were constructed to assess for publication bias. Analyses were performed with RevMan 5.1 [Review Manager (RevMan) (Computer program) Version 5.1. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2011].
Results Search results Figure 1 outlines the search strategy. Our search strategy yielded 251 studies, of which 238 were excluded on review of the title and abstract. A further 7 studies [3, 10] were excluded after careful review of the full text. Where only partial information on the outcomes of interest was reported, the authors were contacted and asked to provide additional information. The RADIAL PUMP UP registry (Radial versus Femoral Approach PCI in Patients with IABP support) is a retrospective analysis of 321 consecutive patients receiving intra-aortic balloon pump support during RA or FA PCI [15]. 69 % of patients included in this study had a diagnosis of cardiogenic shock. The RIFLE-STEACS trial (Radial Versus Femoral Randomized Investigation in ST-Elevation Acute Coronary Study) was a
Comparison of radial to femoral PCI
platelet transfusion, or an arterial access site complication requiring surgery [21], TIMI major bleeding [16], intracranial, respiratory, gastrointestinal, genitourinary bleeding that was life threatening or required blood transfusion [18], bleeding requiring transfusion [19], and bleeding requiring transfusion, delaying hospital discharging or resulting in death [20]. We assessed the quality of included studies using the Newcastle–Ottawa quality assessment scales (Table 1). A score C5 was considered adequate quality for inclusion. Overall, the quality of included studies was high. Three studies scored 8 points [16, 20, 21], two studies score 7 points [18, 19], and one study scored 6 points [17]. There was no publication bias detected in comparing access site related bleeding, 30-day mortality, major bleeding, and final TIMI 3 flow between both groups based on the symmetry of the funnel plots. Fig. 1 Study flow diagram: flow chart showing literature search strategy, and selection process for inclusion in systematic review
Results randomized comparison of RA to FA PCI in patients admitted with STEMI [3]. Unfortunately, the authors of these studies could not provide specific outcomes and characteristics exclusively to patients with cardiogenic shock, and therefore were excluded from our analysis. Overall 6 studies [16–21] were eligible for inclusion in the systematic review. Among these, 4 studies allowed calculation of RR for access site related bleeding, 6 studies allowed calculation of RR for 30-day mortality, 5 studies allow for calculation of major bleeding, 4 studies allowed for calculation of final TIMI 3 flow, 3 studies allowed for calculation of weighted mean difference (WMD) for fluoroscopy time, and 5 studies allowed for calculation of WMD for amount of contrast volume administered.
Access site related bleeding Four observational studies [16, 18–20] that assessed access site related bleeding met inclusion criteria, with 286 patients who underwent RA PCI, and 199 patients who underwent FA PCI (Fig. 2). Overall, access site related bleeding occurred in 16 of the 485 patients (3.3 %); 1 of the 286 in the RA PCI group (0.3 %), and 15 of the 199 in the FA PCI group (7.5 %). There was a significant pooled RR of 0.11 [(95 % CI 0.03–0.41), p = 0.001, I2 = 0 %]. Sensitivity analysis demonstrated similar results when each individualized study was removed. 30-day all cause mortality
Characteristics of included studies Characteristics of all eligible studies, and patient and procedure characteristics are outlined in Table 1 and Table 2. 7,753 patients met inclusion; 5,347 (69 %) with STEMI, 2,406 (31 %) with non-STEMI. The mean age of subjects was 67.8 years, 25 % were female. Study specific outcomes are outlined in Table 3. All studies included patients with a diagnosis of STEMI, and three studies [18, 20, 21] included patients with non-STEMI. Two studies [16, 17] defined access site related bleeding as TIMI major bleeding [22], one study [18] defined it as severe life threatening bleeding requiring transfusion, and one study [19] defined it as bleeding requiring transfusion, one study defined it as bleeding requiring transfusion, delaying hospital discharge, or resulting in death. Major bleeding was defined as gastrointestinal bleed, intra-cerebral bleed, retroperitoneal hematoma, blood or
Six observational studies [16–21] that assessed 30-day all cause mortality met inclusion criteria, with 2,185 patients having underwent RA PCI, and 5,568 patients who underwent FA PCI (Fig. 3). Overall, 30-day all cause mortality occurred in 2,512 of the 7,753 patients (32.4 %); 471 of the 2,185 in the RA PCI group (21.6 %), and 2,041 of the 5,568 in the FA PCI group (36.7 %). There was a significant pooled RR of 0.65 [(95 % CI 0.52–0.80), p \ 0.0001, I2 = 56 %]. Sensitivity analysis demonstrated similar results when each individualized study was removed. Major bleeding Five observational studies [16, 18–21] that assessed major bleeding met inclusion criteria, with 2,163 patients having underwent RA PCI, and 5,553 patients who underwent FA
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S. Gandhi et al. Table 1 Study characteristics Study, year
Study design
Inclusion
Quality assessmenta
Mamas, 2014
Retrospective analysis of prospectively collected data, January 2006–December 2012, United Kingdom
1. STEMI or non-STEMI undergoing PCI
8
Iga, 2014
Retrospective study, 2006–20012, Japan
2. Cardiogenic Shock: SBP \100 mmHg with pulse [100 bpm combined with signs of peripheral hypoperfusion (cold, clammy, pallor, etc.), or a requirement for inotropes or intraaortic balloon pump to support the circulation and maintain a blood pressure 1. STEMI undergoing primary PCI
8
2. Non-STEMI undergoing emergent PCI 3. Cardiogenic shock: SBP persistently B90 mmHg in the presence of systemic hypoperfusion and adequate left ventricular filling pressure Bernat, 2013
RodriguezLeor, 2013
Retrospective analysis of prospectively collected data, 2006–2010, Czech Republic
1. STEMI undergoing primary PCI
Prospective study, enrollment February 2007– January 2012, Spain
1. STEMI undergoing primary PCI or rescue angioplasty
8
2. Cardiogenic shock: SBP B90 mmHg for at least 30 min, heart rate C60 bpm, signs of systemic hypoperfusion or required inotropes to maintain a SBP C90 mmHg 7
2. Non-STEMI 3. Cardiogenic shock: SBP \90 mmHg or the need for or vasopressors to maintain SBP [90 mmHg combined with signs of peripheral hypoperfusion (coldness and/or pallor in the extremities, oliguria, or a decrease in level of consciousness)
Fujii, 2013
Retrospective study, 2005–2011, Japan
1. STEMI
7
2. Cardiogenic shock: SBP \90 mmHg on arrival Fernandez Diaz, 2011 (abstract)
a
Retrospective study, 2005–2010
1. Acute myocardial infarction (Kilip class IV)
6
2. Cardiogenic shock: SBP \90 mmHg for 30 min or vasopressors required to maintain SBP [90 mmHg, evidence of end organ hypoperfusion (urine output \30 mL or cold/ diaphoretic extremities, or altered mental status) and evidence of elevated left ventricle filling pressures (pulmonary congestion on examination or chest X-ray)
Newcastle–Ottawa quality assessment scale
bpm beats per minute, PCI percutaneous coronary intervention, SBP systolic blood pressure, STEMI ST elevation myocardial infarction
PCI (Fig. 4). Overall, major bleeding occurred in 258 of the 7,716 patients (3.3 %); 53 of the 2,163 in the RA PCI group (2.5 %), and 205 of the 5,553 in the FA PCI group (3.7 %). There was a significant pooled RR of 0.46 [(95 % CI 0.34–0.62), p \ 0.0001, I2 = 0 %]. Sensitivity analysis demonstrated similar results when each individualized study was removed. Final TIMI 3 flow Four observational studies [16, 18–20] that assessed final TIMI 3 flow met inclusion criteria with 286 patients who underwent RA PCI, and 199 patients that underwent FA PCI (Fig. 5). Overall, final TIMI 3 flow was achieved in 373 of the 485 patients (77 %); 230 of the 286 in the RA PCI group (80.4 %), and 143 of the 199 in the FA PCI group (71.9 %). There was a non-significant pooled RR of
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1.08 [(95 % CI 0.94–1.24), p = 0.27, I2 = 58 %] demonstrating no significant difference in final TIMI 3 flow between groups. Fluoroscopy time Three observational studies [16–18] that assessed fluoroscopy time met inclusion criteria with 210 patients who underwent RA PCI, and 146 patients who underwent FA PCI (Fig. 6). WMD in fluoroscopy time was 0.12 min (p = 0.95) demonstrating no significant difference in total fluoroscopy time between groups. Amount of contrast volume administered Five observational studies [16–20] that assessed amount of contrast volume administered met inclusion criteria with
Comparison of radial to femoral PCI Table 2 Patient and procedure characteristics Study
Bernat, 2013
RodriguezLeor, 2013
Fujii, 2013
Fernandez Diaz, 2011
Iga, 2014
Mamas, 2014
RA
FA
RA
FA
RA
FA
RA
FA
RA
FA
RA
FA
Subjects
108
90
90
42
Mean age (years)
69
64
65
68
38
43
22
5
60
25
1,877
5,354
71
72.7
70.36
70.35
68.2
70.3
67.2
Female (%)
29
29
11
26
18
39
31
29
17
28
74
Smoking (%)
38
44
36.2
26.2
65.8
51.2
36 %
35 %
58.3
40
30
69 31
Diabetes (%)
13
26
66.2
45.2
63.2
48.8
–
–
31.7
44
17
21
Dyslipidemia (%) Hypertension (%)
38 47
46 54
51.2 57.5
61.9 57.1
52.6 84.2
55.8 90.7
– –
– –
51.7 53.3
32 64
42 44
42 47
Previous MI (%)
14
18
27.5
45.2
7.9
18.6
–
–
10
8
21
25
Crossover (%)
n/a
n/a
7.5
2.4
n/a
n/a
5
0
1.7
0
–
–
IABP (%)
36
55
37.5
52.4
34.2
58.1
40.9
52.9
61.7
84
29
38
Mechanical ventilation before PCI (%)
42
66
41.2
66.7
–
–
–
–
–
–
19
34
Cardiac arrest (%)
16 %
15 %
38.1
32.5
42.1
51.2
–
–
31.7
28
–
–
Mean SBP on admission (mmHg)
n/a
n/a
69
79
72.7 (±34.5) 72.7
–
–
46.2
48.2
–
–
GP IIb/IIIa inhibitor (%)
41
40
56.7
35.7
83.1 (±45.4) 83
–
–
0
0
56
58
Procedure duration (min)
46
47
–
–
126.6
123.7
–
–
–
–
–
–
Circumflex
12
12
–
–
–
–
–
–
5
8
14
14
LAD
57
56
–
–
–
–
–
–
38.3
40
54
52
RCA
29
28
–
–
–
–
–
–
48.3
40
27
27
Left main
1.9
3.4
–
–
–
–
–
–
6.7
12
4
5
Initial TIMI 0 flow (%)
61
65
–
–
76.3
55.8
–
–
63.3
76
–
–
Culprit lesion (%)
– Data not available FA femoral artery group, IABP intra-aortic balloon pump, LAD left anterior descending, RA radial artery group, RCA right coronary artery, SBP systolic blood pressure
308 patients that underwent RA PCI, and 214 patients that underwent FA PCI (Fig. 7). WMD in amount of contrast volume administered was 5.33 mL (p = 0.59) demonstrating no significant difference in total amount of contrast volume administered between groups.
Discussion The results of this systematic review of observational studies show an overall high 30-day all cause mortality in patients with AMI and cardiogenic shock. There was lower observed access site related bleeding, major bleeding, and 30-day all cause mortality in the RA PCI group, with no significant difference in final TIMI 3 flow, fluoroscopy time, and amount of contrast volume administered between both groups. Over the past decade, there has been an increase in uptake of RA approach PCI in high-risk patients, with gaining operator and centre wide experience. The superficial course of the RA allows for early recognition of access
site bleeding and easy compressibility with the ability to provide safe and rapid achievement of hemostasis [5]. In patients with ACS, procedural related bleeding has been independently associated with increased mortality with access site related bleeding as a large contributor [23]. For this reason, strategies have been adopted to decrease major bleeding through augmentation of peri-procedural antithrombotic agents as well as the transition to RA approach PCI. A large Canadian database study of 32,822 patients demonstrated in patients undergoing PCI, RA approach was independently associated with a significant reduction in transfusion rate, 30-day and one-year mortality [24]. The RIVAL (Radial vs. Femoral Access for Coronary Intervention) trial was a parallel group, multicenter, randomized trial which assigned 7,021 patients with ACS to undergo cardiac catheterization via the RA or FA approach [25]. In patients with STEMI, there was significant decrease in the primary composite outcome of death, MI, stroke, or noncoronary artery bypass graft (CABG) related bleeding in the RA PCI group (HR 0.60, p = 0.026). However, there was no major difference in access site related bleeding
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S. Gandhi et al. Table 3 Study outcomes Outcomes assessed: RA vs. FA PCI Mamas, 2014
30-day mortality Propensity score-matched cohort: 30-day mortality In-hospital MACCE Major bleeding
Independent predictors of mortality overall 24.7 vs. 39.8 % (p \ 0.001) 22.8 vs. 29.9 % (p \ 0.001) HR 0.64 (p \ 0.0001) 1.5 vs. 3.5 % (p \ 0.0001)
Radial PCI Glycoprotein IIb/IIIa inhibitor use Primary PCI Poor LV function Inotrope use
HR 0.56 (p \ 0.0001) HR 0.75 (p \ 0.0001) HR 1.11 (p \ 0.0001) HR 2.59 (p \ 0.0001) HR 1.55 (p \ 0.0001)
Iga, 2014
PCI access-site related bleeding Non-PCI access site related bleeding 30-day mortality 30-day stroke Hospitalization (days)
0 vs 12 % (p \ 0.05) 6.7 vs. 16 % (p = 0.23)
n/a
n/a
Radial artery approach
HR 0.65 (p = 0.41)
26.7 vs. 40 % (p = 0.30) 0 vs. 8 % (p = 0.08) 32.5 vs. 43.1 (p = 0.40)
Bernat, 2013
Non-CABG major bleeding Access site-related bleeding Non-access site bleeding 30-day mortality 1-year mortality
13 % vs 25 % (p = 0.42) 0.9 vs. 9.0 % (p = 0.12) 4.6 vs. 5.6 % (p = 0.76) 41 vs. 53 % (p = 0.11)
GP IIb-IIIa receptor inhibitors Baseline creatinine [110 umol/L Initial glycemia [200 mg/ dL Age [65 years
In-hospital mortality Access site complications Requiring transfusion MACE
32.5 vs. 64.3 % (p = 0.001)
C75 years
2.5 vs. 11.9 % (p = 0.03)
Use of IABP
54.1 vs. 42.8 % (p = 0.001)
HR 3.34 (p \ 0.0001) HR 2.02 (p = 0.0008) HR 1.80 (p = 0.006)
44 vs. 64 % (p = 0.0044) Rodriguez-Leor, 2013
HR 0.63 (p = 0.032)
Diuretics before PCI Radial artery PCI Procedure success
OR 3.47 (p = 0.007) OR 3.01 (p = 0.02) OR 2.10 (p = 0,05) OR 0.39 (p \ 0.0001) OR 0.07 (p \ 0.0001)
Fujii, 2013
30-day mortality Stent thrombosis Stroke Hospitalization (days)
28.9 vs. 25.6 % (p \ 0.001)
n/a
n/a
n/a
n/a
0 vs. 2.3 % (p = 0.0495) 2.6 vs. 4.7 % (p = 0.0478) 21.1 vs. 32.7 (p = 0.1253)
Fernandez Diaz, 2011 [abstract]
All cause mortality at 30 days LVEF at discharge
61.9 vs. 79.5 % (p = ns) 29.1 vs. 27.8 % (p = ns)
n/a Not available CABG coronary artery bypass graft, FA femoral artery, RA radial artery, IABP intra-aortic balloon pump, MACE major adverse cardiac event, OR odds ratio; PCI percutaneous coronary intervention
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Comparison of radial to femoral PCI
Fig. 2 Access site related bleeding: forrest plot of pooled data from studies showing the relative risk ratio of access site related bleeding in the RA group compared to the FA group
Fig. 3 30-day all cause mortality: forrest plot of pooled data from studies showing the relative risk ratio of 30-day all cause mortality in the RA group compared to the FA group
Fig. 4 Major Bleeding: forrest plot of pooled data from studies showing relative risk ratio of major bleeding in the RA group compared to the FA group
found between the RA and FA group (0.1 vs. 0.2 %, p = 0.604). The RIFLE-STEACS was a multicenter, randomized parallel-group study that assigned 1,001 patients with STEMI to undergo primary/rescue PCI via the RA or FA approach [3]. The primary composite end point of cardiac death, stroke, MI, target lesion revascularization, and bleeding at 30 days occurred less frequently in the RA group (13.6 vs. 21.0 %, p = 0.003). There was also a significant reduction in access site related bleeding in the RA
PCI group (2.6 vs. 6.8 %, p = 0.002). The STEMIRADIAL Trial was a randomized, multicenter trial of 707 patients with STEMI, assigned to the RA or FA approach PCI. The primary composite endpoint of 30-day major bleeding and MACE was lower in the RA PCI group (11.0 vs. 4.6 %, p = 0.0028) with a reduction in 30-day major bleeding (7.2 vs. 1.4 %, p = 0.0001) [26]. These results were supported by a recent meta-analysis of 12 randomized controlled trials that showed RA approach PCI was
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Fig. 5 Final TIMI 3 flow: forrest plot of pooled data from studies showing no difference in TIMI 3 flow in the RA group compared to the FA group
Fig. 6 Fluoroscopy time (minutes): forrest plot of pooled data from studies showing no difference in fluoroscopy time in the RA group compared to the FA group
Fig. 7 Amount of contrast volume administered (mL): forrest plot of pooled data from studies showing no difference in amount of contrast volume administered in the RA group compared to the FA group
associated with decreased risk of mortality (OR 0.55, p \ 0.001) and access site related bleeding (OR 0.35, p \ 0.001) [5] in STEMI patients. There are several limitations to this analysis. Our analysis included observational studies with two retrospective studies, and therefore our results do not imply causation or a treatment effect. For the primary outcome measures of access site related bleeding and 30-day all cause mortality, only four and five studies were included respectively, limiting study power and the ability to detect statistically significant findings. The absence of a radial pulse in the FA PCI group may represent vasoconstriction and increased illness severity, and therefore these may be sicker patients at increased risk of bleeding complications and higher mortality. The results of our analysis does not account for IABP access, in which FA access is preferred
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or may require double FA access site puncture in the FA group, increasing the risk of access site related bleeding. Although the number of patients that crossed over from each group was low, our analysis cannot incorporate this variable. The pooled analysis cannot control for patient characteristics, clinical variables, procedural outcomes, and anticoagulant/antithrombotic therapy that may account for increased bleeding and mortality. The metaanalysis cannot attest to operator discretion and choice for FA approach PCI. Due to the limited data available, we cannot provide a more robust analysis with a variety of clinical endpoints such as door-to-balloon time, total procedure duration, length of hospitalization, stroke, and other further systemic complications. Individuals with acute myocardial infarction and cardiogenic shock represent the highest risk patients, which
Comparison of radial to femoral PCI
adds to the challenge of radial access. The radial artery is a small caliber vessel, prone to spasm, with further anatomical variance of the often torturous and calcified subclavian artery. In patients with cardiogenic shock, the lack or absence of a palpable pulse may be due to systemic vasoconstriction in which a delay in obtaining arterial access and subsequent revascularization and reperfusion may lead to poor outcomes. Furthermore, operators must also evaluate for preferred bilateral femoral artery access for advanced support devices and guiding catheter sheaths in critically ill patients. Current research has been focused on optimizing and improving radial access with vasodilator and spasmolytic agents, hydrophilic introducer sheaths, and ultrasound guided radial artery puncture. Our analysis is consistent with previous studies assessing outcomes comparing RA to FA PCI in high-risk STEMI patients. Future prospective studies with larger sample size are needed to validate these findings and assess the potential advantage of radial PCI in AMI and cardiogenic shock. A randomized comparison of access site in patients with cardiogenic shock may not be feasible due to issues of patient consent in this complex high acuity setting. Although we believe that the choice of access site in a high-risk setting should be at the operator discretion, if technically feasible, the RA appears to be a reasonable vascular access approach in high-risk patients in cardiogenic shock. Disclosures The authors do not believe that they have any conflicts of interest with regards to this research paper. This article represents original work and is not under consideration for publication elsewhere. All authors meet criteria for authorship.
References 1. Babaev A, Frederick PD, Pasta DJ, Every N, Sichrovsky T, Hochman JS (2005) Trends in management and outcomes of patients with acute myocardial infarction complicated by cardiogenic shock. JAMA 294(4):448–454 2. Hochman JS, Sleeper LA, Webb JG et al (1999) Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investigators. Should we emergently revascularize occluded coronaries for cardiogenic shock. N Engl J Med 341(9):625–634 3. Romagnoli E, Biondi-Zoccai G, Sciahbasi A et al (2012) Radial versus femoral randomized investigation in ST-segment elevation acute coronary syndrome: the RIFLE-STEACS (radial versus femoral randomized investigation in ST-Elevation Acute Coronary Syndrome) study. J Am Coll Cardiol 60(24):2481–2489 4. Jolly SS, Yusuf S, Cairns J et al (2011) Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL): a randomised, parallel group, multicentre trial. Lancet 377(9775):1409–1420 5. Karrowni W, Vyas A, Giacomino B et al (2013) Radial versus femoral access for primary percutaneous interventions in STsegment elevation myocardial infarction patients: a meta-analysis of randomized controlled trials. JACC Cardiovasc Interv 6(8):814–823
6. Vorobcsuk A, Konyi A, Aradi D et al (2009) Transradial versus transfemoral percutaneous coronary intervention in acute myocardial infarction systematic overview and meta-analysis. Am Heart J 158(5):814–821 7. Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6(7):e1000097 8. Riley RD, Higgins JP, Deeks JJ (2011) Interpretation of random effects meta-analyses. BMJ 342:d549 9. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560 10. Johnman C, Pell JP, Mackay DF et al (2012) Clinical outcomes following radial versus femoral artery access in primary or rescue percutaneous coronary intervention in Scotland: retrospective cohort study of 4534 patients. Heart 98(7):552–557 11. Cafri C, Zahger D, Merkin M, Weinstein JM, Kobal S, Ilia R (2013) Efficacy of the radial approach for the performance of primary PCI for STEMI. J Invasive Cardiol 25(3):150–153 12. Kedev S, Kalpak O, Antov S, Kostov J, Pejkov H, Spiroski I, Boshev M (2011) Single centre registry of trasradial versus transfeomral access for primary PCI. J Am Coll Cardiol 57(14s1):E1803 13. Marinucci L, Uguccioni L, Parisi R et al (2012) TCT-428 Radial access does not affect door to balloon time in patients undergoing primary PCI. J Am Coll Cardiol. doi:10.1016/j.jacc.2012.08.1013 14. Ratib K, Mamas M, Large A et al (2012) TCT-424 Trends in access site choice for PCI and influence on mortality—Observational data from the British Cardiovascular Intervention Society PCI database. J Am Coll Cardiol. doi:10.1016/j.jacc.2012.08. 453 15. Romagnoli E, De Vita M, Burzotta F et al (2013) Radial versus femoral approach comparison in percutaneous coronary intervention with intraaortic balloon pump support: the RADIAL PUMP UP registry. Am Heart J 166(6):1019–1026 16. Bernat I, Abdelaal E, Plourde G et al (2013) Early and late outcomes after primary percutaneous coronary intervention by radial or femoral approach in patients presenting in acute STelevation myocardial infarction and cardiogenic shock. Am Heart J 165(3):338–343 17. Diaz JF, Mitroi D, Ruigomez JG et al (2011) OP-020: safety and feasibility of radial approach for primary angioplasty in cardiogenic shock. Int J Cardiol 147:S43–S43 18. Rodriguez-Leor O, Fernandez-Nofrerias E, Carrillo X et al (2013) Transradial percutaneous coronary intervention in cardiogenic shock: a single-center experience. Am Heart J 165(3):280–285 19. Fujii T, Masuda N, Ijichi T et al (2014) Transradial intervention for patients with ST elevation myocardial infarction with or without cardiogenic shock. Catheter Cardiovasc Interv 83(1):E1– E7 20. Iga A, Wagatsuma K, Yamazaki J, Ikeda T (2014) Transradial versus transfemoral coronary intervention for acute myocardial infarction complicated by cardiogenic shock: is transradial coronary intervention suitable for emergency PCI in high-risk acute myocardial infarction? J invasive cardiol 26(5):196–202 21. Mamas MA, Anderson SG, Ratib K et al (2014) Arterial access site utilization in cardiogenic shock in the United Kingdom: is radial access feasible? Am heart j 167(6):900–908 e901 22. Mehran R, Rao SV, Bhatt DL et al (2011) Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation 123(23):2736–2747 23. Eikelboom JW, Mehta SR, Anand SS, Xie C, Fox KA, Yusuf S (2006) Adverse impact of bleeding on prognosis in patients with acute coronary syndromes. Circulation 114(8):774–782 24. Chase AJ, Fretz EB, Warburton WP et al (2008) Association of the arterial access site at angioplasty with transfusion and
123
S. Gandhi et al. mortality: the M.O.R.T.A.L study (mortality benefit of reduced transfusion after percutaneous coronary intervention via the arm or leg). Heart 94(8):1019–1025 25. Mehta SR, Jolly SS, Cairns J et al (2012) Effects of radial versus femoral artery access in patients with acute coronary syndromes with or without ST-segment elevation. J Am Coll Cardiol 60(24):2490–2499
123
26. Bernat I, Horak D, Stasek J et al (2014) ST elevation myocardial infarction treated by RADIAL or femoral approach in a multicenter randomized clinical trial : the STEMI-RADIAL Trial. J Am Coll Cardiol 63(10):964–972
