Transradial access (TRA) is becoming increasingly used worldwide for percutaneous coronary intervention (PCI) after acute coronary syndromes (ACS). TRA compared with transfemoral access has been noted to improve clinical outcomes in clinical trials and large registry cohort studies. However, much of the benefits of TRA PCI are noted in patients with ST elevation myocardial infarction (STEMI) undergoing primary PCI, where TRA PCI has been associated with reductions in major bleeding events and potentially lower short- and long-term mortality rates. Although much less data exist for TRA PCI in unstable angina and/or non–ST elevation myocardial infarction, similar reductions in bleeding and mortality have not been consistently described. Differences in outcome benefit with TRA PCI among various ACS subtypes may be attributable to the potentially increased inherent risk of periprocedural bleeding in STEMI compared with unstable angina and/or non–ST elevation myocardial infarction. Pre- and intra-procedural factors associated with STEMI treatment, such as use of pharmacoinvasive therapy and aggressive antithrombotic regimens likely increase bleeding risk in patients. In conclusion, this review describes the evidence for TRA PCI across the spectrum of ACS and highlights why differences in clinical benefit may exist among ACS subtypes.
Change in vascular access approach for percutaneous coronary intervention (PCI) may have initially been slow. However, over the last decade, use of transradial access (TRA) has been rising steadily, with an increasing body of evidence suggesting that it may be the preferred access route for cardiac catheterization, particularly in the setting of acute coronary syndromes (ACS). Despite reductions in access site complications associated with TRA compared with transfemoral access (TFA) intervention, improvements in clinical outcomes have not been consistently demonstrated across the spectrum of ACS. In the radial versus femoral access for coronary angiography and intervention in patient with acute coronary syndrome (RIVAL) study, the largest randomized clinical trial to date examining the effects of vascular access for PCI in ACS, no clinical outcome benefit was derived from TRA PCI. However, in RIVAL study, >70% of patients presented with unstable angina (UA) and/or non–ST elevation myocardial infarction (NSTEMI). Substudy analysis of RIVAL, as well as evidence from other randomized trials and large registries, has demonstrated that clinical benefit for TRA approach may be most evident in the setting of primary PCI (PPCI) after ST elevation myocardial infarction (STEMI). Thus, the aim of this review is to highlight the potential clinical benefit of using TRA PCI in various ACS subtypes and to determine why benefit of TRA intervention may be different across the spectrum of ACS. In particular, this review will focus on the importance of access site bleeding events in determining further clinical outcomes.
Characterization and Impact of Bleeding Events After ACS
Post-ACS bleeding events can be categorized based on location of bleeding. The percentage of major periprocedural bleeding events defined as access site related has decreased substantially from 80% to around 35% to 45% over the last 20 years, likely due to use of smaller catheter sizes and more conservative anticoagulation strategies before and during PCI. During this time there has been an overall reduction in bleeding events partly attributable to fewer access site bleeds ( Figure 1 ). Despite this, the recent CathPCI registry analysis, involving >300,000 patients undergoing PCI in the United States, suggested that access site bleeding was the most common cause of periprocedural bleeding and was independently associated with increased in-hospital and 1-year mortality. The 1-year mortality rate in patients with access site bleeding was 6.16% compared with 2.54% without bleeding events.
Clinical benefit related to use of TRA PCI after ACS is mainly believed to be due to reductions in periprocedural access site bleeding outcomes. Although the incidence of overall bleeding complications after ACS remains highly variable, recent evidence suggests that in-hospital bleeding occurs from 0.2% to 12% after PCI and accounts for 70% of all post-PCI bleeding events. Periprocedural bleeding has been associated with increased mortality, accounting for up to 1/8 of all in-hospital deaths after PCI. Evidence from both randomized trials and “real-world” registries have suggested that patients with ACS with major in-hospital bleeding events have a twofold to sixfold increased risk of 30-day mortality. Periprocedural bleeding events are associated with worsened long-term prognosis, conferring potentially a greater than sixfold increase in 1-year mortality. Along with mortality outcomes, bleeding events have also been shown to be associated with recurrent ischemia and increased length of stay in hospital.
Despite the obvious importance of bleeding events after ACS, definition of these events may differ substantially among studies. A number of different standardized bleeding scores have been used to determine the severity of bleeding events in both clinical trials and observational studies examining TRA and TFA ( Table 1 ). These include the Thrombolysis In Myocardial Infarction (TIMI), International Society on Thrombosis and Haemostasis (ISTH), Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO), Acute Catheterization and Urgent Intervention Triage strategY (ACUITY), Harmonizing Outcomes With RevasculariZatiON and Stents in Acute Myocardial Infarction (HORIZONS-AMI), Clopidogrel in Unstable angina to prevent Recurrent Events (CURE), Organization to Assess Strategies for Ischemic Syndromes (OASIS), and Bleeding Academic Research Consortium (BARC) bleeding scores. However, these scores have not been uniformly adopted. Disparities also exist among bleeding event rates in clinical trials and real-world registries. Generally, rates of bleeding are higher in registry cohorts. In the National Cardiovascular Data Registry (NCDR)-based ACTION-GWTG registry examining patients with ACS, major bleeding rates were more than twofold higher than those reported in the RIVAL study. Higher bleeding rates may be attributable to the increased complexity of patients in registry cohorts or, alternatively, due to changes in operator behavior noted in the setting of increased monitoring and surveillance during clinical trials. The relatively lower periprocedural bleeding rates described in clinical trials may make access site–based differences in bleeding more difficult to observe.
| STEMI trials | TFA | TRA | MACE | Mortality | Bleeding | GIIb/IIIa | Bivalirudin | UFH | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| TFA | TRA | TFA | TRA | TFA | TRA | TFA | TRA | |||||
| Randomized | ||||||||||||
| RIVAL STEMI | 1003 | 955 | + | + | 9 (0.91%) | 8 (0.84%) | 312 (31.1%) | 329 (34.5%) | 41 (4.1%) | 22 (2.3%) | 657 (65.5%) | 674 (70.6%) |
| RIFLE-STEACS | 501 | 500 | + | + | 61 (12.2%) | 39 (7.8%) | 350 (69.9%) | 337 (67.4%) | 36 (7.2%) | 40 (8.0%) | 351 (70%) | 355 (71%) |
| FARMI | 57 | 57 | 0 | 0 | 3 (5.3%) | 3 (5.3%) | 57 (100%) | 57 (100%) | – | – | 57 (100%) | 57 (100%) |
| RADIAMI | 50 | 50 | 0 | 0 | 7 (14%) | 3 (6%) | 21 (42%) | 22 (44%) | 0 (0%) | 0 (0%) | 50 (100%) | 50 (100%) |
| RADIAL AMI ∗ | 25 | 25 | 0 | 0 | 0 (0%) | 0 (0%) | 23 (92%) | 24 (96%) | 0 (0%) | 0 (0%) | 25 (100%) | 25 (100%) |
| Li et al | 186 | 184 | – | – | – | – | – | – | – | – | 186 (100%) | 184 (100%) |
| RADIAMI II | 59 | 49 | 0 | – | 6 (10.2%) | 4 (8.2%) | 32 (54%) | 25 (51%) | 0 (0%) | 0 (0%) | 59 (100%) | 49 (100%) |
| Yan et al | 46 | 57 | 0 | 0 | 1 (2.2%) | 0 (0%) | 46 (100%) | 57 (100%) | 0 (0%) | 0 (0%) | 46 (100%) | 57 (100%) |
| Genereux et al † | 3134 | 200 | + | + | 252 (8.1%) | 7 (3.5%) | 1648 (52.7%) | 99 (49.5%) | 1555 (49.8%) | 102 (51%) | 1648 (52.7%) | 99 (49.5%) |
| Observational | ||||||||||||
| Valgimigli et al § | 8000 | 3068 | 0 | + | 16 (1.1%) | 37 (2.6%) | 1196 (79.6%) | 1197 (79.7%) | – | – | – | – |
| Johnman et al ∗ | 2142 | 2392 | + | + | – | – | – | – | – | – | – | – |
| Arzamendi et al ‡ | 251 | 238 | + | + | 7 (2.9%) | 36 (14.3%) | 181 (72.1%) | 217 (91.2%) | 0 (0%) | 0 (0%) | 240 (95.6%) | 235 (98.7%) |
| Hetherington et al | 480 | 571 | + | 0 | 9 (1.9%) | 0 (0%) | 438 (91.2%) | 529 (92.7%) | 0 (0%) | 0 (0%) | 480 (100%) | 571 (100%) |
| Barthelemy et al | 82 | 589 | + | + | – | – | – | – | – | – | – | – |
| Yip et al | 810 | 506 | – | 0 | 13 (1.2%) | 0 (0%) | – | – | – | – | 810 (100%) | 506 (100%) |
| UA/NSTEMI trials | ||||||||||||
| PRESTO-ACS | 863 | 307 | 0 | 0 | 21 (2.4%) | 2 (0.7%) | 296 (34%) | 159 (52%) | 0 (0%) | 0 (0%) | 255 (29.5%) | 103 (33.5%) |
| EARLY-ACS | 7896 | 1230 | 0 | 0 | 173 (2.2%) | 20 (1.6%) | – | – | – | – | – | – |
| RIVAL UA/NSTEMI | 2511 | 2512 | 0 | 0 | 24 (0.96%) | 16 (0.63%) | 532 (21.2%) | 558 (21.9%) | 68 (2.7%) | 54 (2.1%) | 1087 (43.3%) | 1096 (42.9%) |
| ACUITY | 11989 | 798 | 0 | 0 | 575 (4.8%) | 24 (3.0%) | – | – | – | – | – | – |
∗ Combined primary and rescue PCI.
† GIIb/IIIa inhibitors were given in a 1:1 ratio with UFH and therefore the same % were outlined—however % for UFH were not explicitly outlined.
‡ GIIb/IIIa inhibitors were only used in patients with TFA, although % were not specified.
§ Combination of major vascular and bleeding complications reported.
Transradial PCI in STEMI
In the setting of STEMI, there have now been several randomized controlled trials and observational studies that have suggested mortality and bleeding reduction benefit with use of TRA PCI. In the Radial versus Femoral Randomized Investigation in ST-segment Elevation in Acute Coronary Syndrome (RIFLE-STEACS) trial, the largest randomized trial comparing TRA versus TFA for patients with STEMI, there was a significant reduction in 30-day cardiac mortality associated with TRA PCI (5.2% vs 9.2%, p = 0.02; Table 2 ; Figure 2 ). There was also a diminution in major bleeding events associated with TRA PCI driven by a reduction in access site bleeding. Vascular approach did not affect ischemic outcomes (myocardial infarction, cerebrovascular accident (CVA), target vessel revascularization (TVR)). The RIVAL substudy examining patients with STEMI similarly noted reductions in 30-day mortality rate with TRA versus TFA PCI (1.3% vs 3.2%, hazard ratio 0.39, p = 0.006). Despite the reduction in mortality, there was no significant difference in TIMI major bleeding or combined ischemic outcomes between TRA and TFA groups in this study. In a substudy of the HORIZONS-AMI trial, there was a suggested trend toward reductions in composite of death and reinfarction at 1 year (7.8% vs 4.0%, p = 0.06) using TRA PCI. This substudy did demonstrate a significant reduction in non–coronary artery bypass graft major bleeding but included only 200 patients undergoing PCI through TRA.
| ST Elevation Myocardial Infarction Trials | Standardized Bleeding Scales |
|---|---|
| Randomized | |
| RIVAL STEMI | TIMI |
| RIFLE-STEACS | N |
| FARMI | TIMI |
| RADIAMI | N |
| RADIAL AMI | N |
| Li et al | N |
| RADIAMI II | N |
| Yan et al | N |
| Genereux et al | HORIZONS-AMI/ACUITY |
| Observational | |
| Valgimigli et al | N |
| Johnman et al | N |
| Arzamendi et al | HORIZONS-AMI/ACUITY |
| Hetherington et al | N |
| Barthelemy et al | TIMI |
| Yip et al | N |
| Unstable angina/non–ST elevation myocardial infarction trials | |
| PRESTO-ACS | TIMI |
| EARLY-ACS | TIMI/GUSTO |
| RIVAL UA/NSTEMI | TIMI |
| ACUITY | HORIZONS-AMI/ACUITY |
Although benefit of TRA PCI was not consistently noted in some initial clinical observational studies involving patients with STEMI, recent large registries and databases have indicated outcomes similar to those observed in clinical trials. In the Italian REgistro regionale AngiopLastiche dell’Emilia-Romagna (REAL) registry involving >11,000 patients with STEMI, 30-day mortality and major bleeding outcomes were reduced by >50% with TRA PCI. In the Scottish PPCI registry, which included patients undergoing rescue and PPCI, there was a 59% relative risk reduction in 30-day mortality with TRA PCI. Finally, in the NCDR involving 294,769 patients undergoing PPCI for STEMI from 2007 to 2011, there were reductions in in-hospital mortality associated with TRA (odds ratio 0.64) and a similar decrease in adjusted in-hospital bleeding outcomes.
Over the last 3 years, a number of meta-analyses have similarly shown reductions in mortality and bleeding with TRA approach in STEMI. A recent comprehensive meta-analysis by De Luca et al included 29,194 patients from both clinical trials and observational studies receiving PCI for STEMI. Pooled analysis revealed significant reductions in short-term mortality with TRA PCI. This mortality benefit was driven predominantly by the 2 aforementioned large clinical trials, RIVAL and RIFLE. Reduction in mortality mirrored reductions in major bleeding complications with the TRA approach.
Transradial PCI in STEMI and long-term mortality
Long-term mortality also appears to be reduced with TRA approach for PPCI. Much of this long-term data are derived from registries with significant follow-up rather than from randomized clinical trials. The Scottish PPCI registry denoted that significant reductions in myocardial infarction and death associated with TRA PCI remained present even 9 years after initial intervention. Similarly, in the REAL registry, a TRA approach for PPCI was associated with reductions in mortality rates at 2 years (9.3% vs 16.7%). This reduction appeared to be driven by differences in initial 30-day mortality. In this registry, in-hospital bleeding or vascular events were associated with a sevenfold increase in 2-year mortality. The investigators attributed 11% of all deaths at 2 years to in-hospital bleeding and vascular complications.
Transradial PCI, bleeding and mortality outcomes in STEMI
The mortality benefit associated with TRA PCI in STEMI has been largely attributed to reductions in access site–related major bleeding outcomes. However, both systematic reviews and clinical trials have described mortality benefit with TRA PCI after STEMI without concurrent bleeding reduction. The disparity in the lack of bleeding reduction among some studies but not others may have in part been due to differing bleeding scale assessments used by various investigators. For example, within the RIVAL study, no difference in the rate of periprocedural bleeding was noted between TRA and TFA PCI when bleeding was characterized by the TIMI criteria (0.5% vs 0.5%). However, post hoc analysis did reveal that major bleeding, when assessed by the ACUITY bleeding scale, was significantly lower in patients undergoing TRA approach for PPCI (1.84% vs 4.46%, p <0.0001).
Large variability exists in the incidence of bleeding after PPCI when defined by different bleeding scales, with 1-year major bleeding rates ranging from 1.3% to 21% in 1 series of patients with STEMI. Additionally, only certain standardized bleeding scores are associated with worsened prognosis. Although most recent randomized and large observational trials have noted similar reductions in bleeding and mortality rates with TRA, the use of a singular bleeding scale assessment may be beneficial for future studies. A uniform bleeding scale may allow improved intrastudy adjudication of events and simpler interstudy comparisons.
It is important to note that all but 2 trials in Table 1 comparing TRA with TFA PCI either did not specify or infrequently (<30%) used vascular closure devices for cessation of femoral artery bleeding. Differences in bleeding outcomes between TRA and TFA PCI may have been less amplified with more consistent vascular closure device use. However, currently, there is conflicting evidence as to whether these devices truly reduce major vascular complications after TFA PCI compared with manual compression.
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
