Bleeding Complications in Acute Coronary Syndrome
Peri-PCI procedural bleeding complications have been consistently associated with worse outcomes and increased short- and longterm mortality.6,17 Access site-related bleeding, accounting for as many as 30-50 % of all causes of bleeding in patients with ACS, has repeatedly been found to be the major contributor for bleeding events.9,18-20
Due to the rm link between bleeding, ischaemic events and mortality, more attention has recently been focused on bleeding avoidance strategies.21 Despite the development of new more potent, selective and safe antithrombotics, the use of TRA remains likely the best way to signicantly inuence access site-related bleeding risk. 22-25
Recently, the REgistro regionale AngiopLastiche dellÔÇÖEmilia-Romagna (REAL) Registry of 11,068 STEMI patients undergoing PPCI, showed that TRA was associated with a decreased two-year mortality rate compared with the traditional TFA (8.8 versus 11.4 %, hazard ratio [HR] 1.303; p=0.025).12 The observed difference in death was not explained by the incidence of MI or stroke, which did not differ between groups. By contrast, TRA was associated with a signicant and marked reduction of in-hospital major bleeding or vascular events.
The available clinical evidence summarised in recent meta-analyses demonstrated a signicant reduction in mortality, major adverse cardiac events (MACE), major bleeding events and major access site complications associated with the TRA.24,25 Therefore, the use of the TRA for high-risk patients with ACS certainly has a key role in the prevention of access site bleeding complications.
Randomised Controlled Trials and Registries of Transradial Access Versus the Femoral Approach in Acute Coronary Syndrome
The radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL) is the largest randomised comparison of radial and femoral artery access of 7,021 patients with ACS; 1,958 with a pre-randomisation diagnosis of STEMI; and 5,063 patients with NSTEACS.11 In patients with STEMI, TRA significantly reduced the primary outcome: death, MI, stroke or non-coronary artery bypass graft surgery (CABG)-related major bleeding within 30 days (3.1 versus 5.2%; HR 0.60; p=0.026) and mortality alone (1.3 versus 3.2%; HR 0.39; p=0.006). In patients presenting with NSTEACS, there were no significant differences in any of these outcomes. In both STEMI and NSTEACS patients, TRA reduced major vascular access site complications (1.4 versus 3.7%; HR 0.37; p<0.0001), and major bleeding as defined by the Acute Catheterization and Urgent Intervention Triage strategy (ACUITY) definition (1.9 versus 4.5 %; HR 043; p<0.0001). In STEMI patients, the reduction in the primary and secondary composite outcomes was driven mainly by a reduction in mortality with a directionally consistent reduction in MI. No such benefit was observed in patients with NSTEACS. Access site crossover was higher in the radial group compared with the femoral group (7.6 versus 2.0 %; HR 3.82; p<0.0001), and this was consistent in both STEMI and NSTEACS cohorts.26
The Radial Versus Femoral Randomized Investigation in ST Elevation Acute Coronary Syndrome (RIFLE-STEACS) is the rst large randomised clinical trial of 1,001 patients with STEMI specically designed to compare the radial (500 patients) and femoral approaches (501 patients) for primary/rescue PCI. In this nearly all-comers study, the TRA was associated with signicantly lower rates of clinically relevant access site bleeding (2.6 versus 6.8 %; p=0.002) and subsequent 30-day mortality (5.2 versus 9.2 %; p=0.020) in comparison with TFA. The reduction in cardiac mortality and clinically relevant access site bleeding by 60 % with a signicant decrease in the need for transfusion in the radial arm of the RIFLE-STEACS, support the link between mortality and 'clinically relevantÔÇÖ access site bleeding. Furthermore, there were no differences in the symptom-to-balloon and door-to-balloon times between the two study groups. Vascular approach crossover was 9.6 % in the radial arm and 2.8 % in the femoral arm with negligible time delay by expert operators.13
Recently, A Prospective Randomized Trial of Radial vs. Femoral Access in Patients with ST-Segment Elevation Myocardial Infarction (STEMIRADIAL) showed that TRA was associated with a signicantly lower incidence of major bleeding and access site complications, and a signicantly better net clinical benet - composite of death, MI and stroke, and major bleeding (4.6 versus 11.0 %; p=0.0028) Moreover, TRA signicantly reduced intensive coronary care unit (ICU) stay (p=0.0016) and contrast volume (p<0.01) compared with TFA.27
The post hoc analysis of the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction Trial (HORIZON-AMI),22 showed improved event-free survival in patients undergoing primary PCI by the TRA and conrmed the advantage of the TRA with regard to haemorrhagic complications also in patients treated with bivalirudin.
Based on data derived from the RIFLE-STEACS and STEMI subgroup of RIVAL, in the latest 2012 European Society of Cardiology (ESC) STEMI Guidelines recommendations, TRA is preferred over TFA if performed by an experienced operator (Class IIa, Level B).28
In a cohort of 21,339 patients suffering from STEMI in the Swedish Coronary Angiography and Angioplasty Registry (SCAAR), the adjusted one-year cumulative risk of death was lower in patients treated via TRA (odds ratio [OR] 0.78, 0.64-0.96; p=0.018).29
A recent meta-analysis of nine randomised controlled studies involving 2,977 patients suggested that the TRA is associated with a 47 % reduction in mortality and a 38 % reduction in major adverse cardiac events in STEMI patients undergoing PCI.24
Similarly, analysis of the North American National Cardiovascular Data Registry - CathPCI┬« Registry - that included 90,879 patients who underwent either primary or rescue PCI for STEMI showed that TRA was independently associated with the reduction of in-hospital mortality (OR 0.76, 95 % condence interval [CI] 0.57-0.99) and of bleeding (OR 0.62, 95 % CI 0.53-0.72).30
Finally, the analysis of 46,128 PPCI cases recorded in the British Cardiovascular Intervention Society database over a ve-year period, suggested that TRA was independently associated with a lower 30-day mortality (HR 0.71, p<0.05), in-hospital major adverse cardiac and cerebrovascular events (MACCE) (HR 0.73, p<0.05), major bleeding (HR 0.37, p<0.01) and access site complications (HR 0.38, p<0.01).31 However, the 0.7 % absolute reduction in major bleeding and 0.3 % absolute reduction in access site-related complications associated with TRA use cannot fully explain the scale of the mortality benet associated with TRA in PPCI.31
Additional unmeasured factors may contribute to the benet of TRA PCI. Although some access site complications will not result in signicant blood loss, they may lead to systemic inammation, activation of prothrombotic pathways and activation of the clotting cascade. This could further increase the risk of cardiovascular events even though the initial insult is not haemodynamically signicant.32,33 Bleeding or access site complications can also lead to withdrawal of antiplatelet agents, increasing the risk of ischaemic complications.