Bleeding is a frequent complication during PCI and 30–70 % of these events are related to the access site. This broad variability depends mostly on the patient’s clinical presentation. In fact, acute patients are more prone to access site bleeding, whereas in stable patients two-thirds are not access site related [6].

The radial approach brings a 65 % reduction of major vascular access site complications, 49 % of non–CABG-related major bleeding, and 35 % reduction of the transfusion rate compared with the femoral approach [7]. Interestingly, radial access benefit persisted when vascular closure devices were used in the femoral cohort [8].

The reduction of bleeding events is of paramount importance considering the strong correlation between major bleeding and mortality [9, 10]. In a study of over 26,000 patients with non–ST-segment elevation ACS, there was a significant interaction between bleeding severity and the rate of death at 30-days, death at 6 months or the composite of death and MI [11].

A sub-analysis of the TRITON-TIMI 38 trial [12] showed that serious spontaneous bleeding tended to have a sustained impact on mortality for approximately 1 month, as it was shown by an elevated hazard ratio within the first 30 days after PCI followed by a non-significant trend thereafter. Similarly, a recent analysis from the PLATO trial also demonstrated that procedure-related bleeding is strongly associated with short-term mortality [13].

To further corroborate these findings, the application of bleeding prevention strategies demonstrated a better survival during an acute coronary syndrome. The OASIS-5 trial compared fondaparinux with enoxaparin in a court of 20,078 patients with non-ST-segment elevation ACS. This study showed that fondaparinux was not inferior to enoxaparin with respect to 9 day composite ischemic endpoints, and superior with respect to major bleeding at 9 days (fondaparinux 2.2 % vs. enoxaparin 4.1 %, p < 0.001) [14] eventually resulting in a significant reduction of death from all causes at 1 month (deaths in fondaparinux arm 574 vs. deaths in enoxaparin arm 638, p = 0.05).

Similarly, in HORIZONS AMI, the implementation of the direct thrombin inhibitor bivalirudin, compared with unfractionated heparin plus glycoprotein IIb/IIIa inhibitors in patients undergoing primary PCI, resulted in both a reduction of major bleeding (4.9 % vs. 8.3 %, p < 0.001) and mortality at 30 days (2.1 % vs. 3.1 %, p = 0.047) [15].

However, it is worth mentioning that patients with a higher bleeding risk usually carry also a higher ischemic risk. In fact, bleeding more frequently occurs in sicker patients, and a possible lack of cause-effect between the two events could be argued, being this correlation driven by host or putative mechanisms [16]. On the other hand, discontinuation of antithrombotic therapy, transfusions and severe anemia after bleeding are likely to be important prognostic modifiers and all need to be prevented [17].

Finally, it has been demonstrated that non-access site related bleeding carries a relatively higher risk of death compared with access site bleeding (HR 2.2) [18, 19]. Access site selection hardly affects non-access-site bleeding, on the other hand, the application of a modern antithrombotic regimen and optimal anti platelet therapy could mitigate the excess bleeding risk and improve the outcome [15, 20].

The limits of the radial technique have been pushed far forward since its first introduction. The advances in experience and technology allow today the treatment of complex PCI cases like bifurcations, unprotected left main coronary artery [21] and chronic total occlusions [22] from the radial access. Importantly, the rates of procedural success are similar to the femoral approach [23] but only for experienced radial operators.

Many studies tried to delineate the learning curve of the radial technique. Ball et al. prospectively collected from 1999 to 2008 a total of 1672 patients with non-urgent, single vessel disease, underwent TR-PCI by 28 operators. The outcomes were stratified into chronological groups of cases for operators starting transracial technique in their institution: the first group from case 1 to case 50 and so on 51–100, 101–150, 151–300. The control group consisted of experienced radial operators with more than 300 TR-PCI. The study found that the PCI failure rate was inversely related with the case volume, with a 32 % decrease in PCI failure every additional 50 PCIs performed. The author’s eventually concluded that a case volume of at least 50 PCI is needed to achieve an outcome comparable with an expert radial operator. However, considering that this study included non-urgent, single vessel disease, the learning curve for more complex PCI is likely to be steeper [24]. Similarly, Looi et al. showed how after 6 months of practice in diagnostic radial angiography, fellows reached results comparable with senior operators [25].

Interestingly, another single study about the radial approach learning curve showed that the left radial approach had a shorter learning curve compared to right radial access [26]. These results could be explained by a lower impact of subclavian tortuosity in the left radial artery (OR 2,7) and by an easier maneuverability of the catheters that, originally designed for the femoral route, adapt better to the left radial anatomy [26].

Certainly, the more complex is the radial anatomy, the more difficult and longer is the procedure with consequences on procedural times and radiation exposure. This is particularly true for the diagnostic angiograms whereas the impact on PCI is milder. As could be expected, procedural times and radiation dose decrease with operator’s expertise [5].

In the past few years an important burden of evidence has been collected for the comparison of femoral and radial access approaches.

The MORTAL registry, published in 2008 by Chase et al. retrospectively analyzed 38,872 patients treated with PCI either via TRA (7,972 patients) or TFA (30,900 patients). The results showed that TRA reduced the need for blood transfusion (1.4 % vs. 2.8 %) and 1-year mortality (3.9 % vs. 2.8 %). Importantly, the patient population mainly consisted of ACS treated on an urgent basis [27]. Other observational studies demonstrated afterwards the same conclusions.

The lack of a randomized trial comparing the two strategies was finally overcome with the presentation of the pivotal radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL) trial. RIVAL recruited 7,021 patients in 32 countries, of which 3,507 patients were randomly assigned to radial access and 3,514 to femoral access. The primary outcome was the composite of death, myocardial infarction, stroke, or non- coronary artery bypass graft (non-CABG)-related major bleeding at 30 days. The trial ultimately failed to demonstrate a significant superiority of the radial access with respect to the primary endpoint (3.7 % vs. 4.0 %, [HR] 0.92, 95 %CI 0.72–1.17; p = 0.50). Major vascular access site complications were significantly reduced in the radial arm (1.4 % vs. 3.7 % P < 0.0001), whereas non-CABG-related TIMI major bleeding (0.5 % vs. 0.5 % P = 1.00) and access site major bleeding (0.2 % vs. 0.3 % P = NS) were similar in the two groups [7].

Importantly, it has been shown that, in patients with STEMI, there was a benefit with radial access for the composite of death, MI and stroke (P_int = 0.011), and death for all causes (interaction P_int = 0.001). A significant interaction for the primary outcome was finally noted in the highest tertile volume radial centers (HR 0.49, 95 %CI 0.28–0.87; p = 0.015). These findings strongly questioned the previous results suggested by the observational studies. However, at a deeper analysis some of the reasons of such a divergence could be identified.

First, a post-hoc analysis that evaluated the actual location of the access-site major bleeding showed that all the six reported events found in the radial group did not consist of real radial-related complications but of consequences of IABP or radial-to-femoral cross-over confounded by the intention-to-treat design of the study. Thus, after reallocating the bleeding events in the pertinent group, a significant relation between access-site major bleeding and femoral access (0 vs. 18 events) was present also in RIVAL [7].

Second, the bleeding definition used to adjudicate the events is of paramount importance. In fact, the use Acute Catheterization and Urgent Intervention strategy (ACUITY) trial bleeding criteria showed a significant reduction of major bleeding in the radial cohort (p < 0.0001).