ACS = acute coronary syndrome; BMS = bare-metal stent;CIN = contrast-induced nephropathy; DEB/S = drug-eluting balloon/stent; HR = hazard ratio; ICU = intensive care unit; MI = myocardial infarction;OR = odds ratio; PCI = percutaneous coronary intervention;RCT = randomised controlled trial; STEMI = ST-segment elevation MI;(T)AVR = transcatheter aortic-valve replacement;TVR = target vessel revascularisation; VSD = ventricular septal defect

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Welcome to the nineteenth issue of Interventional Cardiology Research Review.This issue begins with the STEMI-RADIAL trial, which has reported superior net clinical benefit with primary PCI, performed by experienced operators, via the radial approach over the femoral approach in patients with STEMI. Chinese researchers have reported that although both transcatheter device closure and surgical repair of perimembranous VSDs in children are effective, the former has some advantages over surgery. Validation data have been presented for a new risk score for predicting CIN that can be easily applied in the setting of urgent or elective PCI. This issue concludes with data suggesting transradial coronary catheterisation is feasible and safe across the entire spectrum of Allen test results.

I hope this issue provides interesting reading for you and, as always, I invite you to send me your comments, feedback and suggestions.

Kind Regards,

Associate Professor Craig Juergens

craig.juergens@researchreview.com.au

ST-segment elevation myocardial infarction treated by radial or femoral approach in a multicenter randomized clinical trialAuthors: Bernat I et al.

Summary: The STEMI-RADIAL trial randomised patients referred for STEMI within 12 hours of symptom onset to undergo primary PCI using the radial (n=348) or femoral (n=359) approach. Compared with the femoral approach, the radial approach was associated with significantly lower: i) 30-day cumulative incidence of major bleeding and vascular access-site complications (primary endpoint; 1.4% vs. 7.2% [p=0.0001]); ii) rate of net adverse clinical events (composite of death, MI, stroke and major bleeding/vascular complications; 4.6% vs. 11.0% [p=0.0028]); iii) duration of time in ICU (2.5 vs. 3.0 days [p=0.0038]); and iv) contrast utilisation (170 vs. 182mL [p=0.01]). No significant between-group differences were seen for the 30-day and 6-month mortality rates. The crossover from radial to femoral approach rate was 3.7%.

Comment: Two recent trials, RIVAL and RIFLE-STEACS, showed improved clinical outcomes in patients presenting with an ACS with a radial approach compared with a femoral approach. Neither study examined a pure cohort of STEMI patients presenting within 12 hours of symptom onset, which is what the current study examined. As to be expected from this four high-volume PCI centre study, major bleeding and serious access-site complications were reduced with a radial approach. Notably, glycoprotein IIb/IIIa inhibitors were used in 45% of patients, and bivalirudin was not available for use, which may have affected the results. Crossover from radial to femoral approach was low at 3.7%, and 0.6% of femoral cases crossed over to radial access. Whilst not powered to show a benefit with respect to mortality, the trends were favourable and there were other benefits of the radial approach, including reduced length of ICU stay.

Reference: J Am Coll Cardiol 2014;63(10):964−72http://content.onlinejacc.org/article.aspx?articleID=1777027

In this issue:STEMI treated by radial vs. femoral approach

TAVR with a self-expanding prosthesis

Transcatheter vs. surgical closure of perimembranous VSDs in children

Acute kidney injury risk post-PCI using radial vs. femoral access

Treatment algorithm for effectively, safely eliminating pseudoaneurysm

Prasugrel + high-dose clopidogrel based on platelet function testing in ACS

A new risk score for predicting post-PCI CIN

Everolimus-eluting stents vs. BMSs in octogenarians

DABs vs. everolimus-eluting stents in BMS in-stent restenosis

Transradial access across the spectrum of Allen test results

Issue 19 - 2014Making Education Easy

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Risk of acute kidney injury after percutaneous coronary interventions using radial versus femoral vascular access: insights from the blue cross blue shield of Michigan cardiovascular consortiumAuthors: Kooiman J et al.

Summary: The risks of acute kidney injury (increase in serum creatinine level of ≥0.5 mg/dL) and nephropathy requiring dialysis were compared between transradial and transfemoral PCI in patients from 47 US hospitals; 8915/82,225 PCI procedures performed utilised the transradial approach. Compared with the transfemoral approach, transradial PCI was associated with significantly lower risks of acute kidney injury (primary endpoint; adjusted OR 0.76 [95% CI 0.62−0.92]) and bleeding, and a trend toward less nephropathy requiring dialysis. A propensity-matched analysis of 8857 procedures per group confirmed significantly lower risks of acute kidney injury with transradial PCI (adjusted OR 0.74 [95% CI 0.58−0.96]) and bleeding (0.47 [0.36−0.63]), and no significant effect on nephropathy requiring dialysis. An independent association was seen between postprocedural bleeding and acute kidney injury (OR 2.86 [95% CI 1.75−4.66]), but the lower acute kidney injury risk was not mediated by a reduction in bleeding with transradial PCI. A sensitivity analysis showed that a moderately strong unknown confounder could explain the association between access site and acute kidney injury.

Comment: Transradial PCI has been shown in a number of trials to reduce vascular complications and bleeding when compared with a transfemoral approach. This study suggests further potential benefits of this approach with respect to a reduction in acute kidney injury. This regional registry of 47 hospitals in the US was an observational study using propensity matching and sophisticated risk adjustment to account for baseline differences. The authors concluded that the reduction in adverse renal outcomes was not solely attributed to a reduction in bleeding. It is possible that by avoiding passing catheters through the descending aorta, you may reduce the risk of cholesterol emboli to the renal arteries, which is known to complicate 0.06−1.8% of coronary invasive procedures. Whilst intriguing, the results need to be confirmed in RCTs specifically looking at the risk of renal injury according to access approach.

Reference: Circ Cardiovasc Interv 2014;7(2):190−8http://circinterventions.ahajournals.org/content/7/2/190.abstract

Transcatheter aortic-valve replacement with a self-expanding prosthesisAuthors: Adams DH et al., for the U.S. CoreValve Clinical Investigators

Summary: This study compared TAVR, using a self-expanding transcatheter aortic-valve bioprosthesis, with surgical AVR in 795 patients with severe aortic stenosis and an increased risk of death during surgery; the participants were randomised 1:1 to either TAVR or surgical AVR. At 1 year, TAVR was superior to surgical AVR for the primary endpoint of all-cause mortality (14.2% vs. 19.1% [p values <0.001 and 0.04 for noninferiority and superiority, respectively]). TAVR was also noninferior to AVR for echocardiographic indices of valve stenosis, functional status and quality of life.

Comment: This multicentre, randomised, noninferiority trial compared the Medtronic self-expanding CoreValve® with surgical valve replacement in patients with severe aortic stenosis at increased surgical risk. The results are impressive, with an absolute 4.9% reduction in 1-year mortality in the CoreValve® group. Whilst not directly comparable, the results are consistent and arguably superior to the results from the PARTNER trials of the Edwards balloon expandable valve. Unlike the PARTNER trials where there was an excess of stroke in the TAVR arms, there were numerically less in the CoreValve® arm, which may be accounted for by more vigorous assessment of this endpoint in this trial. There was a price to pay with increased vascular complications and the much higher need for permanent pacemaker implantation in the CoreValve® group, as shown previously. Overall the results emphasise that TAVR is here to stay as it represents an excellent option for a subset of patients with severe aortic stenosis.

Reference: N Engl J Med 2014;370(19):1790−8http://www.nejm.org/doi/full/10.1056/NEJMoa1400590

Transcatheter versus surgical closure of perimembranous ventricular septal defects in childrenAuthors: Yang J et al.

Summary: Children with perimembranous VSD underwent correction with a surgical or transcatheter approach and were followed for 2 years in this prospective RCT. Compared with the surgical approach, the transcatheter approach was associated with significantly fewer minor adverse events (7 vs. 32), significantly less blood transfused and blood loss, significantly lower median hospitalisation costs and significantly shorter procedure duration and median hospital and ICU stays. Left ventricular end-diastolic dimension normalised in both groups, with no between-group difference for closure rate, adverse events or complications.

Comment: Whilst open-heart surgery is the standard of care for repair of perimembranous VSDs, catheter-based treatments have emerged as a potential alternative. There is a paucity of RCTs in the realm of congenital heart disease treatments, which this three-centre study from China addresses. Only children between 3 and 12 years of age were enrolled, and small defects or unsuitable anatomy for device closure were excluded. The results suggest either technique was associated with a low incidence of major adverse events (one surgical death), but percutaneous closure had reduced minor adverse events and length of stay when compared with surgery. Whilst the results apply only to the use of this specific Shanghai perimembranous VSD occluder (Lepu medical technology Co Ltd) it will be interesting to see the performance of the similarly designed Amplatzer device (AGA Medical Corporation), which is more familiar to Australian operators.

Reference: J Am Coll Cardiol 2014;63(12):1159−68http://content.onlinejacc.org/article.aspx?articleID=1828662

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Safety and efficacy of a potential treatment algorithm by using manual compression repair and ultrasound-guided thrombin injection for the management of iatrogenic femoral artery pseudoaneurysm in a large patient cohortAuthors: Dzijan-Horn M et al.

Summary: These authors reported on 432 pseudoaneurysms, managed according to an algorithm based on morphological properties, diagnosed in 29,091 consecutive patients undergoing femoral artery catheterisation. Pseudoaneurysms <20mm, those with no clearly definable neck, those directly adjacent to vessels and those with concomitant arteriovenous fistula were referred for manual compression (n=145), and all others were treated by ultrasound-guided thrombin injection (n=287). Follow-up duplex scans (evaluable n=428) showed an overall success rate of 97.2%, with success achieved in 178 manual compression procedures and 357 ultrasound-guided thrombin injection procedures. The respective procedural complication rates in the ultrasound-guided thrombin injection and manual compression groups were 1.4% and 1.7%. The treatment algorithm was unsuccessful for 12 patients. Two pseudoaneurysms were successfully excluded by implantation of a covered stent-graft, and ten patients required surgical intervention, which had a complication rate of 30%.

Comment: Pseudoaneurysms complicate femoral access procedures in between 0.05% and 6% of cases. Previously, surgical treatment was the only option, but over the last 20 years, ultrasound-guided manual compression and ultrasound-guided thrombin injections have increasingly been used. The authors of this paper propose a treatment algorithm based on their single-centre retrospective experience of >29,000 patients treated between 2007 and 2011. Ultrasound-guided manual compression for 45−60 minutes was preferred for small pseudoaneurysms, those with arteriovenous fistula, those without a definable neck and those directly adjacent to vessels to reduce the risk of embolisation of thrombin. Notably, ultrasound-guided thrombin injections needed to be repeated more than once in 15% of cases. The overall success rate was good, with complications occurring in <2% of cases, and whilst somewhat arbitrary, their approach seems quite reasonable for the management of this iatrogenic complication.

Reference: Circ Cardiovasc Interv 2014;7(2):207−15http://circinterventions.ahajournals.org/content/7/2/207.abstract

Optimizing P2Y12

receptor inhibition in patients with acute coronary syndrome on the basis of platelet function testing: impact of prasugrel and high-dose clopidogrelAuthors: Aradi D et al.

Summary: Consecutive patients with ACS pretreated with clopidogrel who had undergone successful PCI (n=741) were switched to prasugrel or treated with high-dose clopidogrel if they had high platelet reactivity (>46U; n=219) or continued on clopidogrel 75mg if platelet reactivity was not high. Platelet reactivity decreased after treatment adjustments in participants with high platelet reactivity, but prasugrel was associated with significantly greater platelet inhibition compared with high-dose clopidogrel (p<0.0001). Compared with participants without high platelet reactivity, high-dose clopidogrel recipients had a significantly greater 1-year risk of all-cause death, MI, stent thrombosis or stroke (HR 2.27 [95% CI 1.45−3.55; p<0.0001]) and a higher risk of bleeding (2.09 [1.05−4.17; p=0.04]), while prasugrel recipients had similar risks (0.90 [0.44−1.81; p=0.76] and 0.45 [0.11−1.91; p=0.28]). A multivariate analysis showed that high platelet reactivity with high-dose clopidogrel, but not prasugrel, treatment independently predicted the composite ischaemic endpoint (HR 1.90 [95% CI 1.17−3.08; p=0.01]).

Comment: Whilst there is an association between high on-treatment platelet reactivity and adverse cardiac events after stenting, prospective randomised trials of platelet function testing-guided treatment have failed to show a clinical improvement in outcomes. The problem with these studies is they either enrolled low-risk patients for adverse events and/or used high-dose clopidogrel rather than more potent antiplatelet agents such as prasugrel. This single-centre Hungarian registry suggests that switching patients with ACS who have high on-treatment platelet reactivity to prasugrel reduces thrombotic and bleeding events to a similar level to those patients without high on-treatment platelet reactivity, a benefit not seen with the use of high-dose clopidogrel. Importantly, the choice to use high-dose clopidogrel or prasugrel was not randomised, and we do not know how ticagrelor would have performed, so more randomised studies are needed targeting this cohort of patients.

Reference: J Am Coll Cardiol 2014;63(11):1061−70http://content.onlinejacc.org/article.aspx?articleID=1827546

Validation of a new risk score to predict contrast-induced nephropathy after percutaneous coronary interventionAuthors: Tziakas D et al.

Summary: These researchers calculated and validated a simple CIN risk score in 2882 consecutive patients treated with elective or urgent PCI. CIN, defined as an increase in baseline serum creatinine level of ≥25% or ≥0.5 mg/dL within 48 hours of PCI, was seen in 15.7% of study participants. The researchers’ CIN risk score (2 points for each of pre-existing renal disease, metformin use and peripheral arterial disease; 1 point for each of previous PCI and injected volume of contrast medium ≥300mL) was found to have good predictive accuracy (c-statistic 0.741 [95% CI 0.713−0.769]), with a score of ≥3 having the best diagnostic accuracy. Robust predictive ability was demonstrated, as was good discrimination across all predefined subgroups. Compared with two previously published CIN risk scores, these researchers’ risk score had better discriminative ability and resulted in significantly improved net reclassification and integrated discrimination (p<0.001).

Comment: CIN is associated with increased morbidity and mortality. This multicentre, international study attempted to validate a simple risk tool designed to identify patients prospectively undergoing coronary interventional procedures who are at increased risk for CIN. The proposed risk score had been derived from a cohort of 488 patients, of whom 10% developed CIN. The model performed well and could potentially be used to guide decisions around the performance of complex interventions as single or staged procedures, deciding on periods of observation after procedures and perhaps better targeting of renal protective therapies. Further studies are needed, especially with respect to the ability to predict the need for dialysis, which only occurred in 0.4% of patients.

Reference: Am J Cardiol 2014;113(9):1487−93http://www.ajconline.org/article/S0002-9149%2814%2900625-0/abstract

A prospective randomized trial of everolimus-eluting stents versus bare-metal stents in octogenariansAuthors: de Belder A et al.

Summary: The XIMA (Xience or Vision Stents for the Management of Angina in the Elderly) trial randomised patients aged ≥80 years to stent placement for stable angina or ACS with BMSs (n=401) or DESs (n=399). No significant difference was seen between the BMS and DES arms for the primary endpoint event rate (1-year composite of death, MI, cerebrovascular accident, TVR or major haemorrhage; 18.7% and 14.3%, respectively [p=0.09]), mortality rate (7.2% and 8.5% [p=0.50]), major haemorrhage rate (1.7% and 2.3% [p=0.61]) or cerebrovascular accident rate (1.2% and 1.5% [p=0.77]), but the MI and TVR rates were significantly higher in the BMS arm (8.7% and 4.3% [p=0.01] and 7.0% and 2.0% [p=0.001], respectively).

Comment: Due to improvements in healthcare, very elderly patients (age >80 years) are becoming more prevalent in daily clinical cardiology practice. Few clinical trials have included such patients who often have complex anatomy and comorbidities where it is difficult to weigh up the benefits and risks of the use of DESs. This multicentre randomised trial from 22 centres in the UK and Spain provides some clarity around this clinical scenario. Indication for angiography was a troponin-positive ACS in 50% and radial access was used in >50% of patients. The study showed that the use of the second-generation everolimus-eluting Xience stent provided superior outcomes when compared with the BMS, Vision. Despite the use of dual antiplatelet therapy in 94% of DES patients at 1 year (32% BMS group), there was no difference in major haemorrhage between the two groups, suggesting a DES strategy is also reasonably safe.

Reference: J Am Coll Cardiol 2014;63(14):1371−5http://content.onlinejacc.org/article.aspx?articleID=1777025

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Transradial coronary catheterization and intervention across the whole spectrum of Allen test resultsAuthors: Valgimigli M et al.

Summary: The ability of the Allen test to predict ischaemic complications after transradial access was evaluated in 203 patients; 83, 60 and 60 participants had normal, intermediate and abnormal Allen test results, respectively. No significant differences were seen for the normal, intermediate and abnormal Allen test groups for thumb capillary lactate level after the procedure (1.85, 1.85 and 1.97 mmol/L, respectively [p=0.59]) or at other study timepoints. Participants with non-normal Allen test results had improvements in ulnopalmar collateralisation on plethysmography, while the ulnar frame count decreased in those with abnormal Allen test results after transradial access. No difference was seen across Allen test result groups for handgrip strength or discomfort ratings, and no hand ischaemic complications were seen.

Comment: The modified Allen test has been used to evaluate the patency of the ulnopalmar arches, with a somewhat arbitrary threshold of 6−10 seconds to achieve full blushing of the hand, after the release of radial artery compression, described as normal. It has been suggested that if this does not occur, the radial artery should not be used for arterial access. This study performed a number of sophisticated measurements to put this paradigm to the test, and concluded that transradial access may be feasible across the broad spectrum of Allen test results. Planned studies with clinical endpoints in larger groups of patients are needed before totally abandoning the conservative approach of performing the Allen test before considering radial access for interventional procedures.

Reference: J Am Coll Cardiol 2014;63(18):1833−41http://content.onlinejacc.org/article.aspx?articleID=1838327

A randomized comparison of drug-eluting balloon versus everolimus-eluting stent in patients with bare-metal stent–in-stent restenosisAuthors: Alfonso F et al.

Summary: The RIBS V (Restenosis Intra-stent of Bare Metal Stents: Paclitaxel-Eluting Balloon vs. Everolimus-Eluting Stent) clinical trial randomised patients with BMS in-stent restenosis to DEBs (n=95) or everolimus DESs (n=94). Compared with DEBs, the DESs were associated with significantly larger minimal lumen diameter on angiography at median 249 days (primary endpoint; 2.36 vs. 2.01mm [p<0.001]) and a lower percent of diameter stenosis (13% vs. 25% [p<0.001]), but similar late loss (0.04 vs. 0.14mm [p=0.14]) and binary restenosis rate (4.7% vs. 9.5% [p=0.22]). Over median clinical follow-up of 365 days, no significant difference was seen between the DEB and DES arms for the combined clinical outcome measure of cardiac death, MI and TVR (6% vs. 8%; HR 0.76 [95% CI 0.26−2.18; p=0.6]) or the need for TVR (2% vs. 6%; 0.32 [0.07−1.59; p=0.17]).

Comment: The treatment of BMS in-stent restenosis remains a challenge, and the relative benefits of the use of second-generation DESs when compared with the use of a DEB were to date unknown. This 25-hospital study from Spain addresses this knowledge void. The authors concluded that the use of a Xience Prime DES was superior to the use of SeQuent DEB with respect to angiographic outcomes, with clinical outcomes similarly low in both groups. Of note, the use of dual antiplatelet therapy was recommended for 3 months in the DEB group and 12 months in the DES cohort, and this may be relevant in choosing a strategy for an individual patient. Larger studies powered for clinical endpoints are needed, but either strategy appears reasonable for the treatment of BMS in-stent restenosis.

Reference: J Am Coll Cardiol 2014;63(14):1378−86http://content.onlinejacc.org/article.aspx?articleID=1813141

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Privacy Policy: Research Review will record your email details on a secure database and will not release them to anyone without your prior approval. Research Review and you have the right to inspect, update or delete your details at any time. Disclaimer: This publication is not intended as a replacement for regular medical education but to assist in the process. The reviews are a summarised interpretation of the published study and reflect the opinion of the writer rather than those of the research group or scientific journal. It is suggested readers review the full trial data before forming a final conclusion on its merits.

Research Review publications are intended for Australian health professionals.