CABG = coronary artery bypass graft; CV = cardiovascular;DAPT = dual antiplatelet therapy; DES = drug-eluting stent;FFR = fractional flow reserve; HR = hazard ratio; IVUS = intravascular ultrasound; PCI = percutaneous coronary intervention; RCT = randomised controlled trial; ST = stent thrombosis;(STE)MI = (ST-segment elevation) myocardial infarction; SVG = saphenous vein graft; TAVR = transcatheter aortic valve replacement

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Welcome to issue 21 of Interventional Cardiology Research Review.This issue includes an analysis of FAME study data that shows the benefits of FFR-guided PCI are not influenced by age, but older patients do have fewer functionally significant lesions despite similar angiographic appearance. Also on the subject of FFR, researchers from South Korea reported that an IVUS-derived minimum lumen area of ≤4.5 mm2 is a useful index of an FFR of ≤0.80 in patients with isolated ostial and shaft intermediate left main coronary artery stenosis. There is also an interesting, comprehensive meta-analysis demonstrating that FFR has a continuous, independent relationship with subsequent outcomes that is modulated by medical therapy versus revascularisation.

I hope you enjoy the selection for this issue, and I am always happy to respond to questions and comments.

Kind Regards,

Associate Professor Craig Juergenscraig.juergens@researchreview.com.au

A bioresorbable everolimus-eluting scaffold versus a metallic everolimus-eluting stent for ischaemic heart disease caused by de-novo native coronary artery lesions (ABSORB II)Authors: Serruys PW et al.

Summary: This was an interim 1-year RCT analysis of 501 adults with evidence of myocardial ischaemia and 1–2 de novo native lesions in different epicardial vessels randomised to an everolimus-eluting bioresorbable scaffold (n=335) or an everolimus-eluting metallic stent (n=166). Compared with the scaffold arm, the stent recipients had higher and larger dilatation pressure and balloon diameter at the highest pressure during implantation or postdilatation, but the same acute recoil postimplantation at 0.19mm. The scaffold group had significantly lower acute lumen gain, resulting in a smaller postprocedural lumen diameter or area. However, compared with the stent group, the scaffold group had a lower cumulative rate of first new or worsening angina at 1 year (22% vs. 30% [p=0.04]), although performance during maximum exercise, angina status and the 1-year composite device-oriented endpoint were similar between groups. Definite or probable scaffold thromboses were seen in three participants compared with no STs. The respective major cardiac adverse event rates in the scaffold and stent arms were 5% and 3%, most commonly MI (4% and 1%) and clinically indicated target-lesion revascularisation (1% and 2%).

Comment: Bioresorbable scaffolds (not stents) are the latest percutaneous approach to the treatment of coronary artery disease. The steering committee and trial sponsor of the ABSORB II study decided to report secondary clinical and procedural endpoints at 1 year ahead of the primary endpoints, which are 3-year endpoints, due to the rapid commercial uptake of this device. The results are encouraging despite a numerically higher rate of periprocedural non-Q MIs, which may relate to the thicker strut thickness (150µm) of the scaffold compared with the metallic stent comparator (80µm). The lower cumulative rate of angina with the scaffold is so far unexplained but may relate to return of vasomotion or improved conformability of the scaffold, which has been reported previously. We await the results of longer term follow-up with interest.

Reference: Lancet 2015;385(9962):43–54Abstract

In this issue:Everolimus bioabsorbable scaffold vs. metal stent for ischaemic heart disease

The impact of age on FFR-guided PCI

Outcomes 1 year after thrombus aspiration for MI

Outcomes of primary PCI in STEMI with previous CABG

TAVR performed in the catheterisation laboratory

Radial vs. femoral approach for PCI in women

IVUS-derived minimal lumen area for left main coronary artery stenosis

Prognostic value of FFR

Predictors and outcomes of recurrent ST

DAPT for 12 vs. 30 months after DESs

Issue 21 - 2015Making Education Easy

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Independent selection and review of the trials by Associate Professor Craig Juergens,Interventional Cardiologist and Head of Cardiology, Liverpool Hospital, Sydney.

Interventional CardiologyResearch ReviewTM

Interventional CardiologyResearch ReviewTM

* In patients with ACS, BRILINTA reduces the risk of CV death, MI or stroke vs clopidogrel at 12 months (primary composite endpoint: ARR 1.9%, RRR 16%; p<0.001).1,2

improvedoutcomesstart here*

®

Please click here to review full product information before prescribing. Further information available on request from AstraZenecaACS=acute coronary syndromes; CV=cardiovascular; MI=myocardial infarction; ARR=absolute risk reduction; RRR=relative risk reduction. References: 1. Wallentin L et al. N Engl J Med 2009;361:1045–57. 2. BRILlNTA® Approved Product Information. BRILINTA® is a registered trademark of the AstraZeneca group of companies. Registered user AstraZeneca Pty Ltd. ABN 54 009 682 311. 5 Alma Road, North Ryde NSW 2113. Medical Information: 1800 805 342. www.astrazeneca.com.au, 186801.022, WL282043, September 2014

PBS Information: Authority Required (STREAMLINED). Treatment of acute coronary syndrome (myocardial infarction or unstable

angina) in combination with aspirin.

STREAMLINED AUTHORITY CODE 3879

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Interventional CardiologyResearch ReviewTM

The impact of age on fractional flow reserve-guided percutaneous coronary interventionAuthors: Lim H-S et al.

Summary: One-year outcomes according to age group were reported for 512 FAME study participants who underwent FFR- or angiography-guided PCI. The 1-year death, MI or repeat revascularisation rate tended to be higher in the angiography-guided group than in the FFR-guided group for patients aged <65 years (17.2% vs. 12.0% [p=0.098]) and those aged ≥65 years (19.7% vs. 14.3% [p=0.111]); no significant age interaction was evident (p=0.920). Compared with the younger participants, those aged ≥65 years had greater FFR in vessels with 50–70% stenosis (0.83 vs. 0.80 [p=0.028]) and 71–90% stenosis (0.69 vs. 0.65 [p=0.002]), and they also had a lower proportion of functionally significant lesions (FFR ≤0.80) in vessels with 71–90% stenosis (75.3% vs. 84.1% [p=0.013]).

Comment: The FAME study, which enrolled patients aged 32–89 years (median 64), demonstrated that FFR-guided intervention in multivessel disease was superior to an angiographic-guided approach. This post hoc subanalysis of the FAME study showed that whilst patients older than 65 years of age had a higher event rate than younger patients, the benefits of FFR in terms of reducing major adverse cardiac events were the same. The most interesting finding was that despite similar angiographic appearances, the number of functionally significant lesions was lower in the older cohort. This is presumably related to greater degrees of microvascular dysfunction in older patients, although other differences such as lesion length and reference diameter may have played a role.

Reference: Int J Cardiol 2014;177(1):66–70Abstract

Outcomes 1 year after thrombus aspiration for myocardial infarctionAuthors: Lagerqvist B et al.

Summary: Patients with STEMI were randomised to manual thrombus aspiration followed by PCI (n=3621) or PCI alone (n=3623) in this RCT. No significant difference was seen between the thrombus-aspiration and PCI only groups for the 30-day all-cause mortality rate (primary endpoint; 5.3% vs. 5.6%; HR 0.94 [95% CI 0.78–1.15]), rehospitalisation for MI at 1 year (2.7% vs. 2.7%; 0.97 [0.73–1.28]), ST rate at 1 year (0.7% vs. 0.9%; 0.84 [0.50–1.40]) or the 1-year composite of death from any cause, rehospitalisation for MI or ST (8.0% vs. 8.5%; 0.94 [0.80–1.11]). Consistency was seen among the results across all the major subgroups (including thrombus burden grade and pre-PCI coronary flow).

Comment: Whilst primary PCI remains the optimal approach to improve myocardial reperfusion and clinical outcomes, controversy remains over the adjunctive use of thrombus aspiration. Whilst the single-centre, 1071-patient TAPAS trial suggested a mortality benefit out to 1 year, the trial was underpowered for hard clinical endpoints. The TASTE multicentre, prospective RCT enrolled 7244 patients and reported no benefit with thrombus aspiration at 30 days. This paper now reports results out to 1 year. Whilst the outcomes of this trial were recorded on the basis of registry data, which are not as rigorous as in a conventional randomised trial, the results are consistent with the early results in that there was no benefit in routine thrombus aspiration. The yet-to-be-reported, 10,770-patient TOTAL trial is another randomised trial, which should provide the final word on this contentious technique.

Reference: N Engl J Med 2014;371(12):1111–20Abstract

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Outcomes of primary percutaneous coronary intervention in ST-segment elevation myocardial infarction patients with previous coronary bypass surgeryAuthors: Kohl LP et al.

Summary: This paper described the clinical characteristics and outcomes of patients with STEMI and previous CABG, including those with a SVG culprit lesion. Data were obtained from a large, regional STEMI system’s prospective database containing 3542 unique STEMI episodes. A total of 249 patients (7%) had previous CABG. Despite higher comorbidity, patients with versus without previous CABG had similar in-hospital and 1-year mortality rates (4.8% vs. 5.2% [p=0.82] and 10.8% vs. 9.1% [p=0.36], respectively), but the 5-year mortality rate was significantly higher (24.9% vs. 14.2% [p<0.001]). Patients with previous CABG had similar door-to-balloon times. The culprit vessel was the SVG in 34% of patients, a native vessel in 42% and no clear culprit vessel in 24%. The left internal mammary artery graft was not a culprit in any patient. Mortality at 30 days (8.3% vs. 3.9% vs. 1.7% [p=0.19]) and 1 year (14.3% vs. 9.0% vs. 6.8% [p=0.35]) was higher (but not statistically) with a SVG culprit vessel and was equivalent at 5 years (25.0% vs. 26.0% vs. 20.3% [p=0.71]).

Comment: The history of previous CABG in a patient presenting with STEMI poses a diagnostic and therapeutic challenge and represents a risk factor for an adverse outcome. This prospective, nonrandomised, single-centre study reported the outcomes of the 7% of patients presenting with STEMI and a history of CABG. Interesting data include that the left internal mammary artery was never the culprit and the culprit vessel was most often a native vessel. Outcomes were comparable with patients with no prior history of CABG; however, with larger numbers we may see patients presenting with an SVG occlusion to have significantly worse outcomes.

Reference: JACC Cardiovasc Interv 2014;7(9):981–7Abstract

Comparison of transfemoral transcatheter aortic valve replacement performed in the catheterization laboratory (minimalist approach) versus hybrid operating room (standard approach): outcomes and cost analysisAuthors: Babaliaros V et al.

Summary: These researchers compared baseline characteristics, outcomes and hospital costs associated with a minimalist transfemoral TAVR approach in a catheterisation laboratory (n=70) with the standard approach in a hybrid operating theatre (n=72). All the minimal approach procedures were successful and only one patient required intubation, whereas there were three procedure-related deaths with the standard approach, but the between-group 30-day mortality rate did not differ significantly (p=0.12). Compared with the standard approach, the minimalist approach was associated with significant reductions in procedure room time (150 vs. 218 min [p<0.001]), total intensive-care unit time (22 vs. 28h [p<0.001]), length of stay from procedure to discharge (3 vs. 5 days [p<0.001]) and cost (p<0.001). There was no significant between-group difference for the 30-day stroke/transient ischaemic attack, moderate or severe paravalvular leak or device success rate, or survival at median follow-up of 435 days (83% and 82%, respectively).

Comment: As experience with TAVR increases, some centres are performing the procedure in a standard cardiac catheterisation laboratory without general anaesthesia or transoesophageal echocardiography. This retrospective, single-centre study from Emory hospital in the US compared outcomes using this so-called minimalist approach with the standard approach in a hybrid operating room. There was equivalent morbidity and mortality with expected reduced costs and length of stay with the ‘minimalist approach’. Whilst a relatively small study, the results suggest the feasibility of such an approach once operators are comfortable with the technique and should encourage further research into this area.

Reference: JACC Cardiovasc Interv 2014;7(8):898–904Abstract

A registry-based randomized trial comparing radial and femoral approaches in women undergoing percutaneous coronary interventionAuthors: Rao SV et al.

Summary: The registry-based SAFE-PCI for Women study randomised 1787 women undergoing cardiac catheterisation or PCI to the femoral or radial approach; the trial was terminated early due to a lower than expected event rate. No significant difference was seen between radial versus femoral access for the primary efficacy endpoint (Bleeding Academic Research Consortium type 2, 3 or 5 bleeding or vascular complications requiring intervention) among women undergoing PCI (n=691; 1.2% vs. 2.9%; odds ratio 0.39 [95% CI 0.12–1.27]). However, radial access was associated with a significantly lower rate of bleeding or vascular complications among women undergoing cardiac catheterisation or PCI (0.6% vs. 1.7%; 0.32 [95% CI 0.12–0.90]) and significantly higher access-site crossover rates among women undergoing PCI (6.1% vs. 1.7%; 3.65 [1.45–9.17]) and the entire cohort (6.7% vs. 1.9%; 3.70 [2.14–6.40]). Radial access was preferred by more women.

Comment: Using radial access for PCI significantly reduces bleeding and access-site complications when compared with the femoral approach. Females are at higher risk for bleeding complications than males, but have smaller radial arteries that are more prone to spasm. They have also been under-represented in RCTs comparing access sites. This multicentre, prospective, open-label clinical trial used randomisation into a registry to assess radial access in women. An unplanned meeting of the Data Safety Monitoring Board was convened due to a lower than expected primary efficacy endpoint rate, and whilst there was no evidence of harm, they recommended terminating the trial early because it was unlikely to show a significant difference with the planned sample size. The crossover rate from radial to femoral access was 6.7% and women preferred the radial approach, but in the PCI cohort alone there was no significant advantage of this approach, although combining the diagnostic and PCI groups did show an advantage, consistent with other studies.

Reference: JACC Cardiovasc Interv 2014;7(8):857–67Abstract

Intravascular ultrasound-derived minimal lumen area criteria for functionally significant left main coronary artery stenosisAuthors: Park S-J et al.Summary: These researchers reported on 112 patients with isolated ostial and shaft intermediate left main coronary artery stenosis (angiographic diameter stenosis 30–80%) who underwent IVUS and FFR measurements. The FFR was ≤0.80 in 59% of lesions, and these had smaller reference vessels, a smaller minimal lumen diameter, greater stenosis diameter, longer lesion length, smaller minimal lumen area, larger plaque burden and more frequent plaque rupture. Factors significantly, independently associated with an FFR of ≤0.80 were plaque rupture (odds ratio 4.47 [95% CI 1.35–14.8]), body mass index (1.19 [1.00–1.41]), age (0.95 [0.90–1.00]) and IVUS minimal lumen area (0.37 [0.25–0.56]). An optimal IVUS minimal lumen area cutoff of 4.5mm2 for an FFR of ≤0.80 had sensitivity and specificity of 77% and 82%, respectively, positive and negative predictive values of 84% and 75%, respectively, and an area under the curve of 0.83 (95% CI 0.76–0.96); the optimal cutoffs were 4.1–4.5mm2 among various subgroups. The diagnostic accuracy of the IVUS minimal lumen area was not improved by adjustments for body surface area, body mass index or left ventricular mass.

Comment: An IVUS minimal luminal area of 6mm2 has conventionally been considered an indication for revascularisation of equivocal angiographic left main lesions. However, since the development of FFR, this value has been called into question. This study from South Korea of Asian patients, which excluded patients with significant left anterior descending and/or left circumflex artery disease, suggests that a minimal luminal area of <4.5mm2 is a more useful predictor of an FFR of <0.80. It remains to be seen if adopting this threshold translates into a clinically safe strategy in a larger study, as the current study did not present clinical outcomes of their patients. It should also be tested in different racial groups to ensure it applies.

Reference: JACC Cardiovasc Interv 2014;7(8):868–74Abstract

Prognostic value of fractional flow reserve: linking physiologic severity to clinical outcomesAuthors: Johnson NP et al.Summary: This meta-analysis of 9173 study-level and 6961 patient-level lesions followed for 16 and 14 months, respectively, reported on the prognostic value of FFR measurements. Decreasing FFR corresponded to increases in clinical events, and revascularisation revealed a larger net benefit for lower baseline FFR values. Thresholds for outcome-derived FFR values were generally 0.75–0.80, but were limited due to confounding by indication. There was also an inverse association between FFR measured immediately after stenting and prognosis (HR 0.86 [95% CI 0.80–0.93]). Revascularisations were reduced by about half using an FFR-assisted strategy versus an anatomy-based strategy, but with a 20% reduction in adverse events and a 10% improvement in angina relief.

Comment: FFR has become an important tool for selecting appropriate lesions for revascularisation with studies using a dichotomous cutoff value of <0.75 or 0.80 to decide if a lesion is haemodynamically significant. This study demonstrated that there is in fact a continuous relationship between FFR values and clinical events by looking at raw data for every patient identified in manuscripts published on the topic. This meta-analysis represents thousands of patients from more than 12 countries spanning more than 15 years of publications. Whilst the number of patients with very low FFR values was small, as one would expect given the trials predominantly looked at intermediate angiographic lesions, it would appear that the lower the FFR the greater the benefit.

Reference: J Am Coll Cardiol 2014;64(16):1641–54Abstract

®

* In patients with ACS, BRILINTA reduces the risk of CV death, MI or stroke vs clopidogrel at 12 months (primary composite endpoint: ARR 1.9%, RRR 16%; p<0.001).1,2

* BRILINTA is initiated with a single 180mg dose and then continued at 90mg twice daily in combination with aspirin.2

improved outcomesstart here*

As with other antiplatelet agents, BRILINTA prolongs bleeding time and should be used with caution in ACS patients who may be at risk of increased bleeding. Premature discontinuation could result in an increased risk of cardiovascular death, or myocardial infarction due to the patient’s underlying disease2.

Please click here to review full product information before prescribing. Further information available on request from AstraZenecaACS=acute coronary syndromes; CV=cardiovascular; MI=myocardial infarction; ARR=absolute risk reduction; RRR=relative risk reduction. References: 1. Wallentin L et al. N Engl J Med 2009;361:1045–57. 2. BRILlNTA® Approved Product Information. BRILINTA® is a registered trademark of the AstraZeneca group of companies. Registered user AstraZeneca Pty Ltd. ABN 54 009 682 311. 5 Alma Road, North Ryde NSW 2113. Medical Information: 1800 805 342. www.astrazeneca.com.au, 186801.022, WL282043, September 2014

PBS Information: Authority Required (STREAMLINED). Treatment of acute coronary syndrome (myocardial infarction or unstable

angina) in combination with aspirin.

STREAMLINED AUTHORITY CODE 3879

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Interventional CardiologyResearch ReviewTM

Predictors and outcomes of recurrent stent thrombosisAuthors: Armstrong EJ et al.

Summary: This research used multicentre registry data to explore the incidence, predictors and outcomes of recurrent ST in 221 patients with an initial ST followed for a median of 3.3 years; 29 patients developed definite or probable recurrent ST, including 19 with angiographic definite recurrent ST. The respective 1- and 5-year cumulative HRs of definite/probable recurrent ST were 16% and 24% and of definite recurrent ST on angiography were 11% and 20%. Compared with patients without recurrent ST, those with recurrent ST had a significantly greater mean peak creatine kinase level at the time of their initial ST (2655 vs. 1654 mg/dL [p=0.05]), despite similar angiographic findings, and a significantly higher 3-year major adverse CV event rate (50% vs. 22% [p=0.01]). Independent predictors of definite/probable recurrent ST were age (adjusted HR, for every 10-year increase, 1.4 [95% CI 1.1–1.8]), bifurcation ST (4.4 [1.8–10.9]) and proximal vessel diameter (per mm, 1.8 [1.1–3.2]).

Comment: ST occurs infrequently but is associated with a high morbidity and a 30-day mortality rate of between 10% and 25%. For those who survive the first ST, recurrent ST is not uncommon with little published data on the predictors of recurrence and outcomes. This registry study from five academic interventional centres in California, US, provides some insights into this phenomenon. Patients were not routinely tested for antiplatelet ‘resistance’ and there was infrequent use of more potent antiplatelet agents such as ticagrelor or prasugrel, which most would prescribe these days after ST if not before. The main findings were that during 5-year follow-up, definite recurrent ST occurred in 20% of patients – predictors were coronary bifurcation and large proximal reference vessel diameter – and mortality and major adverse CV event rates were higher than the first ST event.

Reference: JACC Cardiovasc Interv 2014;7(10):1105–13Abstract

Twelve or 30 months of dual antiplatelet therapy after drug-eluting stentsAuthors: Mauri L et al., for the DAPT Study Investigators

Summary: This study enrolled 9961 patients who received DAPT (aspirin and either clopidogrel or prasugrel) for 12 months after receiving a DES, and then randomised them 1:1 to continue with DAPT or to switch to aspirin alone for a further 18 months. Compared with aspirin alone, DAPT reduced the rates of ST (0.4% vs. 1.4%; HR 0.29; [95% CI 0.17–0.48]) and major adverse CV and cerebrovascular events (4.3% vs. 5.9%; 0.71 [0.59–0.85]) in the 12–30 months after stent placement. The rate of MI was lower with DAPT than with aspirin alone (2.1% vs. 4.1% [p<0.001]), but the rates of all-cause mortality (2.0% vs. 1.5% [p=0.05]) and moderate or severe bleeding (2.5% vs. 1.6% [p=0.001]) were higher.

Comment: Whilst DESs reduce the rate of restenosis when compared with bare-metal stents, concerns remain around risk of ST beyond 1 year of DAPT. Several trials have suggested prolonged DAPT beyond 1 year increases the bleeding risk without a reduction in major adverse cardiac events. This study represents the largest study to date and confirms the increased bleeding risk, but suggests a reduction in major adverse cardiac events and ST. There was a higher rate of non-CV death in the prolonged DAPT group, which is in part due to increased fatal bleeding but also due to increased cancer-related deaths. There were more patients with a history of cancer in the prolonged DAPT group and seven more cases of cancer diagnosed at randomisation in this group, so this difference may be due to the play of chance. The patients who benefited most with prolonged DAPT were those who received a paclitaxel eluting stent, suggesting the benefits of prolonged therapy may depend on which DES is used, and as always we should weigh the bleeding risk with the consequences of potential ST.

Reference: N Engl J Med 2014;371(23):2155–66Abstract

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