Updates on PCI Guidelines and Trials From the European Society of Cardiology (ESC) Congress

Every year, cardiologists from around the world convene for the European Society of Cardiology (ESC) Congress, which was held this August in Munich, Germany. New study results are presented, updates to guidelines and consensus papers are reviewed, and differences in practice patterns from around the globe are shared. While I could not attend personally, I try to keep abreast of the most interesting news and information applicable to cath lab practices. I thought I’d review some points of interest for us here.

Published just recently in the European Heart Journal¹, the ESC guidelines for revascularization were updated after being reviewed by general and interventional cardiologists alike. Historically, compared with American College of Cardiology (ACC)/American Heart Association (AHA)/Society for Cardiovascular Angiography and Interventions (SCAI) guidelines, the ESC guidelines have been faster to change in response to new data, and thus arguably more progressive, though this tendency may also lead to more retractions as further data arise.

Pharmacology, BVS and DES

In the new ESC/European Association for Cardio-Thoracic Surgery (EACTS) recommendations (Figures 1-2), the use of distal protection devices for percutaneous coronary intervention (PCI) in saphenous vein graft lesions was downgraded to IIa (should be considered) and bivalirudin in acute coronary syndrome (ACS) was downgraded to an IIb level (may be considered). Current generation bioresorbable vascular scaffolds (BVS) were not recommended for routine clinical practice (class III). Future designs and developments of BVS will likely alter our thinking on their use going forward (Figure 3).

ESC guidelines addressed concerns regarding the use of prasugrel preloading from the ACCOAST trial. Safety data on prasugrel come predominantly from one trial, TRITON-TIMI 38, and thus, the drug should only be used in the same fashion as in that study, i.e., mainly after a decision to proceed to PCI is made. The recommendation follows that prasugrel should not be administered routinely before angiography, such as in an emergency department or be used in patients who have not undergone PCI. For patients who remain hospitalized after unstable angina/non ST-elevation myocardial infarction (NSTEMI) and are candidates for coronary artery bypass graft surgery (CABG), prasugrel should be discontinued at least 7 days prior to a planned surgery, because of the significant bleeding risk compared with clopidogrel.

The ESC guidelines recommend that contemporary drug-eluting stents (DES) should be preferred over bare-metal stents regardless of clinical presentation, how long the patients can take dual antiplatelet therapy, or the clinical setting. While there may be a limited role for bare-metal stents for specific indications in highly selected patients, multiple studies have demonstrated that the vast majority of patients would be better served with a DES to prevent restenosis.

Radial Access and Provisional T-Stenting Preferred for PCI

Another important procedural recommendation from the ESC was that radial access should be the preferred approach for coronary angiography and PCI (class I recommendation). While this approach has been a standard for many years in the European communities, it has now been codified as part of the ESC guidelines and may one day be part of the ACC/SCAI guidelines. For those addressing bifurcations with stenting, the ESC/EACTS guidelines upgraded provisional T-stenting for bifurcation lesions from class IIa to class I, and upgraded the use of optical coherence tomography (OCT) for stent optimization from class IIb to class IIa. 

PCI in Stable Angina, ACS, and STEMI With Shock 

In patients with stable angina or silent ischemia, the ESC/EACTS supports myocardial revascularization based on symptoms not responding to medical therapy.¹ The guidelines state that physicians should take into account shared patient decision making and compliance in relation to the intensity of antianginal therapy. As has been the practice for the stable angina patients in recent years, when evidence of ischemia is not available, fractional flow reserve (FFR) and now instantaneous wave-free ratio (iFR) are recommended to assess the hemodynamic relevance of intermediate-grade stenosis (class I) before proceeding to intervention. Based on the FAME trial results, FFR in general still has a class IIa recommendation for use in patients with multivessel disease. 

In patients with ACS, particularly NSTEMI, early invasive angiography (<12 hours [h]) was of no benefit over later PCI (48-72h). The VERDICT trial² of very early invasive angiography in NSTE-ACS patients indicated that only in high-risk patients (those with a GRACE score over 140) were there measurable clinical benefits from early intervention with PCI. VERDICT randomized 2147 patients with NSTE-ACS to angiography within 12h or 48-72h hours after diagnosis. All patients were treated with aspirin, a P2Y12 inhibitor, fondaparinux, and a beta-blocker before randomization. Interestingly, 30% of patients had no coronary stenosis. Although the primary endpoint was not different, at 4.3 years follow-up, nonfatal MI was significantly lower in the very early group (8% vs 11%), with a nonsignificant trend toward less hospitalization for heart failure (9% vs 11%; hazard ratio [HR] 0.78; 95% confidence interval [CI] 0.60-1.01). Importantly, the patients with a high GRACE score >140, (approximately 50% of the patient group) had better outcomes with the early invasive approach (HR 0.81; 95% CI 0.67-1.00). Remember that the ideal timing of invasive angiography and PCI in the NSTE-ACS patient is not entirely clear. 

For patients with STEMI and shock, more data supported the ESC/EACTS guidelines, which discourage the use of routine revascularization of non-culprit lesions during primary PCI in MI patients with cardiogenic shock, based in large part on the Danish Shock studies. In the CULPRIT-SHOCK study³, the primary outcome, all-cause mortality or need for renal replacement therapy (RRT), for culprit lesion only vs multivessel PCI at 30 days, was 46% vs 55%, (P=.01). Secondary endpoints for culprit lesion only vs multivessel PCI were not statistically different for recurrent MI, any bleeding, or stroke. The controversy around complete revascularization in the non-shock, STEMI, or NSTEMI patients also continues, with the use of FFR for the non-culprit PCI decision contributing to a favorable outcome. 

The FUTURE Trial

One of the few negative trials of FFR is the FUTURE trial⁴, a multicenter French study of patients with multivessel disease randomized to FFR-guided vs angio-guided PCI, which was stopped early due to excess mortality in the FFR group. The final results were presented by Gilles Rioufol, MD, PhD, at ESC 2018. To recap, the two groups had similar baseline characteristics. However, the FFR group had many patients with FFR >0.80 (43% of lesions) with a mean FFR of 0.77±0.13. The primary endpoint — a composite of all-cause death, MI, stroke and revascularization — was not different, but at one year, the rate of all-cause death was still higher in the FFR group (3.7% vs 1.5%, P=.036), stopping the trial after only 938 patients had been recruited. The explanations for the excess of mortality was 1) a lower-than-expected rate of CABG in multivessel disease patients; 2) a high rate of PCI in patients with a high SYNTAX score >32; 3) a high rate of ad hoc PCI. Greater use of PCI for high SYNTAX score patients may explain the higher rate of all-cause death. Professor Patrick Serruys, now of the Imperial College London, commented that the higher rate of all-cause mortality could have been a “play of chance” and that the Data Safety Monitoring Board could have just as easily stopped the trial because of a higher rate of stroke in the angiogram cohort. My bottom line for the FUTURE study is to carefully consider the role of PCI vs CABG in the most complex and high risk — high SYNTAX score patients. 

Update on the MitraClip

The MITRA-FR trial⁵, a randomized study of the MitraClip (Abbott Vascular) vs medical therapy in 305 patients with severe functional mitral regurgitation (MR), was presented at the ESC. These types of patients, where the valve is structurally normal but leaky due to ventricular dilatation, have poor outcomes not typically improved with mitral valve surgery, and it was hoped that the MitraClip would be beneficial. Unfortunately, the MitraClip showed no impact on 12-month all-cause mortality and unplanned heart failure hospitalization rates (55% compared with 51% on medical therapy alone, P=.53). Thirty-seven patients (24.3%) in the MitraClip group and 34 (22.4%) in the medical therapy group died over follow-up (P=NS). Similarly, 49% and 47% of patients in the MitraClip and medical groups, respectively, had an unplanned hospitalization (P=NS). The safety profile regarding stroke, need for dialysis, and severe hemorrhage, more common with the intervention than medicine alone, was similar to the 3.5% rate of complications in those requiring surgery. Experts suggested that the study outcomes are due more to the underlying cardiomyopathy than the mitral regurgitation, so that treatment of regurgitation alone would not be sufficient to improve clinical results. Most agreed that the results of this one study should not preclude the selective use of MitraClip, as some patients, especially those at highest risk, may benefit. Better medical management and a more restrictive indication may be appropriate while further study continues. 

In striking contrast to the MITRA-FR trial⁵, Gregg Stone, presenting for the COAPT MitraClip investigators, shared their initial results at the September 2018 TCT meeting. To summarize, COAPT demonstrated that MitraClip reduces repeat hospitalizations and mortality in functional mitral regurgitation patients with severe heart failure. Full COAPT results were also published online in the New England Journal of Medicine⁶ in September 2018.  Over an 8-year study period, 610 patients with moderate (3+) or severe (4+) mitral regurgitation were enrolled and randomized to guideline-directed medical care or intensive medical management plus MitraClip implantation. All hospitalizations (primary endpoint) over 2 years were significantly lower in the MitraClip versus the medical care group (36% vs 68%, respectively (P<.001), with a number needed to treat of 3.1. Two-year mortality, a prespecified secondary endpoint, was significantly lower among MitraClip-treated patients: 29.1% vs 46.1% (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.46-0.82), with a number needed to treat of 5.9. This result was stunning in its positive responses. Differences between COAPT and MITRA-FR were speculated to occur due to patient selection, better imaging, and more operator experience. It is certainly worthwhile to read the NEJM report of this trial — a true game changer.

The Bottom Line

I hope that the updates of the ESC guidelines and trials will stimulate our thinking on our current practices in the management of patients. Change and progress in medicine are a constant, and a sign of a vibrant and dynamic field, one we are all fortunate to be a part of.

Acknowledgment: My thanks to Dr. Arnold Seto for his thoughts on the ESC this year.

References

1. Neumann FJ, Sousa-Uva M, Ahlsson A, et al; ESC Scientific Document Group. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J. 2018 Aug 25. doi: 10.1093/eurheartj/ehy394. [Epub ahead of print] 
2. Kofoed KF, Kelbæk H, Hansen PR, et al. Early versus standard care invasive examination and treatment of patients with non-ST-segment elevation acute coronary syndrome: The VERDICT (Very EaRly vs Deferred Invasive evaluation using Computerized Tomography) - randomized controlled trial. Circulation 2018; Aug 28: [Epub ahead of print]. https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.037152. Presented by Dr. Thomas Engstrom at the European Society of Cardiology Congress, Munich, Germany, August 28, 2018.
3. Thiele H, Akin I, Sandri M, et al.; CULPRIT-SHOCK Investigators. One-year outcomes after PCI strategies in cardiogenic shock. N Engl J Med. 2018; Aug 25: [Epub ahead of print]. Presented by Dr. Holger Thiele at the European Society of Cardiology Congress, Munich, Germany, August 25, 2018.
4. Rioufol G, Roubille F, Perret T, et al.; FUTURE (FUnctional Testing Underlying Revascularization) trial investigators, France NCT01881555. Treatment strategy in multivessel coronary disease patients based on fractional flow reserve. Presented at: ESC 2018. August 25, 2018. Munich, Germany.
5. Obadia J-F, Messika-Zeitoun D, Leurent G, et al. Percutaneous repair or medical treatment for secondary mitral regurgitation. N Engl J Med. 2018 Aug 27. doi: 10.1056/NEJMoa1805374. [Epub ahead of print]
6. Stone GW, Lindenfeld J, Abraham WT, et al; COAPT Investigators. Transcatheter mitral-valve repair in patients with heart failure. N Engl J Med. 2018 Sep 23. doi: 10.1056/NEJMoa1806640. [Epub ahead of print]

Disclosure: Dr. Kern reports he is a consultant for Abiomed, Abbott Vascular, Philips Volcano, ACIST Medical, Opsens Inc., and Heartflow Inc.