Journal Wrap: Results from PRAMI, INSTEAD, AND Valentines II

Jon C. George, MD; Srihari S. Naidu, MD; and Sandeep Nathan, MD, present relevant articles from recent journals

The PRAMI Trial: Breaking One of the Final Taboos in the Treatment of Multivessel Coronary Artery Disease?

Dr. Nathan: The recently published PRAMI trial was a multicenter randomized trial conducted in the United Kingdom evaluating the value of preemptive PCI of non-culprit obstructive CAD in addition to, and performed at the same time as, primary PCI for STEMI in patients with concomitant multivessel CAD. A total of 465 patients with acute STEMI who were undergoing infarct-artery (primary) PCI at five participating centers, were randomly assigned to immediately undergo “preventive PCI” (PCI in non-culprit vessels containing stenosis >50%) or “no preventive PCI” (culprit-vessel PCI alone). The primary outcome was a composite of CV death, nonfatal MI, or refractory angina with repeat PCI reserved for refractory angina with evidence of ischemia. The trial was terminated prematurely by the data and safety monitoring committee after a mean follow-up of 23 months because an excess of primary outcome events had accrued in the no preventive PCI group. In total, 21 patients in the preventive PCI group and 53 patients in the no preventive PCI group sustained major adverse cardiovascular events (hazard ratio [HR] 0.35; 95% CI 0.21-0.58; p < 0.001). All individual components of the primary composite outcome were similarly reduced, but the reduction in death from cardiac causes alone failed to achieve statistical significance. The full magnitude of benefit associated with the preventive PCI strategy was evident by 6 months post-randomization and persisted for the duration of the follow-up period. While there was crossover from assigned therapy in 13 patients (2 in the no preventive PCI group and 11 in the preventive PCI group), the results of the on-treatment analysis were consistent with the reported intention-to-treat analysis and, if anything, suggest an even stronger association than the primary results.

Current guidelines support treatment of the culprit-vessel alone in the setting of STEMI presenting for primary PCI. Indeed, the notion of tackling non-culprit vessels in the absence of a compelling circumstance has largely remained verboten. The results from PRAMI, which demonstrate the early and enduring value of multivessel revascularization in patients with unstable ischemic heart disease, greatly challenge this conventional wisdom. While this trial may be regarded as groundbreaking in this regard, several important caveats apply: patients with cardiogenic shock, prior CABG, and significant left main coronary disease were all excluded from this study and thus the study results may not be relevant to those populations. It also remains unknown if immediate non-culprit PCI or staged non-culprit PCI is the best approach, or if incorporation of physiologic lesion testing would enhance or detract from the overall strategy. Finally, it is well recognized that the long-term morbidity and mortality associated with NSTEMI is at least as high as it is for STEMI, and that multivessel CAD is also quite common in this population. Unfortunately, this study does not give us answers regarding multivessel revascularization in this commonly-encountered population of patients. All qualifiers and caveats notwithstanding however, PRAMI gives us unprecedented insight into the value of immediate, complete percutaneous revascularization in unstable multivessel CAD, and will set the stage for future investigations in this population.

Wald DS, Morris JK, Wald NJ, et al. N Engl J Med. 2013;369:1115-23.

Drug-Coated Balloons for De Novo Coronary Lesions: Results from the Valentines II Trial

Dr. George: Transluminal balloon angioplasty heralded the world of PCI. The limitations of balloon angioplasty, including recoil and dissection, were resolved with the advent of bare-metal stents (BMS), and the subsequent shortcomings of neointimal hyperplasia and restenosis with drug-eluting stents (DES). The current failures of DES are primarily limited to late stent thrombosis and refractory restenosis, prompting the need for additional treatment modalities. Drug-coated balloons (DCB) have emerged as a potential alternative to combat restenosis. The authors of the Valentines II study report the results of DCB for de novo coronary lesions in 103 patients treated in prospective fashion in a multicenter, international registry. Procedural success was 99% with mean post-treatment stenosis at 10.4%. Coronary dissections occurred in 14.7% and bail-out BMS implantation in 11.9%. Cumulative rate of major adverse cardiac events at follow-up of 6-9 months was 8.7% with target vessel revascularization of 6.9%, target lesion revascularization of 2.9%, and no vessel thrombosis. The results of this study demonstrate the feasibility of DCB as an adjunct to traditional balloon angioplasty in de novo coronary lesions and offer an alternative for revascularization in patients unsuitable for DES.

Waksman R, Serra A, Loh JP, et al. EuroIntervention. 2013;9(5):613-9.

Endovascular Repair of Type B Aortic Dissection: Long-Term Results from INSTEAD

Dr. Naidu: Traditionally, type A aortic dissection required emergent surgical intervention while type B aortic dissection was managed conservatively with blood pressure control, serial CT scans, and surgery reserved for complications. However, an increasing body of evidence supports elective thoracic endovascular aortic repair (TEVAR) in this setting. The authors evaluated longer-term outcomes among patients with type B dissection randomized to optimal medical therapy (OMT) versus TEVAR and OMT. 140 patients were followed. Elective TEVAR resulted in lower mortality (11.1% vs. 19.3%), aorta-specific mortality (6.9% vs. 19.3%), and progression (27.0% vs. 46.1%) at 5 years (all statistically significant) compared to OMT alone. The benefits were associated with TEVAR-induced thrombosis of the false lumen. The data provide good evidence that patients with type B aortic dissection with suitable anatomy should undergo TEVAR, with special attention paid to closing off and thrombosing the false lumen. TEVAR may represent an opportunity for interventional cardiologists, and training in this procedure should be considered as part of peripheral training within interventional programs.

Nienaber CA, Kische S, Rousseau H, et al. Circ Cardiovasc Interv. 2013 August 6. [Epub ahead of print]

Jon C. George, MD, is director of clinical research and assistant director of the cardiac catheterization laboratory at the Deborah Heart and Lung Center in Brown Mills, New Jersey.

Srihari S. Naidu, MD, is director of the cardiac catheterization laboratory and the interventional cardiology fellowship program at Winthrop-University Hospital in Mineola, New York.

Sandeep Nathan, MD, is assistant professor of medicine and director of the interventional cardiology fellowship program at the University of Chicago Medicine.

Keywords: Coronary Artery Disease, Follow-Up Studies, Drug-Eluting Stents, Taboo, Constriction, Pathologic, Hyperplasia, Angioplasty, Balloon, Coronary, Stents, Shock, Cardiogenic, Registries, Intention, Thrombosis

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