Total revascularization of coronary disease at the time of primary percutaneous coronary intervention.

Abstract

Future CardiologyVol. 10, No. 4 EditorialFree AccessTotal revascularization of coronary disease at the time of primary percutaneous coronary interventionIwan Harries & Steve RamcharitarIwan Harries Wiltshire Cardiac Centre, Department of Interventional Cardiology, Marlborough Road, Swindon, SN3 6BB, UKSearch for more papers by this author & Steve Ramcharitar*Author for correspondence: E-mail Address: steve.ramcharitar@chem.ox.ac.uk Wiltshire Cardiac Centre, Department of Interventional Cardiology, Marlborough Road, Swindon, SN3 6BB, UKSearch for more papers by this authorPublished Online:10 Oct 2014https://doi.org/10.2217/fca.14.30AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInRedditEmail Keywords: angioplastymultivessel diseasepercutaneous coronary interventionPRAMIprimary PCIstentAt the time of primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI), 40–65% of patients have multivessel coronary artery disease. Historical data suggest that these patients have a worse prognosis compared with those with single vessel disease [1]. Because the optimal revascularization strategy is yet to be established, it is not surprising that these patients present a clinical dilemma in the acute setting.Current guidelines (European Society of Cardiology, American College of Cardiology Foundation and the American Heart Association) recommend that primary percutaneous coronary intervention for STEMI be limited to the culprit artery except in the presence of cardiogenic shock or persistent ischemia where the concept of multivessel revascularization is generally accepted [2,3]. This approach is corroborated by a recent multicenter, prospective observational study that reported a significant survival benefit in favor of multivessel PCI (MV-PCI) in patients with resuscitated cardiac arrest and cardiogenic shock at presentation (n = 266) compared with those treated with culprit vessel PCI (CV-PCI) alone (43.9 vs 20.4%; p < 0.002) [4]. Verification of these results by randomized trials is awaited.In hemodynamically stable patients with multivessel coronary disease, MV-PCI is generally discouraged. Functional evaluation of a lesion or refractory symptoms despite optimal medical therapy have traditionally been used to guide intervention to nonculprit lesions in line with the results of the FAME and COURAGE trials, respectively. Similarly, current societal guidelines for patients presenting with STEMI and multivessel disease recommend either staged revascularization after confirmation of stenosis severity by fractional flow reserve (FFR) assessment, or a conservative strategy, which relies on symptoms or objective evidence of ischemia to guide intervention to nonculprit arteries [2,3]. However, these STEMI-specific guidelines are mainly based on retrospective, observational studies prone to confounding factors and selection bias and small randomized trials with inadequate power to demonstrate a treatment effect on cardiac mortality. They were also conducted under technological and pharmacological conditions that have evolved to such a degree that they might now be considered historic. Certainly, there is robust evidence of significant outcome improvements alongside the evolution from bare metal stents used in early studies to the second-generation drug-eluting stents used in current practice [5]. Furthermore, the studies had significant methodological heterogeneity, significant between-group differences in baseline characteristics and, not surprisingly, reported conflicting results. In broad terms, MV-PCI at the time of STEMI is purported to be superior [6], equivalent [7,8] and inferior [9] to CV-PCI alone.Several meta-analyses have attempted to make sense of this conflicting body of evidence. Early meta-analyses (Navarese et al. [10] n = 31,224; two randomized control trials [RCTs] and eight non-RCTs, and Sethi et al. [11] n = 31,853; two RCTs and eight non-RCTs) concluded that MV-PCI at the time of STEMI, or during the same hospitalization (Bangalore et al. [12] n = 61,764; two RCTs, 17 non-RCTs) was safe in comparison to CV-PCI alone. Furthermore, no significant difference in major adverse cardiac events were observed either in the short or long term and in one analysis [10], MV-PCI reduced the rate of repeat intervention (odds ratio [OR]: 0.47; p = 0.003), albeit without conferring a mortality benefit (p = 0.31). A large, recent meta-analysis by Bagai et al. [13] (n = 35,239; three RCTs and 11 non-RCTs) echoed these findings and, in addition, reported that in a subanalysis of RCTs, the primary end point was significantly lower for MV-PCI as compared with CV-PCI in the long-term (OR: 0.55).In contrast, one large meta-analysis (Lu et al. [14] n = 60,238; three RCTs and ten non-RCTs) reported increased short (OR: 1.39) and long-term mortality (OR: 1.35) for patients undergoing MV-PCI as compared with CV-PCI alone. However, only one of the non-RCT studies included in the analysis had undertaken propensity score matching. This is an important point because patients that undergo MV-PCI at the time of STEMI, particularly at the discretion of the operator, are usually more unwell and higher risk; the fact that they subsequently do worse is not entirely surprising. Interestingly, Jaguszewski et al. [15] reported that after stratifying patients according to risk, MV-PCI did not appear to be associated with higher mortality (p = 1.00).Several studies have drawn comparisons between extreme ends of the management spectrum, that is, immediate MV-PCI versus CV-PCI alone while ignoring the middle ground. In practice, a staged approach to revascularization is commonly pursued, often guided by objective evidence of ischemia in nonculprit artery territories. Meta-analysis evidence to support this approach was first provided by Vlaar et al. [16] who reported lower short and long-term mortality for staged revascularization as compared with MV-PCI and CV-PCI alone. Kornowski et al. [17] also advocated a staged revascularization strategy for nonculprit lesions owing to a greater risk of mortality (9.2 vs 2.3%; p < 0.0001) and stent thrombosis (5.7 vs 2.3%; p = 0.02) in patients undergoing MV-PCI at the time of STEMI. A recent large, comprehensive meta-analysis reinforced this viewpoint. Bainey et al. [18] (n = 46,234; three RCTs and 23 non-RCTs) reported that staged revascularization reduced short (OR: 0.35; p < 0.001) and long-term mortality (OR: 0.74; p < 0.001) and reduced the need for repeat PCI (OR: 0.65; p = 0.01) when compared with either immediate MV-PCI or CV-PCI alone. Furthermore, a worrying trend toward in-hospital mortality was demonstrated in patients undergoing MV-PCI at the time of STEMI even after studies with patients in cardiogenic shock were excluded. To date, the majority of studies have drawn differing conclusions regarding STEMI patients with multivessel disease. However, they have been unanimous in calling for large-scale randomized trials to delineate the optimal revascularization strategy.The recently published randomized trial of Preventive Angioplasty in Myocardial Infarction (PRAMI) garnered attention for showing a significant reduction in the composite end point of nonfatal myocardial infarction, refractory angina and cardiac death (hazard ratio: 0.32, 0.35 and 0.34, respectively) in patients undergoing ‘preventive’ MV-PCI compared with CV-PCI [19]. The findings are intriguing and the PRAMI investigators are to be congratulated, however the results warrant wider scrutiny prior to the incorporation of MV-PCI into routine clinical practice. First, the control arm (medical therapy alone) was a nonstandardized comparator; staged revascularization, which is the strategy of choice for many clinicians, was actively discouraged. Second, the study was of relatively small size. This was influenced to a large degree by its premature termination by the safety monitoring committee. Third, apart from randomization, all treatment decisions were left at the discretion of the responsible clinician, which inevitably introduces bias. For example, a borderline lesion encountered in a well patient during the daytime is a different proposition to a borderline lesion in a frail, comorbid patient with complex anatomy in the middle of the night, particularly when the operator has the choice whether or not to intervene.Despite the perceived limitations of PRAMI there is a case to be made for MV-PCI and there are, in principle, several advantages to performing MV-PCI at the time of STEMI. Complete revascularization is known to be associated with a better long-term prognosis in stable coronary disease and plaque instability is not thought to be limited to the culprit artery. Performing MV-PCI at the time of STEMI addresses both these issues and obviates the need for further procedures, their associated cost and hospital stay while also providing peace of mind for the patient and physician that all lesions have been treated. These perceived advantages must be balanced against the inherent risks of a longer procedure, additional contrast agent and increased procedural complexity in patients that are prothrombotic, proinflammatory and often in a precarious hemodynamic and physiological state. Furthermore, the severity of nonculprit lesions is frequently overestimated in the context of STEMI; up to 40% prove to be of no hemodynamic significance when subsequently interrogated by FFR [8]. This introduces the potential to intervene unnecessarily on so called ‘cosmetic’ lesions, exposing the patient to additional risk without conferring benefit. Current angiographic techniques do not permit the operator to discriminate between high-risk plaques and cosmetic lesions. COMPARE-ACUTE is currently evaluating the role of FFR-guided MV-PCI in this context. However, we are yet to understand whether arterial physiology in the stable patient can reliably be extrapolated to this setting. The recently published ATHEROREMO-IVUS study [20] reported encouraging results using radiofrequency IVUS to identify high-risk plaques (28.7% study population STEMI/non-STEMI) and the PROSPECT study [21] used IVUS virtual histology to characterize predictors of subclinical plaque rupture in nonculpri22t arteries. Independent predictors of plaque rupture included lesion length, plaque burden, vessel area (all p < 0.0001) and thin cap fibroatheroma phenotype (p = 0.016) although outcomes were unaffected in patients receiving optimal medical therapy. In time, these may yet prove useful tools to guide MV-PCI to nonculprit lesions.Randomized trials currently investigating MV-PCI in STEMI patients with multivessel disease should also prove instructive (Table 1). Several approaches are being scrutinized and some of the perceived shortcomings of PRAMI are being addressed; staged revascularization is being investigated as a comparator in the COCUA, CVLPRIT and COMPARE-ACUTE trials and COMPLETE is a large trial that will not be limited by sample size.ConclusionOverall, it may be that in selected patients, or even selected lesions, MV-PCI at the time of STEMI proves beneficial. However, we cannot currently identify the patient groups and/or lesions that stand to benefit from MV-PCI and we lack the robust, large-scale, randomized evidence required to guide practice. So what should we do with these patients in the meantime? Until compelling evidence to support MV-PCI emerges or the means to definitively identify high-risk nonculprit lesions in the context of STEMI become available, current guidelines should be upheld; a staged revascularization strategy should be adopted, preferably guided by objective evidence of ischemia in nonculprit territories.Table 1. Current randomized trials evaluating multivessel percutaenous coronary intervention in ST-elevation myocardial infarction.StudyLocationPatients (n)Expected completion dateTrial armsFollow-up (years)Primary outcome measuresRef. Trial arm 1Trial arm 2 COCUAKorea646July 2014Acute MV-PCICV-PCI + staged PCI3Cardiac mortality STEMI Target lesion revascularization[22]COMPARE-ACUTEEurope and Asia885January 2018FFR-guided MV-PCI during index admission (acute or subacute)CV-PCI + staged PCI guided by proven ischemia or refractory angina3All-cause mortality Nonfatal MI Any revascularization CVA[23]COMPLETEUSA and Canada3900March 2018CV-PCI + staged revascularizationCV-PCI + medical therapy4Cardiovascular death MI[24]CROSS-AMISpain400September 2014CV-PCI + staged revascularization during index admissionCV-PCI + stress ECHO-guided revascularization1Cardiovascular death Re-MI Any revascularization Heart failure admission[25]CVLPRIT (2013)UK300–CV-PCI + staged revascularization during index admissionCV-PCI + medical therapy1All-cause mortality Re-MI Heart failure Any revascularization[26]PRAGUE-13Czech Republic400May 2014CV-PCI + staged revascularization within 3–40 daysCV-PCI + medical therapy2Death Nonfatal MI CVA[27]CV-PCI: Culprit vessel percutaneous coronary intervention; CVA: Cerebral vascular accident; FFR: Fractional flow reserve; MI: Myocardial infarction; MV-PCI: Multivessel percutaneous coronary intervention; PCI: Percutaneous coronary intervention; STEMI: ST-elevation myocardial infarction.Financial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. 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(Prague-13). www.clinicaltrials.gov/ct2/show/NCT01332591 Google ScholarFiguresReferencesRelatedDetailsCited ByEconomic Evaluation of Complete Revascularization for Patients with Multivessel Disease Undergoing Primary Percutaneous Coronary InterventionValue in Health, Vol. 20, No. 6 Vol. 10, No. 4 Follow us on social media for the latest updates Metrics History Published online 10 October 2014 Published in print July 2014 Information© Future Medicine LtdKeywordsangioplastymultivessel diseasepercutaneous coronary interventionPRAMIprimary PCIstentFinancial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.No writing assistance was utilized in the production of this manuscript.PDF download