Catheterization and Cardiovascular Interventions 84:932–933 (2014)
Editorial Comment Direct Stenting for STEMI: Does it really make a difference? Arnold Seto,* MD, and Morton Kern, MD Department of Medicine, Division of Cardiology, Long Beach Veterans Affairs Medical Center, Long Beach, California
ST-elevation myocardial infarctions (MIs) are characterized by thrombotic occlusions precipitated by plaque rupture. The composition of aspirated thrombi includes a metabolically toxic brew of activated platelets, necrotic cells, lipid, and fibrin. Distal embolization of such material during percutaneous coronary intervention (PCI) is a major contributor to microvascular injury, resulting in persistent ST-segment changes, larger infarct size, hemodynamic instability, and death. Direct stenting (DS) without balloon predilatation may reduce vessel wall damage and distal embolization, potentially reducing the incidence of no-reflow, MI, and death. However, there are significant downsides to DS including: underestimation of true vessel size, failure to cross, nondilatable lesions, inadequate stent expansion, geographic miss, late stent malapposition, and restenosis. As a result, in practice DS has been reserved for simple lesions without angulation, calcification, or tortuosity. Studies of DS for both stable angina and STelevation MI have had mixed results. A meta-analysis of 24 randomized controlled trials of DS versus conventional stenting (CS) in PCI found that DS was associated with reduction in MI [odds ratio (OR) of 0.77; 95% CI 0.55–0.99, P ¼ 0.04], driven by a reduction in periprocedural MI [1]. However, only three small randomized trials of DS in ST-segment elevation MI have been conducted, with conflicting results. Ozdemir et al. [2] found a benefit to DS in corrected TIMI frame count (cTFC) and TIMI 3 flow rates in a small trial of 50 patients. Loubeyre et al. [3] in 206 patients found no difference in cTFC or TIMI flow, but a benefit in ST-segment resolution (no ST-segment resolution in 20.2% versus 38.1% in DS versus CS, P ¼ 0.01) and a composite endpoint of no- or slow-reflow, electrocardiographic changes, and clinical outcome (11.7% vs. 26.9%, P ¼ 0.01). In contrast, Gasior et al. [4] found in C 2014 Wiley Periodicals, Inc. V
217 patients no difference in TIMI flow, perfusion score, ST-segment resolution, or 5 year clinical outcome, but a higher risk of restenosis (30% vs. 16%, P ¼ 0.024) with DS. It is with this background that Dziewierz et al. [5] examine the impact of DS on the outcome of STsegment MI patients from their EUROTRANSFER registry. From a population of 1,419 patients, DS was used in 276 (19.5%) of patients and was associated with greater rates of TIMI 3 flow (94.9% vs. 91.5%), lower rates of no-reflow (1.4% vs. 3.4%), higher rates of ST-segment resolution (86.2% vs. 76.3%), and a reduction in 1-year mortality (adjusted OR 0.45 (0.21– 0.99), P ¼ 0.047). Their retrospective, nonrandomized analysis suggests that DS in primary PCI was associated with improved angiographic results and long-term survival. While a positive result, determining causation from an association is difficult from a retrospective study, particularly of an operator-selected technique. In this study, patients who received DS were significantly younger, more likely to have TIMI 2 or 3 flow at baseline (44% vs. 26%), and more likely to have received aspiration thrombectomy (26% vs. 8%) and preloaded clopidogrel (42% vs. 31%). They were less likely to have an left anterior descending infarct or multivessel disease. Any of these factors might have had a greater impact on outcome than accounted for in the authors’ statistical model. Propensity score adjustment typically does not sufficiently account for the impact of measured factors, compared with the more robust propensity matching approach. Propensity matching would have excluded much of the cohort because of the significant baseline differences between the two groups. Finally, unmeasured confounders in the form of operator, patient, and lesion characteristics almost certainly influenced the operators’ choice to use DS rather than CS. Conflict of interest: Nothing to report. *Correspondence to: Arnold Seto, MD; Long Beach Veterans Affairs Medical Center, 5901 East 7th Street, 111C, Long Beach, CA 90822. E-mail: [email protected] Received 22 September 2014; DOI: 10.1002/ccd.25681 Published online 29 October 2014 in Wiley Online Library (wileyonlinelibrary.com)
Direct Stenting for STEMI
What then, does the work by Dziewierz et al. tell us for clinical practice? At most, one can take away that experienced operators are able to identify lesions at low risk and choose a simplified PCI approach. Their large estimated mortality reduction is of borderline statistical significance and unreliable. Nevertheless, DS may be a reasonable option in selected patients undergoing primary PCI, with the emphasis on selection: arteries that are tortuous, angulated, calcified, or totally occluded are poor candidates for DS and require lesion preparation. DS is only one option to reduce distal embolization and no-reflow, and may have more risks than the alternatives. Thrombus removal in the form of aspiration or rheolytic thrombectomy prior to stent placement may be safer and more effective. A pharmacoinvasive strategy of gentle balloon angioplasty with glycoprotein inhibitors and deferred stent implantation (DEFER– STEMI) also holds promise, particularly for vessels with a large thrombus burden. Newer technologies may allow the operator to trap thrombotic material behind the stent struts (MGuard, InspireMD, Tel Aviv, Israel) or use a self-expanding stent (Stentys, Paris, France) to maintain stent apposition as the thrombus is slowly resorbed. With such promising strategies on the
933
horizon, DS may be obsolete before it is ever proven to be effective. REFERENCES 1. Piscione F, Piccolo R, Cassese S, Galasso G, D’Andrea C, De Rosa R, Chiariello M. Is direct stenting superior to stenting with predilation in patients treated with percutaneous coronary intervention? Results from a meta-analysis of 24 randomised controlled trials. Heart 2010;96:588–594. 2. Ozdemir R, Sezgin AT, Barutcu I, Topal E, Gullu H, Acikgoz N. Comparison of direct stenting versus conventional stent implantation on blood flow in patients with ST-segment elevation myocardial infarction. Angiology 2006;57:453–458. 3. Loubeyre C, Morice MC, Lefe`vre T, Piechaud JF, Louvard Y, Dumas P. A randomized comparison of direct stenting with conventional stent implantation in selected patients with acute myocardial infarction. J Am Coll Cardiol 2002;39:15–21. 4. Gasior M, Gierlotka M, Lekston A, Wilczek K, Zebik T, Hawranek M, Wojnar R, Szkodzinski J, Piegza J, Dyrbus K, Kalarus Z, Zembala M, Polonski L. Comparison of outcomes of direct stenting versus stenting after balloon predilation in patients with acute myocardial infarction (DIRAMI). Am J Cardiol 2007; 100:798–805. 5. Dziewierz A, Siudak Z, Rakowski T, Kleczynski P, Zasada W, Dubiel JS, Dudek D. Impact of direct stenting on outcome of patients with ST-elevation myocardial infarction transferred for primary percutaneous coronary intervention (from the EUROTRANSFER registry). Catheter Cardiovasc Interv 2014;84:925–931.
Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
Editorial Comment Direct Stenting for STEMI: Does it really make a difference? Arnold Seto,* MD, and Morton Kern, MD Department of Medicine, Division of Cardiology, Long Beach Veterans Affairs Medical Center, Long Beach, California
ST-elevation myocardial infarctions (MIs) are characterized by thrombotic occlusions precipitated by plaque rupture. The composition of aspirated thrombi includes a metabolically toxic brew of activated platelets, necrotic cells, lipid, and fibrin. Distal embolization of such material during percutaneous coronary intervention (PCI) is a major contributor to microvascular injury, resulting in persistent ST-segment changes, larger infarct size, hemodynamic instability, and death. Direct stenting (DS) without balloon predilatation may reduce vessel wall damage and distal embolization, potentially reducing the incidence of no-reflow, MI, and death. However, there are significant downsides to DS including: underestimation of true vessel size, failure to cross, nondilatable lesions, inadequate stent expansion, geographic miss, late stent malapposition, and restenosis. As a result, in practice DS has been reserved for simple lesions without angulation, calcification, or tortuosity. Studies of DS for both stable angina and STelevation MI have had mixed results. A meta-analysis of 24 randomized controlled trials of DS versus conventional stenting (CS) in PCI found that DS was associated with reduction in MI [odds ratio (OR) of 0.77; 95% CI 0.55–0.99, P ¼ 0.04], driven by a reduction in periprocedural MI [1]. However, only three small randomized trials of DS in ST-segment elevation MI have been conducted, with conflicting results. Ozdemir et al. [2] found a benefit to DS in corrected TIMI frame count (cTFC) and TIMI 3 flow rates in a small trial of 50 patients. Loubeyre et al. [3] in 206 patients found no difference in cTFC or TIMI flow, but a benefit in ST-segment resolution (no ST-segment resolution in 20.2% versus 38.1% in DS versus CS, P ¼ 0.01) and a composite endpoint of no- or slow-reflow, electrocardiographic changes, and clinical outcome (11.7% vs. 26.9%, P ¼ 0.01). In contrast, Gasior et al. [4] found in C 2014 Wiley Periodicals, Inc. V
217 patients no difference in TIMI flow, perfusion score, ST-segment resolution, or 5 year clinical outcome, but a higher risk of restenosis (30% vs. 16%, P ¼ 0.024) with DS. It is with this background that Dziewierz et al. [5] examine the impact of DS on the outcome of STsegment MI patients from their EUROTRANSFER registry. From a population of 1,419 patients, DS was used in 276 (19.5%) of patients and was associated with greater rates of TIMI 3 flow (94.9% vs. 91.5%), lower rates of no-reflow (1.4% vs. 3.4%), higher rates of ST-segment resolution (86.2% vs. 76.3%), and a reduction in 1-year mortality (adjusted OR 0.45 (0.21– 0.99), P ¼ 0.047). Their retrospective, nonrandomized analysis suggests that DS in primary PCI was associated with improved angiographic results and long-term survival. While a positive result, determining causation from an association is difficult from a retrospective study, particularly of an operator-selected technique. In this study, patients who received DS were significantly younger, more likely to have TIMI 2 or 3 flow at baseline (44% vs. 26%), and more likely to have received aspiration thrombectomy (26% vs. 8%) and preloaded clopidogrel (42% vs. 31%). They were less likely to have an left anterior descending infarct or multivessel disease. Any of these factors might have had a greater impact on outcome than accounted for in the authors’ statistical model. Propensity score adjustment typically does not sufficiently account for the impact of measured factors, compared with the more robust propensity matching approach. Propensity matching would have excluded much of the cohort because of the significant baseline differences between the two groups. Finally, unmeasured confounders in the form of operator, patient, and lesion characteristics almost certainly influenced the operators’ choice to use DS rather than CS. Conflict of interest: Nothing to report. *Correspondence to: Arnold Seto, MD; Long Beach Veterans Affairs Medical Center, 5901 East 7th Street, 111C, Long Beach, CA 90822. E-mail: [email protected] Received 22 September 2014; DOI: 10.1002/ccd.25681 Published online 29 October 2014 in Wiley Online Library (wileyonlinelibrary.com)
Direct Stenting for STEMI
What then, does the work by Dziewierz et al. tell us for clinical practice? At most, one can take away that experienced operators are able to identify lesions at low risk and choose a simplified PCI approach. Their large estimated mortality reduction is of borderline statistical significance and unreliable. Nevertheless, DS may be a reasonable option in selected patients undergoing primary PCI, with the emphasis on selection: arteries that are tortuous, angulated, calcified, or totally occluded are poor candidates for DS and require lesion preparation. DS is only one option to reduce distal embolization and no-reflow, and may have more risks than the alternatives. Thrombus removal in the form of aspiration or rheolytic thrombectomy prior to stent placement may be safer and more effective. A pharmacoinvasive strategy of gentle balloon angioplasty with glycoprotein inhibitors and deferred stent implantation (DEFER– STEMI) also holds promise, particularly for vessels with a large thrombus burden. Newer technologies may allow the operator to trap thrombotic material behind the stent struts (MGuard, InspireMD, Tel Aviv, Israel) or use a self-expanding stent (Stentys, Paris, France) to maintain stent apposition as the thrombus is slowly resorbed. With such promising strategies on the
933
horizon, DS may be obsolete before it is ever proven to be effective. REFERENCES 1. Piscione F, Piccolo R, Cassese S, Galasso G, D’Andrea C, De Rosa R, Chiariello M. Is direct stenting superior to stenting with predilation in patients treated with percutaneous coronary intervention? Results from a meta-analysis of 24 randomised controlled trials. Heart 2010;96:588–594. 2. Ozdemir R, Sezgin AT, Barutcu I, Topal E, Gullu H, Acikgoz N. Comparison of direct stenting versus conventional stent implantation on blood flow in patients with ST-segment elevation myocardial infarction. Angiology 2006;57:453–458. 3. Loubeyre C, Morice MC, Lefe`vre T, Piechaud JF, Louvard Y, Dumas P. A randomized comparison of direct stenting with conventional stent implantation in selected patients with acute myocardial infarction. J Am Coll Cardiol 2002;39:15–21. 4. Gasior M, Gierlotka M, Lekston A, Wilczek K, Zebik T, Hawranek M, Wojnar R, Szkodzinski J, Piegza J, Dyrbus K, Kalarus Z, Zembala M, Polonski L. Comparison of outcomes of direct stenting versus stenting after balloon predilation in patients with acute myocardial infarction (DIRAMI). Am J Cardiol 2007; 100:798–805. 5. Dziewierz A, Siudak Z, Rakowski T, Kleczynski P, Zasada W, Dubiel JS, Dudek D. Impact of direct stenting on outcome of patients with ST-elevation myocardial infarction transferred for primary percutaneous coronary intervention (from the EUROTRANSFER registry). Catheter Cardiovasc Interv 2014;84:925–931.
Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
