Clinical and Economic Outcomes of Embolic Complications
and Strategies for Distal Embolic Protection during Percutaneous Corona

Over 500,000 coronary artery bypass grafts in 314,000 cases were performed in the United States in 2000, however, over half of all vein grafts develop significant stenosis within 10 years.^1,2 Percutaneous coronary intervention in saphenous vein grafts is consequently an increasingly common therapeutic modality utilized in the treatment of vein graft stenosis. In contemporary practice, vein grafts develop bulky lesions composed of loose atheroma and thrombotic material, and are often degenerated.³ This poses a significant risk for distal embolization and no-reflow, resulting in a major adverse event in up to 20% of procedures.⁴ Since management of the no-reflow phenomenon is frequently unsuccessful and its outcome unpredictable,⁵ prevention is a more effective strategy. Distal embolic protection devices have been shown to reduce the frequency of distal embolization and sequelae. The SAFER trial was first to demonstrate that distal embolic protection provided a 42% relative risk reduction (16.5% versus 9.6%; p 6 The Food and Drug Administration (FDA) approved the PercuSurge Guardwire™ system (Medtronic, Inc., Minneapolis, Minnesota) utilized in SAFER, as well as the FilterWireEX™ (Boston Scientific Corp., Natick, Massachusetts), a second device with similar effectiveness. Cost analysis from SAFER shows increased initial procedure costs (median $1,547; p p 7 Despite the medical utility of distal embolic protection for vein graft interventions, the incremental cost is not reimbursed by the Centers for Medicare and Medicaid Services. In a cost-conscious era of medicine, strategies for the most cost-effective use of resources are imperative. Distal embolic protection could be routinely used in all patients, but the substantial costs may be prohibitive. However, not utilizing distal embolic protection would result in a significant number of otherwise preventable embolic complications and sequelae, including death. A better strategy may be to balance these competing alternatives to maximize clinical benefit and minimize the economic impact by selectively using distal embolic protection in patients at high risk for embolic complications. Numerous investigators have consistently identified similar clinical and angiographic variables predictive of embolic complication.^8–17 These factors could potentially identify patients at higher risk for embolic complications to receive distal embolic protection. To assess the optimal strategy, we analyzed data from patients undergoing percutaneous coronary intervention in saphenous vein grafts without distal embolic protection to determine the incidence and cost of embolic complications. We then analyzed the effect routine and selective distal embolic protection strategies might have on clinical outcome and resource utilization in comparison to the referent strategy of no distal embolic protection. Methods Study design. Between 1997 and 2001, a total of 142 consecutive patients at a single academic medical center underwent percutaneous coronary intervention in a saphenous vein graft without distal embolic protection. Sixteen patients were excluded from this study due to incomplete clinical and/or financial data, resulting in a cohort of 126 consecutive patients. Patient and procedural characteristics were prospectively collected in our catheterization laboratory database and defined as prespecified by the National Cardiovascular Data Registry (NCDR) and the Society of Cardiac Angiography and Interventions (SCAI).¹⁸ Embolic complications were defined as angiographic evidence of no-reflow/slow flow with or without postprocedure myocardial infarction. No-reflow/slow flow was quantified as Thrombolysis In Myocardial Infarction (TIMI) grade 2 or less.⁶ Myocardial infarction was defined as elevation of creatine kinase > 200 mg/dl and a CK-MB index > 10%, or troponin I > 2 mg/dl. Major adverse coronary events, or MACE, includes myocardial infarction, emergency coronary artery bypass graft, and death as defined by the NCDR and SCAI. Patients were classified into two comparison groups according to the occurrence (EC; n = 22) or absence (non-EC; n = 104) of an embolic complication. Clinical and angiographic predictors of embolic complications previously reported by various investigators^2,8–14 have been confirmed by the NCDR^14,15 and in our own laboratory.^16,17 Furthermore, multivariate analyses demonstrates that graft age greater than or equal to 8 years and preprocedural thrombus are the strongest independent predictors of embolic complication. Patients with one or both characteristics were identified as high-risk, with all others considered low-risk. Based on risk status, three different distal embolic protection strategies were compared: (1) no distal embolic protection (referent); (2) routine distal embolic protection in all patients; and (3) selective distal embolic protection only in high-risk patients. By intent, no patients in this analysis actually received a distal embolic protection device. The incidence of embolic complication and cost attributed to routine and selective strategies represent theoretical calculations based on a 42% relative risk reduction,³ while the referent analysis represents actual incidence and costs. Cost analysis. The finance department prospectively collected financial data as patient charges using a consistent accounting method. Charges were converted to costs using a cost center specific ratio of cost-to-charges (RCC) to calculate both direct and indirect costs.¹⁹ All cost data are adjusted to 2003 dollars using the United States Consumer Price Index.²⁰ The cost of the distal embolic protection device was based on the average cost of the two FDA-approved distal embolic protection systems: PercuSurge Guardwire™ (Medtronic), a balloon occlusion device, and FilterWireEX™ (Boston Scientific), a filter device. These two different types of distal embolic protection systems provide similar reductions in the incidence of embolic complications.²¹ Total procedure cost equals cost per individual in the catheterization lab, where the cost of an embolic complication is the difference in mean total procedure cost between patients with and without an embolic complication, adjusted for the relative risk reduction of the distal protection device. Total procedure cost is less confounded than total hospital cost, making it a more direct and accurate measure of embolic complication cost. The cost to theoretically prevent an embolic complication per individual equals total procedure cost plus distal embolic protection device cost, less the cost of an embolic complication. The analysis also accounts for correct and incorrect classification of patients by the model. Statistical analysis. Categorical variables are expressed as percentages and were compared using the Chi-square or Fisher’s Exact test for differences in proportions when appropriate. Continuous variables are expressed as mean ± standard deviation and median, then compared using the Student’s t-test if normally distributed, or the Mann-Whitney test if not normally distributed. All p-values are two-tailed with statistical significance considered at p (SPSS Inc., Chicago, Illinois). Results Patient and procedural characteristics. A total of 126 consecutive patients at a single academic medical center underwent percutaneous intervention in a saphenous vein graft without distal embolic protection. Patients in both groups were similar in age and predominantly male, and not significantly different across other baseline characteristics, including diabetes (Table 1). Patients with vein grafts greater than or equal to 8 years and/or preprocedural thrombus were considered at high risk for embolic complications and would receive distal embolic protection under a selective strategy. Of 126 total patients, 70 (55%) had vein grafts greater than or equal to 8 years of age, 28 (22%) had a preprocedural thrombus, and 18 (14%) patients had both (Table 2). Patients with embolic complications were three times more likely to have a preprocedural thrombus and a higher frequency of vein grafts greater than or equal to 8 years (median graft age 117 months versus 96 months) (Table 2). A similar frequency of SCAI/AHA Type C lesions in degenerated vein grafts with a high degree of preprocedural stenosis was observed in both groups (Table 2). Balloon angioplasty, stent use and indications for intervention were equal between groups (Table 3). Worsening angina was the most common indication, with acute myocardial infarction in approximately 25% of patients. Clinical outcomes. Embolic complications occurred in 22 of 126 patients (17%), with 4 patients experiencing MACE: 1 (4.5%) myocardial infarction, 1 (4.5%) emergency coronary artery bypass graft surgery, and 2 (9.1%) deaths. All 4 patients had both vein grafts greater than or equal to 8 years old and a preprocedural thrombus. Under a selective strategy, all 4 patients would have been considered high-risk and received distal embolic protection. Identifying patients as high-risk by the prespecified model correctly suggests the use of distal embolic protection in 86% (19/22) of cases with embolic complications. Of these 19 high-risk patients, 15 (80%) fulfilled both selective criteria of graft age greater than or equal to 8 years and preprocedural thrombus, while the remaining 4 (20%) had only grafts greater than or equal to 8 years. Just 3 (14%) patients with embolic complications were not identified as high-risk by selective criteria, and none experienced MACE. Across the entire cohort, 63% (80/126) were identified as high-risk, and 37% (46/126) were identified as low-risk. Of these 46 low-risk patients, 43 (93%) patients did not have an embolic complication, while only 3 (7%) patients did (as mentioned above, none experienced MACE). Of the 80 high-risk patients, embolic complications occurred in 19 (24%) patients and were absent in 61 (76%) patients. Cost analysis. Embolic complications significantly increased total procedure costs from $7,228 to $9,953, or an additional $2,725 per embolic complication (p p = 0.015) (Table 4). The cost of an embolic complication is more than twice the cost of the distal embolic protection device ($1,350). Under a routine strategy, total procedure cost would theoretically increase in both patients with an embolic complication from $9,953 to $10,158, and those without embolic complication from $7,228 to $8,578 (Table 5). The difference in total procedure cost between patient groups would decrease from $2,725 to $1,580 (p = 0.017), a large difference relative to mean total procedure cost that still exceeds the mean cost of the distal protection device ($1,350). Alternately, a selective strategy in high-risk patients would theoretically decrease total procedure cost for patients with an embolic complication without increasing the cost for patients without an embolic complication (difference $2,111; p = 0.003) (Table 5). Cumulative total procedure cost (n = 126) for selective distal embolic protection would cost $86,254 more than no distal embolic protection, and would still cost $58,667 less than routine distal embolic protection (Table 6). As a result, routine protection would result in an additional cumulative cost of $144,921, or $1,150 per patient, versus only $685 per patient if distal embolic protection devices were used selectively in high-risk patients only. The 2 deaths during the index hospitalization occurred in patients stratified as high-risk. Avoiding these deaths would cost $43,127 per death prevented using a selective strategy, compared to $72,461 under a routine strategy; the cost per MACE averted is $21,564 versus $36,230, respectively. The data suggest that selective distal embolic protection in high-risk patients would theoretically cost about 60% of the cost to routinely use distal embolic protection indiscriminately in all patients. Discussion Clinical and angiographic predictors of embolic complications have been previously reported in various studies.^8–17 Myler et al. were among the first to demonstrate factors predictive of complications; in their original study, the presence of thrombus was the only characteristic to predict complications.¹⁰ Hong et al. additionally concluded thrombus and age both predicted complications.¹² Subsequently, Hong et al. found that degenerated SVG and thrombus were present more often in patients with subsequent CK-MB elevations, and even more importantly, this CK-MB elevation was the strongest multivariate predictor of 1-year mortality in all patients, including the 15% who experienced no in-hospital complications.¹³ Using the ACC-NCDR database, preprocedural thrombus and degenerated vein grafts were independent multivariate predictors of complications; interestingly, the ACC-AHA lesion type was not predictive.^9,15 The first randomized multicenter trial investigating percutaneous intervention in saphenous vein grafts (CAVEAT II) concluded that preprocedural thrombus was the only independent lesion characteristic predictive of complications, both in-hospital and at 1 year.⁸ The SAFER trial also showed that degenerated vein graft and furthermore, the degree of degeneration in addition to total plaque volume, were the only multivariate predictors of 30-day MACE.¹¹ Embolic complications in our cohort resulted in significant adverse clinical and economic outcomes consistent with previously published data. The prespecified model identified patients at high risk for embolic complication, using only two known multivariate predictors: vein grafts age greater than or equal to 8 years and preprocedural thrombus. Furthermore, the model predicted the majority of embolic complications and all MACE, with a sensitivity of 86% and a negative predictive value of 93%. Since the consequences of failing to identify an embolic complication are much worse, our model provides important clinical utility in the treatment of saphenous vein grafts using distal embolic protection devices. The majority of patients do not experience an embolic complication. As the data in our study suggest, routine distal embolic protection merely distributes costs across a majority of patients with no embolic complication, provides clinical benefit to a minority of patients and substantially increases cumulative and individual total procedure cost. This expense incurred without clinical benefit represents an opportunity cost to society. The model uses two clinical characteristics to correctly identify 86% (19/22) of patients with an embolic complication. Relying on the strong predictive ability of the model, a selective strategy enhances patient selection for distal embolic protection without obviating the interventionist’s discretion to utilize or conserve the device. Discriminating between patients at high versus low risk for an embolic complication may maximize the clinical benefit of distal embolic protection, while lessening overall cost burden to the patient and the healthcare system. The cost of an embolic complication was more than twice the cost of the distal embolic protection device. The additional cumulative total procedure cost would be substantially decreased to $86,254 from $144,921 ($685 versus $1,150 per patient), or nearly half the additional cost under a strategy of routine protection. In summary, a selective strategy would result in significant cost-savings over routine protection, suggesting the financial utility of our model. The major limitation of our model is identifying patients as high risk who receive distal embolic protection, but who would not have had an embolic complication. These patients would receive distal embolic protection under either strategy, with an equivocal effect on both clinical and economic outcomes. This limitation is acceptable until future investigations elucidate other characteristics that might be incorporated into the model. Selective distal embolic protection using the prespecified model would correctly identify the majority of patients who experience an embolic complication. Substantial cost savings over routine protection would be gained via decreased utilization in low-risk patients who represent a majority of all patients, and an even larger proportion of patients without embolic complications.

1. Rates of PCI in 2000. http://www.cdc.gov/nchs/fastats/pdf/ad319t8.pdf. Accessed December 10, 2003. 2. DeFeyter PJ, van Suylen R, de Jaegere PPT, et al. Balloon angioplasty for the treatment of lesions in saphenous vein grafts. J Am Coll Cardiol 1993;21:1539–1549. 3. Hong MK, Mehran R, Dangas G, et al. Are we making progress with percutaneous saphenous vein graft treatment? J Am Coll Cardiol 2001;38:150–154. 4. Piana RN, Paik GY, Moscucci M, et al. Incidence and treatment of “no-flow” after percutaneous coronary intervention. Circulation 1994;89:2514–2518. 5. Klein LW, Kern MJ, Berger P, et al. on behalf of the Interventional Committee of the Society of Cardiac Angiography and Interventions. Suggested management of the no-reflow phenomenon in the cardiac catheterization laboratory. Catheter Cardiovasc Interv 2003;60:194–201. 6. Baim DS, Wahr D, George D, et al. on behalf of the Saphenous vein graft Angioplasty Free of Emboli Randomized (SAFER) Trial Investigators. Randomized trial of distal embolic protection device during percutaneous intervention in saphenous vein aorto-coronary bypass grafts. Circulation 2002;105:1285–1290. 7. Cohen DJ, Murphy SA, Baim DS, et al., for the SAFER Investigators. Cost-effectiveness of distal embolic protection for patients undergoing percutaneous intervention of saphenous vein bypass grafts: Results from the SAFER trial. J Am Coll Cardiol 2004;44:1801–1808. 8. Lefkovits J, Holmes DR, Califf RM, et al. for the CAVEAT-II Investigators. Predictors and sequelae of distal embolization during saphenous vein graft intervention From the CAVEAT-II Trial. Circulation 1995; 92:734–740. 9. Zaacks SM, Allen JE, Calvin JE, et al. Value of the American College of Cardiology/American Heart Association stenosis morphology classification for coronary interventions in the late 1990s. Am J Cardiol 1998;82:43–49. 10. Myler RK, Shaw RE, Stertzer SH, et al. Lesion morphology and coronary angioplasty: Current experience and analysis. J Am Coll Cardiol 1992;19:1641–1652. 11. Giugliano GR, Kuntz RE, Popma JJ, et al. for the Saphenous Vein Graft Angioplasty Free of Emboli Randomized (SAFER) Trial Investigators. Determinants of 30-day adverse events following saphenous vein graft intervention with and without a distal occlusion embolic protection device. Am J Cardiol 2005;95:173–177. 12. Hong MK, Popma JJ, Pichard AD, et al. Clinical significance of distal embolization after transluminal extraction atherectomy in diffusely diseased saphenous vein grafts. Am Heart J 1994;127:1496–1503. 13. Hong M, Mehran R, Dangas G, et al. Creatine-kinase-MB enzyme elevation following successful saphenous vein graft intervention is associated with late mortality. Circulation 1999;1000:2400–2405. 14. Krone RJ, Shaw RE, Klein LW, et al. on behalf of the ACC-NCDR. Evaluation of the ACC/AHA and the SCAI lesion classification system in the current “stent” era of coronary interventions (from the ACC-NCDR). Am J Cardiol 2003;92:389–394. 15. Klein LW, Brindis RG, Kutcher MA, et al. for the ACC-NCDR Registry. Intervention in saphenous vein grafts: A predictive model based on clinical presentation of 5,899 consecutive cases in the ACC-NCDR Registry. J Am Coll Cardiol 2002;39:8A. 16. Nathan S, Gupta A, Satran A, et al. Predictors of short and long-term adverse outcomes following saphenous vein graft percutaneous intervention. J Am Coll Cardiol 2003;41:47A. 17. Nathan S, Satran A, Almeda FQ, et al. Angiographic and clinical predictors of major embolic complications during percutaneous saphenous vein graft intervention. Am J Cardiol 2002;90:40H. 18. American College of Cardiology National Data Registry: Data elements and definitions. American College of Cardiology, 2003. 19. Taira DA, Seto TB, Siegrist R, et al. Comparison of analytic approaches for the economic evaluation of new technologies alongside multicenter clinical trials. Am Heart J 2003;145:452–458. 20. Consumer Price Index. ftp://ftp.bls.gov/pub/special.requests/cpi/cpiai.txt. Accessed December 12, 2004. 21. Stone GW, Rogers C, Hermiller J, et al. for the FilterWire EX Randomized Evaluation Investigators. Randomized comparison of distal protection with a filter-based catheter and a balloon occlusion and aspiration system during percutaneous intervention of diseased saphenous vein aorto-coronary bypass grafts. Circulation 2003;108:548–553.