- Email: [email protected]
Comparison of treatment outcomes in patients ≥80 years undergoing transradial versus transfemoral coronary intervention
these results argue for pharmacodynamic and clinical reevaluations of the tirofiban HCl dose in the setting of PCI. Acknowledgment: The investigators thank Cori Grant, MS, for expert assistance in the statistical analyses for this study. 1. Lefkovits J, Plow EF, Topol EJ. Platelet glycoprotein IIb/IIIa receptors in cardiovascular medicine. N Engl J Med 1995;332:1553–1559. 2. The RESTORE Investigators. Effects of platelet glycoprotein IIb/IIIa blockade with tirofiban on adverse cardiac events in patients with unstable angina or acute myocardial infarction undergoing coronary angioplasty. Circulation 1997;96: 1445–1453. 3. Topol EJ, Moliterno DJ, Herrmann HC, Powers ER, Grines CL, Cohen DJ, Cohen EA, Bertrand M, Neumann FJ, Stone GW, et al, for the TARGET Investigators. Comparison of two platelet glycoprotein IIb/IIIa inhibitors, tirofiban and abciximab, for the prevention of ischemic events with percutaneous coronary revascularization. N Engl J Med 2001;344:1888 –1894. 4. The ESPRIT Investigators. Novel dosing regimen of eptifibatide in planned coronary stent implantation (ESPRIT): a randomised, placebo-controlled trial. Lancet 2000;356:2037–2044. 5. Gilchrist IC, O’Shea JC, Kosoglou T, Jennings LK, Lorenz TJ, Kitt MM, Kleiman NS, Talley D, Aguirre F, Davidson C, et al. Pharmacodynamics and pharmacokinetics of higher-dose, double-bolus eptifibatide in percutaneous coronary intervention. Circulation 2001;104:406 –411. 6. Born GVR, Cross MJ. The aggregation of blood platelets. J Physiol 1963;168: 178 –195. 7. Herrmann HC, Swierkosz TA, Kapoor S, Tardiff DC, DiBattiste PM, Hirshfeld JW, Klugherz BD, Kolansky DM, Magness K, Valettas N, Wilensky RL. Comparison of degree of platelet inhibition by abciximab versus tirofiban in patients with unstable angina pectoris and non–Q-wave myocardial infarction undergoing percutaneous coronary intervention. Am J Cardiol 2002;89:1293–1297. 8. Batchelor WB, Tolleson TR, Huang Y, Larsen RL, Mantell RM, Dillard P, Davidian M, Zhang D, Cantor WJ, Sketch MH Jr, et al. Randomized comparison of platelet inhibition with abciximab, tirofiban and eptifibatide during percutaneous coronary intervention in acute coronary syndromes: the COMPARE trial. Comparison of Measurements of Platelet Aggregation With Aggrastat, ReoPro, and Eptifibatide. Circulation 2002;106:1470 –1476. 9. Kereiakes DJ, Kleiman NS, Ambrose J, Cohen M, Rodriguez S, Palabrica T,
Herrmann HC, Sutton JM, Weaver WD, McKee DB, et al. Randomized, doubleblind, placebo-controlled dose ranging study of tirofiban (MK-383) platelet IIb/IIIa blockade in high risk patients undergoing coronary angioplasty. J Am Coll Cardiol 1996;27:536 –542. 10. The IMPACT-II Investigators. Randomised placebo-controlled trial of effect of eptifibatide on complications of percutaneous coronary intervention: IMPACT-II. Lancet 1997;349:1422–1428. 11. Harrington RA, Kleiman NS, Kottke-Marchant K, Lincoff AM, Tcheng JE, Sigmon KN, Joseph D, Rios G, Trainor K, Rose D, et al. Immediate and reversible platelet inhibition after intravenous administration of a peptide glycoprotein IIb/IIIa inhibitor during percutaneous coronary intervention. Am J Cardiol 1995;76:1222–1227. 12. Jennings LK, Phillips DR. Purification of glycoproteins IIb and III from human platelet plasma membranes and characterization of a calcium-dependent glycoprotein IIb–III complex. J Biol Chem 1982;257:10458 –10466. 13. Fitzgerald LA, Phillips DR. Calcium regulation of the platelet membrane glycoprotein IIb–IIIa complex. J Biol Chem 1985;260:11366 –11374. 14. Phillips DR, Charo IF, Parise LV, Fitzgerald LA. The platelet membrane glycoprotein IIb–IIIa complex. Blood 1988;71:831–843. 15. Phillips DR, Teng W, Arfsten A, Nannizzi-Alaimo L, White MM, Longhurst C, Shattil SJ, Randolph A, Jakubowski JA, Jennings LK, Scarborough RM. Effect of Ca2⫹ on GP IIb–IIIa interactions with Integrilin: enhanced GP IIb–IIIa binding and inhibition of platelet aggregation by reductions in the concentration of ionized calcium in plasma anticoagulated with citrate. Circulation 1997;96: 1488 –1494. 16. Tcheng JE, Talley JD, O’Shea JC, Gilchrist IC, Kleiman NS, Grines CL, Davidson CJ, Lincoff AM, Califf RM, Jennings LK, et al. Clinical pharmacology of higher dose eptifibatide in percutaneous coronary intervention (the PRIDE study). Am J Cardiol 2001;88:1097–1102. 17. Choo J, Gretter DD, Gold HK. Platelet aggregation inhibition with single and double bolus regimens of eptifibatide (Integrilin) (abstr). Am J Cardiol 2000; 86(suppl):71I. 18. Kereiakes DJ, Lorenz T, Young JJ, Kukielka G, Mueller NM, NanniazziAlaimo L, Phillips DR. Differential effects of citrate versus PPACK anticoagulation on measured platelet inhibition by abciximab, eptifibatide and tirofiban. J Thromb Thrombolysis 2001;12:123–127. 19. Jennings LK, Jacoski MV, White MM. The pharmacodynamics of parenteral glycoprotein IIb/IIIa inhibitors. J Interv Cardiol 2002;15:45–60. 20. Kleiman NS, Raizner AE, Jordan R, Wang AL, Norton D, Mace KF, Joshi A, Coller BS, Weisman HF. Differential inhibition of platelet aggregation induced by adenosine diphosphate or a thrombin receptor-activating peptide in patients treated with bolus chimeric 7E3 Fab: implications for inhibition of the internal pool of GPIIb/IIIa receptors. J Am Coll Cardiol 1995;26:1665–1671.
Comparison of Treatment Outcomes in Patients >80 Years Undergoing Transradial Versus Transfemoral Coronary Intervention W. Peter Klinke, MD, J. David Hilton, MD, Rebecca N. Warburton, William P. Warburton, PhD, and Ren P. Tan, MD We assessed the effect of transradial access (vs transfemoral access) for percutaneous coronary intervention on postprocedure length of stay and patient outcomes (in-hospital complications and all-cause and cardiac death at 6 and 12 months) in 225 elderly patients (>80 years old). Raw differences between transradial and transfemoral accesses were compared, and 3 forms of propensity score analysis were used to determine the true effect of transradial access. From the Victoria Heart Institute Foundation and the School of Public Administration, University of Victoria, Victoria, British Columbia, Canada; and the Department of Finance and Management Science, School of Business, University of Alberta, Edmonton, Alberta, Canada. Dr. Klinke’s address is: Victoria Heart Institute Foundation, 315-1900 Richmond Avenue, Victoria, British Columbia V8R 4R2, Canada. E-mail: [email protected]. Manuscript received December 1, 2003; revised manuscript received and accepted February 5, 2004.
1282
©2004 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 93 May 15, 2004
PhD,
After matching to adjust for baseline differences in patient characteristics, remaining differences in outcomes and postprocedure length of stay were small and not statistically significant at the 95% level, but a decrease in postprocedural length of stay of nearly 1 day was observed and likely was not due to chance. Transradial access in patients >80 years old undergoing percutaneous coronary intervention should be preferred due to equivalent success rate and safety and likely reduction in postprocedural hospitalization. 䊚2004 by Excerpta Medica, Inc. (Am J Cardiol 2004;93:1282–1285)
ercutaneous coronary intervention (PCI) is increasingly used in elderly patients with coronary P artery disease. The procedure is routinely performed according to standard methods (i.e., through the fem0002-9149/04/$–see front matter doi:10.1016/j.amjcard.2004.02.015
situation permitting verification of an adequate radial artery and a positive p Value Allen’s test. Radial Femoral (trans radial ⫽ To determine the true effect of (n ⫽ 125) (n ⫽ 128) transfemoral) access route in elderly patients, we Baseline examined short- and intermediateMen 75 (60%) 56 (44%) 0.012* term outcomes of elderly patients Women 50 (40%) 72 (56%) 0.012* (ⱖ80 years old) who underwent Age, (mean ⫾ SD) 83.3 ⫾ 2.5 83.4 ⫾ 2.5 0.860 transfemoral and transradial coroCo-morbidities Hypertension 83 (67%) 98 (77%) 0.069 nary interventions and adjusted for Diabetes mellitus 19 (15%) 38 (30%) 0.007* differences in baseline clinical charHyperlipidemia 69 (55%) 76 (59%) 0.445 acteristics using propensity score Cerebrovascular accident 10 (8.0%) 19 (15%) 0.113 analysis. Mean patient age was 83.4 Creatinine ⬎150 15 (12%) 15 (12%) 1.000 years (range 80 to 94). Baseline clinPeripheral vascular disease 24 (19%) 29 (23%) 0.538 Smoking 5 (4.0%) 7 (5.5%) 0.769 ical characteristics are presented in Prior PCI 26 (21%) 38 (30%) 0.112 Table 1. The study database contains Prior coronary bypass 22 (18%) 23 (18%) 1.000 comprehensive clinical information Prior myocardial infarct 45 (36%) 42 (33%) 0.596 on all patients, including ⬎150 clinCanadian Cardiac Society angina class III 20 (16%) 16 (12%) 0.474 Canadian Cardiac Society angina class IV 94 (75%) 104 (81%) 0.287 ical, treatment, and follow-up charAcute coronary syndrome 71 (57%) 63 (49%) 0.258 acteristics. Selected clinical and outAcute myocardial infarct 4 (3.2%) 20 (16%) 0.001* come data have been reported.15 3-vessel coronary artery disease 48 (38%) 51 (40%) 0.898 Overall, our patients would be conLeft main disease 13 (10%) 10 (7.8%) 0.518 sidered at high risk due to their adProximal left anterior descending artery 76 (61%) 74 (58%) 0.701 Procedure and outcomes vanced age, multiple co-morbidities, Emergent 5 (4.0%) 25 (20%) ⬍0.001* and angina class according to the CaUrgent 90 (72%) 82 (64%) 0.181 nadian Cardiac Society. Only 20% of Lesion type B-2 98 (78%) 89 (70%) 0.608 PCIs were elective, 12% were urLesion type C 42 (34%) 52 (41%) 0.156 Procedural success 120 (96%) 112 (88%) 0.014* gent, and 53% were performed in Clinical success 117 (94%) 106 (83%) 0.008* patients presenting with acute coroStent (primary vessel) 89 (71%) 89 (70%) 0.777 nary syndrome. No patients required Non-Q-wave myocardial infarct 2 (1.6%) 4 (3.1%) 0.427 emergency coronary bypass surgery. Procedure time (min) 54.8 58.1 0.369 Postdischarge follow-up included 30-d major adverse cardiac event 4 (3.2%) 18 (14%) 0.002* 6-mo major adverse cardiac event 3 (2.4%) 17 (13%) 0.002* telephone and mail contacts at 30 days and at 6 and 12 months. A stan*Statistically significant difference (p ⬍0.05 that the transradial and transfemoral results are the same). dard questionnaire was completed for each patient. For all 225 patients, British Columbia Vital Statistics oral artery) with high procedural success (ⱖ85%).1,2 Agency death files were checked; for registered Improved outcomes, compared with medical treat- deaths, we obtained the date, place, and all recorded ment,3–7 support the use of invasive procedures in causes of death. Differences between transradial and transfemoral older patients. There is a small but growing body of literature demonstrating the effectiveness of angio- procedures were analyzed with simple comparisons plasty performed from a transradial approach,8 –11 and t tests (raw differences) and 3 different forms of including in patients with acute coronary syn- propensity score matching to adjust for baseline difdromes.12–14 Transradial coronary intervention, al- ferences.16,17 All analyses examined differences in though a relatively new procedure, has the potential to postprocedural length of stay and 6 treatment outshorten hospitalization, speed patient mobilization, comes: in-hospital complications, in-hospital death, decrease nursing care, and lower complication rates. cardiac death within 6 and 12 months, and all-cause To date, limited data are available comparing transra- death within 6 and 12 months. dial access with transfemoral access in the elderly, and “Cardiac death” means the immediate cause of no large multicenter randomized trials have been re- death was cardiac arrest, acute myocardial infarct, ported. Because patients selected for transradial ac- ischemic heart disease, cardiogenic shock, congestive cess may differ from patients selected for transfemoral heart failure, atherosclerotic heart disease, or ventricaccess, raw comparisons may be misleading. ular arrhythmia. Patients with an immediate noncardiac cause of death (e.g., cancer, stroke, or pneumo••• From July 1998 to December 2000, 225 elderly nia) were excluded from cardiac deaths. All-cause patients (ⱖ80 years old) underwent 253 PCIs (8.7% of mortality was analyzed to avoid possible bias due to all PCIs) at the Royal Jubilee Hospital in Victoria, errors in classifying cause of death. All p values were British Columbia, Canada. All physicians performing calculated with 2-tailed tests and indicate the probaangioplasty were skilled in transfemoral and transra- bility of observing the difference we did, if the true dial angiography and PCI, and accepted practice was difference were actually zero. A p value of 0.05 inditransradial access in all patients, subject to the clinical cates a statistically significant difference between TABLE 1 Clinical Characteristics
BRIEF REPORTS
1283
Table 2 presents the raw comparison of outcomes with significance Femoral Radial testing. Raw outcomes were superior Outcome (n ⫽ 125) (n ⫽ 128) Difference p Value for transradial procedures on every measure. Length of stay and in-hosLength of stay after coronary intervention (d) 3.1 1.7 ⫺1.4 0.012* In-hospital complication rate 31.3% 24.0% ⫺7.3% 0.199 pital death rate were statistically sigIn-hospital death rate 11.7% 2.4% ⫺9.3% 0.004* nificant at the 95% level. These raw Cardiac death within 6 mo 5.5% 2.4% ⫺3.1% 0.212 results indicate that outcomes were All-cause death within 6 mo 6.3% 4.8% ⫺1.5% 0.616 better for transradial procedures; Cardiac death within 12 mo 9.2% 5.1% ⫺4.0% 0.230 All-cause death within 12 mo 10.9% 10.3% ⫺0.7% 0.868 however, because transradial procedures were performed in patients *Statistically significant difference (p ⬍0.05, that the transradial and transfemoral results are the with less acute cardiac disease and same). fewer co-morbidities (Table 1), raw outcomes cannot show whether or not transradial access benefitted patients. Three methods were used to find appropriate matches for transradial procedures (from transfemoral). (1) Nearest-neighbor matching selected the single transfemoral procedure with the closest propensity score (all within ⫾0.02 of the transradial score); (2) radius matching selected and averaged all transfemoral procedures within ⫾0.1; and (3) kernel matching used a normal-distribution weighted average17 of all transfemoral procedures (the weight assigned to each transfemoral procedure being the frequency of its propensity score FIGURE 1. Propensity score distribution. in a normal distribution centered on the propensity score of the transradial procedure being matched). FigTABLE 3 Propensity Score Matching, Bootstrapped Results ure 1 shows that close matches exNearest-Neighbor isted for all transradial procedures. Effect Radius Effect Kernel Effect Nearest-neighbor matching did not Outcome (p value) (p value) (p value) match patients who underwent the Length of stay after coronary ⫺0.72 (0.414) ⫺0.89 (0.111) ⫺0.70 (0.225) transfemoral procedure with a prointervention (d) pensity score of ⬍0.1 because no In-hospital death rate 0.02 (0.643) ⫺0.01 (0.770) ⫺0.00 (0.860) In-hospital complication rate 0.05 (0.619) 0.01 (0.852) 0.01 (0.854) patient who underwent the transraCardiac death within 6 mo 0.02 (0.663) ⫺0.02 (0.516) ⫺0.01 (0.713) dial procedure had a score that low. All-cause death within 6 mo 0.04 (0.331) 0.01 (0.789) 0.01 (0.622) Because our results were robust to Cardiac death within 12 mo ⫺0.07 (0.311) ⫺0.04 (0.270) ⫺0.05 (0.300) the matching method used and All-cause death within 12 mo ⫺0.02 (0.729) 0.00 (0.943) ⫺0.00 (0.940) passed the balancing test suggested by Dehejia and Wahba,18 we believe transradial and transfemoral procedures at the 95% we established reliable estimates of the average effect of transradial versus transfemoral PCI. confidence level. Table 3 shows the effect of transradial access on Transradial PCI was completed in 125 procedures (117 patients); transfemoral PCI was completed in 128 each patient’s outcome; all 3 matching methods indiprocedures (118 patients). As presented in Table 1, cated shorter length of stay for transradial procedures. patients who underwent transradial access were of None of the results were significant at the 95% level, similar age to those who underwent transfemoral ac- although the chance of seeing the observed 0.7- to cess but generally had less acute cardiac disease and 0.9-day reduction in stay for transradial procedures (if fewer co-morbidities. The transradial and transfemo- there were no differences) was 11% to 41%. ral groups differed significantly in the proportions of ••• women, diabetics, acute myocardial infarction, and Elderly patients are at increased risk of vascular emergency PCIs. Short-term outcomes were also bet- access complications due to their increased prevalence ter in patients who underwent transradial (vs trans- of peripheral vascular disease, long-term high blood femoral) access, with angiographic success rates of pressure, and related conditions. Transradial angio96% versus 88% and clinical success rates of 94% plasty with stenting has been shown to be a safe and versus 83%. effective method of revascularization,11,14 and its apTABLE 2 Raw Outcomes
1284 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 93
MAY 15, 2004
plication in elderly patients may lead to decreased hospital stay and fewer vascular complications compared with the transfemoral approach.14 The transradial approach has also been shown to facilitate care of elderly patients after PCI, with easier management of the vascular access site (especially after administration of glycoprotein IIb/IIIa inhibitors), early mobilization and the possibility of same-day discharge, and greater patient comfort and satisfaction.12,19,20 However, there are no large randomized multicenter trials of transradial versus transfemoral angioplasty in patients ⱖ80 years old. Our results are based on 225 consecutive patients ⱖ 80 years old who underwent PCI (including cases of acute myocardial infarct and cardiogenic shock) between July 1998 and December 2000. We found that patients who underwent the transradial procedure were significantly less likely to be women, diabetic, emergent, experiencing acute myocardial infarct, or to have a major adverse cardiac event within 30 days or 6 months of the procedure. They were significantly more likely to have angiographic and clinical successes. Raw differences in outcomes between the transradial and transfemoral PCI groups (which appeared to indicate decreased in-hospital deaths with transradial access) are misleading due to large baseline differences between groups. However, propensity score analysis indicated that transradial access likely (probability 59% to 89%) decreased postprocedure stay by between 0.7 and 0.9 days, with no detectable effect on in-hospital complication or mortality rates, in high-risk elderly (ⱖ80 years old) patients. Pending large randomized studies, these results are reassuring. We found no evidence of harm and some evidence of benefit from our strategy of preferring transradial access and using it whenever feasible. Acknowledgment: We thank Bernard J. Gersh, MD (Mayo Clinic) and Allan M. Ross, MD (George Washington University Cardiovascular Research Institute) for helpful comments on a draft of the manuscript. We also gratefully acknowledge the following: Aaron T. Clark, MD, for clinical data entry; Patricia M. Smith, MDA, for clinical data entry and retrieval; Paul Mick, MD, and Kurston Theman, MD, for collection of patient follow-up data from physicians and patients; the Vital Statistics Division of the Ministry of Health Services for death data extractions; Tara Bambrick, MA, for assistance in editing the first draft of the manuscript; Andrea Ichino, PhD, and Sascha O. Becker, PhD, for use of their statistical analysis software for propensity score matching (http://www.iue.it/ Personal/Ichino/#pscore, accessed January 2004); and
Annette Dobson, PhD, Anne Young, PhD, Robert Gibberd, PhD, and the SurfStat Project Team for use of the SurfStat statistical Web site at University of Newcastle, Australia (t statistic tables accessed October 2003, http://www.anu.edu.au/nceph/surfstat/ surfstat-home/tables/t.php). 1. Beydoun HK, O’Neill BJ, Teskey RJ, Kells CM, Title LM, Foster CJ. Is coronary angioplasty safe in the elderly? Can J Cardiol 2001;17:401–406. 2. Thompson RC, Holmes DR, Gersh BJ, Bailey KR. Predicting early and intermediate-term outcome of coronary angioplasty in the elderly. Circulation 1993;88:1579 –1587. 3. The TIME Investigators. Outcome of elderly patients with chronic symptomatic coronary artery disease with an invasive versus optimized medical treatment strategy. JAMA 2003;289:1117–1123. 4. Graham MM, Ghali WA, Faris PH, Galbraith D, Norris CM, Knudtson ML. Survival after coronary revascularization in the elderly. Circulation 2002;105: 2378 –2384. 5. Weintraub WS, Veledar E, Thompson T, Burnette J, Jurkovitz C, Mahoney E. Percutaneous coronary intervention outcomes in octogenarians during the stent era (National Cardiovascular Network). Am J Cardiol 2001;88:1407–1410. 6. Batchelor WB, Anstrom KJ, Muhlbaier LH, Grosswald R, Weintraub WS, O’Neill WW, Peterson ED. Contemporary outcome trends in the elderly undergoing percutaneous coronary interventions: results in 7,472 octogenarians. J Am Coll Cardiol 2000;36:723–730. 7. Gravina Taddei CF, Weintraub WS, Douglas JS, Ghazzal Z, Mahoney E, Thompson T, King S III. Influence of age on outcome after percutaneous transluminal coronary angioplasty. Am J Cardiol 1999;84:245–251. 8. Klinke WP, Hilton JD, Tan RP, Smith PM, Clark AT, Mick PT. Immediate and long-term outcomes in high-risk octogenarians undergoing coronary intervention (abstr). J Am Coll Cardiol 2002;39:329B. 9. Caputo RP, Simons A, Giambartolomei A, Grant W, Fedele K, Abraham S, Reger MJ, Walford GD, Esente P. Transradial cardiac catheterization in elderly patients. Catheter Cardiovasc Interv 2000;51:287–290. 10. Delarche N, Idir M, Estrade G, Leblay M. Direct angioplasty for acute myocardial infarction in elderly patients using transradial approach. Am J Geriatr Cardiol 1999;8:32–35. 11. Kiemeneij F, Laarman GJ, Odekerken D, Slagboom T, van der Wieken R. A randomized comparison of percutaneous transluminal coronary angioplasty by the radial, brachial and femoral approaches: the access study. J Am Coll Cardiol 1997;29:1269 –1275. 12. Ziakas A, Klinke P, Mildenberger R, Fretz E, Williams M, Della Siega A, Kinloch D, Hilton D. Comparison of the radial and the femoral approaches in percutaneous coronary intervention for acute myocardial infarction. Am J Cardiol 2002;91:598 –600. 13. Louvard Y, Ludwig J, Lefevre T, Schmeisser A, Bruck M, Scheinert D, Loubeyre C, Klinghammer L, Morice M, Flachskampf F, Daniel W. Transradial approach for coronary angioplasty in the setting of acute myocardial infarction: a dual center registry. Catheter Cardiovasc Interv 2002;55:206 –211. 14. Mann T, Cubeddu G, Bowen J, Schneider J, Arrowood M, Newman W, Zellinger M, Rose G. Stenting in acute coronary syndromes: a comparison of radial vs. femoral access sites. J Am Coll Cardiol 1998;32:572–576. 15. Klinke WP, Hilton JD, Tan RP, Clark AT, Smith PM, Mick PT. Transradial coronary intervention in octogenarians (abstr). J Am Coll Cardiol 2002;39:430B. 16. Rosenbaum PR, Rubin DB. Constructing a control group using multivariate matched sampling methods that incorporate the propensity score. Am Stat 1985; 39:33–38. 17. Heckman JJ, Ichimura H, Todd P. Matching as an econometric evaluation estimator. Rev Econ Stud 1998;65:261–294. 18. Dehejia RH, Wahba S. Causal effects in non-experimental studies: reevaluating the evaluation of training programs. J Am Stat Assoc 1999;94:1053– 1062. 19. Cooper CJ, El-Shiekh RA, Cohen DJ, Blaesing L, Burket MW, Basu A, Moore JA. Effect of transradial access on quality of life and cost of cardiac catheterization: a randomized comparison. Am Heart J 1999;138:430 –436. 20. Ziakas AA, Klinke WP, Mildenberger CR, Fretz DE, Williams EM, Kinloch FR, Hilton JD. Safety of same-day-discharge radial percutaneous coronary intervention: a retrospective study. Am Heart J 2003;146:699 –704.
BRIEF REPORTS
1285
Herrmann HC, Sutton JM, Weaver WD, McKee DB, et al. Randomized, doubleblind, placebo-controlled dose ranging study of tirofiban (MK-383) platelet IIb/IIIa blockade in high risk patients undergoing coronary angioplasty. J Am Coll Cardiol 1996;27:536 –542. 10. The IMPACT-II Investigators. Randomised placebo-controlled trial of effect of eptifibatide on complications of percutaneous coronary intervention: IMPACT-II. Lancet 1997;349:1422–1428. 11. Harrington RA, Kleiman NS, Kottke-Marchant K, Lincoff AM, Tcheng JE, Sigmon KN, Joseph D, Rios G, Trainor K, Rose D, et al. Immediate and reversible platelet inhibition after intravenous administration of a peptide glycoprotein IIb/IIIa inhibitor during percutaneous coronary intervention. Am J Cardiol 1995;76:1222–1227. 12. Jennings LK, Phillips DR. Purification of glycoproteins IIb and III from human platelet plasma membranes and characterization of a calcium-dependent glycoprotein IIb–III complex. J Biol Chem 1982;257:10458 –10466. 13. Fitzgerald LA, Phillips DR. Calcium regulation of the platelet membrane glycoprotein IIb–IIIa complex. J Biol Chem 1985;260:11366 –11374. 14. Phillips DR, Charo IF, Parise LV, Fitzgerald LA. The platelet membrane glycoprotein IIb–IIIa complex. Blood 1988;71:831–843. 15. Phillips DR, Teng W, Arfsten A, Nannizzi-Alaimo L, White MM, Longhurst C, Shattil SJ, Randolph A, Jakubowski JA, Jennings LK, Scarborough RM. Effect of Ca2⫹ on GP IIb–IIIa interactions with Integrilin: enhanced GP IIb–IIIa binding and inhibition of platelet aggregation by reductions in the concentration of ionized calcium in plasma anticoagulated with citrate. Circulation 1997;96: 1488 –1494. 16. Tcheng JE, Talley JD, O’Shea JC, Gilchrist IC, Kleiman NS, Grines CL, Davidson CJ, Lincoff AM, Califf RM, Jennings LK, et al. Clinical pharmacology of higher dose eptifibatide in percutaneous coronary intervention (the PRIDE study). Am J Cardiol 2001;88:1097–1102. 17. Choo J, Gretter DD, Gold HK. Platelet aggregation inhibition with single and double bolus regimens of eptifibatide (Integrilin) (abstr). Am J Cardiol 2000; 86(suppl):71I. 18. Kereiakes DJ, Lorenz T, Young JJ, Kukielka G, Mueller NM, NanniazziAlaimo L, Phillips DR. Differential effects of citrate versus PPACK anticoagulation on measured platelet inhibition by abciximab, eptifibatide and tirofiban. J Thromb Thrombolysis 2001;12:123–127. 19. Jennings LK, Jacoski MV, White MM. The pharmacodynamics of parenteral glycoprotein IIb/IIIa inhibitors. J Interv Cardiol 2002;15:45–60. 20. Kleiman NS, Raizner AE, Jordan R, Wang AL, Norton D, Mace KF, Joshi A, Coller BS, Weisman HF. Differential inhibition of platelet aggregation induced by adenosine diphosphate or a thrombin receptor-activating peptide in patients treated with bolus chimeric 7E3 Fab: implications for inhibition of the internal pool of GPIIb/IIIa receptors. J Am Coll Cardiol 1995;26:1665–1671.
Comparison of Treatment Outcomes in Patients >80 Years Undergoing Transradial Versus Transfemoral Coronary Intervention W. Peter Klinke, MD, J. David Hilton, MD, Rebecca N. Warburton, William P. Warburton, PhD, and Ren P. Tan, MD We assessed the effect of transradial access (vs transfemoral access) for percutaneous coronary intervention on postprocedure length of stay and patient outcomes (in-hospital complications and all-cause and cardiac death at 6 and 12 months) in 225 elderly patients (>80 years old). Raw differences between transradial and transfemoral accesses were compared, and 3 forms of propensity score analysis were used to determine the true effect of transradial access. From the Victoria Heart Institute Foundation and the School of Public Administration, University of Victoria, Victoria, British Columbia, Canada; and the Department of Finance and Management Science, School of Business, University of Alberta, Edmonton, Alberta, Canada. Dr. Klinke’s address is: Victoria Heart Institute Foundation, 315-1900 Richmond Avenue, Victoria, British Columbia V8R 4R2, Canada. E-mail: [email protected]. Manuscript received December 1, 2003; revised manuscript received and accepted February 5, 2004.
1282
©2004 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 93 May 15, 2004
PhD,
After matching to adjust for baseline differences in patient characteristics, remaining differences in outcomes and postprocedure length of stay were small and not statistically significant at the 95% level, but a decrease in postprocedural length of stay of nearly 1 day was observed and likely was not due to chance. Transradial access in patients >80 years old undergoing percutaneous coronary intervention should be preferred due to equivalent success rate and safety and likely reduction in postprocedural hospitalization. 䊚2004 by Excerpta Medica, Inc. (Am J Cardiol 2004;93:1282–1285)
ercutaneous coronary intervention (PCI) is increasingly used in elderly patients with coronary P artery disease. The procedure is routinely performed according to standard methods (i.e., through the fem0002-9149/04/$–see front matter doi:10.1016/j.amjcard.2004.02.015
situation permitting verification of an adequate radial artery and a positive p Value Allen’s test. Radial Femoral (trans radial ⫽ To determine the true effect of (n ⫽ 125) (n ⫽ 128) transfemoral) access route in elderly patients, we Baseline examined short- and intermediateMen 75 (60%) 56 (44%) 0.012* term outcomes of elderly patients Women 50 (40%) 72 (56%) 0.012* (ⱖ80 years old) who underwent Age, (mean ⫾ SD) 83.3 ⫾ 2.5 83.4 ⫾ 2.5 0.860 transfemoral and transradial coroCo-morbidities Hypertension 83 (67%) 98 (77%) 0.069 nary interventions and adjusted for Diabetes mellitus 19 (15%) 38 (30%) 0.007* differences in baseline clinical charHyperlipidemia 69 (55%) 76 (59%) 0.445 acteristics using propensity score Cerebrovascular accident 10 (8.0%) 19 (15%) 0.113 analysis. Mean patient age was 83.4 Creatinine ⬎150 15 (12%) 15 (12%) 1.000 years (range 80 to 94). Baseline clinPeripheral vascular disease 24 (19%) 29 (23%) 0.538 Smoking 5 (4.0%) 7 (5.5%) 0.769 ical characteristics are presented in Prior PCI 26 (21%) 38 (30%) 0.112 Table 1. The study database contains Prior coronary bypass 22 (18%) 23 (18%) 1.000 comprehensive clinical information Prior myocardial infarct 45 (36%) 42 (33%) 0.596 on all patients, including ⬎150 clinCanadian Cardiac Society angina class III 20 (16%) 16 (12%) 0.474 Canadian Cardiac Society angina class IV 94 (75%) 104 (81%) 0.287 ical, treatment, and follow-up charAcute coronary syndrome 71 (57%) 63 (49%) 0.258 acteristics. Selected clinical and outAcute myocardial infarct 4 (3.2%) 20 (16%) 0.001* come data have been reported.15 3-vessel coronary artery disease 48 (38%) 51 (40%) 0.898 Overall, our patients would be conLeft main disease 13 (10%) 10 (7.8%) 0.518 sidered at high risk due to their adProximal left anterior descending artery 76 (61%) 74 (58%) 0.701 Procedure and outcomes vanced age, multiple co-morbidities, Emergent 5 (4.0%) 25 (20%) ⬍0.001* and angina class according to the CaUrgent 90 (72%) 82 (64%) 0.181 nadian Cardiac Society. Only 20% of Lesion type B-2 98 (78%) 89 (70%) 0.608 PCIs were elective, 12% were urLesion type C 42 (34%) 52 (41%) 0.156 Procedural success 120 (96%) 112 (88%) 0.014* gent, and 53% were performed in Clinical success 117 (94%) 106 (83%) 0.008* patients presenting with acute coroStent (primary vessel) 89 (71%) 89 (70%) 0.777 nary syndrome. No patients required Non-Q-wave myocardial infarct 2 (1.6%) 4 (3.1%) 0.427 emergency coronary bypass surgery. Procedure time (min) 54.8 58.1 0.369 Postdischarge follow-up included 30-d major adverse cardiac event 4 (3.2%) 18 (14%) 0.002* 6-mo major adverse cardiac event 3 (2.4%) 17 (13%) 0.002* telephone and mail contacts at 30 days and at 6 and 12 months. A stan*Statistically significant difference (p ⬍0.05 that the transradial and transfemoral results are the same). dard questionnaire was completed for each patient. For all 225 patients, British Columbia Vital Statistics oral artery) with high procedural success (ⱖ85%).1,2 Agency death files were checked; for registered Improved outcomes, compared with medical treat- deaths, we obtained the date, place, and all recorded ment,3–7 support the use of invasive procedures in causes of death. Differences between transradial and transfemoral older patients. There is a small but growing body of literature demonstrating the effectiveness of angio- procedures were analyzed with simple comparisons plasty performed from a transradial approach,8 –11 and t tests (raw differences) and 3 different forms of including in patients with acute coronary syn- propensity score matching to adjust for baseline difdromes.12–14 Transradial coronary intervention, al- ferences.16,17 All analyses examined differences in though a relatively new procedure, has the potential to postprocedural length of stay and 6 treatment outshorten hospitalization, speed patient mobilization, comes: in-hospital complications, in-hospital death, decrease nursing care, and lower complication rates. cardiac death within 6 and 12 months, and all-cause To date, limited data are available comparing transra- death within 6 and 12 months. dial access with transfemoral access in the elderly, and “Cardiac death” means the immediate cause of no large multicenter randomized trials have been re- death was cardiac arrest, acute myocardial infarct, ported. Because patients selected for transradial ac- ischemic heart disease, cardiogenic shock, congestive cess may differ from patients selected for transfemoral heart failure, atherosclerotic heart disease, or ventricaccess, raw comparisons may be misleading. ular arrhythmia. Patients with an immediate noncardiac cause of death (e.g., cancer, stroke, or pneumo••• From July 1998 to December 2000, 225 elderly nia) were excluded from cardiac deaths. All-cause patients (ⱖ80 years old) underwent 253 PCIs (8.7% of mortality was analyzed to avoid possible bias due to all PCIs) at the Royal Jubilee Hospital in Victoria, errors in classifying cause of death. All p values were British Columbia, Canada. All physicians performing calculated with 2-tailed tests and indicate the probaangioplasty were skilled in transfemoral and transra- bility of observing the difference we did, if the true dial angiography and PCI, and accepted practice was difference were actually zero. A p value of 0.05 inditransradial access in all patients, subject to the clinical cates a statistically significant difference between TABLE 1 Clinical Characteristics
BRIEF REPORTS
1283
Table 2 presents the raw comparison of outcomes with significance Femoral Radial testing. Raw outcomes were superior Outcome (n ⫽ 125) (n ⫽ 128) Difference p Value for transradial procedures on every measure. Length of stay and in-hosLength of stay after coronary intervention (d) 3.1 1.7 ⫺1.4 0.012* In-hospital complication rate 31.3% 24.0% ⫺7.3% 0.199 pital death rate were statistically sigIn-hospital death rate 11.7% 2.4% ⫺9.3% 0.004* nificant at the 95% level. These raw Cardiac death within 6 mo 5.5% 2.4% ⫺3.1% 0.212 results indicate that outcomes were All-cause death within 6 mo 6.3% 4.8% ⫺1.5% 0.616 better for transradial procedures; Cardiac death within 12 mo 9.2% 5.1% ⫺4.0% 0.230 All-cause death within 12 mo 10.9% 10.3% ⫺0.7% 0.868 however, because transradial procedures were performed in patients *Statistically significant difference (p ⬍0.05, that the transradial and transfemoral results are the with less acute cardiac disease and same). fewer co-morbidities (Table 1), raw outcomes cannot show whether or not transradial access benefitted patients. Three methods were used to find appropriate matches for transradial procedures (from transfemoral). (1) Nearest-neighbor matching selected the single transfemoral procedure with the closest propensity score (all within ⫾0.02 of the transradial score); (2) radius matching selected and averaged all transfemoral procedures within ⫾0.1; and (3) kernel matching used a normal-distribution weighted average17 of all transfemoral procedures (the weight assigned to each transfemoral procedure being the frequency of its propensity score FIGURE 1. Propensity score distribution. in a normal distribution centered on the propensity score of the transradial procedure being matched). FigTABLE 3 Propensity Score Matching, Bootstrapped Results ure 1 shows that close matches exNearest-Neighbor isted for all transradial procedures. Effect Radius Effect Kernel Effect Nearest-neighbor matching did not Outcome (p value) (p value) (p value) match patients who underwent the Length of stay after coronary ⫺0.72 (0.414) ⫺0.89 (0.111) ⫺0.70 (0.225) transfemoral procedure with a prointervention (d) pensity score of ⬍0.1 because no In-hospital death rate 0.02 (0.643) ⫺0.01 (0.770) ⫺0.00 (0.860) In-hospital complication rate 0.05 (0.619) 0.01 (0.852) 0.01 (0.854) patient who underwent the transraCardiac death within 6 mo 0.02 (0.663) ⫺0.02 (0.516) ⫺0.01 (0.713) dial procedure had a score that low. All-cause death within 6 mo 0.04 (0.331) 0.01 (0.789) 0.01 (0.622) Because our results were robust to Cardiac death within 12 mo ⫺0.07 (0.311) ⫺0.04 (0.270) ⫺0.05 (0.300) the matching method used and All-cause death within 12 mo ⫺0.02 (0.729) 0.00 (0.943) ⫺0.00 (0.940) passed the balancing test suggested by Dehejia and Wahba,18 we believe transradial and transfemoral procedures at the 95% we established reliable estimates of the average effect of transradial versus transfemoral PCI. confidence level. Table 3 shows the effect of transradial access on Transradial PCI was completed in 125 procedures (117 patients); transfemoral PCI was completed in 128 each patient’s outcome; all 3 matching methods indiprocedures (118 patients). As presented in Table 1, cated shorter length of stay for transradial procedures. patients who underwent transradial access were of None of the results were significant at the 95% level, similar age to those who underwent transfemoral ac- although the chance of seeing the observed 0.7- to cess but generally had less acute cardiac disease and 0.9-day reduction in stay for transradial procedures (if fewer co-morbidities. The transradial and transfemo- there were no differences) was 11% to 41%. ral groups differed significantly in the proportions of ••• women, diabetics, acute myocardial infarction, and Elderly patients are at increased risk of vascular emergency PCIs. Short-term outcomes were also bet- access complications due to their increased prevalence ter in patients who underwent transradial (vs trans- of peripheral vascular disease, long-term high blood femoral) access, with angiographic success rates of pressure, and related conditions. Transradial angio96% versus 88% and clinical success rates of 94% plasty with stenting has been shown to be a safe and versus 83%. effective method of revascularization,11,14 and its apTABLE 2 Raw Outcomes
1284 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 93
MAY 15, 2004
plication in elderly patients may lead to decreased hospital stay and fewer vascular complications compared with the transfemoral approach.14 The transradial approach has also been shown to facilitate care of elderly patients after PCI, with easier management of the vascular access site (especially after administration of glycoprotein IIb/IIIa inhibitors), early mobilization and the possibility of same-day discharge, and greater patient comfort and satisfaction.12,19,20 However, there are no large randomized multicenter trials of transradial versus transfemoral angioplasty in patients ⱖ80 years old. Our results are based on 225 consecutive patients ⱖ 80 years old who underwent PCI (including cases of acute myocardial infarct and cardiogenic shock) between July 1998 and December 2000. We found that patients who underwent the transradial procedure were significantly less likely to be women, diabetic, emergent, experiencing acute myocardial infarct, or to have a major adverse cardiac event within 30 days or 6 months of the procedure. They were significantly more likely to have angiographic and clinical successes. Raw differences in outcomes between the transradial and transfemoral PCI groups (which appeared to indicate decreased in-hospital deaths with transradial access) are misleading due to large baseline differences between groups. However, propensity score analysis indicated that transradial access likely (probability 59% to 89%) decreased postprocedure stay by between 0.7 and 0.9 days, with no detectable effect on in-hospital complication or mortality rates, in high-risk elderly (ⱖ80 years old) patients. Pending large randomized studies, these results are reassuring. We found no evidence of harm and some evidence of benefit from our strategy of preferring transradial access and using it whenever feasible. Acknowledgment: We thank Bernard J. Gersh, MD (Mayo Clinic) and Allan M. Ross, MD (George Washington University Cardiovascular Research Institute) for helpful comments on a draft of the manuscript. We also gratefully acknowledge the following: Aaron T. Clark, MD, for clinical data entry; Patricia M. Smith, MDA, for clinical data entry and retrieval; Paul Mick, MD, and Kurston Theman, MD, for collection of patient follow-up data from physicians and patients; the Vital Statistics Division of the Ministry of Health Services for death data extractions; Tara Bambrick, MA, for assistance in editing the first draft of the manuscript; Andrea Ichino, PhD, and Sascha O. Becker, PhD, for use of their statistical analysis software for propensity score matching (http://www.iue.it/ Personal/Ichino/#pscore, accessed January 2004); and
Annette Dobson, PhD, Anne Young, PhD, Robert Gibberd, PhD, and the SurfStat Project Team for use of the SurfStat statistical Web site at University of Newcastle, Australia (t statistic tables accessed October 2003, http://www.anu.edu.au/nceph/surfstat/ surfstat-home/tables/t.php). 1. Beydoun HK, O’Neill BJ, Teskey RJ, Kells CM, Title LM, Foster CJ. Is coronary angioplasty safe in the elderly? Can J Cardiol 2001;17:401–406. 2. Thompson RC, Holmes DR, Gersh BJ, Bailey KR. Predicting early and intermediate-term outcome of coronary angioplasty in the elderly. Circulation 1993;88:1579 –1587. 3. The TIME Investigators. Outcome of elderly patients with chronic symptomatic coronary artery disease with an invasive versus optimized medical treatment strategy. JAMA 2003;289:1117–1123. 4. Graham MM, Ghali WA, Faris PH, Galbraith D, Norris CM, Knudtson ML. Survival after coronary revascularization in the elderly. Circulation 2002;105: 2378 –2384. 5. Weintraub WS, Veledar E, Thompson T, Burnette J, Jurkovitz C, Mahoney E. Percutaneous coronary intervention outcomes in octogenarians during the stent era (National Cardiovascular Network). Am J Cardiol 2001;88:1407–1410. 6. Batchelor WB, Anstrom KJ, Muhlbaier LH, Grosswald R, Weintraub WS, O’Neill WW, Peterson ED. Contemporary outcome trends in the elderly undergoing percutaneous coronary interventions: results in 7,472 octogenarians. J Am Coll Cardiol 2000;36:723–730. 7. Gravina Taddei CF, Weintraub WS, Douglas JS, Ghazzal Z, Mahoney E, Thompson T, King S III. Influence of age on outcome after percutaneous transluminal coronary angioplasty. Am J Cardiol 1999;84:245–251. 8. Klinke WP, Hilton JD, Tan RP, Smith PM, Clark AT, Mick PT. Immediate and long-term outcomes in high-risk octogenarians undergoing coronary intervention (abstr). J Am Coll Cardiol 2002;39:329B. 9. Caputo RP, Simons A, Giambartolomei A, Grant W, Fedele K, Abraham S, Reger MJ, Walford GD, Esente P. Transradial cardiac catheterization in elderly patients. Catheter Cardiovasc Interv 2000;51:287–290. 10. Delarche N, Idir M, Estrade G, Leblay M. Direct angioplasty for acute myocardial infarction in elderly patients using transradial approach. Am J Geriatr Cardiol 1999;8:32–35. 11. Kiemeneij F, Laarman GJ, Odekerken D, Slagboom T, van der Wieken R. A randomized comparison of percutaneous transluminal coronary angioplasty by the radial, brachial and femoral approaches: the access study. J Am Coll Cardiol 1997;29:1269 –1275. 12. Ziakas A, Klinke P, Mildenberger R, Fretz E, Williams M, Della Siega A, Kinloch D, Hilton D. Comparison of the radial and the femoral approaches in percutaneous coronary intervention for acute myocardial infarction. Am J Cardiol 2002;91:598 –600. 13. Louvard Y, Ludwig J, Lefevre T, Schmeisser A, Bruck M, Scheinert D, Loubeyre C, Klinghammer L, Morice M, Flachskampf F, Daniel W. Transradial approach for coronary angioplasty in the setting of acute myocardial infarction: a dual center registry. Catheter Cardiovasc Interv 2002;55:206 –211. 14. Mann T, Cubeddu G, Bowen J, Schneider J, Arrowood M, Newman W, Zellinger M, Rose G. Stenting in acute coronary syndromes: a comparison of radial vs. femoral access sites. J Am Coll Cardiol 1998;32:572–576. 15. Klinke WP, Hilton JD, Tan RP, Clark AT, Smith PM, Mick PT. Transradial coronary intervention in octogenarians (abstr). J Am Coll Cardiol 2002;39:430B. 16. Rosenbaum PR, Rubin DB. Constructing a control group using multivariate matched sampling methods that incorporate the propensity score. Am Stat 1985; 39:33–38. 17. Heckman JJ, Ichimura H, Todd P. Matching as an econometric evaluation estimator. Rev Econ Stud 1998;65:261–294. 18. Dehejia RH, Wahba S. Causal effects in non-experimental studies: reevaluating the evaluation of training programs. J Am Stat Assoc 1999;94:1053– 1062. 19. Cooper CJ, El-Shiekh RA, Cohen DJ, Blaesing L, Burket MW, Basu A, Moore JA. Effect of transradial access on quality of life and cost of cardiac catheterization: a randomized comparison. Am Heart J 1999;138:430 –436. 20. Ziakas AA, Klinke WP, Mildenberger CR, Fretz DE, Williams EM, Kinloch FR, Hilton JD. Safety of same-day-discharge radial percutaneous coronary intervention: a retrospective study. Am Heart J 2003;146:699 –704.
BRIEF REPORTS
1285