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Outcomes of elderly patients with cardiogenic shock treated with early percutaneous revascularization
Interventional Cardiology
Outcomes of elderly patients with cardiogenic shock treated with early percutaneous revascularization Abhiram Prasad, MBBS, MD, MRCP,a Ryan J. Lennon, MS,b Charanjit S. Rihal, MD, FACC,a Peter B. Berger, MD, FACC,a and David R. Holmes, Jr, MD, FACCa Rochester, Minn
Background Subgroup analysis from the Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) trial indicated that patients with acute myocardial infarction (MI) complicated by cardiogenic shock (CS) who were ⱖ75 years old did not benefit from early revascularization and may have been harmed; their mortality rate at 30 days was 75%. The applicability of this subset analysis from a select patient population enrolled in a randomized trial to the general population is unclear. Methods At the Mayo Clinic between 1991 and 2000, we evaluated the outcome of all patients ⱖ75 years old with CS caused by MI who underwent urgent percutaneous coronary intervention (PCI). Results
The study included 61 patients with a mean age of 79.5 ⫾ 3 years; 21% of these patients had a history of prior coronary artery bypass grafting (CABG), 41% had had a prior MI, 28% had diabetes mellitus, and 18% had a history of a cerebrovascular accident (CVA). PCI was performed 8.0 ⫾ 7.2 hours after onset of MI. Angiographic success (⬍50% residual stenosis) was achieved in 91% of the lesions that were dilated. In hospital outcomes included death (44%), CABG (1.6%), and CVA (4.9%). The 30-day mortality rate was 47%. The estimated survival rate 1 year after discharge (Kaplan Meier method) was 75%.
Conclusions
These data confirm a high early mortality rate among patients ⱖ75 years old with MI complicated by CS, but suggest that among patients referred for angiography, outcomes may be better than previously believed when early revascularization is performed. In this population, 56% of patients survived to be discharged from the hospital, and of the hospital survivors, 75% were alive at 1 year. (Am Heart J 2004;147:1066 –70.)
See related Editorial on page 950.
Cardiogenic shock (CS) occurs in approximately 7% to 10% of patients with acute myocardial infarction (MI) and is the leading cause of inhospital death.1,2 Advanced age with markers of left ventricular dysfunction such as heart rate, blood pressure, and Killip class are powerful risk factors for the development of CS after ST-elevation and non ST-elevation acute coronary syndrome.3 Thrombolytic therapy alone does not appear to reduce mortality once shock has occurred.4
From the aDivision of Cardiovascular Diseases and Department of Internal Medicine and bSection of Biostatistics, Mayo Clinic and Mayo Foundation, Rochester, Minn. Submitted February 12, 2003; accepted July 12, 2003. Reprint requests: David R. Holmes, MD, Mayo Clinic, 200 First St SW, Rochester, MN 55905. E-mail: [email protected] 0002-8703/$ - see front matter © 2004, Elsevier Inc. All rights reserved. doi:10.1016/j.ahj.2003.07.030
The Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) trial demonstrated that emergency revascularization with either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in patients with CS caused by transmural MI resulted in a survival advantage at 6 months.5,6 Pre-specified subgroup analysis indicated that the benefit was restricted to patients ⬍75 years old, whereas revascularization was associated with a worse outcome in the small number of elderly patients who were ⱖ75 years old. This observation has resulted in the widespread perception that an early invasive strategy should be avoided in elderly patients with CS. Indeed, the American College of Cardiology and American Heart Association guidelines on the management of acute MI recommend primary PCI only for patients with CS who are ⬍75 years old.7 This has important implications because of the aging population and increasing incidence of elderly patients with MI at presentation. We hypothesized that the subset
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analysis from the SHOCK trial may not apply to the general elderly population. Therefore, the aim of this study was to evaluate the outcome of patients ⱖ75 years old with CS caused by MI at presentation who were treated with early PCI at the Mayo Clinic.
Methods Since 1979, all patients undergoing percutaneous revascularization at the Mayo Clinic in Rochester, Minn, have been prospectively observed, and data are entered in a registry on the based of a protocol approved by the Institutional Review Board. The registry includes demographic, clinical, angiographic, and procedural data. Immediate and inhospital events are recorded, and each patient is surveyed by telephone with a standardized questionnaire at 6 months, 1 year, and then annually after the procedure. All adverse events are confirmed by reviewing the medical records of the patients observed at our institution and by contacting the patients’ physicians and reviewing the hospital records of patients observed elsewhere. This study included all patients from the database for the period of January 1, 1991, through December 31, 2000, who were ⱖ75 years old and came for treatment within 24 hours of a MI that was complicated by CS. Patients with and without ST-segment elevation were included because the mortality rate from CS is similarly high in both groups.8,9 Patients were excluded when they had hypotension caused by arrhythmia, mechanical complication of MI, hypovolemia, sepsis, or medications. Hospital charts of each patient were reviewed to verify the data, and the study was approved by the Institutional Review Board. The following definitions were used for the database. CS was diagnosed when systolic blood pressure was ⬍90 mm Hg for ⬎30 minutes or inotropic therapy was required to maintain the blood pressure ⱖ90 mm Hg. MI was defined by the presence of 2 of 3 criteria: chest pain, electrocardiographic changes, and increased cardiac enzyme levels at least twice the upper limit of the reference range. The number of diseased coronary arteries was defined by the number of major coronary arteries with luminal diameter stenosis ⱖ70%. Patients with ⱖ50% stenosis in the left main coronary artery were considered to have 2-vessel disease when there was right dominance and 3-vessel disease when there was left dominance. Angiographic success was defined as PCI with residual stenosis ⬍50% in at least 1 treatment site. Complete revascularization was achieved when there were no remaining stenoses ⱖ70%.
Statistical analysis Data are presented as the mean plus or minus SD or as a percentage. All analyses were performed with SAS software (SAS, Inc, Cary, NC). An event-free survival curve was constructed with Kaplan-Meier estimates.
Results Baseline characteristics A total of 61 patients were included in the study. Baseline data for the total population and also by pa-
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Table I. Baseline patient characteristics All Survivors (n ⴝ 61) (n ⴝ 34)
Deaths (n ⴝ 27)
Mean age (y) 79.5 ⫾ 3 79.5 ⫾ 2 Male (%) 51 44 Prior myocardial infarction (%) 41 35 Hypertension (%) 70 76 Hypercholesterolemia (%) 61 63 Diabetes mellitus (%) 28 24 Current smokers (%) 10 12 Former smokers (%) 45 52 Congestive heart failure (%) 48 45 Prior stroke (%) 18 17 Peripheral vascular disease (%) 17 14 Prior PCI (%) 25 26 Prior CABG (%) 21 21 Ejection Fraction (%) 30 ⫾ 10 28 ⫾ 11 Creatinine clearance 56 ⫾ 20 58 ⫾ 20
80.7 ⫾ 4 59 48 63 59 33 7 37 52 20 20 22 22 33 ⫾ 9 52 ⫾ 18
P ⬎ .1 for all comparison between inhospital survivors and deaths.
tients who survived to hospital discharge and patients who died are listed in Table I. The mean patient age was 79.5 ⫾ 3 years (range, 76 – 87 years). There was an equal distribution of men and women. There was a high prevalence of a history of congestive heart failure, hypertension, and hyperlipidemia. Forty-one percent of patients had a prior MI, 28% had diabetes mellitus, 45% were prior smokers, and 21% had prior CABG. Most patients had not received thrombolytic therapy befire PCI. The mean left ventricular ejection fraction was 30% ⫾ 10%. All patients were treated with intravenous inotropes, and 39% were treated with an intra-aortic balloon pump. There were no differences in baseline characteristic between patients who survived to hospital discharge and patients who died.
Angiographic characteristics Twenty six percent, 33%, and 41% of patients had single, 2-vessel, and 3-vessel disease, respectively, and there was no difference in disease severity between patients who survived to hospital discharge and patients who died (Table II). Of the 53 lesions with American College of Cardiology/American HeartAssociation lesion complexity recorded, 4 were B1-, 8 were B2-, and 41 were C-type lesions. PCI was performed 8.0 ⫾ 7.2 hours after the onset of symptoms of MI. A total of 100 lesions were treated, with an angiographic success rate was 91%. Post-procedure Thrombolysis in Myocardial Infarction (TIMI) grade 2 and 3 flow was present in 17 and 67 lesions, respectively, and was less frequently achieved in the patients who died while hospitalized. Fifty-two percent of patients had angioplasty alone, and 44% had at least 1 stent deployed. One patient was treated with rheolytic thrombectomy, and 1 patient was treated with atherectomy. Both of
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Table II. Angiographic and procedural characteristics
No. of diseased vessels (%) 1 2 3 Thrombolytic pre-PCI (%) Postprocedure TIMI 2/3 (%) Angiographic success (%) Complete revascularization (%) Time to PCI No of lesions treated/patient Stent implantation (%) GP IIb/IIIa inhibitor (%)
All (n ⴝ 61)
Survivors (n ⴝ 34)
Deaths (n ⴝ 27)
26 33 41 12 84 93 28 8.0 ⫾ 7.2 1.6 ⫾ 0.8 44 43
28 38 34 13 94 97 35 8.6 ⫾ 8.1 1.6 ⫾ 0.8 47 44
23 27 50 9 72 89 19 7.1 ⫾ 6.0 1.7 ⫾ 0.8 41 41
P .31
Figure 1
.64 .022 .20 .15 .41 .82 .62 .79
Of the patients who survived to hospital discharge, the median follow-up period was 49 months (range, ⬍1– 88 months). During this time, there were 13 additional deaths. The estimated Kaplan-Meier 1-year survival rate for patients discharged from the hospital was 75% (Figure 1).
Discussion
Kaplan-Meier survival estimates.
these patients also underwent coronary stent deployment. Glycoprotein (GP) IIb/IIIa inhibitors were given in 43% of the procedures. There was no difference in the frequency of GP IIb/IIIa inhibitor, stent, and prePCI thrombolytic use between patients who survived to hospital discharge and patients who died. Complete revascularization was achieved in 28% of patients.
Outcomes The inhospital mortality rate was 44% (27 patients). One additional patient died at 30 days. Other inhospital complications included renal failure in 6 patients (9.8%). Of the 6 patients in whom renal failure developed, 4 had abnormal creatinine clearance at baseline; baseline creatinine data was not available for the other 2 patients. Vascular complications, predominantly caused by a hematoma formation, occurred in 3 patients (4.9%). A stroke developed in 3 patients (4.9%) and was fatal in 2 patients. Elective CABG was performed in 1 patient (1.6%).
Our study illustrates that emergency percutaneous revascularization may be performed with angiographic success in most elderly patients with CS caused by MI. Furthermore, the outcome may be better than previously reported,5,6 despite the high inhospital mortality rate. Retrospective studies have demonstrated that early revascularization is associated with an improved survival rate in patients with CS after MI.2,10 –12 These studies formed the basis for the SHOCK trial, in which patients with ST-elevation MI complicated by CS were randomly assigned to recieve either immediate invasive strategy or initial stabilization and late or no revascularization. The study reported an absolute 9% (P ⫽ .11) and 13% (P ⫽ .027) reduction in the rate of the primary and secondary end points of 30-day and 6-month mortality, respectively, in the entire study population. This benefit was durable and persisted, increasing slightly after 12 months of follow-up.6 The mortality rates at 30 days and 6 months in the immediate invasive strategy group were 46.7% and 50.3%, respectively. However, in the small number of patients aged ⱖ75 years, the outcome was worse with an immediate invasive strategy (n ⫽ 24; 30-day mortality rate, 75%) compared with initial medical therapy (n ⫽ 32; 30-day mortality rate, 53%; P ⫽ .01). In this study, we report lower inhospital and 30-day mortality rates of 44% and 47%, respectively, in our series of elderly patients, despite a similar mean age. Furthermore, most patients (75%, Figure 1) in this study who survived to hospital
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discharge were alive at 1 year, as observed previously.13 Adverse events such as stroke and renal failure caused by the low cardiac output state were not uncommon, but occurred at a similar rate as that reported in the SHOCK trial.5 The acceptable outcomes were observed despite the high-risk profile of our patients with advanced age (mean age, 79.5 ⫾ 3 years) and the high prevalence of prior MI (41%), congestive heart failure (48%), and multivessel disease (74%). A recently published study from the concurrent SHOCK registry that included patients with CS who were not randomized in the SHOCK trial supports our findings and provides a group for comparison who were treated with initial medical management. An early invasive strategy (n ⫽ 44) among elderly patients, most of whom were underwent revascularization with PCI (n ⫽ 39), compared with patients treated with initial medical management (n ⫽ 233), was associated with a lower inhospital mortality rate (48% vs 81%, P ⫽ .0002).6,14 Patients selected to undergo PCI were more likely to have been transferred from another hospital, to have prior history of PCI, to have prior history of hypertension, and to have higher creatinine kinase clearance. The association with an early invasive strategy appeared to be independent of these baseline differences with multivariate analysis (hazard ratio, 0.46; 95% CI, 0.28 – 0.75; P ⫽ .002) and persisted on follow-up to 60 days. A potential reason for the superior outcomes in our study and the SHOCK registry compared with that of the SHOCK trial may have been selection because the attending physicians, rather than a randomization protocol, determined the choice of treatment for each patient. Furthermore, in our study, PCI was performed a mean of 8 hours after the onset of symptoms of MI, faster than in the SHOCK trial. Further evidence for a beneficial effect of early revascularization with PCI in elderly patients with CS is provided by data from a community-based registry that included 16 hospitals in Worcester, Mass, that compared outcomes between 1986 to 1991 and 1993 to 1997.15 A significant reduction in inhospital mortality rate (80% vs 69%, P ⫽ .03) was noted with time and was associated with an increased performance of an early revascularization strategy (2% vs 16%, P ⬍.001) that was an independent determinant of survival. Angiographic success is an important determinant of outcome in primary angioplasty, and this is underscored by the observation in our study that patients who died in the hospital were significantly less likely to have TIMI 2 or 3 flow after PCI.16 There was also a trend toward lower rates of complete revascularization in patients who died, but this did not reach statistical significance. A high success rate (91%) was achieved in our elderly population. This is consistent with an increasing body of evidence indicating that, in the current era, primary angioplasty may be performed with
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procedural success rates similar to that in younger patients despite the presence of more complex lesions.17 At our institution, we have observed an improvement in clinical success rates and a reduction in mortality when comparing the periods of 1979 to 1993 with 1994 to 1997 among very elderly patients who require primary angioplasty.18 Recently, a randomized trial in elderly patients (⬎75 years) confirmed the superiority of primary angioplasty over streptokinase for the treatment of MI. Angiographic success was achieved in 90% of patients, with 51% receiving a stent, and there was no use of GP IIb/IIIa receptor inhibitors.19 Potentially, future success rates may be even better with more widespread use of stents and GP IIb/IIIa receptor inhibitors.20
Limitations Although the data were collected prospectively, this is a retrospective analysis and is subject to the limitations of such analyses. The study included only patients enrolled in the catheterization laboratory database and does not account for patients who were not referred for urgent coronary angiography. This may have led to referral bias because of the exclusion of the sickest patients because either they died shortly after the development of shock and hence revascularization could not have been performed or the attending physicians may have selected the more stable patients for angiography. Nevertheless, as aforementioned, the patients in our study represented a high-risk cohort. Finally, the data are derived from a single center, which limits their applicability; however, they are likely to be representative of outcomes in high-volume catheterization laboratories with experienced operators.
Conclusions The mortality rate associated with CS in patients aged ⱖ75 years remains high, but is lower than previously reported in a randomized trial. This may be because of the use of early revascularization in appropriately selected patients. We believe that early revascularization should be considered the treatment of choice for elderly patients with CS after MI. However, treatment needs to be individualized by the attending physicians on the basis of comorbidity and patient preferences.
References 1. Goldberg RJ, Samad NA, Yarzebski J, et al. Temporal trends in cardiogenic shock complicating acute myocardial infarction. N Engl J Med 1999;340:1162– 8. 2. Holmes DR Jr, Bates ER, Kleiman NS, et al. Contemporary reperfusion therapy for cardiogenic shock: the GUSTO-I trial experience. The GUSTO-I Investigators. Global Utilization of Streptokinase and
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Tissue Plasminogen Activator for Occluded Coronary Arteries. J Am Coll Cardiol 1995;26:668 –74. Hasdai D, Topol EJ, Califf RM, et al. Cardiogenic shock complicating acute coronary syndromes. Lancet 2000;356:749 –56. Gruppo Italiano per lo Studio della Streotichinasi nell’Infarto Miocardico (GISSI). Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986;1:397– 402. Hochman JS, Sleeper LA, Webb JG, et al. Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investigators. Should We Emergently Revascularize Occluded Coronaries for Cardiogenic ShocK. N Engl J Med 1999; 341:625–34. Hochman JS, Sleeper LA, White HD, et al. Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock: oneyear survival following early revascularization for cardiogenic shock. JAMA 2001;285:190 –2. Ryan TJ, Antman EM, Brooks NH, et al. 1999 update: ACC/AHA guidelines for the management of patients with acute myocardial infarction. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction). J Am Coll Cardiol 1999;34:890 –911. Holmes DR Jr, Berger PB, Hochman JS, et al. Cardiogenic shock in patients with acute ischemic syndromes with and without ST-segment elevation. Circulation 1999;100:2067–73. Jacobs AK, French JK, Col J, et al. Cardiogenic shock with non-STsegment elevation myocardial infarction: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded coronaries for Cardiogenic shock? J Am Coll Cardiol 2000;36(Suppl A):1091– 6. Berger PB, Holmes DR Jr, Stebbins AL, et al. Impact of an aggressive invasive catheterization and revascularization strategy on mortality in patients with cardiogenic shock in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial: an observational study. Circulation 1997;96:122–7.
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11. Hibbard MD, Holmes DR Jr, Bailey KR, et al. Percutaneous transluminal coronary angioplasty in patients with cardiogenic shock. J Am Coll Cardiol 1992;19:639 – 46. 12. Antoniucci D, Valenti R, Santoro GM, et al. Systematic direct angioplasty and stent-supported direct angioplasty therapy for cardiogenic shock complicating acute myocardial infarction: in-hospital and long-term survival. J Am Coll Cardiol 1998;31:294 –300. 13. Berger PB, Tuttle RH, Holmes DR Jr, et al. One-year survival among patients with acute myocardial infarction complicated by cardiogenic shock, and its relation to early revascularization: results from the GUSTO-I trial. Circulation 1999;99:873– 8. 14. Dzavik V, Sleeper LA, Cocke TP, et al. Early revascularization is associated with improved survival in elderly patients with acute myocardial infarction complicated by cardiogenic shock: a report from the SHOCK Trial Registry. Eur Heart J 2003;24:828 –37. 15. Dauerman HL, Goldberg RJ, Malinski M, et al. Outcomes and early revascularization for patients ⬎ or ⫽ 65 years of age with cardiogenic shock. Am J Cardiol 2001;87:844 – 8. 16. Hochman JS, Buller CE, Sleeper LA, et al. Cardiogenic shock complicating acute myocardial infarction-etiologies, management and outcome: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK? J Am Coll Cardiol 2000;36(Suppl A):1063–70. 17. Lane GE, Holmes DR Jr. Primary angioplasty for acute myocardial infarction in the elderly. Coron Artery Dis 2000;11:305–13. 18. Singh M, Mathew V, Garratt KN, et al. Effect of age on the outcome of angioplasty for acute myocardial infarction among patients treated at the Mayo Clinic. Am J Med 2000;108:187–92. 19. de Boer MJ, Ottervanger JP, van’t Hof AW, et al. Reperfusion therapy in elderly patients with acute myocardial infarction: a randomized comparison of primary angioplasty and thrombolytic therapy. J Am Coll Cardiol 2002;39:1723– 8. 20. Hasdai D, Harrington RA, Hochman JS, et al. Platelet glycoprotein IIb/IIIa blockade and outcome of cardiogenic shock complicating acute coronary syndromes without persistent ST-segment elevation. J Am Coll Cardiol 2000;36:685–92.
Outcomes of elderly patients with cardiogenic shock treated with early percutaneous revascularization Abhiram Prasad, MBBS, MD, MRCP,a Ryan J. Lennon, MS,b Charanjit S. Rihal, MD, FACC,a Peter B. Berger, MD, FACC,a and David R. Holmes, Jr, MD, FACCa Rochester, Minn
Background Subgroup analysis from the Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) trial indicated that patients with acute myocardial infarction (MI) complicated by cardiogenic shock (CS) who were ⱖ75 years old did not benefit from early revascularization and may have been harmed; their mortality rate at 30 days was 75%. The applicability of this subset analysis from a select patient population enrolled in a randomized trial to the general population is unclear. Methods At the Mayo Clinic between 1991 and 2000, we evaluated the outcome of all patients ⱖ75 years old with CS caused by MI who underwent urgent percutaneous coronary intervention (PCI). Results
The study included 61 patients with a mean age of 79.5 ⫾ 3 years; 21% of these patients had a history of prior coronary artery bypass grafting (CABG), 41% had had a prior MI, 28% had diabetes mellitus, and 18% had a history of a cerebrovascular accident (CVA). PCI was performed 8.0 ⫾ 7.2 hours after onset of MI. Angiographic success (⬍50% residual stenosis) was achieved in 91% of the lesions that were dilated. In hospital outcomes included death (44%), CABG (1.6%), and CVA (4.9%). The 30-day mortality rate was 47%. The estimated survival rate 1 year after discharge (Kaplan Meier method) was 75%.
Conclusions
These data confirm a high early mortality rate among patients ⱖ75 years old with MI complicated by CS, but suggest that among patients referred for angiography, outcomes may be better than previously believed when early revascularization is performed. In this population, 56% of patients survived to be discharged from the hospital, and of the hospital survivors, 75% were alive at 1 year. (Am Heart J 2004;147:1066 –70.)
See related Editorial on page 950.
Cardiogenic shock (CS) occurs in approximately 7% to 10% of patients with acute myocardial infarction (MI) and is the leading cause of inhospital death.1,2 Advanced age with markers of left ventricular dysfunction such as heart rate, blood pressure, and Killip class are powerful risk factors for the development of CS after ST-elevation and non ST-elevation acute coronary syndrome.3 Thrombolytic therapy alone does not appear to reduce mortality once shock has occurred.4
From the aDivision of Cardiovascular Diseases and Department of Internal Medicine and bSection of Biostatistics, Mayo Clinic and Mayo Foundation, Rochester, Minn. Submitted February 12, 2003; accepted July 12, 2003. Reprint requests: David R. Holmes, MD, Mayo Clinic, 200 First St SW, Rochester, MN 55905. E-mail: [email protected] 0002-8703/$ - see front matter © 2004, Elsevier Inc. All rights reserved. doi:10.1016/j.ahj.2003.07.030
The Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) trial demonstrated that emergency revascularization with either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in patients with CS caused by transmural MI resulted in a survival advantage at 6 months.5,6 Pre-specified subgroup analysis indicated that the benefit was restricted to patients ⬍75 years old, whereas revascularization was associated with a worse outcome in the small number of elderly patients who were ⱖ75 years old. This observation has resulted in the widespread perception that an early invasive strategy should be avoided in elderly patients with CS. Indeed, the American College of Cardiology and American Heart Association guidelines on the management of acute MI recommend primary PCI only for patients with CS who are ⬍75 years old.7 This has important implications because of the aging population and increasing incidence of elderly patients with MI at presentation. We hypothesized that the subset
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analysis from the SHOCK trial may not apply to the general elderly population. Therefore, the aim of this study was to evaluate the outcome of patients ⱖ75 years old with CS caused by MI at presentation who were treated with early PCI at the Mayo Clinic.
Methods Since 1979, all patients undergoing percutaneous revascularization at the Mayo Clinic in Rochester, Minn, have been prospectively observed, and data are entered in a registry on the based of a protocol approved by the Institutional Review Board. The registry includes demographic, clinical, angiographic, and procedural data. Immediate and inhospital events are recorded, and each patient is surveyed by telephone with a standardized questionnaire at 6 months, 1 year, and then annually after the procedure. All adverse events are confirmed by reviewing the medical records of the patients observed at our institution and by contacting the patients’ physicians and reviewing the hospital records of patients observed elsewhere. This study included all patients from the database for the period of January 1, 1991, through December 31, 2000, who were ⱖ75 years old and came for treatment within 24 hours of a MI that was complicated by CS. Patients with and without ST-segment elevation were included because the mortality rate from CS is similarly high in both groups.8,9 Patients were excluded when they had hypotension caused by arrhythmia, mechanical complication of MI, hypovolemia, sepsis, or medications. Hospital charts of each patient were reviewed to verify the data, and the study was approved by the Institutional Review Board. The following definitions were used for the database. CS was diagnosed when systolic blood pressure was ⬍90 mm Hg for ⬎30 minutes or inotropic therapy was required to maintain the blood pressure ⱖ90 mm Hg. MI was defined by the presence of 2 of 3 criteria: chest pain, electrocardiographic changes, and increased cardiac enzyme levels at least twice the upper limit of the reference range. The number of diseased coronary arteries was defined by the number of major coronary arteries with luminal diameter stenosis ⱖ70%. Patients with ⱖ50% stenosis in the left main coronary artery were considered to have 2-vessel disease when there was right dominance and 3-vessel disease when there was left dominance. Angiographic success was defined as PCI with residual stenosis ⬍50% in at least 1 treatment site. Complete revascularization was achieved when there were no remaining stenoses ⱖ70%.
Statistical analysis Data are presented as the mean plus or minus SD or as a percentage. All analyses were performed with SAS software (SAS, Inc, Cary, NC). An event-free survival curve was constructed with Kaplan-Meier estimates.
Results Baseline characteristics A total of 61 patients were included in the study. Baseline data for the total population and also by pa-
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Table I. Baseline patient characteristics All Survivors (n ⴝ 61) (n ⴝ 34)
Deaths (n ⴝ 27)
Mean age (y) 79.5 ⫾ 3 79.5 ⫾ 2 Male (%) 51 44 Prior myocardial infarction (%) 41 35 Hypertension (%) 70 76 Hypercholesterolemia (%) 61 63 Diabetes mellitus (%) 28 24 Current smokers (%) 10 12 Former smokers (%) 45 52 Congestive heart failure (%) 48 45 Prior stroke (%) 18 17 Peripheral vascular disease (%) 17 14 Prior PCI (%) 25 26 Prior CABG (%) 21 21 Ejection Fraction (%) 30 ⫾ 10 28 ⫾ 11 Creatinine clearance 56 ⫾ 20 58 ⫾ 20
80.7 ⫾ 4 59 48 63 59 33 7 37 52 20 20 22 22 33 ⫾ 9 52 ⫾ 18
P ⬎ .1 for all comparison between inhospital survivors and deaths.
tients who survived to hospital discharge and patients who died are listed in Table I. The mean patient age was 79.5 ⫾ 3 years (range, 76 – 87 years). There was an equal distribution of men and women. There was a high prevalence of a history of congestive heart failure, hypertension, and hyperlipidemia. Forty-one percent of patients had a prior MI, 28% had diabetes mellitus, 45% were prior smokers, and 21% had prior CABG. Most patients had not received thrombolytic therapy befire PCI. The mean left ventricular ejection fraction was 30% ⫾ 10%. All patients were treated with intravenous inotropes, and 39% were treated with an intra-aortic balloon pump. There were no differences in baseline characteristic between patients who survived to hospital discharge and patients who died.
Angiographic characteristics Twenty six percent, 33%, and 41% of patients had single, 2-vessel, and 3-vessel disease, respectively, and there was no difference in disease severity between patients who survived to hospital discharge and patients who died (Table II). Of the 53 lesions with American College of Cardiology/American HeartAssociation lesion complexity recorded, 4 were B1-, 8 were B2-, and 41 were C-type lesions. PCI was performed 8.0 ⫾ 7.2 hours after the onset of symptoms of MI. A total of 100 lesions were treated, with an angiographic success rate was 91%. Post-procedure Thrombolysis in Myocardial Infarction (TIMI) grade 2 and 3 flow was present in 17 and 67 lesions, respectively, and was less frequently achieved in the patients who died while hospitalized. Fifty-two percent of patients had angioplasty alone, and 44% had at least 1 stent deployed. One patient was treated with rheolytic thrombectomy, and 1 patient was treated with atherectomy. Both of
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Table II. Angiographic and procedural characteristics
No. of diseased vessels (%) 1 2 3 Thrombolytic pre-PCI (%) Postprocedure TIMI 2/3 (%) Angiographic success (%) Complete revascularization (%) Time to PCI No of lesions treated/patient Stent implantation (%) GP IIb/IIIa inhibitor (%)
All (n ⴝ 61)
Survivors (n ⴝ 34)
Deaths (n ⴝ 27)
26 33 41 12 84 93 28 8.0 ⫾ 7.2 1.6 ⫾ 0.8 44 43
28 38 34 13 94 97 35 8.6 ⫾ 8.1 1.6 ⫾ 0.8 47 44
23 27 50 9 72 89 19 7.1 ⫾ 6.0 1.7 ⫾ 0.8 41 41
P .31
Figure 1
.64 .022 .20 .15 .41 .82 .62 .79
Of the patients who survived to hospital discharge, the median follow-up period was 49 months (range, ⬍1– 88 months). During this time, there were 13 additional deaths. The estimated Kaplan-Meier 1-year survival rate for patients discharged from the hospital was 75% (Figure 1).
Discussion
Kaplan-Meier survival estimates.
these patients also underwent coronary stent deployment. Glycoprotein (GP) IIb/IIIa inhibitors were given in 43% of the procedures. There was no difference in the frequency of GP IIb/IIIa inhibitor, stent, and prePCI thrombolytic use between patients who survived to hospital discharge and patients who died. Complete revascularization was achieved in 28% of patients.
Outcomes The inhospital mortality rate was 44% (27 patients). One additional patient died at 30 days. Other inhospital complications included renal failure in 6 patients (9.8%). Of the 6 patients in whom renal failure developed, 4 had abnormal creatinine clearance at baseline; baseline creatinine data was not available for the other 2 patients. Vascular complications, predominantly caused by a hematoma formation, occurred in 3 patients (4.9%). A stroke developed in 3 patients (4.9%) and was fatal in 2 patients. Elective CABG was performed in 1 patient (1.6%).
Our study illustrates that emergency percutaneous revascularization may be performed with angiographic success in most elderly patients with CS caused by MI. Furthermore, the outcome may be better than previously reported,5,6 despite the high inhospital mortality rate. Retrospective studies have demonstrated that early revascularization is associated with an improved survival rate in patients with CS after MI.2,10 –12 These studies formed the basis for the SHOCK trial, in which patients with ST-elevation MI complicated by CS were randomly assigned to recieve either immediate invasive strategy or initial stabilization and late or no revascularization. The study reported an absolute 9% (P ⫽ .11) and 13% (P ⫽ .027) reduction in the rate of the primary and secondary end points of 30-day and 6-month mortality, respectively, in the entire study population. This benefit was durable and persisted, increasing slightly after 12 months of follow-up.6 The mortality rates at 30 days and 6 months in the immediate invasive strategy group were 46.7% and 50.3%, respectively. However, in the small number of patients aged ⱖ75 years, the outcome was worse with an immediate invasive strategy (n ⫽ 24; 30-day mortality rate, 75%) compared with initial medical therapy (n ⫽ 32; 30-day mortality rate, 53%; P ⫽ .01). In this study, we report lower inhospital and 30-day mortality rates of 44% and 47%, respectively, in our series of elderly patients, despite a similar mean age. Furthermore, most patients (75%, Figure 1) in this study who survived to hospital
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discharge were alive at 1 year, as observed previously.13 Adverse events such as stroke and renal failure caused by the low cardiac output state were not uncommon, but occurred at a similar rate as that reported in the SHOCK trial.5 The acceptable outcomes were observed despite the high-risk profile of our patients with advanced age (mean age, 79.5 ⫾ 3 years) and the high prevalence of prior MI (41%), congestive heart failure (48%), and multivessel disease (74%). A recently published study from the concurrent SHOCK registry that included patients with CS who were not randomized in the SHOCK trial supports our findings and provides a group for comparison who were treated with initial medical management. An early invasive strategy (n ⫽ 44) among elderly patients, most of whom were underwent revascularization with PCI (n ⫽ 39), compared with patients treated with initial medical management (n ⫽ 233), was associated with a lower inhospital mortality rate (48% vs 81%, P ⫽ .0002).6,14 Patients selected to undergo PCI were more likely to have been transferred from another hospital, to have prior history of PCI, to have prior history of hypertension, and to have higher creatinine kinase clearance. The association with an early invasive strategy appeared to be independent of these baseline differences with multivariate analysis (hazard ratio, 0.46; 95% CI, 0.28 – 0.75; P ⫽ .002) and persisted on follow-up to 60 days. A potential reason for the superior outcomes in our study and the SHOCK registry compared with that of the SHOCK trial may have been selection because the attending physicians, rather than a randomization protocol, determined the choice of treatment for each patient. Furthermore, in our study, PCI was performed a mean of 8 hours after the onset of symptoms of MI, faster than in the SHOCK trial. Further evidence for a beneficial effect of early revascularization with PCI in elderly patients with CS is provided by data from a community-based registry that included 16 hospitals in Worcester, Mass, that compared outcomes between 1986 to 1991 and 1993 to 1997.15 A significant reduction in inhospital mortality rate (80% vs 69%, P ⫽ .03) was noted with time and was associated with an increased performance of an early revascularization strategy (2% vs 16%, P ⬍.001) that was an independent determinant of survival. Angiographic success is an important determinant of outcome in primary angioplasty, and this is underscored by the observation in our study that patients who died in the hospital were significantly less likely to have TIMI 2 or 3 flow after PCI.16 There was also a trend toward lower rates of complete revascularization in patients who died, but this did not reach statistical significance. A high success rate (91%) was achieved in our elderly population. This is consistent with an increasing body of evidence indicating that, in the current era, primary angioplasty may be performed with
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procedural success rates similar to that in younger patients despite the presence of more complex lesions.17 At our institution, we have observed an improvement in clinical success rates and a reduction in mortality when comparing the periods of 1979 to 1993 with 1994 to 1997 among very elderly patients who require primary angioplasty.18 Recently, a randomized trial in elderly patients (⬎75 years) confirmed the superiority of primary angioplasty over streptokinase for the treatment of MI. Angiographic success was achieved in 90% of patients, with 51% receiving a stent, and there was no use of GP IIb/IIIa receptor inhibitors.19 Potentially, future success rates may be even better with more widespread use of stents and GP IIb/IIIa receptor inhibitors.20
Limitations Although the data were collected prospectively, this is a retrospective analysis and is subject to the limitations of such analyses. The study included only patients enrolled in the catheterization laboratory database and does not account for patients who were not referred for urgent coronary angiography. This may have led to referral bias because of the exclusion of the sickest patients because either they died shortly after the development of shock and hence revascularization could not have been performed or the attending physicians may have selected the more stable patients for angiography. Nevertheless, as aforementioned, the patients in our study represented a high-risk cohort. Finally, the data are derived from a single center, which limits their applicability; however, they are likely to be representative of outcomes in high-volume catheterization laboratories with experienced operators.
Conclusions The mortality rate associated with CS in patients aged ⱖ75 years remains high, but is lower than previously reported in a randomized trial. This may be because of the use of early revascularization in appropriately selected patients. We believe that early revascularization should be considered the treatment of choice for elderly patients with CS after MI. However, treatment needs to be individualized by the attending physicians on the basis of comorbidity and patient preferences.
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