Early percutaneous intervention improves survival in elderly patients with acute myocardial infarction complicated by cardiogenic shock
LLiiaanngg GGuuoo,, XXiiaaooyyaann MMaaii,, JJiiee DDeenngg,, AAnnhheenngg LLiiuu,, LLuunn BBuu,, HHaaiicchhaanngg WWaanngg
Xijing Hospital, the Fourth Military Medical University, China
A b s t r a c t B
Baacckkggrroouunndd:: The safety and effectiveness of emergency percutaneous coronary intervention (PCI) in elderly patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) are currently unknown.
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Aiimm:: To compare the outcome of elderly patients with AMI complicated by CS who were treated with primary PCI or thrombolysis.
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Meetthhooddss:: Between 2001 and 2006 at Xijing Hospital we evaluated the outcome of 94 patients ≥75 years old with AMI complicated by CS, of whom 33 underwent emergency PCI (PCI group), whereas the other 61 received initially conventional medication (CM group).
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Reessuullttss:: Baseline characteristics, infarct location, rate of intra-aortic balloon pump support and time from AMI onset to therapy were similar between the two groups. The success rate of revascularisation in the PCI group was 90.9% and the success rate of thrombolysis in the CM group was 60.7% (p=0.004). The PCI group had a lower in-hospital mortality than the CM group (42.4 vs.
65.6%, p=0.026). Kaplan-Meier curves showed a significant difference in survival (48.48 vs. 21.31%, p=0.006), favouring early PCI.
Multiple logistic regression identified time from AMI onset to therapy as an independent predictor of in-hospital death (p=0.036).
Cox regression analysis indicated early PCI as an independent factor to improve mid-term survival (p=0.015).
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Coonncclluussiioonnss:: Emergency PCI improves 1-year survival compared with initial conventional medication for elderly patients with AMI complicated by CS.
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Keeyy wwoorrddss:: myocardial infarction, shock, aging, revascularisation, survival
Kardiol Pol 2008; 66: 722-726
Address for correspondence:
Haichang Wang PhD, Xijing Hospital, the Fourth Military Medical University, Chang Le West Street, No. 15, Xi’an, Shaanxi Province 710032, PR China, tel.: +86 13309886925, e-mail: doctorguol@gmail.com
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Reecceeiivveedd:: 17 March 2008. AAcccceepptteedd:: 23 April 2008.
Introduction
Acute myocardial infarction (AMI) is the most serious disease of the cardiovascular system, and cardiogenic shock (CS) is one of the most dangerous complications of it.
Cardiogenic shock occurs in approximately 7-10% of patients with AMI and formerly led to 70-80% in-hospital death. In recent years, with the development of interventional technology, the mortality rate has decreased to about 50%.
Many retrospective studies report percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) resulting in lower in-hospital mortality rate in comparison with conventional medication [1-4]. The ‘SHould we emergently revascularise Occluded Coronaries in cardiogenic shocK’ (SHOCK) trial reported significantly lower 6- and 12-month mortality in the early revascularisation group than in the initial medical stabilisation group, but in the elderly population subgroup the patients derived no apparent treatment benefit from early revascularisation [5]. This has
important implications because of the aging population and increasing incidence of elderly patients with AMI at presentation. We hypothesised that the results from the small sample size of the elderly patients in the SHOCK trial may not apply to the general elderly population. In this study, we evaluated the clinical outcome of 94 elderly patients with AMI complicated by CS who were treated with PCI or conventional medication.
Methods
Study population
Since 2001, all patients with AMI in the Department of Cardiology, Xijing Hospital, have been prospectively observed, and data were entered in a registry. The registry included demographic, clinical, angiographic, and procedural data.
Immediate and in-hospital events were recorded, and each patient was surveyed by telephone with a standardised questionnaire at 6 months and 1 year.
This study included all the patients aged over 75 years old who were diagnosed with AMI complicated by CS from the database for the period of January 1, 2001 to December 31, 2006.
Acute MI was defined by the presence of 2 of 3 criteria:
prolonged (>30 minutes) chest pain or equivalent symptoms, typical electrocardiographic changes, and increased cardiac enzyme levels at least twice the upper limit of the reference range. Cardiogenic shock was diagnosed when systolic blood pressure was <90 mmHg for >30 minutes, or vasopressors or intra-aortic balloon pump (IABP) was required to maintain the blood pressure
≥90 mmHg, or there was evidence of decreased organ perfusion [6].
Those patients that developed CS 36 hours after AMI onset or died within 24 hours of hospital admission were excluded from the study [7]. Those who were diagnosed with any other factors predisposing to hypotension, such as pain, vagus reflex, arrhythmia, drugs, haemorrhage and other non-AMI induced hypotension, were also excluded [8].
Definitions
The patients that underwent emergency PCI within 6 hours after hospitalisation were defined as the PCI group.
The other patients were defined as the conventional medication group (CM group) and they received only conventional medication therapy including thrombolysis.
In the PCI group, only the infarct-related artery was treated and angioplasty success was defined as an infarct-related artery stenosis <20% associated with a TIMI grade flow of 2 or 3 in the presumed infarct-related artery in coronary angiography. Failed angioplasty was determined when the TIMI flow rate was 0-I or the patient died [9].
Successful thrombolysis was determined when it was suggested by the clinical indices, early creatine kinase peak (reached within the first 12 hours), early pain disappearance, early reduction of >50% of the ST-T segment shifts, or presence of reperfusion arrhythmias.
Failed thrombolysis was determined when the same clinical criteria failed to indicate it or the patient died [10].
Procedures and pharmacotherapy
Coronary angioplasty was performed using standard percutaneous techniques with a femoral approach and standard techniques for stent implantation. The intra- -aortic baloon pomp (IABP) catheter was inserted percutaneously via the femoral artery. Following insertion of the device, the IABP was used in a 1:1 ratio with full augmentation. The IABP was left in situ for up to 48 hours where possible.
Initial management of CS was with fluid infusion and supplemental oxygen. Systolic blood pressure increased
≥90 mmHg with inotropic drugs, using either beta- -agonists or phosphodiesterase inhibitors or combination therapy for a synergistic effect. All patients received
standard dose aspirin 160 to 325 mg; clopidogrel was also given (300-600 mg as loading dose, followed by 75 mg/d).
Either unfractionated heparin (UFH) or enoxaparin was used based on the discretion of treating physician.
Statistical analysis
Continuous variables are presented as mean±SD, and categorical variables as percentages. Student’s t-test was used for continuous variables, and chi-square test for absolute categorical variables. Survival estimates were calculated by the Kaplan-Meier product technique and compared with the log rank test. A logistic regression model was fitted to assess risk factors for any in-hospital mortality. A Cox proportional hazard model was used to identify the independent predictors for patients' mid-term survival. Statistical analyses were conducted using SPSS for Windows version 11.5.0 (SPSS Inc., Chicago, IL).
A p value of <0.05 was considered statistically significant.
Results
Baseline characteristics
A total of 94 patients were included, of whom 33 underwent emergency PCI, while the other 61 received only conventional medication. Delayed revascularisation was attempted in 6 patients (9.8%) from the CM group at a median of 126 hours after hospitalisation. The baseline characteristics of all 94 patients are summarised in Table I. There were no significant differences in mean age, gender, and other baseline characteristics between the PCI group and the CM group.
Procedure and clinical outcome
There were no differences in infarct location and the rate of IABP support between patients who were subjected to PCI or conventional medication (Table II). Time from AMI onset to therapy was similar between the two groups. The success rate of revascularisation in the PCI group was
P
Paarraammeetteerr PPCCII ggrroouupp CCMM ggrroouupp pp ((nn==3333)) ((nn==6611)) D
Deemmooggrraapphhiiccss
Mean age [years] 77.8±2.2 78.4±2.8 0.268
Male 19 (57.6%) 35 (57.4%) 0.580
Smoking 12 (36.4%) 29 (47.5%) 0.205
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Meeddiiccaall hhiissttoorryy
Hypertension 18 (54.5%) 27 (44.3%) 0.231 Diabetes mellitus 27 (81.8%) 49 (80.3%) 0.546 Dyslipidaemia 15 (45.5%) 26 (42.6%) 0.480 Renal insufficiency 4 (12.1%) 13 (21.3%) 0.207 Previous MI 23 (69.7%) 43 (70.5%) 0.558 Family history 24 (72.7%) 46 (75.4%) 0.480 of ischaemic heart disease
T
Taabbllee II.. Baseline characteristics
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Early percutaneous intervention improves survival in elderly patients with acute myocardial infarction complicated by cardiogenic shock
90.9% and the success rate of thrombolysis in the CM group was 60.7% (p=0.004).
The PCI group had a lower in-hospital mortality rate compared with the CM group [14 (42.4%) vs. 40 (65.6%), p=0.026]. The patients were followed up for one year after their initial procedure. Kaplan-Meier curves showed a significant difference in survival [16 (48.48%) vs. 13 (21.31%), p=0.006], with a 27.2% absolute difference in survival at one year, favouring early PCI (Figure 1).
Clinical and angiographic factors related to in-hospital death and mid-term survival The baseline characteristics and clinical data were analysed to assess their correlation with in-hospital death.
Univariate analysis of 16 clinical and angiographic factors revealed a significant correlation of in-hospital mortality with 3 variables: PCI, previous MI, and time from AMI onset to therapy. A multiple logistic regression analysis identified the time from AMI onset to therapy as an independent predictor of in-hospital death (Table III). Cox regression analysis using a forward stepwise variable selection procedure indicated PCI as an independent factor to improve survival of patients with AMI complicated by CS (hazard ratio=0.500 for PCI group against CM group, p =0.015 and 95% confidence interval 0.286-0.872).
Discussion
Our study illustrates that emergency PCI has a more favourable impact on outcome than conventional medication in AMI in elderly patients complicated by CS. Furthermore, our study shows that the time from AMI onset to therapy is an independent predictor of in-hospital death, and that emergency PCI is an independent factor improving survival rate in elderly patients with AMI complicated by CS.
The American College of Cardiology/American Heart Association guidelines excluded elderly patients with CS from class I recommendation for emergency revascularisation. This exclusion is subsequent to the results of the SHOCK trial, the only randomised trial that compared an early revascularisation strategy with an initial medical stabilisation. In the SHOCK trial, patients with ST-elevation MI complicated by CS were randomly assigned to receive either immediate invasive strategy or initial medical stabilisation and late or no revascularisation. The study reported an absolute 9% (p=0.11) and 13% (p=0.027) reduction in the rate of 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. 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 >75 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%;
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Paarraammeetteerr PPCCII ggrroouupp CCMM ggrroouupp pp ((nn==3333)) ((nn==6611)) Infarct location
anterior 11 (33.3%) 28 (45.9%) 0.168 inferior 17 (51.5%) 24 (31.3%) 0.179
other 6 (18.2%) 21 (34.4%) 0.075
IABP usage 14 (42.4%) 26 (42.6%) 0.580 Time to therapy [hours] 11.8±5.3 10.3±5.9 0.203
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Taabbllee IIII.. Clinical characteristics
FFiigguurree 11.. Kaplan-Meier estimates for overall 12-month survival. The 12-month survival rate was 48.48% for patients in the PCI group and 21.31%
for those in the CM group
0 1 2 3 4 5 6 7 8 9 10 11 12
ppeerrcceenntt ssuurrvviivviinngg [[%%]]
100
80
60
40
20
0
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moonntthhss ffrroomm ttrreeaattmmeenntt LLoogg RRaannkk pp==00..000066
PCI group CM group
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Paarraammeetteerr UUnniivvaarriiaattee aannaallyyssiiss MMuullttiippllee llooggiissttiicc rreeggrreessssiioonn d
deeaatthh ssuurrvviivvaall pp ooddddss rraattiioo 9955%% CCII pp
PCI 14 (25.9%) 19 (47.5%) 0.026 – – 0.061
Previous MI 19 (35.2%) 7 (17.5%) 0.047 – – 0.088
Time to therapy [hours] 12.9±5.3 10.0±5.5 0.011 1.098 1.01-1.20 0.036
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Taabbllee IIIIII.. Multiple logistic regression analysis of predictors for in-hospital death
p <0.01). Moreover, a number of studies have shown that there is a selection bias of patients referred for emergency revascularisation favouring younger patients and those less sick among elderly patients. This selection bias makes a correct analysis of the effectiveness of emergency PCI in elderly patients with CS very difficult [9].
In this study, there were no significant differences in the baseline characteristics between the PCI group and the CM group. A high success rate (90.9%) of emergency PCI was achieved in our population. This is consistent with an increasing body of evidence which indicates that, in the current era, primary angioplasty may be performed with a high procedural success rate similar to that in younger patients despite the presence of more complex lesions [9, 11]. We identified the time from AMI onset to therapy as an independent predictor of in-hospital death with multiple logistic regression. Time is myocardium [12], as a familiar adage in the cardiovascular community says;
shortening the time from symptom onset to treatment may make reduction of mortality attainable. Several studies have established that if fibrinolytic therapy is initiated within 3 hours of symptom onset, early mortality can be reduced by 25-30% as compared with conservative therapy. If treated later, only a 15% reduction may be observed [13]. Our study showed similar results. Maybe due to the high incidence of complications in elderly patients, emergency PCI does not show relevance with in- hospital death. However, Cox regression analysis identified emergency PCI as an independent factor to improve survival rate, which means that early revascularisation may benefit elderly patients with AMI complicated by CS in the long run.
In summary, emergency PCI improves 1-year survival in comparison with conventional medication for elderly patients with AMI complicated by CS. We recommend revascularisation as soon as possible for patients with AMI complicated by CS, even if older than 75 years.
Limitation
The present study is limited by being a retrospective observational analysis of outcomes. The study is further limited by the small sample size. However, because of the low incidence of AMI complicated by CS, this study may
give useful information on the treatment of the elderly with AMI.
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Reeffeerreenncceess
1. Moosvi AR, Khaja F, Villanueva L, et al. Early revascularization improves survival in cardiogenic shock complicating acute myocardial infarction. J Am Coll Cardiol 1992; 19: 907-14.
2. Yamamoto H, Hayashi Y, Oka Y, et al. Efficacy of percutaneous transluminal coronary angioplasty in patients with acute myocardial infarction complicated by cardiogenic shock. Jpn Circ J 1992; 56: 815-21.
3. Seydoux C, Goy JJ, Beuret P, et al. Effectiveness of percutaneous transluminal coronary angioplasty in cardiogenic shock during acute myocardial infarction. Am J Cardiol 1992; 69: 968-9.
4. Prasad A, Lennon RJ, Rihal CS, et al. Outcomes of elderly patients with cardiogenic shock treated with early percutaneous revascularization. Am Heart J 2004; 147: 1066-70.
5. 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.
6. Hochman JS, Sleeper LA, Godfrey E, et al. SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK: an international randomized trial of emergency PTCA/CABG-trial design.
The SHOCK Trial Study Group. Am Heart J 1999; 137: 313-21.
7. Zhang M, Li J, Cai YM, et al. A risk-predictive score for cardiogenic shock after acute myocardial infarction in Chinese patients. Clin Cardiol 2007; 30: 171-6.
8. Okuda M. A multidisciplinary overview of cardiogenic shock. Shock 2006; 25: 557-70.
9. Migliorini A, Moschi G, Valenti R, et al. Routine percutaneous coronary intervention in elderly patients with cardiogenic shock complicating acute myocardial infarction. Am Heart J 2006; 152: 903-8.
10. Goldhammer E, Kharash L, Abinader EG. Circadian fluctuations in the efficacy of thrombolysis with streptokinase. Postgrad Med J 1999; 75: 667-71.
11. Lane GE, Holmes DR, Jr. Primary angioplasty for acute myocardial infarction in the elderly. Coron Artery Dis 2000; 11: 305-13.
12. Gibson CM. Time Is Myocardium and Time Is Outcomes. Circulation 2001; 104: 2632-4.
13. Boersma E; The Primary Coronary Angioplasty vs. Thrombolysis Group. Does time matter? A pooled analysis of randomized clinical trials comparing primary percutaneous coronary intervention and in-hospital fibrinolysis in acute myocardial infarction patients. Eur Heart J 2006; 27: 779-88.
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Early percutaneous intervention improves survival in elderly patients with acute myocardial infarction complicated by cardiogenic shock
Wczesna przezskórna interwencja wieńcowa zwiększa przeżycie osób starszych z zawałem serca powikłanym wstrząsem kardiogennym
LLiiaanngg GGuuoo,, XXiiaaooyyaann MMaaii,, JJiiee DDeenngg,, AAnnhheenngg LLiiuu,, LLuunn BBuu,, HHaaiicchhaanngg WWaanngg
Szpital Xijing, 4. Wojskowy Uniwersytet Medyczny, Chiny
Adres do korespondencji:
Haichang Wang PhD, Xijing Hospital, the Fourth Military Medical University, Chang Le West Street, No. 15, Xi’an, Shaanxi Province 710032, PR China, tel.: +86 13309886925, e-mail: doctorguol@gmail.com
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Prraaccaa wwppłłyynnęęłłaa:: 17.03.2008. ZZaaaakkcceeppttoowwaannaa ddoo ddrruukkuu:: 23.04.2008.
S t r e s z c z e n i e W
Wssttęępp:: Wstrząs kardiogenny (CS) należy do najpoważniejszych powikłań zawału serca (MI). W wielu retrospektywnych obser- wacjach stwierdzono, że leczenie inwazyjne metodą przezskórnej interwencji wieńcowej (PCI) lub pomostowania tętnic wieńcowych (CABG) jest skuteczniejsze niż farmakoterapia. W prospektywnym badaniu SHOCK wykazano obniżenie śmiertelności 6- i 12-mie- sięcznej w grupie chorych z CS poddanych wczesnemu leczeniu inwazyjnemu w porównaniu z grupą chorych objętych początkowo tylko farmakoterapią dla uzyskania stabilizacji hemodynamicznej. Te pozytywne wyniki nie dotyczyły jednak podgrupy osób star- szych. Dlatego bezpieczeństwo i skuteczność pilnej PCI u starszych chorych z CS wikłającym ostry MI nie są ciągle jednoznacznie określone.
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Ceell:: Porównanie rokowania po MI u starszych osób leczonych pierwotną PCI lub zachowawczo.
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Meettooddyykkaa:: Badaniami objęto grupę 94 chorych w wieku≥75 lat hospitalizowanych w latach 2001–2006 w szpitalu Xijing (Chiny) z powodu MI powikłanego CS. Badanie miało charakter prospektywnie prowadzonego rejestru. W obserwowanej grupie u 33 chorych zastosowano wczesną strategię inwazyjną – PCI (grupa PCI), pozostałych 61 chorych początkowo leczono jedynie farmako- logicznie (grupa FAR). Grupy PCI i FAR były porównywalne pod względem charakterystyki klinicznej chorych, lokalizacji MI, częstości stosowania kontrapulsacji wewnątrzaortalnej i czasu upływającego od początku objawów MI do rozpoczęcia terapii. W grupie PCI skuteczność zabiegu w uzyskaniu przepływu TIMI 2/3 w tętnicy odpowiedzialnej za MI wyniosła 90,9%, a w grupie FAR leczenie trom- bolityczne było skuteczne u 60,7% chorych.
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Wyynniikkii:: Śmiertelność szpitalna i w obserwacji odległej w ciągu roku była niższa w grupie PCI niż w grupie FAR – odpowiednio 42,4 vs 65,6% (p=0,026) i 51,5 vs 78,7% (p=0,006). Czas upływający od początku objawów MI do rozpoczęcia terapii był niezależnym czynnikiem prognostycznym w przewidywaniu zgonu wewnątrzszpitalnego w analizie wieloczynnikowej (p=0,036). Analiza regresji Coksa wskazała na wczesną PCI jako niezależny czynnik wpływający na śmiertelność odległą (p=0,015).
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Wnniioosskkii:: Pilna PCI u chorych w wieku≥75 lat w CS wikłającym MI zwiększa przeżycie roczne w porównaniu z leczeniem farma- kologicznym.
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Słłoowwaa kklluucczzoowwee:: zawał serca, wstrząs, starszy wiek, rewaskularyzacja, przeżycie
Kardiol Pol 2008; 66: 722-726
