Includes total shock at hospital presentation and shock that develops
after hospital presentation as a clinical event. For hospitals with open-heart
surgery and percutaneous coronary intervention capability, the ST-elevation
myocardial infarction population was 293 633. Data are through May 2004.
NRMI indicates National Registry of Myocardial Infarction.
Data are through May 2004. P values indicate
trends over time: total percutaneous coronary intervention (PCI), P<.001; primary PCI, P<.001; total coronary
artery bypass graft (CABG) surgery, P<.001; and
immediate CABG surgery, P = .88.
Asterisk indicates that there were 4830 cardiogenic shock patients and
211 929 ST-elevation myocardial infarction (STEMI) patients. Data are
through May 2004. In 2004, there were 223 cardiogenic shock patients and 9428
STEMI patients. Dagger indicates that there were 2526 cardiogenic shock patients
and 81 704 STEMI patients. Data are through May 2004. In 2004, there
were 117 cardiogenic shock patients and 3658 STEMI patients.
Babaev A, Frederick PD, Pasta DJ, Every N, Sichrovsky T, Hochman JS, NRMI Investigators FT. Trends in Management and Outcomes of Patients With Acute Myocardial Infarction Complicated by Cardiogenic Shock. JAMA. 2005;294(4):448-454. doi:10.1001/jama.294.4.448
Author Affiliations: Cardiovascular Clinical
Research Center, New York University School of Medicine, New York, NY (Drs
Babaev and Hochman); Ovation Research Group, Seattle, Wash (Mr Frederick);
Ovation Research Group and University of California, San Francisco (Mr Pasta);
Department of Cardiology, School of Medicine, University of Washington, Seattle
(Dr Every); and Division of Cardiology, St Luke’s-Roosevelt Medical
Center, New York, NY (Dr Sichrovsky).
Context Early mechanical revascularization in patients with acute myocardial
infarction (AMI) complicated by cardiogenic shock is a therapeutic strategy
that reduces mortality. It has been a class I recommendation in guidelines
from the American College of Cardiology and the American Heart Association
since 1999 for patients younger than 75 years. However, little is known about
implementation of these guidelines in practice.
Objectives To assess trends in early revascularization and mortality for patients
with cardiogenic shock complicating AMI and to determine whether the national
guidelines affect revascularization rates.
Design, Setting, and Patients Prospective, observational study of 293 633 patients with ST-elevation
myocardial infarction (25 311 [8.6%] had cardiogenic shock; 7356 [29%]
had cardiogenic shock at hospital presentation) enrolled in the National Registry
of Myocardial Infarction (NRMI) from January 1995 to May 2004 at 775 US hospitals
with revascularization capability (defined as the capability to perform cardiac
catheterization, percutaneous coronary intervention [PCI], and open-heart
Main Outcome Measures Management patterns and in-hospital mortality rates.
Results There was an increase in primary PCI rates from 27.4% to 54.4% (P<.001) in hospitals with revascularization capability
that paralleled the change in PCI for ST-elevation myocardial infarction.
There was no significant change in rates of immediate coronary artery bypass
graft surgery (from 2.1% to 3.2%). Propensity-adjusted multivariable analyses
demonstrated that primary PCI was associated with a decreased odds of death
during hospitalization (odds ratio, 0.46; 95% confidence interval, 0.40-0.53).
There were no differences in the rates of change in revascularization rates
based on the date when the guidelines were released regardless of patient
age. Overall in-hospital cardiogenic shock mortality decreased from 60.3%
in 1995 to 47.9% in 2004 (P<.001).
Conclusions The use of PCI for patients with cardiogenic shock was associated with
improved survival in a large group of hospitals with revascularization capability.
The American College of Cardiology and American Heart Association guidelines
had no detectable temporal impact on revascularization rates. These findings
support the need for increased adherence to these guidelines.
Cardiogenic shock remains the leading cause of death in patients hospitalized
with acute myocardial infarction (AMI).1 The
SHOCK randomized trial2,3 demonstrated
that in patients with AMI complicated by cardiogenic shock, early mechanical
revascularization reduced 6- and 12-month mortality compared with initial
medical stabilization (including intra-aortic balloon pump [IABP] counterpulsation
and fibrinolytic therapy) followed by late or no revascularization. There
was a significant interaction between treatment and age, with apparent lack
of benefit of early revascularization for the small subset of patients aged
75 years or older.2,3 Based on
these findings, the American College of Cardiology (ACC) and the American
Heart Association (AHA) elevated early mechanical revascularization for cardiogenic
shock to a class I recommendation for patients younger than 75 years with
ST-elevation left bundle-branch block AMI in their revised guidelines for
the management of AMI published in September 1999.4
Evidence-based guidelines hold considerable promise for continued improvement
of health care delivery. However, the availability of clinical practice guidelines
does not automatically lead to changes in practice.5 For
example, the first guidelines from the ACC and the AHA for the management
of ST-elevation AMI, published in 1990, recommended β-blocker therapy
for all eligible patients.6 Three years later,
intravenous β-blocker use had increased only from 8% to 12% and oral
administration from 27% to 36%.7 Its use in
recipients of intravenous fibrinolytic therapy 9 years later was 66.9%.8 Several recent studies have also reported that quality
of care for patients with AMI was far from optimal, and compliance with guidelines
from the ACC and the AHA was not satisfactory.9- 11
The National Registry of Myocardial Infarction (NRMI) is a national
database that has tracked practice patterns and outcomes of patients with
AMI in the United States since 1990. We used the NRMI database to determine
trends in the use of early mechanical revascularization for patients with
AMI complicated by cardiogenic shock, and the relationship between mortality
and the use of these procedures overall and among those younger or older than
the cut point of 75 years specified in the guidelines from the ACC and the
AHA. We also sought to determine the impact of the new guidelines on revascularization
rates in patients with AMI complicated by cardiogenic shock managed in a non–protocol-directed
The NRMI is a series of 5 industry-sponsored, prospective, observational
studies of patients hospitalized with AMI throughout the United States. The
data collection process and quality-control features of the NRMI have been
described.7,8 Participation in
the registry is voluntary. Registry hospitals tend to be larger than nonparticipating
hospitals, are more likely to be certified by the Joint Commission on Accreditation
of Healthcare Organizations, are more likely to be affiliated with a medical
school, and are more likely to have available facilities for cardiac catheterization,
coronary percutaneous coronary intervention (PCI), and cardiac surgery.7
To be included in the NRMI, patients must have had a documented AMI
according to local hospital criteria such as history, serial cardiac markers,
and electrocardiographic findings. Concomitant medications, invasive procedures,
transfer status, and adverse events are recorded if they occur at any time
during hospitalization. Participating hospitals are encouraged to enter consecutive
patients with AMI irrespective of treatment strategy and outcome.7,8
A total of 293 633 nontransfer patients admitted with ST-elevation
or left bundle-branch block AMI to a prospectively selected cohort of 775
hospitals with revascularization capability defined
as the capability to perform cardiac catheterization, PCI, and open-heart
surgery were extracted from the 1.97 million AMI patients reported to the
NRMI-2, NRMI-3, and NRMI-4 registries from June 1994 through May 2004. Of
the 293 633 ST-elevation myocardial infarction (STEMI) patients, 25 311
(8.6%) were diagnosed with cardiogenic shock. Twenty-nine percent of these
patients had shock at presentation (n = 7356) and 71% (n = 17 955)
subsequently developed cardiogenic shock during hospitalization in 656 hospitals
during the 10-year study period. We analyzed trends over time in baseline
characteristics as well as management patterns, and in-hospital mortality
rates in both STEMI patients and cardiogenic shock patients. A subset of hospitals
were evaluated to determine whether the trends demonstrated for all hospitals
were similar in this subset of core hospitals that consistently reported cardiogenic
shock patients in the registry. Inclusion criteria for this core set of hospitals
required that each hospital report at least 10 cardiogenic shock patients
over the reporting life of NRMI-2, NRMI-3, and NRMI-4, with at least one of
the cardiogenic shock cases discharged in each year of the 10-year analysis.
We performed separate analyses for patients younger than 75 years and 75 years
or older as well as for study hospitals and core hospitals. This study was
deemed exempt from review by the institutional review board at New York University.
For categorical data, the Mantel-Haenszel χ2 statistic
was used as the measure of trend. For continuous data, linear regression analysis
was used to test whether the slope of the regression or trend differed significantly
from zero, and whether it differed before and after a specified date. Considering
all possible bimonthly cutoff dates, linear and multivariable regression techniques
were used to model the proportion of procedure use and to test whether the
slope after the cutoff date was statistically different from the slope before
the cutoff date separately for cardiogenic shock patients younger than 75
years and aged 75 years or older. The period showing the strongest effect
in the patients younger than 75 years was then used to examine rate changes
in the populations, including core hospitals and all STEMI patients. We also
specifically considered the periods before and after the publication of the
guidelines from the ACC and the AHA in September 1999.
The association between primary PCI use and mortality is well established
even after adjusting for confounders; however, selection bias relating to
procedure use can obscure this finding. Therefore, propensity scores were
calculated using logistic regression for patients who received primary PCI
and for those patients who did not receive primary PCI to identify patients
who shared similar clinical and demographic characteristics. Independent variables
were included in a forward logistic regression model and were used to model
primary PCI as the dependent variable. The clinically relevant variables considered
important in matching on patient characteristics between the 2 patient groups
were demographics (patient age, sex, race, weight, payer), medical history
(MI, angina, congestive heart failure, coronary artery bypass graft [CABG]
surgery, stroke, diabetes, hypertension, current smoker, hypercholesterolemia,
prior PCI), and clinical presentation (prehospital delay, chest pain, pulse,
anterior MI, and year of discharge). The hospital characteristics of teaching
hospital, annualized primary PCI volume, and US region also were considered
to be important in generating the propensity score.
Using in-hospital mortality as the dependent variable, logistic regression
models were constructed using successive blocks of relevant predictor fields.
Primary PCI use was incorporated first into the model, followed by demographics
(patient age, sex, race, weight, and payer), medical history (MI, angina,
congestive heart failure, CABG surgery, stroke, diabetes, hypertension, current
smoker, hypercholesterolemia, and prior PCI), clinical presentation (prehospital
delay, chest pain, pulse, anterior MI, year of discharge, and treatment factors
[IABP and immediate CABG surgery]), and propensity score. The adjusted odds
ratios (AORs) and their 95% confidence intervals (CIs) were used to relate
mortality to primary PCI by using successive blocks of predictors. To assess
if any improvement in mortality occurred during the 10-year period, the 95%
CIs and their AORs were generated and examined for the years 1995 through
2003, with reference to 2004. An AOR was considered statistically significant
if its 95% CI did not include 1.0.
All statistical analyses were performed using SAS software version 8.2
(SAS Institute Inc, Cary, NC). All P values use 2-tailed
tests of significance; P<.05 was considered significant.
The rate of total shock (cardiogenic shock at presentation and/or clinical
event shock, which was diagnosed after admission) in patients in the STEMI
population (n = 293 633) was 8.6% (n = 25 311).
Approximately 29% (n = 7356) of total shock patients presented with
cardiogenic shock, and the remaining 71% (n = 17 955) with
total shock experienced shock only later during their stay (Figure 1). Patients younger than 75 years had cardiogenic shock
at presentation less often (2.3%) than patients aged 75 years or older (3.1%).
There was a slight but statistically significant upward trend in rates over
time for those younger than 75 years (P<.001)
but not for those aged 75 years or older (P = .14).
Demographics and clinical characteristics of the 7356 patients with
cardiogenic shock at presentation appear in Table
1. There were no differences over time in history of diabetes mellitus,
congestive heart failure, stroke, and prior CABG surgery. There were fewer
patients in recent years with history of MI, but more patients with prior
PCI, hypertension, and dyslipidemia. Mean age and the proportion of women
decreased over time. Time-related differences for several variables were statistically
significant but small.
We evaluated rates of fibrinolytic therapy, IABP, diagnostic cardiac
catheterization, PCI (total and primary), and CABG surgery (immediate and
total). There was an increase in the rate of cardiac catheterization (from
51.5% to 74.4%), no change in IABP use (39.2%), and a reduction in the rates
of fibrinolytic therapy (from 19.9% to 5.6%). We found an increase in rates
of primary PCI (from 27.4% to 54.4%) and total PCI (from 34.3% to 64.1%),
a decrease in overall CABG surgery rates (from 11.5% to 8.8%), and no significant
change in immediate CABG surgery rates (Figure
2). Among the 7356 patients with cardiogenic shock at presentation,
238 (3.24%) died prior to the median door-to-PCI time without having received
PCI. For each year in the trend analysis, the median time was calculated using
the set of nontransfer PCI patients. For cardiogenic shock patients, the median
door-to-PCI times declined over time from 117 to 103 minutes (P = .001).
Overall in-hospital mortality decreased from 60.3% in 1995 to 47.9%
in 2004 (P<.001; Table 2). This paralleled the increasing use of revascularization.
Furthermore, the mortality rate decreased over time for patients who underwent
primary PCI for cardiogenic shock (Table 3).
Multivariable analysis of in-hospital mortality adjusted for demographics,
medical history, clinical presentation, hospital characteristics, year of
discharge, and procedures demonstrated that primary PCI remained strongly
independently associated with a lower in-hospital mortality rate (AOR, 0.46;
95% CI, 0.40-0.53 for confounding and propensity; Table 4). Among the covariates in the model using all predictor
blocks and propensity score, immediate CABG surgery during hospitalization
was associated with lower mortality (AOR, 0.34; 95% CI, 0.25-0.47) in the
full model including propensity score. A history of diabetes and a history
of PCI were associated with increased mortality.
We found increases in primary PCI rates over time in patients younger
than 75 years (from 31.4% to 63.7%; P<.001) and
aged 75 years or older (from 18.8% to 36.8%; P<.001; Figure 3). Use rates of immediate CABG surgery
remained low and did not show a time trend in patients younger than 75 years
(from 2.4% to 3.6%; P = .87) or in patients
aged 75 years or older (from 1.3% to 2.6%; P = .46).
Mortality rates decreased significantly over time in patients younger
than 75 years and in patients aged 75 years or older (Table 2). After adjusting for demographics, previous medical history,
and clinical and hospital characteristics, there was still a steady decrease
in the likelihood of death with each increase in year. Primary PCI outcomes
improved in patients younger than 75 years, with postprocedure mortality declining
from 34.4% to 28.2% (P≤.001), but there was no
significant change in mortality in patients aged 75 years or older (Table 3).
We performed a multivariable analysis to assess if the revised guidelines
from the ACC and the AHA published in September 1999 had a detectable impact
on rates of early mechanical revascularization (primary PCI, immediate CABG
surgery) in patients with cardiogenic shock. There was no statistically significant
difference in the slopes of revascularization based on the published guidelines
for either all patients or those younger than 75 years of age or aged 75 years
or older. However, after looking at the slope of primary PCI use divided at
any possible 2-month increments, we observed a significant change only in
patients younger than 75 years, which was strongest in April 2003 (P = .02). The slopes of rates of primary PCI use were similar
for patients with cardiogenic shock in the subset of core hospitals. In comparison,
the slopes of primary PCI rates in all patients with acute STEMI in the NRMI
(n = 293 633) demonstrated consistently significant increases
in rate at all cut points, including April 2003 and guideline-era periods
(Figure 3). The change in slope of primary
PCI rate in patients younger than 75 years with cardiogenic shock in 2003
parallels the increasing primary PCI rates in all patients with STEMI.
This large observational study of patients hospitalized with AMI suggests
that over the last 10 years there has been a relatively stable rate of AMI
complicated by cardiogenic shock, but there has been a decline in the associated
in-hospital mortality rate for hospitals with revascularization capability.
There was a significant increase in total and primary PCI rates. Primary
PCI also was independently associated with a reduction in the odds of death
during hospitalization even after adjustment with the propensity score. There
were low and unchanging rates of IABP use, while fibrinolytic therapy use
diminished over time. The association of increasing primary PCI rates for
patients with cardiogenic shock and lower mortality rates is consistent with
a benefit of early mechanical revascularization compared with initial medical
stabilization and late or no revascularization that was shown in the SHOCK
mortality rates were similar for those who underwent PCI in the SHOCK trial,
SHOCK registry, and in the NRMI hospitals.2,3,6,7,12 This
suggests that the randomized trial results are broadly applicable. The magnitude
of the benefit of emergency revascularization is better estimated by the randomized
SHOCK trial because selection bias is never fully accounted for even in a
A notable difference between the SHOCK trial experience and the NRMI
community experience is the marked difference in the use of CABG surgery.
In the SHOCK trial, the protocol recommendation was for CABG surgery in subsets
with severe 3-vessel coronary artery disease (CAD) or left main CAD disease;
more than two thirds had moderate or severe 3-vessel CAD and more than 20%
had severe 3-vessel CAD.2 Cardiac surgeons
were active SHOCK investigators, likely contributing to the finding that nearly
40% of those randomized to early revascularization had urgent early CABG surgery.
In the current study, immediate and overall CABG surgery rates were low and
unchanged over time.
The Cooperative Cardiovascular Project demonstrates that implementation
of guidelines into clinical practice in pilot states results in better performance
on the defined quality indicators and reduced mortality.11 Furthermore,
the Guidelines Applied in Practice initiative has shown that implementation
of guidelines-based tools for AMI may facilitate quality improvement among
a variety of institutions, patients, and caregivers.13
Based on the SHOCK trial findings, the ACC and AHA revised guidelines
elevated early mechanical revascularization for the management of AMI complicated
by cardiogenic shock as a class I recommendation for patients younger than
75 years. Despite considerable investment in the development and dissemination
of national guidelines for the management of AMI, several recent studies reported
that quality of care for patients with AMI was far from optimal, with 30%
of all reperfusion-eligible patients not receiving such therapy.9- 11 The
situation is even worse in patients aged 65 years or older, in which 80% of
reperfusion-eligible patients did not receive this potentially life-saving
therapy.10 We observed no difference in early
mechanical revascularization use in all patients or in those younger than
75 years with AMI complicated by cardiogenic shock after publication of the
guidelines. Fear of high PCI-associated mortality rates in states with public
reporting of operator “scorecards” may lead to less intervention
in high-risk patients as reported by Moscucci et al.14 Reluctance
to perform PCI on high-risk patients with cardiogenic shock in New York state
did not appear to explain our findings because only 1.65% of our cardiogenic
shock cohort was from New York state hospitals. Analysis of the slope of primary
PCI rates in cardiogenic shock patients demonstrated a significant increase
in rates only late during the study period for any bimonthly interval in patients
younger than 75 years. For the cardiogenic shock group (n = 7356),
we saw a significant increase in rates only late during the period studied
(around April 2003); this increase may be more a result of the overall increasing
rates for all STEMI patients (n = 293 633), and may be related
to the publication of reports favorable to primary PCI.15,16
The SHOCK trial reported no apparent benefit of early revascularization
for patients older than 75 years, but there were only 56 elderly patients
in the cohort and there were imbalances between the 2 treatment groups.2,17 The 1999 guidelines from the ACC and
the AHA made no recommendation for the elderly. Recent analysis of the SHOCK
trial registry demonstrated that early mechanical revascularization is associated
with improved survival in patients aged 75 years or older or those who were
clinically selected (approximately 20%) for early mechanical revascularization.13 Our study and other nonrandomized studies18,19 of elderly patients support the latter
and demonstrate decreasing mortality in elderly patients in association with
increasing PCI use in hospitals with revascularization capability. The 2004
guidelines on the management of AMI gave a class IIA recommendation for early
revascularization in those older than 75 years who are suitable candidates
(36.7% of the cohort in the NRMI registries).20
Approximately 15% of cardiogenic shock complicating AMI is due to mechanical
complications,21 but the exact number is not
known in this study because these data were not systematically collected.
Even after adjusting for an estimated 15% of mechanical complications, emergency
revascularization was underused for pump failure. The use of primary PCI was
not examined in patients who were admitted to hospitals without revascularization
In this registry, as in all registries, there was no independent review
of source documents to confirm the diagnosis of cardiogenic shock. However,
the rate of cardiogenic shock we found was similar to that found in other
studies,22 supporting the validity of the diagnoses.
There was a general increase in the overall use of primary PCI and a
parallel increase in the rate of primary PCI for shock in all age categories
in hospitals with revascularization capability. This increase in PCI for shock
patients was associated with improved survival, suggesting that the SHOCK
trial results are applicable to a large group of hospitals with PCI and open
heart surgery capability. The recommendation from the ACC and the AHA for
early mechanical revascularization as a class I indication for treatment of
patients with AMI complicated by cardiogenic shock had no detectable temporal
impact on clinical management of these patients. Early CABG surgery was underused
in the NRMI compared with the SHOCK trial.
In accordance with guidelines from the ACC and the AHA, we recommend
more aggressive use of early mechanical revascularization, including early
CABG surgery, in patients with AMI complicated by cardiogenic shock. The findings
of our study support the need for efforts aimed at guideline adherence to
improve survival of patients with cardiogenic shock.
Corresponding Author: Judith S. Hochman,
MD, Cardiovascular Clinical Research Center, NYU School of Medicine, 530 First
Ave, HCC 1173, New York, NY 10016 (firstname.lastname@example.org).
Author Contributions: All of the authors had
full access to all of the data in the study and take responsibility for the
integrity of the data and the accuracy of the data analysis.
Study concept and design: Babaev, Hochman.
Acquisition of data: Babaev, Sichrovsky.
Analysis and interpretation of data: Babaev,
Frederick, Pasta, Every, Sichrovsky, Hochman.
Drafting of the manuscript: Babaev, Sichrovsky.
Critical revision of the manuscript for important
intellectual content: Babaev, Frederick, Pasta, Every, Hochman.
Statistical analysis: Frederick, Pasta, Every.
Obtained funding: Every.
Administrative, technical, or material support:
Babaev, Sichrovsky, Hochman.
Study supervision: Hochman.
Financial Disclosures: None reported.
Funding/Support: Genentech Inc provided funding
for the data management and statistical analysis.
Role of the Sponsor: Genentech Inc was not
involved in the analysis of this study other than providing funds for data
management and statistical analysis.