Diabetes mellitus and trends in hospital survival after myocardial infarction, 1994 to 2006: data from the national registry of myocardial infarction.

BACKGROUND: Patients with diabetes mellitus (DM) are at high risk for mortality after myocardial infarction (MI). Despite an overall trend of reduced mortality after MI, the mortality gap between MI patients with and without DM did not decrease over time in previous analyses. We assessed recent trends in hospital mortality for patients with MI according to DM status. METHODS AND RESULTS: We analyzed data from the National Registry of Myocardial Infarction, a contemporary registry of MI patients treated in 1964 hospitals, representing approximately one fourth of all US acute care hospitals. The study comprised 1734431 MI patients enrolled from 1994 to 2006, including 502315 (29%) with DM. Crude hospital mortality decreased in all patients between 1994 and 2006 but remained higher in patients with DM compared with those without DM throughout the study. The absolute difference in mortality between patients with and without DM significantly narrowed over time, from 15.6% versus 11.5% in 1994 to 8.0% versus 6.8% in 2006 (P<0.001 for DM × time interaction). The adjusted odds ratio for mortality associated with DM declined from 1.24 (95% confidence interval, 1.16-1.32) in 1994 to 1.08 (95% confidence interval, 0.99-1.19) in 2006 (P<0.001 for trend). The largest improvement in hospital mortality was observed in diabetic women (17.9% in 1994 versus 8.4% in 2006; P<0.001). CONCLUSIONS: The hospital mortality gap between MI patients with and without DM narrowed significantly from 1994 to 2006, with the greatest improvement observed in women with DM.

Effectiveness and safety of glycoprotein IIb/IIIa inhibitors and clopidogrel alone and in combination in non-ST-segment elevation myocardial infarction (from the National Registry of Myocardial Infarction-4).

We investigated whether a combination of clopidogrel and glycoprotein (GP) IIb/IIIa inhibitors safely decreases hospital mortality, reinfarction, and major bleeding beyond either therapy alone in patients with non-ST-elevation myocardial infarction (NSTEMI). GP IIb/IIIa inhibitors and clopidogrel, separately, have been shown to decrease adverse outcomes in patients with non-ST-elevation acute coronary syndromes, but the need for combination therapy is uncertain. Multivariate and propensity analyses compared the frequency of death, reinfarction, and major bleeding during hospitalization in 38,691 patients with NSTEMI who were enrolled in the National Registry of Myocardial Infarction 4 from July 2000 to December 2003. Of these, 65% received GP IIb/IIIa inhibitors only, 16.1% clopidogrel only, and 18.8% combination therapy. Among patients who did not undergo percutaneous coronary intervention (PCI), the composite end point of death, reinfarction, and major bleeding was significantly lower with combination therapy than with GP IIb/IIIa inhibitors alone (odds ratio 0.77, 95% confidence interval 0.67 to 0.88). In contrast, this composite end point was significantly higher when combination therapy was employed rather than clopidogrel alone (odds ratio 1.55, 95% confidence interval 1.33 to 1.81). However, among patients who underwent PCI, the composite end point was similar between combination therapy and GP IIb/IIIa inhibitor-only groups (odds ratio 1.01, 95% confidence interval 0.89 to 1.14). Further, there was a strong trend toward a higher composite end point among patients who received combination therapy rather than clopidogrel alone (odds ratio 1.31, 95% confidence interval 0.99 to 1.72). In conclusion, commonly employed strategies using a GP IIb/IIIa inhibitor alone or with the combination of clopidogrel plus GP IIb/IIIa inhibitor in NSTEMI may not be justified in comparison with a simpler strategy of clopidogrel used alone, especially in patients who have not undergone PCI.

Quality of care by classification of myocardial infarction: treatment patterns for ST-segment elevation vs non-ST-segment elevation myocardial infarction.

BACKGROUND: Practice guidelines for acute ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) recommend similar therapies and interventions, but differences in patterns of care between MI categories have not been well described in contemporary practice. METHODS: In-hospital treatments with similar recommendations from practice guidelines were compared with outcomes in 185 968 eligible patients (without listed contraindications) with STEMI (n = 53 417; 29%) vs NSTEMI (n = 132 551; 71%) from 1247 US hospitals participating in the National Registry of Myocardial Infarction 4 between July 1, 2000, and June 30, 2002. Hierarchical logistic regression modeling was used to determine adjusted differences in treatment patterns in MI categories. RESULTS: Unadjusted in-hospital mortality rates were high for NSTEMI (12.5%) and STEMI (14.3%), and the use of guideline-recommended medications and interventions was suboptimal in both categories of patients with MI. The adjusted likelihood of receiving early (within 24 hours of presentation) aspirin, beta-blockers, and angiotensin-converting enzyme inhibitors was higher in patients with STEMI. Similar patterns of care were noted at hospital discharge: the adjusted likelihood of receiving aspirin, beta-blockers, angiotensin-converting enzyme inhibitors, lipid-lowering agents, smoking cessation counseling, and cardiac rehabilitation referral was higher in patients with STEMI. CONCLUSIONS: Evidence-based medications and lifestyle modification interventions were used less frequently in patients with NSTEMI. Quality improvement interventions designed to narrow the gaps in care between NSTEMI and STEMI and to improve adherence to guidelines for both categories of patients with MI may reduce the high mortality rates associated with acute MI in contemporary practice.

Is there evidence of implicit exclusion criteria for elderly subjects in randomized trials? Evidence from the GUSTO-1 study.

BACKGROUND: Some experts have raised concerns about the ability to generalize randomized trials, emphasizing that patients who participate in these studies are often not representative of those seen in clinical practice, particularly in the case of elderly patients. To determine the effect of implicit exclusion criteria on a trial study sample, we compared data from the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) trial with data from a retrospective registry from selected hospitals, the National Registry of Myocardial Infarction (NRMI), and a nationally representative study of myocardial infarction care, the Cooperative Cardiovascular Project (CCP). METHODS: We compared GUSTO subjects aged 65 years and older who were enrolled in the United States with similarily aged patients in the 2 observational studies who met the trial's eligibility criteria. We examined baseline characteristics, clinical presentation, treatments, procedures, clinical events, and in-hospital mortality rates. RESULTS: We found modest, although significant, differences between patients in NRMI, CCP, and GUSTO in demographic and clinical characteristics, treatment, and outcome. For example, GUSTO patients were significantly younger (73.1 +/- 5.7 vs 74.7 +/- 6.8 for NRMI and 75.8 +/- 7.2 for CCP), less likely to have Killip class III/IV at presentation (3.1% vs 6.2% for NRMI and 32.7% for CCP), and more likely to receive aspirin (95.5% vs 86.3% for NRMI and 86.5% for CCP) and beta-blockers (71.9% vs 43.5% for NRMI and 52.7% for CCP). Overall, NRMI and CCP patients had a lower risk of 30-day mortality after adjustment for demographic, clinical, and hospital characteristics than patients in GUSTO (odds ratio, 0.79; 95% CI, 0.73-0.86 for NRMI; odds ratio, 0.65; 95% CI, 0.59-0.71 for CCP). CONCLUSIONS: Older patients enrolled in a randomized trial without an age restriction had many similarities compared with patients seen in clinical practice. The higher mortality rate of the GUSTO patients does not support the hypothesis that the trial enrolled a healthier cohort than is seen in practice.

Relation between hospital intra-aortic balloon counterpulsation volume and mortality in acute myocardial infarction complicated by cardiogenic shock.

BACKGROUND: Increasing evidence suggests an inverse relationship between outcome and the total number of invasive cardiac procedures performed at a given hospital. The purpose of the present study was to determine if a similar relationship exists between the number of intra-aortic balloon counterpulsation (IABP) procedures performed at a given hospital per year and the in-hospital mortality rate of patients with acute myocardial infarction complicated by cardiogenic shock. METHODS AND RESULTS: We analyzed data of 12 730 patients at 750 hospitals enrolled in the National Registry of Myocardial Infarction 2 from 1994 to 1998. The hospitals were divided into tertiles (low-, intermediate-, and high-IABP volume hospitals) according to the number of IABPs performed at the given hospital per year. The median number of IABPs performed per hospital per year was 3.4, 12.7, and 37.4 IABPs at low-, intermediate-, and high-volume hospitals, respectively. Of those patients who underwent IABP, there were only minor differences in baseline patient characteristics between the 3 groups. Crude mortality rate decreased with increasing IABP volume: 65.4%, lowest volume tertile; 54.1%, intermediate volume tertile; and 50.6%, highest volume tertile (P for trend <0.001). This mortality difference represented 150 fewer deaths per 1000 patients treated at the high IABP hospitals. In the multivariate analysis, high hospital IABP volume for patients with acute myocardial infarction was associated with lower mortality (OR=0.71, 95% CI=0.56 to 0.90), independent of baseline patient characteristics, hospital factors, treatment, and procedures such as PTCA. CONCLUSIONS: Among the myocardial infarction patients with cardiogenic shock who underwent IABP placement, mortality rate was significantly lower at high-IABP volume hospitals compared with low-IABP volume hospitals.

Early use of glycoprotein IIb/IIIa inhibitors in non-ST-elevation acute myocardial infarction: observations from the National Registry of Myocardial Infarction 4.

OBJECTIVES: We sought to identify patient and hospital features associated with early glycoprotein (GP) IIb/IIIa inhibitor therapy for non-ST-elevation (NSTE) myocardial infarction (MI) and to relate this treatment to in-hospital outcomes. BACKGROUND: Glycoprotein IIb/IIIa inhibitors have improved outcomes in randomized trials of NSTE MI, leading national treatment guidelines to recommend their use. Their actual use, safety, and effectiveness have not been well characterized beyond trial populations. METHODS: We studied 60,770 patients with NSTE MI treated between July 2000 and July 2001 at 1,189 hospitals in a U.S. registry. Using logistic regression, we identified patient and hospital features associated with GP IIb/IIIa inhibition within 24 h after presentation. We also compared outcomes by early treatment versus no treatment after adjusting for patient and hospital characteristics and treatment propensity. RESULTS: Only 25% of eligible patients received early GP IIb/IIIa therapy. Elderly patients, women, minority patients, and those without private insurance received such therapy less often than their counterparts. Treated patients had lower unadjusted in-hospital mortality (3.3% vs. 9.6%, p < 0.0001) remaining significantly lower after adjustment for patient risk, treatment propensity, and hospital characteristics (adjusted odds ratio, 0.88; 95% confidence interval, 0.79 to 0.97). Hospitals that adopted early GP IIb/IIIa inhibition more rapidly also had lower adjusted mortality rates than those slower to adopt such therapy. CONCLUSIONS: Glycoprotein IIb/IIIa inhibitor therapy appears to be underused in early management of NSTE MI patients. Because this therapy is associated with better outcomes, it represents a target for quality improvement.

Primary angioplasty and selection bias inpatients presenting late (>12 h) after onset of chest pain and ST elevation myocardial infarction.

OBJECTIVES: This study was designed to compare the in-hospital outcome of patients presenting with >12 h from onset of chest pain and acute ST elevation myocardial infarction (AMI) who received either immediate invasive or conservative therapy. BACKGROUND: The benefits of fibrinolytic therapy diminish in patients presenting with AMI and onset of chest pain >12 h. Primary angioplasty has been suggested as a possible treatment for such patients, but they have been excluded from most trials of primary angioplasty. It remains unclear if an invasive treatment strategy is beneficial to these patients. METHODS: Patients presenting with >12 h of chest pain and AMI were identified from the National Registry of Myocardial Infarction 2 database. Patients receiving invasive therapy <6 h after hospital admission were compared with those receiving conservative therapy. Short-term outcomes were compared on the basis of the initial therapy received. To help control for baseline differences in the groups, patients were matched with controls by propensity score methodology. RESULTS: On preliminary analysis, in-hospital outcome was improved in terms of recurrent ischemia, angina, myocardial infarction and mortality in patients receiving initial invasive therapy (odds ratio [OR] = 0.67; 95% confidence interval [CI] 0.49 to 0.92 for mortality). After matching by propensity score, the mortality benefit persisted on bivariate analysis (3.5% vs. 5.0%, p = 0.036), though on multivariate analysis, only a non-significant but strong trend toward decreased mortality remained (OR = 0.73; 95% CI 0.53 to 1.01). CONCLUSIONS: Patients receiving early invasive therapy had lower risk features on presentation. Selection bias may play an important role in choosing these patients' course of treatment and their subsequent outcomes. Certain patients presenting with AMI and duration of chest pain >12 h may benefit from early invasive therapy. These patients could be characterized in a randomized trial.

Does enrollment in a randomized clinical trial lead to a higher cost of routine care?

BACKGROUND: Reimbursement for the routine care of patients enrolled in clinical trials is controversial. Our objective was to determine the added medical costs, if any, associated with enrollment in a randomized clinical trial. METHODS: We analyzed data from the Myocardial Infarction Triage and Intervention (MITI) Trial (1988-1991) and the registry of all patients admitted to 19 Seattle area coronary care units (1988-1993). The major trial entry criteria were age 35 to 71 years, symptom duration 15 minutes to 6 hours, and acute myocardial infarction on electrocardiogram. The trial group consisted of 264 of 324 randomized patients who received thrombolytics and had available cost data. From 11,932 registry patients, we identified a control group who met trial entry criteria but who were not enrolled because of logistic barriers or presentation outside the trial enrollment period, 335 of whom received thrombolytics and had available cost data. The groups were compared for total cost for initial hospitalization, with and without multivariable adjustment for baseline characteristics. RESULTS: Total hospital cost was not different between trial patients (median $11,516) and control subjects (median $14,200) (trial/control mean cost ratio 0.91 [95% CI 0.82-1.02]). Participation in the trial had an insignificant effect on costs in the multivariable model (cost ratio 1.04, 95% CI 0.95-1.16). Significant predictors of cost included hospital of admission, length of stay, and coronary revascularization procedures. CONCLUSION: Participation in the MITI randomized trial had no effect on the cost of routine care.