Nathan R. Every

Sex-Based Differences in Early Mortality after Myocardial Infarction

Background There is conflicting information about whether short-term mortality after myocardial infarction is higher among women than among men after adjustment for age and other prognostic factors. We hypothesized that younger, but not older, women have higher mortality rates during hospitalization than their male peers. Methods We analyzed data on 384,878 patients (155,565 women and 229,313 men) who were 30 to 89 years of age and who had been enrolled in the National Registry of Myocardial Infarction 2 between June 1994 and January 1998. Patients who had been transferred from or to other hospitals were excluded. Results The overall mortality rate during hospitalization was 16.7 percent among the women and 11.5 percent among the men. Sex-based differences in the rates varied according to age. Among patients less than 50 years of age, the mortality rate for the women was more than twice that for the men. The difference in the rates decreased with increasing age and was no longer significant after the age ...

The volume of primary angioplasty procedures and survival after acute myocardial infarction. National Registry of Myocardial Infarction 2 Investigators.

BACKGROUND There is an inverse relation between mortality from cardiovascular causes and the number of elective cardiac procedures (coronary angioplasty, stenting, or coronary bypass surgery) performed by individual practitioners or hospitals. However, it is not known whether patients with acute myocardial infarction fare better at centers where more patients undergo primary angioplasty or thrombolytic therapy than at centers with lower volumes. METHODS We analyzed data from the National Registry of Myocardial Infarction to determine the relation between the number of patients receiving reperfusion therapy (primary angioplasty or thrombolytic therapy) and subsequent in-hospital mortality. A total of 450 hospitals were divided into quartiles according to the volume of primary angioplasty. Multiple logistic-regression models were used to determine whether the volume of primary angioplasty procedures was an independent predictor of in-hospital mortality among patients undergoing this procedure. Similar analyses were performed for patients receiving thrombolytic therapy at 516 hospitals. RESULTS In-hospital mortality was 28 percent lower among patients who underwent primary angioplasty at hospitals with the highest volume than among those who underwent angioplasty at hospitals with the lowest volume (adjusted relative risk, 0.72; 95 percent confidence interval, 0.60 to 0.87; P<0.001). This lower rate, which represented 2.0 fewer deaths per 100 patients treated, was independent of the total volume of patients with myocardial infarction at each hospital, year of admission, and use or nonuse of adjunctive pharmacologic therapies. There was no significant relation between the volume of thrombolytic interventions and in-hospital mortality among patients who received thrombolytic therapy (7.0 percent for patients in the highest-volume hospitals vs. 6.9 percent for those in the lowest-volume hospitals, P=0.36). CONCLUSIONS Among hospitals in the United States that have full interventional capabilities, a higher volume of angioplasty procedures is associated with a lower mortality rate among patients undergoing primary angioplasty, but there is no association between volume and mortality for thrombolytic therapy.

A Comparison of Thrombolytic Therapy with Primary Coronary Angioplasty for Acute Myocardial Infarction

BACKGROUND Several relatively small randomized trials have shown that primary angioplasty results in a better short-term outcome than thrombolytic therapy in patients with acute myocardial infarction. These results, however, have not been duplicated other than in investigational trials. METHODS We compared mortality during hospitalization and long-term mortality, as well as the use of resources, among 1050 patients in a primary-angioplasty group and 2095 patients in a thrombolytic-therapy group. Patients were selected from the Myocardial Infarction Triage and Intervention Project Registry cohort of 12,331 consecutive patients admitted with acute myocardial infarction to 19 Seattle hospitals between 1988 and 1994. Because of the potential for selection bias, several subgroup analyses were performed that included patients eligible for thrombolysis, high-risk patients, and patients in the primary-angioplasty group who were treated at hospitals with high volumes of angioplasty. RESULTS There was no significant difference in mortality during hospitalization or long-term follow-up between patients in the thrombolytic-therapy group and those in the primary-angioplasty group (mortality during hospitalization, 5.6 percent and 5.5 percent, respectively; P=0.93; adjusted hazard ratio for the risk of death within three years after primary angioplasty, 0.95; 95 percent confidence interval, 0.8 to 1.2). There was also no significant difference in mortality between high-risk subgroups of patients in the two treatment groups. The rates of procedures and costs were lower among patients in the thrombolytic-therapy group both at the time of hospital discharge and after three years of follow-up (30 percent fewer coronary angiograms, 15 percent fewer coronary angioplasties, and 13 percent lower costs after three years of follow-up). CONCLUSIONS In a community setting, we observed no benefit in terms of either mortality or the use of resources with a strategy of primary angioplasty rather than thrombolytic therapy in a large cohort of patients with acute myocardial infarction.

Hospital outcomes in patients presenting with congestive heart failure complicating acute myocardial infarction: A report from the Second National Registry of Myocardial Infarction (NRMI-2)

OBJECTIVES The purpose of this study was to examine treatment and outcomes in patients admitted to the hospital with acute myocardial infarction (AMI) complicated by congestive heart failure (CHF). BACKGROUND Although cardiogenic shock complicating AMI has been studied extensively, the hospital course of patients presenting with CHF is less well established. METHODS The Second National Registry of Myocardial Infarction (NRMI-2) was analyzed to determine hospital outcomes for patients with ST-elevation AMI admitted with CHF (Killip classes II or III). RESULTS Of 190,518 patients with AMI, 36,303 (19.1%) had CHF on admission. Patients presenting with CHF were older (72.6 +/- 12.5 vs. 63.2 +/- 13.5 years), more often female (46.8% vs. 32.1%), had longer time to hospital presentation (2.80 +/- 2.6 vs. 2.50 +/- 2.4 h), and had higher prevalence of anterior/septal AMI (38.8% vs. 33.3%), diabetes (33.1% vs. 19.5%), and hypertension (54.6% vs. 46.1%) (all p < 0.0005). Also, they had longer lengths of stay (8.1 +/- 7.1 vs. 6.8 +/- 5.3 days, p < 0.00005) and greater risk for in-hospital death (21.4% vs. 7.2%; p < 0.0005). Patients with CHF were less likely to receive aspirin (75.7% vs. 89.0%), heparin (74.6% vs. 91.1%), oral beta-blockers (27.0% vs. 41.7%), fibrinolytics (33.4% vs. 58.0%), or primary angioplasty (8.6% vs. 14.6%), and more likely to receive angiotensin-converting enzyme inhibitors (25.4% vs. 13.0%). Congestive heart failure on admission was one of the strongest predictors of in-hospital death (adjusted odds ratio 1.68; 95% confidence interval 1.62, 1.75). CONCLUSIONS Patients with AMI presenting with CHF are at higher risk for adverse in-hospital outcomes. Despite this, they are less likely to be treated with reperfusion therapy and medications with proven mortality benefit.

Critical Pathways A Review

Critical pathways, also known as critical paths, clinical pathways, or care paths, are management plans that display goals for patients and provide the sequence and timing of actions necessary to achieve these goals with optimal efficiency.1 As competition in the healthcare industry has increased, managers have embraced critical pathways as a method to reduce variation in care, decrease resource utilization, and potentially improve healthcare quality. Cardiovascular medicine in particular is an area in which critical pathways have been embraced. This is due in part to the high volume and high cost associated with cardiovascular diseases and procedures. In addition, the relatively mature guideline process has also contributed to the growth in use of critical pathways in cardiology. Although anchored in clinical guidelines, the critical pathway is a distinct tool that details processes of care and highlights inefficiencies regardless of whether there is evidence to warrant changes in those processes. Clinical guidelines, on the other hand, are consensus statements that are systematically developed to assist practitioners in making patient management decisions related to specific clinical circumstances.2 Although clinical guidelines can and should be used in pathway development, the majority of processes included in a pathway have not been rigorously tested and are generally not addressed in guidelines. Another term that should also be distinguished from critical pathways is clinical protocols. Protocols are treatment recommendations that are often based on guidelines. Like the critical pathway, the goal of the clinical protocol may be to decrease treatment variation. However, protocols are most often focused on guideline compliance rather than the identification of rate-limiting steps in the patient care process. In further contrast to critical pathways, protocols may or may not include a continuous monitoring and data-evaluation component. Critical pathway techniques were first developed for use in industry as a tool to …

Predictors of door-to-balloon delay in primary angioplasty

In the treatment of acute myocardial infarction, delayed reperfusion therapy is associated with increased mortality. Predictors of delay have been described for fibrinolysis but not for primary percutaneous transluminal coronary angioplasty (pPTCA). Therefore, we studied 40,017 consecutive patients with acute myocardial infarction who underwent pPTCA in the National Registry of Myocardial Infarction between June 1994 and April 2000. Median door-to-balloon times were calculated, and factors independently associated with a delay of >120 minutes were determined by logistic regression. The median door-to-balloon time among all patients was 111 minutes (interquartile range 84 to 152). The proportion of patients with a delay of >2 hours was greater among those aged > or = 65 years (49% vs 41%), women (50% vs 42%), patients with contraindications to fibrinolysis (60% vs 41%), and those without chest pain on admission (61% vs 43%, all p <0.0001). Delay was also more common with transfer from another hospital (87% vs 38%), with presentation outside the hours of 8 A.M. to 4 P.M. (51% vs 38%), and in hospitals performing <49 pPTCAs/year (47% vs 41%, all p <0.0001). The strongest independent predictor of delay was hospital transfer, along with non-daytime presentation and low-volume centers. Older age, female sex, and non-white race were weaker predictors. Both patient and hospital factors are associated with delay in pPTCA after presentation. These findings may help design treatment algorithms to minimize delay, thus improving the survival benefit of pPTCA. These results may also help design trials of combination reperfusion strategies.

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.

Treatment and outcome of myocardial infarction in hospitals with and without invasive capability

Abstract OBJECTIVES We sought to determine the extent to which the capability of a hospital to perform invasive cardiovascular procedures influences treatment and outcome of patients admitted with acute myocardial infarction (AMI). BACKGROUND Patients with AMI are usually transported to the closest hospital. However, relatively few hospitals have the capability for immediate coronary arteriography, percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft surgery (CABG), should these interventions be needed. METHODS The 1,506 hospitals participating in the National Registry of Myocardial Infarction 2 were classified according to their highest level of invasive capability: 1) none (noninvasive, 28.1%); 2) coronary arteriography (cath-capable, 25.2%); 3) coronary angioplasty (PTCA-capable, 7.4%); and 4) bypass surgery (CABG-capable, 39.2%). Treatment and in-hospital outcomes were assessed for 305,812 patients admitted from June 1994 through October 1996. Follow-up through 90 days was ascertained in a subset of 30,402 patients enrolled simultaneously in both the National Registry of Myocardial Infarction (NRMI) 2 and the Cooperative Cardiovascular Project (CCP). RESULTS The proportion of patients receiving initial reperfusion intervention was only slightly higher at the more invasive hospitals (noninvasive 32.5%, cath-capable 31.2%, PTCA-capable 32.9% and CABG-capable 35.9%, p CONCLUSIONS Although patients with AMI admitted to hospitals without invasive cardiac facilities have a high likelihood of subsequent transfer to other facilities, their likelihood of receiving a reperfusion intervention at the first hospital, their door to thrombolytic drug intervals and their 90-day survival rates are similar to those of patients initially admitted to more invasively equipped hospitals. These data suggest that a policy of initial treatment of myocardial infarction at the closest medical facility is appropriate medical practice.

Combining enoxaparin and glycoprotein IIb/IIIa antagonists for the treatment of acute coronary syndromes: Final results of the National Investigators Collaborating on Enoxaparin-3 (nice-3) study

BACKGROUND In high-risk patients with acute coronary syndromes (ACS), there have been concerns relating to the safety of using low molecular weight heparins (LMWH) in combination with a glycoprotein (GP) IIb/IIIa antagonist, and the continued use of LMWH in patients brought to the cardiac catheterization laboratory for percutaneous coronary intervention (PCI). METHODS The National Investigators Collaborating on Enoxaparin-3 (NICE-3) study was an open-label observational study of enoxaparin in combination with any 1 of 3 available GP IIb/IIIa antagonists in patients presenting with non-ST-elevation ACS. The primary end point was the incidence of major bleeding not related to coronary artery bypass graft (CABG) surgery. Data were also recorded on the incidence of death, myocardial infarction (MI), and urgent revascularization for repeat ischemia. RESULTS A total of 671 patients with validated data were treated with enoxaparin; 628 of these patients also received a GP IIb/IIIa antagonist (tirofiban, n = 229; eptifibatide, n = 272; abciximab, n = 127); 283 of 628 underwent percutaneous coronary intervention (PCI). The 30-day incidence of non-CABG major bleeding was 1.9%, and was not significantly higher than a prespecified historical control rate of 2.0%. Outcome events included death (1.0% at hospital discharge and 1.6% at 30 days), MI (3.5% and 5.1%, respectively), and urgent revascularization (2.7% and 6.8%, respectively). CONCLUSIONS The safety of enoxaparin plus a GP IIb/IIIa antagonist was comparable to that of unfractionated heparin plus a GP IIb/IIIa antagonist, as reported in other recent major trials. Patients undergoing PCI can be safely managed with enoxaparin and a GP IIb/IIIa antagonist, without supplemental use of unfractionated heparin.

Potential Cost-Effectiveness of Prophylactic Use of the Implantable Cardioverter Defibrillator or Amiodarone after Myocardial Infarction

More than 1 million Americans per year have acute myocardial infarction (1). Those who survive to hospital discharge have a 5% to 10% risk for dying suddenly within the first year (27). Prevention of those sudden deaths is an important goal, and several approaches have been used to accomplish it. Secondary prevention with type I antiarrhythmic drugs has been unsuccessful (8). Prophylactic use of amiodarone has significantly reduced death after myocardial infarction in some but not all randomized trials. Quantitative overviews of these studies suggest that amiodarone reduces mortality rates by 10% to 20% (9, 10). Recent studies of the implantable cardioverter defibrillator (ICD) in patients who have no history of sustained arrhythmia have also had mixed results, with positive results in patients with unsustained ventricular tachycardia (11, 12) and negative results in patients with reduced ejection fraction and positive results on signal-averaged electrocardiography (13). The use of prophylactic ICD has nevertheless attracted great interest because of the demonstrated efficacy of the device in patients who have had a documented episode of ventricular fibrillation or sustained ventricular tachycardia (1416). Although ongoing or planned randomized, controlled trials (17, 18) will clarify the role of ICDs and amiodarone therapy in patients who have had myocardial infarctions, the results of these trials will not be available until late 2001 at the earliest. We previously showed that ICDs can be cost-effective in patients who have survived an episode of ventricular fibrillation or sustained ventricular tachycardia (19). These findings cannot be extrapolated to prophylactic use of ICDs in patients who have had myocardial infarctions because the risk for sudden death in such patients is lower. Indeed, the current standard of care for patients who have had myocardial infarction does not include prophylactic antiarrhythmic therapy. With recent evidence of the efficacy of antiarrhythmia management in patients who have had myocardial infarctions, the potential cost-effectiveness of prophylactic antiarrhythmic therapy should be reassessed. In this study, we estimated survival and costs for patients with past myocardial infarction who were treated with amiodarone, ICD, or no specific antiarrhythmic therapy. We evaluated the level of efficacy needed to make prophylactic therapy with an ICD or amiodarone cost-effective in three groups of patients with past myocardial infarction who were stratified by left ventricular ejection fraction. Methods We used a decision model to estimate the length of life and expenditures for patients who had myocardial infarction without symptomatic, sustained ventricular arrhythmia and who received one of three treatment strategies: ICD, amiodarone therapy, or no antiarrhythmic therapy (Figure 1). We stratified patients into three groups according to ejection fraction: less than or equal to 0.3, 0.31 to 0.4, and greater than 0.4. Although the ability of many clinical factors to predict the risk for sudden cardiac death has been analyzed and several independent risk factors have been identified (20), ejection fraction has consistently been the single most powerful predictor of sudden cardiac death (2124). Figure 1. The decision model. The square node on the left represents a choice among three alternative treatments: implantable cardiac defibrillator (ICD), amiodarone, and no antiarrhythmic treatment. Circles represent chance nodes. Patients who receive an ICD are at risk for death from the implant procedure. Patients who do not die of ICD implantation and patients who are receiving amiodarone or no treatment enter the Markov tree (denoted by rectangles containing circles and an arrow). The Markov tree represents the clinical events that can occur during each 1-month period as a patient is followed until death. During each 1-month period, a patient may die from arrhythmic or nonarrhythmic cardiac causes and may also die of noncardiac causes. If none of these events occur, the patient remains well for the 1-month period. Patients who have an ICD may have a lead infection or failure that causes them to withdraw from treatment (and to switch to no antiarrhythmic therapy). Patients who receive amiodarone are at risk for amiodarone toxicity. In our analysis, a patient may die of toxicity, withdraw from treatment (and switch to no antiarrhythmic therapy), or have acute toxicity that does not require discontinuation. We adhered to the recommendations of the Panel on Cost-effectiveness in Health and Medicine (25, 26). We used a societal perspective to evaluate health benefits and costs, discounting each at a rate of 3% per year. We performed one-way sensitivity analyses on all of the model variables, as well as selected two-way, three-way, and n-way (Monte Carlo) probabilistic sensitivity analyses (27). Decision Model We developed a Markov model (28, 29) (SMLTree decision analysis software, version 2.9, J. Hollenberg, New York, New York) by modifying a model used previously to assess the cost-effectiveness of ICDs or amiodarone in patients who had experienced sustained ventricular arrhythmia (19, 30) (Figure 1). Our current model includes the possibility of no antiarrhythmic therapy and uses data relevant to the lower-risk population of patients who have survived myocardial infarction. The model tracks a cohort of patients who received prophylactic ICD (implanted without a thoracotomy), amiodarone therapy, or no antiarrhythmic therapy. Patients who received an ICD were at risk for procedural death. Patients who survived ICD implantation, patients treated with amiodarone, and patients who received no antiarrhythmic therapy entered a Markov tree (Figure 1). Each month, these patients were at risk for sudden cardiac death, nonsudden cardiac death, and noncardiac death. We assumed that 2% of the ICD-treated patients would have the ICD removed because of infection or lead complications during the first year and that 1% of surviving patients would withdraw from ICD therapy in each subsequent year (3133). Similarly, we assumed that 10% of the amiodarone-treated patients would withdraw from therapy because of toxicity during the first year and that 5% of surviving patients would withdraw in each subsequent year (3445). Because the use of antiarrhythmic therapy in the postmyocardial infarction population would be prophylactic, we assumed that crossovers between the ICD and amiodarone strategies would be less likely. Therefore, patients who withdrew from one antiarrhythmic treatment would be withdrawn from prophylactic treatment. Patient Sample Our base-case analyses evaluated the cost-effectiveness of each antiarrhythmic management strategy in three cohorts of patients defined by ejection fraction (Table 1). We obtained mortality and inpatient cost data for patients from the Myocardial Infarction Triage and Intervention (MITI) patient registry (46) who had had myocardial infarction. Between 1988 and 1994, approximately 40 000 patients were admitted to cardiac care units in 19 hospitals in Seattle, Washington. Hospitals participating in the registry include 2 university hospitals, 2 staff-model health maintenance organization hospitals, 1 Veterans Affairs hospital, and 14 community hospitals. During most of the study period, 10 of the participating hospitals had on-site catheterization laboratories and 5 performed bypass surgery. During the study period, 12 000 patients presented with an acute myocardial infarction; of these, ejection fraction was measured in approximately 3000. Table 1. Clinical Characteristics of the Myocardial Infarction Triage and Intervention Patient Sample Patients with ejection fractions of 0.3 or less had a mean age (SD) of 66.5 11.92 years (range, 26 to 95 years), 24.6% 43.1% had a history of congestive heart failure, 62.8% 48.4% received an initial catheterization, and 26.6% 44.3% underwent initial revascularization. Patients with ejection fractions between 0.31 and 0.4 had a mean age of 63.5 12.22 years (range, 36 to 97 years), 11.0% 31.3% had a history of congestive heart failure, 73.2% 44.3% underwent catheterization, and 37.6% 48.4% had revascularization. Finally, patients with ejection fractions greater than 0.4 had a mean age of 61.5 11.83 years (range, 26 to 92 years), 3.5% 18.4% had a history of congestive heart failure, 88.0% 32.4% received an initial catheterization, and 48.0% 50% underwent revascularization. We compared the characteristics of patients who had ejection fraction measurements with those of patients in the MITI registry for whom ejection fraction was not measured. The clinical characteristics listed in Table 1 differed significantly between these groups, but the rates of sudden cardiac, nonsudden cardiac, noncardiac, and overall mortality did not differ significantly after we controlled for age, sex, and cardiac history (24). From the MITI registry, we obtained monthly probabilities of cardiac death for the three ejection fraction cohorts. The MITI project used hospital discharge summaries and death certificates to identify patients who died of cardiac causes during follow-up while in or out of the hospital (47). We classified cardiac deaths that occurred in neither a hospital nor a nursing home as sudden and potentially preventable by arrhythmic therapy; we classified as nonsudden the cardiac deaths that occurred in a hospital or a nursing home. We recognized the limitations of this classification system and therefore analyzed a range of ICD efficacies. Table 1 summarizes the probabilities of sudden and nonsudden cardiac death for the three cohorts over time. To estimate life expectancy after the end of follow-up in the MITI cohort, we extrapolated the annual cardiac mortality rate for subsequent years from that observed during follow-up and assumed that the noncardiac mortality rate would equal that in the general U.S. population (48). Effectiveness of Implantab