Eva Kline-Rogers

Impact of Combination Evidence-Based Medical Therapy on Mortality in Patients With Acute Coronary Syndromes

Background—Several individual pharmacological agents, such as antiplatelet drugs, &bgr;-blockers, ACE inhibitors, and lipid-lowering agents, have proven efficacy in reducing mortality in patients with acute coronary syndromes. However, the impact of the combination of these agents on clinical outcomes has not been studied before. Methods and Results—A total of 1358 consecutive patients presenting with acute coronary syndromes between January 1999 and March 2002 were identified, and data on baseline demographics, comorbidities, and in-hospital management were collected. On the basis of discharge use of evidence-based therapies, we created a composite appropriateness score depending on the number of the drugs used divided by the number of the drugs potentially indicated for each patient. The impact of the composite score on 6-month mortality was analyzed using a risk-adjusted logistic regression model. The odds ratio for death for all indicated medications used (appropriateness level IV) versus none of the indicated medications used (appropriateness level 0) was 0.10 (95% CI, 0.03 to 0.42; P <0.0001); similarly, odds ratio for appropriateness level III versus level 0 was 0.17 (95% CI, 0.04 to 0.75; P =0.0018), odds ratio for appropriateness level II versus level 0 was 0.18 (95% CI, 0.04 to 0.77; P =0.01), and odds ratio for appropriateness level I versus level 0 was 0.36 (95% CI, 0.08 to 1.75; P =0.20). Conclusions—Use of combination evidence-based medical therapies was independently and strongly associated with lower 6-month mortality in patients with acute coronary syndromes. Such therapies, most of which are generic and inexpensive today, seem to offer a marked survival advantage compared with patients in whom such therapies are omitted.

A Campaign to Improve the Timeliness of Primary Percutaneous Coronary Intervention : Door-to-Balloon: An Alliance for Quality

OBJECTIVES We sought to describe the rationale and methods for Door-to-Balloon (D2B): An Alliance for Quality, an international effort organized by the American College of Cardiology in partnership with the American Heart Association and 37 other organizations to rapidly translate research about how best to achieve outstanding D2B times for patients with ST-segment elevation myocardial infarction (STEMI) into practice. BACKGROUND The D2B time, the time between hospital arrival and primary percutaneous coronary intervention for patients with STEMI, is strongly associated with the likelihood of survival, yet the majority of patients are not treated within the guideline-recommended time of </=90 min. Recent research has revealed key and underused strategies that are associated with achieving faster D2B times. METHODS The D2B Alliance has enrolled approximately 1,000 hospitals. Its goal is to achieve a D2B time of </=90 min for at least 75% of non-transferred patients. The key strategies chosen by the D2B Alliance include having the emergency medicine physician activate the catheterization laboratory with a single call, having the team prepared within 20 to 30 min of the call; rapid data feedback; a team-based approach; and administrative support. The use of a pre-hospital electrocardiogram by emergency medical services personnel to activate the catheterization laboratory was also noted as an additional optional strategy. The project has many approaches to promote participation and adoption of effective strategies. An evaluation component is also described. CONCLUSIONS The design of the D2B: An Alliance for Quality, a novel campaign to improve D2B time, is described.

Influence of concurrent renal dysfunction on outcomes of patients with acute coronary syndromes and implications of the use of glycoprotein IIb/IIIa inhibitors.

OBJECTIVES The purpose of this study was to examine the in-hospital outcome and influence of glycoprotein (GP) IIb/IIIa antagonists on patients with acute coronary syndromes (ACS) across a range of renal function. BACKGROUND Recent studies demonstrate increasing cardiovascular risk with progressive renal dysfunction. Previous studies investigating GP IIb/IIIa antagonist use have excluded patients with renal dysfunction. METHODS Patients presenting with ACS between January 1999 and May 2000 were identified, and data on demographics, in-hospital management, and clinical events were collected using standardized definitions. Patients were stratified according to renal function assessed by calculated creatinine clearance (CrCl) at presentation. Primary outcome measures included in-hospital mortality and major bleeding events. RESULTS Renal insufficiency was present in 312 of 889 patients. There were 40 in-hospital deaths. In non-dialysis-dependent patients, as CrCl worsened, there was a decline in utilization of routine diagnostics and therapeutics, an increase in in-hospital mortality (p = 0.002), and an increase in major bleeding (p = 0.03). Although the use of GP IIb/IIIa antagonists was associated with an increase in major bleeding (p < 0.001), there was a protective effect on in-hospital mortality (p = 0.04) after controlling for CrCl. CONCLUSIONS Renal dysfunction is present in a substantial proportion of patients with ACS and is associated with increased in-hospital death. Although GP IIb/IIIa antagonist use in patients with ACS and renal insufficiency resulted in increased bleeding events, its administration was associated with a decreased risk of in-hospital mortality. These preliminary findings need to be confirmed in future randomized clinical trials.

Relationship of treatment delays and mortality in patients undergoing fibrinolysis and primary percutaneous coronary intervention. The Global Registry of Acute Coronary Events.

Objective: Treatment delays may result in different clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) who receive fibrinolytic therapy vs primary percutaneous coronary intervention (PCI). The aim of this analysis was to examine how treatment delays relate to 6-month mortality in reperfusion-treated patients enrolled in the Global Registry of Acute Coronary Events (GRACE). Design: Prospective, observational cohort study. Setting: 106 hospitals in 14 countries. Patients: 3959 patients who presented with STEMI within 6 h of symptom onset and received reperfusion with either a fibrin-specific fibrinolytic drug or primary PCI. Main outcome measures: 6-month mortality. Methods: Multivariable logistic regression was used to assess the relationship between outcomes and treatment delay separately in each cohort, with time modelled with a quadratic term after adjusting for covariates from the GRACE risk score. Results: A total of 1786 (45.1%) patients received fibrinolytic therapy, and 2173 (54.9%) underwent primary PCI. After multivariable adjustment, longer treatment delays were associated with a higher 6-month mortality in both fibrinolytic therapy and primary PCI patients (p<0.001 for both cohorts). For patients who received fibrinolytic therapy, 6-month mortality increased by 0.30% per 10-min delay in door-to-needle time between 30 and 60 min compared with 0.18% per 10-min delay in door-to-balloon time between 90 and 150 min for patients undergoing primary PCI. Conclusions: Treatment delays in reperfusion therapy are associated with higher 6-month mortality, but this relationship may be even more critical in patients receiving fibrinolytic therapy.

National Efforts to Improve Door-to-Balloon Time. Results From the Door-to-Balloon Alliance

OBJECTIVES The purpose of this study was to determine if enrollment in the Door-to-Balloon (D2B) Alliance, a national quality campaign sponsored by the American College of Cardiology and 38 partner organizations, was associated with increased likelihood of patients who received primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI) being treated within 90 min of hospital presentation. BACKGROUND The D2B Alliance, launched in November 2006, sought to achieve the goal of having 75% of patients with STEMI treated within 90 min of hospital presentation. METHODS We conducted a longitudinal study of D2B times in 831 hospitals participating in the National Cardiovascular Data Registry (NCDR) CathPCI Registry, April 1, 2005, to March 31, 2008. RESULTS By March 2008, >75% of patients had D2B times of < or = 90 min, compared with only about one-half of patients with D2B times within 90 min in April 2005. Trends since the launch of the D2B Alliance showed that patients treated in hospitals enrolled in the D2B Alliance for at least 3 months were significantly more likely than patients treated in nonenrolled hospitals to have D2B times within 90 min, although the magnitude of the difference was modest (odds ratio: 1.16; 95% confidence interval: 1.07 to 1.27). CONCLUSIONS The D2B Alliance reached its goal of 75% of patients with STEMI having D2B times within 90 min by 2008.

Does Simplicity Compromise Accuracy in ACS Risk Prediction? A Retrospective Analysis of the TIMI and GRACE Risk Scores

Background The Thrombolysis in Myocardial Infarction (TIMI) risk scores for Unstable Angina/Non-ST–elevation myocardial infarction (UA/NSTEMI) and ST-elevation myocardial infarction (STEMI) and the Global Registry of Acute Coronary Events (GRACE) risk scores for in-hospital and 6-month mortality are established tools for assessing risk in Acute Coronary Syndrome (ACS) patients. The objective of our study was to compare the discriminative abilities of the TIMI and GRACE risk scores in a broad-spectrum, unselected ACS population and to assess the relative contributions of model simplicity and model composition to any observed differences between the two scoring systems. Methodology/Principal Findings ACS patients admitted to the University of Michigan between 1999 and 2005 were divided into UA/NSTEMI (n = 2753) and STEMI (n = 698) subpopulations. The predictive abilities of the TIMI and GRACE scores for in-hospital and 6-month mortality were assessed by calibration and discrimination. There were 137 in-hospital deaths (4%), and among the survivors, 234 (7.4%) died by 6 months post-discharge. In the UA/NSTEMI population, the GRACE risk scores demonstrated better discrimination than the TIMI UA/NSTEMI score for in-hospital (C = 0.85, 95% CI: 0.81–0.89, versus 0.54, 95% CI: 0.48–0.60; p<0.01) and 6-month (C = 0.79, 95% CI: 0.76–0.83, versus 0.56, 95% CI: 0.52–0.60; p<0.01) mortality. Among STEMI patients, the GRACE and TIMI STEMI scores demonstrated comparably excellent discrimination for in-hospital (C = 0.84, 95% CI: 0.78–0.90 versus 0.83, 95% CI: 0.78–0.89; p = 0.83) and 6-month (C = 0.72, 95% CI: 0.63–0.81, versus 0.71, 95% CI: 0.64–0.79; p = 0.79) mortality. An analysis of refitted multivariate models demonstrated a marked improvement in the discriminative power of the TIMI UA/NSTEMI model with the incorporation of heart failure and hemodynamic variables. Study limitations included unaccounted for confounders inherent to observational, single institution studies with moderate sample sizes. Conclusions/Significance The GRACE scores provided superior discrimination as compared with the TIMI UA/NSTEMI score in predicting in-hospital and 6-month mortality in UA/NSTEMI patients, although the GRACE and TIMI STEMI scores performed equally well in STEMI patients. The observed discriminative deficit of the TIMI UA/NSTEMI score likely results from the omission of key risk factors rather than from the relative simplicity of the scoring system.

Adherence to Medications by Patients After Acute Coronary Syndromes

BACKGROUND Nonadherence to medication may lead to poor medical outcomes. OBJECTIVE To describe medication-taking behavior of patients with a history of acute coronary syndromes (ACS) for 4 classes of drugs and determine the relationship between self-reported adherence and patient characteristics. METHODS Consenting patients with the diagnosis of ACS were interviewed by telephone approximately 10 months after discharge. The survey elicited data characterizing the patient, current medication regimens, beliefs about drug therapy, reasons for discontinuing medications, and adherence. The survey included the Beliefs About Medicine Questionnaire providing 4 scales: Specific Necessity, Specific Concerns, General Harm, and General Overuse, and the Medication Adherence Scale (MAS). Multivariate regression was used to determine the independent variables with the strongest association to the MAS. A p value ≤0.05 was considered significant for all analyses. RESULTS Two hundred eight patients were interviewed. Mean ± SD age was 64.9 ± 13.0 years, with 60.6% male, 95.7% white, 57.3% with a college education, 87.9% living with ≥1 other person, and 42% indicating excellent or very good health. The percentage of patients continuing on medication at the time of the survey category ranged from 87.4% (aspirin) to 66.0% (angiotensin-converting enzyme inhibitors). Reasons for stopping medication included physician discontinuation or adverse effects. Of patients still on drug therapy, the mean MAS was 1.3 ± 0.4, with 53.8% indicating nonadherence (score >1). The final regression model showed R2 = 0.132 and included heart-related health status and Specific Necessity as significant predictor variables. CONCLUSIONS After ACS, not all patients continue their drugs or take them exactly as prescribed. Determining beliefs about illness and medication may be helpful in developing interventions aimed at improving adherence.

The relative safety and efficacy of abciximab and eptifibatide in patients undergoing primary percutaneous coronary intervention: insights from a large regional registry of contemporary percutaneous coronary intervention.

OBJECTIVES This study sought to assess whether the use of eptifibatide instead of abciximab is associated with a difference in outcomes of patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). BACKGROUND Pooled data from randomized controlled trials suggest that the use of abciximab may be associated with a survival advantage in patients undergoing primary PCI for acute STEMI. However, a large proportion of patients in the community are treated with eptifibatide, an agent that shares some but not all pharmacological properties with abciximab. METHODS We evaluated the outcomes of 3,541 patients who underwent primary PCI for STEMI from October 2002 to July 2006 in a large regional consortium and who were treated with abciximab (n = 729) or with eptifibatide (n = 2,812). RESULTS There was no difference in the incidence of in-hospital death (4.1% with abciximab vs. 3.5% with eptifibatide, p = 0.39), recurrent myocardial infarction (0.8% vs. 1.2%, p = 0.42), or stroke/transient ischemic attack (0.7% vs. 0.6%, p = 0.80). There was no difference in the need for blood transfusion (12.4% vs. 11.7%, p = 0.61), whereas there was a greater incidence of gastrointestinal bleeding with abciximab (4.8% vs. 2.8%, p = 0.01). In parsimonious risk-adjusted models, no significant difference between abciximab and eptifibatide was observed with respect to any of the outcomes measures. CONCLUSIONS Currently, eptifibatide is used as the adjunct antiplatelet agent in the majority of patients undergoing primary PCI. There is no apparent difference in early outcomes of patients treated with eptifibatide compared with patients treated with abciximab.

Gender differences in adverse outcomes after contemporary percutaneous coronary intervention: An analysis from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2) percutaneous coronary intervention registry

BACKGROUND Prior studies have shown a relationship between female gender and adverse outcomes after percutaneous coronary interventions (PCIs). Whether this relationship still exists with contemporary PCI remains to be determined. METHODS We evaluated gender differences in clinical outcomes in a large registry of contemporary PCI. Data were prospectively collected from 22,725 consecutive PCIs in a multicenter regional consortium (Blue Cross Blue Shield of Michigan Cardiovascular Consortium) between January 2002 and December 2003. The primary end point was in-hospital all-cause mortality; other clinical outcomes evaluated included in-hospital death, vascular complications, transfusion, postprocedure myocardial infarction, stroke, and a combined major cardiovascular adverse event (MACE) end point including myocardial infarction, death, stroke, emergency coronary artery bypass grafting, and repeated PCI at the same site. Independent predictors of adverse outcomes were identified using multivariate logistic regression analysis. RESULTS Compared with men, women were older, had a higher prevalence of comorbidities, and had a significantly higher frequency of adverse outcomes after PCI. After adjustment for baseline demographics, comorbidities, clinical presentation, and lesion characteristics, female gender was associated with an increased risk of in-hospital death, vascular complication, blood transfusion, stroke, and MACE. The relationship between female gender and increased risk of death and MACE was no longer present after further adjustment for kidney function and low body surface area. CONCLUSIONS Differences in mortality rates between men and women no longer exist after PCI. However, our data suggest that technological advancements have not completely offset the relationship between gender and adverse outcomes after PCI.

Validation of the EQ-5D in patients with a history of acute coronary syndrome.

ABSTRACT Objective: To analyze the construct validity of the EQ‐5D in patients with acute coronary syndromes (ACS). Methods: All ACS-diagnosed patients discharged from a university-affiliated hospital during a 3‐year period were mailed a questionnaire that included the EQ‐5D and the SF‐8. The EQ‐5D includes a visual analogue scale (EQ VAS) to measure self-reported current health-status (0–100) and a five-item descriptive system measuring mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Also included were disease severity measures [Duke Activity Status Index (DASI), cardiac symptom count (SC), patient-perceived cardiac disease severity], comorbidity measures (Charlson comorbidity index, total medication count), and other demographic and disease-related items. Results: Of 1217 patients, 490 (40.3%) responded. Patients averaged 65.2 (SD 11.3) years of age; 71.0% male; 91.9% Caucasian; 64.3% history of MI. Only 0.2%–0.4% of EQ‐5D items and 8% of the EQ VAS were left unanswered by respondents. The nine most common health states were identified based on the five EQ‐5D item scores. Levels of responses to EQ‐5D items and the EQ VAS score were significantly better for patients with very mild/mild perceived disease severity compared to severe/very severe, for patients with lower comorbidity, for patients with lower symptom responses, and for patients with a higher cardiac-related functioning. EQ VAS score and SF‐8 subscale score correlation coefficients ranged from 0.527 to 0.798 (all p < 0.0001). Significant differences were observed between the response level of individual EQ‐5D items and scores of comparable SF‐8 subscales. Conclusions: This study demonstrated the construct validity of the EQ‐5D in a population-based sample of patients with a history of ACS.