### Evidence Report/Technology Assessment: Number 31

# Prediction of Risk for Patients with Unstable Angina

## Summary

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Under its Evidence-based Practice Program, the Agency for Health Care Research and Quality (AHRQ) is developing scientific information for other agencies and organizations on which to base clinical guidelines, performance measures, and other quality improvement tools. Contractor institutions review all relevant scientific literature on assigned clinical care topics and produce evidence reports and technology assessments, conduct research on methodologies and the effectiveness of their implementation, and participate in technical assistance activities. 

Overview / Reporting the Evidence / Methodology / Findings / Future Research / Availability of Full Report

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## Overview

Coronary heart disease is the leading cause of death for both men and women in the United States. One of the most characteristic and troubling features of coronary disease is the sudden and unexpected onset of symptoms in clinically stable patients and sometimes in even previously healthy individuals.

 The development of symptoms is associated with an increased risk of sudden death, acute myocardial infarction, and other life-threatening complications. The development of symptoms suggestive of coronary disease therefore mandates prompt and accurate diagnosis and treatment.

The cardinal symptom of coronary artery disease (CAD) is angina, which classically presents as a squeezing or strangulating deep chest discomfort that may radiate to the arm or jaw. Angina that is brought on by exercise stress and is relieved promptly after cessation of exertion is termed "typical angina." Stable angina is a pattern of symptoms that has been unchanged for 6 or more weeks. Unstable angina is a pattern of symptoms that is new in onset, changing in severity or frequency, occurring at rest, or lasting longer than 20 minutes.

The evaluation of suspected coronary disease is complicated by the fact that chest discomfort has many causes, and bona fide coronary disease may present in an atypical fashion. Thus, a population of patients with symptoms suggestive of coronary disease includes some patients with acute, life-threatening medical problems, some patients with other medical problems mimicking CAD, and even some "worried well" in need only of reassurance.

The evaluation and treatment of this highly heterogeneous population is the difficult task for clinicians in emergency departments (ED) and in office practice. The key goal of these clinicians must be to identify the patient's short-term risk. The high-risk patient may develop life-threatening complications and require hospitalization and immediate therapy. The low-risk patient may need further evaluation, but in a less urgent and less costly setting. Because identification of patient risk is central to all further patient management in unstable angina, this evidence report focuses on clinical and laboratory markers of patient risk, such as results of diagnostic tests (troponin values, stress testing, echocardiography, and nuclear scintigraphy).

Because chest pain units attempt to "risk stratify" (group patients according to their degree of risk) based on readily available data, an assessment of the efficacy of chest pain units is significant to this report. Our in-depth review focused on information that would be readily available to all providers caring for patients with suspected unstable angina. Information in this report applies to adult men and women.

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## Reporting the Evidence

### Key Questions

- 	What are the immediate clinical and electrocardiographic characteristics that are independently associated with an increased risk of adverse outcomes in patients with either chest pain that raises suspicion of cardiac ischemia or diagnosed unstable angina? 
- What is the prognostic value of a positive or negative troponin test in patients with proven or suspected unstable angina?
- Are chest pain units and ED protocols effective, cost-saving, and safe for triaging patients with suspected unstable angina or myocardial infarction (MI)?

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## Methodology

### Prognostic Value of the History, Physical Examination, and Electrocardiogram

We conducted a systematic literature search of MEDLINE for relevant articles published between 1966 through 1998, and we manually searched references of retrieved articles to identify additional applicable published studies. Our search criteria included MEDLINE exact subject and keyword searches for: 

-  Chest pain, angina pectoris, unstable angina, variant angina, vasospastic angina, or acute coronary syndrome combined with the terms risk, stratification, prognosis, outcome, and multivariate analysis.

We restricted our review only to those studies that performed a multivariate analysis of the clinical and/or electrocardiographic predictors of adverse clinical events in patients with either chest pain suspected to be ischemia or diagnosed unstable angina in the ED or hospital. We sought to determine those variables that provided independent risk prediction. Therefore, studies were excluded if they performed a multivariate analysis but did not provide the quantitative results with measures of significance (e.g., p value, standard error) in the form of regression estimates, relative risks, odds ratios, or rate ratios. A p value of < 0.05 was considered statistically significant. We also excluded non-English-language studies.

Predictor variables of interest included: 

- Demographic characteristics (age, sex, race/ethnicity).
-  Medical history (prior MI, unstable or stable angina, revascularization, congestive heart failure, cerebrovascular disease, hypertension, diabetes, and smoking history).
- Symptom characteristics (frequency, duration, and pattern of chest pain).
-  Initial physical exam findings (blood pressure, heart rate, and pulmonary rales or Killip class I-IV for congestive heart failure).
- Initial electrocardiographic features (ST-segment depression, transient ST elevation, isolated T-wave inversions, other findings, or a normal electrocardiogram).

We included studies that measured at least one of the following outcomes:

- Cardiac death.
-  Myocardial infarction.
-  Other major cardiac complication.

Candidate titles and abstracts were reviewed, and appropriate studies were selected for data extraction by an internist and a cardiologist with training in health services research. 

Studies were stratified by type of patients evaluated (chest pain or diagnosed unstable angina), and multivariate results were grouped into:

- Categories of demographic characteristics.
- Medical history features.
- Symptom characteristics.
- Initial physical findings.
- Electrocardiographic features.

### Prognostic Value of Troponin

We searched MEDLINE (1966-98) and EMBASE (1974-98) and reviewed cited references of retrieved articles to identify relevant published studies. Our search criteria were: (1) the text word *troponin*, (2) the text words *angina* or *unstable* or *myocardial infarction* or *ischemia*, and (3) language English, excluding (4) the MeSH heading *animal*.

Using this criteria set, we searched MEDLINE, then EMBASE. Finally, we reviewed the bibliographies of identified trials to locate other relevant studies.

We restricted our review to studies that evaluated patient cohorts with suspected ischemia. We excluded studies that only enrolled patients with myocardial infarction. We also excluded case-control studies and studies that did not report the outcomes of MI or death.

Study selection was performed initially by title review. Candidate abstracts were then reviewed and selected for data abstraction. Two independent reviewers abstracted data from each article on standardized electronic data forms. A third reviewer compared their results and settled any differences. In general, at least one reviewer of the pair had clinical cardiology expertise.

We used standard methods of meta-analysis to combine outcome data across trials and the Peto (fixed-effects) and DerSimonian-Laird (random-effects) methods to estimate summary odds ratios. We examined differences between study subgroups using analysis of variance. The previously specified subgroup comparisons of interest were studies for all patients with suspected ischemia versus patients in whom myocardial infarction had already been excluded. The former patients would be recruited from emergency departments, while the latter patients would all be hospitalized. Reported p values are two tailed with statistical significance at *p* < 0.05.

### Chest Pain Units and EmergencyDepartment Protocols

We conducted a systematic literature search of MEDLINE for articles published between 1966 and 1998:

- The first search strategy included the following terms: (random* [All Fields] AND ( chest pain  [MeSH Terms] OR  chest pain  [Text Word]) AND ( emergencies  [MeSH Terms] OR  emergency  [Text Word])). 
-  The second search strategy included the following terms: (controlled clinical trial [All Fields] AND ( chest pain  [MeSH Terms] OR  chest pain  [Text Word]) AND ( emergencies  [MeSH Terms] OR  emergency  [Text Word])).

Abstracts and titles from both searches were reviewed for appropriate studies. Randomized trials or controlled clinical trials were selected. Studies that assessed chest pain units, accelerated or rapid diagnostic protocols, or emergency department triage protocols were reviewed. Noncontrolled studies were selected if they reported outcomes for at least 1,000 patients with suspected acute coronary syndromes. We recorded the outcomes of hospital admission rate, cost of care, myocardial infarction, and death when available. Other outcomes reported by the trial were recorded if comparisons were made between control and intervention groups.

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## Findings

### Prognostic Value of the History, Physical Examination, and Electrocardiogram

- 	Demographic characteristics associated with worse outcomes included increasing age and male sex.
- 	Prior medical conditions that consistently predicted poor outcomes included previous myocardial infarction and diabetes. In addition, prior congestive heart failure, hypertension, and smoking also may be important prognostic factors.
- 	Congestive heart failure on presentation increased the risk of cardiac events.
- 	Among patients with suspected or confirmed unstable angina, specific characteristics of the chest pain did not uniformly add any independent information useful in predicting adverse outcomes among the studies reviewed.
- 	ST depression > 0.1 mV was the strongest electrocardiographic predictor of adverse outcomes, while a completely normal electrocardiogram was a strong predictor of reduced risk.

### Prognostic Value of Troponin

- 	A positive troponin value increased the risk of death 5.3-fold over the 4 weeks subsequent to testing (95 percent CI: 3.6-7.9).
- 	The absolute increase in mortality was 3.9 percent (95 percent CI: 3.0-4.4 percent) for patients with a positive troponin level.
- 	A positive troponin value increased the risk of subsequent death or MI 12.3-fold at 4 weeks (95 percent CI: 6.4-23.8).
- 	The absolute increase in the rate of death or subsequent MI was 14 percent (95 percent CI: 10-18 percent) for patients with a positive troponin level.
- 	The increased absolute risk associated with a positive troponin value was proportional to the overall risk of death. 
- 	The increased risk of death associated with a positive troponin value decreased over time.
- 	The increased risk of death at 4 weeks was similar for elevated troponin T and troponin I values.
- 	An increased troponin value was associated with a similar risk of death for both patients with unstable angina (MI excluded) and patients with suspected acute ischemia (chest pain with or without MI).

### Evaluation of Chest Pain Units and Emergency Department Protocols

- 	The few randomized trials of chest pain units have consistently shown decreased hospital days and hospital costs for patients as compared with usual emergency care for the duration of the initial encounter.
- 	There is no evidence of increased harm from the more selective admissions that result from evaluation with chest pain units or protocols, but statistical power is limited in studies to date. 
- 	Patient satisfaction may be improved by chest pain units.

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## Future Research

More studies are needed that combine data from history, physical examination, and biochemical markers to determine the independent prognostic ability of each variable. Our qualitative review of clinical and electrocardiographic predictors of prognosis suggests that future studies should include the following variables in a multivariate prediction model:

- Age.
-  ST depression.
-  ST elevation.
- Troponin levels.

More randomized trials of chest pain units or chest pain protocols are needed to more fully determine their health and economic benefits.

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## Availability of the Full Report

The full evidence report from which this summary was derived was prepared for the Agency for Healthcare Research and Quality by the UCSF-Stanford Evidence-based Practice Center under contract  No. 290-97-0013. Print copies of this report are available free of charge from the AHRQ Publications Clearinghouse by calling 800-358-9295. Requestors should ask for Evidence Report/Technology Assessment  No. 31, *Prediction of Risk for Patients With Unstable Angina* (AHRQ Publication  No. 01-E001).

The Evidence Report is also online on the National Library of Medicine Bookshelf, or can be downloaded as a zipped file.

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*AHRQ Publication Number 00-E030Current as of August 2000*

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**Internet Citation:**

*Prediction of Risk for Patients With Unstable Angina*. Summary, Evidence Report/Technology Assessment: Number 31. AHRQ Publication  No. 00-E030, August 2000. Agency for Health Care Research and Quality, Rockville, MD. http://www.ahrq.gov/clinic/epcsums/unstabsum.htm

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