CRD summary

This review compared exercise and pharmacological stress myocardial perfusion imaging for risk stratification in known or suspected coronary disease. There were weaknesses in the review process and reporting of results. The conclusion that both tests have comparable risk stratification ability appears robust, but the greater risk of cardiac events for pharmacological stress test patients is not supported by the data presented.

Authors' objectives

To compare the relative value, for coronary risk stratification, of pharmacological stress myocardial perfusion imaging (MPI) and exercise stress MPI.

Searching

MEDLINE was searched from inception to August 2001 for publications in the English language; the search terms were reported. The bibliographies of review articles were checked for additional publications. Unpublished studies were not sought.

Study selection

Assessment of study quality

The methodological quality of the included studies was assessed using published criteria for diagnostic studies (see Other Publications of Related Interest no.1), modified for use with prognostic studies. These criteria assessed: study design (prospective versus retrospective), patient selection, sample size, reporting of indications for testing, description of methodology, accounting for follow-up drop-outs, percentage follow-up and data presentation. Each criterion was scored (1 to 5), and the scores were summed and reported as a percentage of the maximum (40 for pharmacological studies and 35 for exercise studies). Studies with scores over 80% were considered high quality, scores of 61 to 80% indicated medium quality, and scores of 60% or less indicated low quality. The authors did not state how the quality criteria were applied, or how many reviewers performed the quality assessment.

Data extraction

The data were extracted using a written form and were entered into a database. The authors did not state how many reviewers performed the data extraction. Study details, test details, participant characteristics, test results and outcome data were extracted. Test results were recorded as normal or abnormal scans and, where possible, further classified by type of defect or severity of abnormality.

Methods of synthesis

Results of the review

Eleven studies using pharmacological stress MPI (n=4,988) were included; seven used dipyridamole, two used adenosine and two used dobutamine. Thirteen studies using exercise stress MPI (n=9,930) were included.

Four studies of pharmacological stress MPI were considered to be of high quality and seven medium quality. Three studies of exercise stress MPI were considered to be of high quality, six medium quality, and four low quality. There was no significant correlation between study quality and reported event rates (r2 0.13, P=0.084). There were no significant differences in cardiac event rates between studies reporting a clear indication for the use of pharmacological stress agents and those that did not.

Comparative predictive ability.

The summary OR for predicting any cardiac event (cardiac death or MI) was similar for exercise stress (OR 7.4, 95% CI: 5.7, 9.5) and pharmacological stress (OR 6.6, 95% CI: 4.9, 8.9). There was no evidence of statistical heterogeneity between the studies (P>0.05 for both exercise and pharmacological stress). The sROC curve analysis also showed no difference in discriminatory power between the stressors (t= -0.98, P=0.338).

Comparative follow-up event rates.

There were a total of 343 cardiac deaths and 216 nonfatal MIs in the pharmacological stress group over a median follow-up period of 22 months. There were a total of 180 cardiac deaths and 277 nonfatal MIs in the exercise stress group over a median follow-up period of 20 months.

Prognostic value of MPI.

In the pharmacological stress group, the pooled annualised event rate for cardiac death and MI was 1.78% for patients with normal images and 9.98% for patients with abnormal images. In the exercise stress group, the pooled annualised event rate for cardiac death and MI was 0.65% for patients with normal images and 4.30% for patients with abnormal images. Both MI and cardiac death were significantly higher in patients undergoing pharmacological stress testing than in those undergoing exercise stress testing (P<0.05).

Confounding factors.

Patients undergoing pharmacological stress testing had a higher prevalence of poor prognostic factors (e.g. age, hypertension, diabetes mellitus, previous MI and revascularisation) than those undergoing exercise stress testing. Regression analyses of clinical variables indicated that an inability to exercise was the strongest predictor of cardiac events; male gender and history of hypertension, diabetes mellitus and prior MI were also significant predictors (P-values were not reported).

Authors' conclusions

Exercise stress MPI and pharmacological stress MPI are similarly useful in risk stratification of cardiac patients. However, patients undergoing pharmacological stress testing had a higher risk of subsequent cardiac events, even where the test result was normal.

CRD commentary

The report presented a complex set of analyses using a large number of outcome measures, but some important information was missing from the data presented: e.g. CI on graphs, annualised event rates for each included study, evidence of statistical testing where significance or lack of significance were reported. There were also significant weaknesses in the data gathering process. A clinically relevant research question was clearly stated and defined by the inclusion criteria of the review. The search strategy employed was weak; the searching of only one bibliographic database and the exclusion of non-English language publications may well have resulted in the omission of relevant data. In addition, no attempt was made to identify unpublished studies. The methodological quality of the included studies was assessed using appropriate criteria. However, the amalgamation of the results of this assessment into overall quality scores represents a loss of potentially useful information; the authors presented an analysis of correlation between quality score and event rate and, whilst there was no correlation with overall quality score, correlation with individual quality criteria may have been obscured.

The methods used to compare the predictive ability of the two stressors (summary ORs and the sROC curve) were appropriate. However, the lack of detail about the numbers of cardiac events in the individual studies, or the annualised event rates, makes it difficult to comment on the reliability of the methods used or the conclusions from the event rate analyses. The authors fully discussed the limitations of their analysis, in terms of the limited data available on severity of disease and other cardiac risk factors. Regression analyses were used in an attempt to investigate the impact of other cardiac risk factors on event rate, but it is doubtful whether the available data were sufficient to support these analyses and full details of the results were not reported.

The authors' conclusions on the comparability of pharmacological and exercise stress MPI for cardiac risk stratification are supported by the data presented. However, their conclusion that patients undergoing pharmacological stress testing are at higher risk of cardiac events than those undergoing exercise stress testing should be treated with caution, given that only limited investigation of confounding factors was possible; as the authors stated, a causal link could not be established with the available data.

Implications of the review for practice and research

Practice: The authors stated that it is important to include intrinsic cardiac risk, type of stress testing, and perfusion imaging in risk stratification for patients with known or suspected CAD.

Research: The authors made no specific recommendations for research.

Bibliographic details

Navare S M, Mather J F, Shaw L J, Fowler M S, Heller G V. Comparison of risk stratification with pharmacologic and exercise stress myocardial perfusion imaging: a meta-analysis. Journal of Nuclear Cardiology 2004; 11(5): 551-561. [PubMed: 15472640]

Other publications of related interest

1. Kymes SM, Bruns DE, Shaw LJ, Gillespie KN, Fletcher JW. Anatomy of a meta-analysis: a critical review of 'Exercise echocardiography or exercise SPECT imaging? A meta-analysis of diagnostic test performance'. J Nucl Cardiol 2000;7:599-615. 2. Chrisensen E, Gluud C. Glucocorticoids are ineffective in alcoholic hepatitis: a meta-analysis adjusting for confounding variables. Gut 1995;37:113-8.

Indexing Status

Subject indexing assigned by NLM

MeSH

Comorbidity; Coronary Artery Disease /mortality /radionuclide imaging; Exercise Test /methods /statistics & numerical data; Humans; Reproducibility of Results; Risk Assessment /methods /statistics & numerical data; Risk Factors; Sensitivity and Specificity; Vasodilator Agents /diagnostic use; Ventricular Dysfunction, Left /mortality /radionuclide imaging

AccessionNumber

12005003242

Database entry date

31/10/2006

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.