Invasive vs Conservative Management Strategy for ACS
Invasive vs Conservative Management Strategy for ACS
Abstract & Commentary
By Jonathan Abrams, MD Professor of Medicine, Division of Cardiology, University of New Mexico, Albuquerque Dr. Abrams serves on the speaker's bureau for Merck, Pfizer, and Parke-Davis
Source: Qayyum R, et al. Systematic Review: Comparing routine and selective invasive strategies for the acute coronary syndrome Ann Int Med. 2008;148:186-196.
It remains debatable as to whether individuals who present with a non-ST-segment elevation MI (NSTEMI) or acute coronary syndrome (ACS) should be managed with a selective or elective invasive strategy vs an approach performing angiography in all patients. Qayyum and colleagues carried out an extremely complex statistical analysis of the existing data. They performed a comprehensive review of the literature, utilizing the COCHRANE central registry of controlled trials. Ten contemporary studies were selected for analysis. The results demonstrated a trend toward benefit in trials with a routine invasive strategy for both non-fatal MI and death; however, confidence limits were not exceeded, and the superiority of the routine invasive strategy was not proven. In addition, of the ten trials reviewed in the meta-analysis, there was a wide variety of treatment approaches and algorithms for both the non invasive and invasive strategies. The selective invasive subjects were enrolled in trials with differing strategies for determining whether angiography should be used; for instance, some trials used risk stratification with ischemia-provoking techniques, while others did not.
The data synthesis of the ten trials in this analysis consists of a total of 10,648 patients, mean age of 72, and a median follow-up of 16 months. The studies enrolled individuals with classic unstable angina with or without ECG or biomarker evidence of myocardial ischemia.
Results: For non-fatal MI, there was a relative risk reduction for the routine invasive strategy of 10% 0.90, 95% (CI 0.742, 1.08, p = NS). Deaths were also lower in the routine invasive strategy group by 5% (CI, 0.80-1.14), with a 14% reduction in non-fatal MI (CI 0.68-1.08, p = NS). Of interest, but not emphasized in the discussion, is that the selective invasive strategy patients who had NSTEMI all received was coronary angiography, in addition to aggressive pharmacologic therapy, with "revascularization performed only in the presence of refractory ischemia or an inducible abnormality on provocative testing." Results were calculated for outcomes at discharge from hospital and one year.
The inclusion of these ten trials totaling almost 11,000 patients was based on inclusion criteria culled from 5,000 articles! The largest trial was FRISC-II, and TIMI IIIB was the earliest (reported 1995). Five trials were done in Europe and four in North America. The VANQWISH trial influenced the gender populations toward males, as it was a VA study. Average time from randomization to angiography was 48 hours in the routine invasive group (average across all ten studies of 6-96 hours). Sixty percent of patients had elevated enzymes and 39% had ST segment depression. Stents were employed in six trials, four others did not report on stent utilization. Greater than 80% of patients received a GPIIa/IIIb inhibitor in three trials; fewer than 25% in three other trials; four trials did not report. Differences between the studies included definitions of procedure-rated myocardial infarction, duration of follow-up, and management of patients in the selective strategy groups. Stress testing for ischemia was not performed routinely in the four studies.
The main outcome demonstrated a 14% reduction in non-fatal MI in the routine invasive strategy group and a 10% reduction in death, both NS. Confidence intervals were wide. The composite outcomes were better in the routine angiographic cohort, with a 16% reduction in the composite end point and a 23% reduction in non-fatal MI, data NS.
Qayyum et al conclude that the "systematic review of heterogeneous studies did not find sufficient evidence to support routine use of an invasive strategy to reduce mortality or non-fatal MI in patients with NSTEMI. The results remained unchanged...at time of discharge or at one year follow-up." Of note, when the ICTUS trial data were excluded, there was greater support for the routine invasive strategy due to a decreased risk for non-fatal MI. ICTUS reported an increased risk of death (NS) and non fatal MI in patients in the routine invasive strategy group. This trial employed aggressive management, with Qayyum et al suggesting that these patients may have had a lower one year mortality rate than in other trails. In addition, differences in bio markers may have played a role. ICTUS defined reinfarction with CKMB elevations but not troponin in patients with and without procedures. Qayyum et al suggest that higher revascularization rates in the selective invasive group may have contributed to the ICTUS results, thus favoring the selective invasive strategy in high-risk patients.
Regarding the failure of a routine strategy over a selective approach, Qayyum et al state "clinicians should consider other factors when choosing a treatment for particular patient." Identification of patients who would be expected to benefit from a routine invasive strategy may be an important study in the future. They point out that studies in the elderly and women "are likely to benefit from a routine invasive strategy" and are the subject of ongoing trials, as is another trial looking at the optimal timing of coronary intervention. Heterogeneity in therapies and differences in the magnitude of risk of adverse outcomes in different populations are noted to further muddy the waters. Conversely, low-to-intermediate risk patients in some trials may have "diluted the benefit of a particular strategy to high-risk patients." Although there appears to be some advantage to the routine invasive strategy, they conclude "this systematic review does not support a routine invasive strategy as clearly superior to a selective invasive strategy for managing patients with non ST segment elevation ACS."
Commentary
This is a carefully done and detailed report of ten major trials, all relatively recent, assessing various strategies for care of patients with ACS. Qayyum et al's conclusions have been reached by others, usually in reports that favor a selective invasive strategy. If there had been a robust and unequivocal improvement in outcome for the routine invasive group, there would be little debate on how to proceed. The widespread use of troponin levels driving decision making is not specifically mentioned in this report. In addition, data regarding the usefulness of non-invasive testing after the event is mentioned, but not in detail. The recent COURAGE trial used aggressive pharmacologic therapy for both arms of an invasive or non-invasive strategy for a stable angina population, and this current data analysis is similar. The paradigm that cardiologists must use evidence-based pharmacologic therapy in every patient with ACS is strengthened by this analysis. Prior reports have indicated a risk scoring system for assessment of NSTEMI individuals, with troponin positivity and ST segment depression, as well as recent aspirin use having significant impact on results. It has been assumed that diabetics would particularly benefit from an aggressive pharmacologic therapy. However, the very recent report of stopping an NHLBI study because of adverse outcomes in the aggressive insulin treatment group raises the question as to how diabetics are to be best treated, and could influence physicians to focus more on routine intervention rather than pharmacotherapy in diabetics. Finally, the take home message is that there is food for thought supporting a policy of routine angiography in NSTEMI, but not to the point that we need to change our strategies in these individuals. More to come!
It remains debatable as to whether individuals who present with a non-ST-segment elevation MI (NSTEMI) or acute coronary syndrome (ACS) should be managed with a selective or elective invasive strategy vs an approach performing angiography in all patients.Subscribe Now for Access
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