Invasive or Conservative Strategy in Diabetics with ACS?

Abstract & Commentary

By Andrew J. Boyle, MBBS, PhD

Assistant Professor of Medicine, Interventional Cardiology, University of California, San Francisco

Dr. Boyle reports no financial relationships relevant to this field of study.

This article originally appeared in the August 2012 issue of Clinical Cardiology Alert. It was edited by Michael H. Crawford, MD, and peer reviewed by Ethan Weiss, MD. Dr. Crawford is Professor of Medicine, Chief of Clinical Cardiology, University of California, San Francisco, and Dr. Weiss is Assistant Professor of Medicine, Division of Cardiology and CVRI, University of California, San Francisco. Dr. Crawford reports no financial relationships relevant to this field of study, and Dr. Weiss is a scientific advisory board member for Bionovo.

Source: O’Donoghue ML, et al. An invasive or conservative strategy in patients with diabetes mellitus and non–ST-segment elevation acute coronary syndromes. A collaborative meta-analysis of randomized trials. J Am Coll Cardiol 2012;60:106-111.

Patients with diabetes mellitus (DM) are at increased risk of developing acute coronary syndromes (ACS). Furthermore, after hospitalization with ACS, patients with DM are at increased risk of suffering repeat hospitalization for ACS. In recent years, a number of trials have tested the strategy of routine early invasive approach (i.e., diagnostic angiography with a view to revascularization) vs an early conservative strategy (i.e., medical management with coronary angiography only performed in cases of refractory ischemia). The invasive strategy is generally preferable in patients at high risk of clinical events, and this is reflected in the ACC/AHA guidelines. Diabetes is known to confer an increased risk of clinical events. Whether patients with DM and ACS should routinely undergo an invasive strategy is not known. O’Donoghue and colleagues performed a collaborative meta-analysis of nine clinical trials that tested invasive vs conservative strategies in patients with ACS, comparing outcomes between diabetic and non-diabetic patients. The primary endpoint was a composite of death, myocardial infarction (MI), and repeat hospitalization for ACS.

The authors studied 9904 patients in nine trials, of whom 18.2% were diabetic. Patients with DM tended to be older and were more likely to be female, have hypertension, hyperlipidemia, and a history of MI. In addition, patients with DM had more extensive coronary artery disease and were more likely to undergo coronary artery bypass graft (CABG) surgery than non-diabetics. Diabetics had higher rates of death (9.3% vs 3.2%; P < 0.001), nonfatal MI (11.3% vs 7.1%; P < 0.001), and rehospitalization with ACS (18.1% vs 13.0%; P < 0.001) compared with non-diabetic patients. The primary endpoint was reduced by an invasive strategy to a similar extent in patients with DM (relative risk [RR] 0.87; 95% confidence interval [CI] 0.73-1.03) and those without (RR 0.86; 95% CI, 0.70-1.06). Randomization to an invasive strategy reduced non-fatal MI in diabetic patients (RR 0.71; 95% CI, 0.55-0.92) but not in non-diabetics (RR 0.98; 95% CI, 0.74-1.29). The absolute risk reduction in MI with an invasive strategy was greater in diabetic than non-diabetic patients (absolute risk reduction: 3.7% vs 0.1%). There were no differences in death or stroke between diabetics and non-diabetics. Interestingly, patients with DM received a benefit from an invasive strategy regardless of whether they had positive biomarkers. In contrast, non-diabetics only received benefit from an invasive strategy if they were biomarker positive.

The authors conclude that an early invasive strategy yielded similar RR reductions in overall cardiovascular events in diabetic and non-diabetic patients. However, an invasive strategy appeared to reduce recurrent non-fatal MI to a greater extent in diabetic patients. These data support the updated guidelines that recommend an invasive strategy for patients with DM and non-ST-segment elevation ACS.

Commentary

This meta-analysis confirms that diabetics have a higher risk of cardiac events than non-diabetics. It also demonstrates that diabetics and non-diabetics who present with ACS receive a similar benefit from an early invasive strategy. This confirms the current ACC/AHA guidelines that suggest markers of increased risk in patients with ACS should include the presence of diabetes.

Several limitations of this study should be mentioned. First, meta-analyses are subject to biases including which studies were included, selection bias, and individual study protocol differences that are not mentioned. Second, diabetics were more often treated with CABG than non-diabetics (31% vs 25%) and we are not told whether the outcomes were influenced by the use of CABG instead of PCI. It is possible that the higher rates of CABG in diabetics resulted in superior clinical outcomes. Third, this meta-analysis was a study-level rather than a patient-level meta-analysis. Thus, individual covariates were not examined.

Importantly, many of the studies included in this meta-analysis were in the era of bare-metal stents (BMS). Drug-eluting stents (DES), particularly the newest generation of DES, lead to better outcomes in diabetics compared to BMS. Use of DES may result in an even greater magnitude of improvement in outcomes in diabetic patients who undergo invasive treatment. Patients with ACS should be risk-stratified and higher-risk patients considered for an invasive strategy. Diabetic patients should be considered in this high-risk group.