Management of the Asymptomatic Diabetic Patient with Evidence of Ischaemia
large perfusion defects. There were no differences observed between the two randomised groups in terms of all-cause death, cardiac death, MI and unstable angina. Of note, however, is that even among this low- risk group of patients, when outcomes were assessed in the screened group according to the amount of quantifiable ischaemia on stress testing, patients with moderate or large defects had a six-fold greater risk of events compared with patients with normal scans or small defects seen on SPECT. These findings are consistent with those of a pilot study of asymptomatic high-risk diabetics, in whom there was a 22% risk reduction in cardiac events among patients screened with exercise electrocardiogram (ECG) and stress echocardiography.12
As a result of these considerations, asymptomatic diabetic patients are often screened non-invasively for CAD, and patients without demonstrable ischaemia are thought to be at low to intermediate risk of subsequent cardiovascular events. On the other hand, the management of asymptomatic diabetic patients with demonstrable ischaemia on stress testing can often be vexing to the clinician, who must weigh the up-front assumed risk of invasive procedures (both diagnostic angiography and/or revascularisation) against the putative benefits of a reduction in ischaemic burden. The presence of myocardial ischaemia predicts poorer long-term survival in diabetics than non-diabetics, and the higher mortality associated with diabetes may be mediated by ischaemia to a large extent, with limited differences observed in subsequent mortality among diabetic and non-diabetic patients without ischaemia.13
High-risk findings on SPECT
imaging have been observed in 18% of asymptomatic diabetics with a subsequent annual mortality rate of 5.9%, as opposed to a mortality rate of 2.9% in patients with low-risk SPECT findings.14
Of note, among
patients with high-risk SPECT findings in this study who subsequently underwent coronary angiography, 61% had high-risk CAD. These data are consistent with other studies demonstrating a strong association between the amount of ischaemia on stress SPECT and subsequent cardiovascular events in patients with stable CAD.15,16
On demonstration of significant myocardial ischaemia, the majority of patients with diabetes (even those who are asymptomatic) should typically undergo further risk stratification through diagnostic coronary angiography. Some would argue whether this is necessary for patients with minimal or small amounts of ischaemia, and in these patients there is undoubtedly an emerging role for non- invasive anatomical risk assessment, for example through coronary computerised tomography angiography (CTA). Clearly, the decision to proceed with diagnostic angiography is a clinical decision that should take into account not only the amount of ischaemia but also the baseline clinical risk (including co-morbidities), the functional capacity of the patient and other high-risk features of the stress test. However, it should be noted, that current clinical paradigms, as well as clinical trials randomising patients to revascularisation versus medical therapy, have typically required anatomical delineation of the extent of CAD in order to adequately assess patient risk in individuals with demonstrable ischaemia. Individuals undergoing diagnostic angiography with low-risk CAD are often managed medically, whereas patients with more critical CAD are often presented with options for revascularisation.
The clinical justification for revascularisation of patients with significant CAD is largely based on prior data associating revascularisation of at- risk myocardial territories with improved clinical outcomes. In an analysis of patients included in the Cedars Sinai database, revascularisation has been shown to be associated with a reduction in
EUROPEAN CARDIOLOGY
cardiac mortality among patients with a high-risk stress SPECT scan, defined as greater than 10–20% ischaemic myocardium – a finding even more pronounced among diabetic patients.15
In this database,
mortality rates were observed to increase progressively, with greater amounts of ischaemia among patients undergoing medical therapy but not in patients referred for revascularisation, reinforcing the ‘protective’ benefit of revascularisation for patients with the highest ischaemic risk. Further data from the nuclear sub-study of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial have corroborated a greater degree of ischaemia reduction with revascularisation compared with medical therapy, with a clear association between ischaemia reduction and improved clinical outcomes.16
Additionally, medically managed patients with residual
ischaemia on SPECT scans were more likely to subsequently receive revascularisation. In another series, revascularisation provided a 43% relative risk reduction in mortality in asymptomatic diabetics with a high-risk SPECT scan.17
Finally, in the Asymptomatic Cardiac Ischemia
Pilot (ACIP) and Swiss Interventional Study on Silent Ischemia Type II (SWISSI II) studies, ischaemia-guided therapy with revascularisation in addition to medical therapy was shown to reduce cardiac death and MI compared with medical therapy alone.18,19
Despite these prior observational data associating revascularisation of appropriately selected patients with improved clinical outcomes, recent randomised studies (COURAGE and Bypass Angioplasty Revascularization Investigation 2 Diabetes [BARI 2D]) have called into question the benefit of revascularisation in such patients, suggesting that a strategy of medical therapy should be the first line of therapy for stable CAD.20,21
However, a
critical factor that is often missing in the discussion of these trials relates to the characteristics of the patients enrolled in these studies. For example, while the COURAGE trial did not demonstrate an improvement in clinical outcomes with percutaneous coronary intervention (PCI) compared with medical therapy, despite the low-risk features of patients enrolled in the trial, the nuclear sub-study of the trial clearly demonstrated an association between ischaemia reduction and improved clinical outcomes, a finding that was more pronounced among patients undergoing revascularisation with PCI.16
More recently, the results of the
BARI 2D trial have been published, and are additionally instructive. BARI 2D randomised diabetic patients with angiographically demonstrated CAD to a strategy of prompt revascularisation (PCI or coronary artery bypass grafting [CABG], based on the discretion of the treating physicians) versus medical therapy. In the trial, the prompt revascularisation strategy was not superior to medical therapy in preventing so-called ‘hard’ cardiovascular events. Interestingly, among patients deemed suitable for randomisation to PCI or medical therapy, there was no significant difference between revascularisation and medical therapy, while among patients with more extensive CAD deemed suitable for randomisation to CABG versus medical therapy, the rate of subsequent cardiovascular events was significantly lower with revascularisation compared with medical therapy.
BARI 2D was a test of prompt revascularisation versus initial intensive medical therapy in patients who did not require a “definite need for invasive intervention as determined by the attending cardiologist.” Thus, in a sense, BARI 2D was a study of the utility of prophylactic revascularisation in patients with diabetes deemed suitable for either management approach. The finding that prompt revascularisation appeared to benefit a subset of enrolled patients – namely, those with more complex disease who were referred for CABG – is evidence in support of the merit of revascularisation for prevention of hard clinical outcomes even in appropriately selected patients with stable forms of
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