Cabg

treated medically (25,26). This was suggested in a report from the BARI trial, which evaluated patients with and without diabetes who had undergone revascularization with CABG or PTCA within three months after study entry (25). Among the patients with diabetes, CABG significantly reduced the mortality after a subsequent MI (relative risk 0.09 compared to angioplasty). BARI trial data and results from three other trials that reported results for patients with diabetes (EAST, CABRI, and RITA) were analyzed in a meta-analysis (27). All-cause mortality was significantly lower with CABG than PTCA at four years (absolute risk difference 8.6%) but not longer at six years.

Stenting versus CABG in Multivessel Disease

Diabetics with multivessel disease undergoing coronary stenting may have a worse outcome compared to those undergoing CABG. This was illustrated in the ARTS I trial in which 1205 patients with stable or unstable angina and multivessel disease were randomly assigned to PCI with a bare-metal stent or CABG (28). The 208 patients with diabetes had a lower eventfree survival with stenting than with CABG at one year (63 vs. 84% for CABG) and at three years (53 vs. 81%), primarily because of a higher incidence of repeat revascularization (29). In contrast to these findings, the AWESOME trial in patients at high risk for CABG was not able to detect a difference between PCI and CABG in diabetic patients (30). A total of 454 patients with medically refractory angina, who had one or more risk factors for an adverse outcome, were evaluated by an interventional cardiologist and a cardiac surgeon after coronary angiography and found to be acceptable candidates for either CABG or PCI. Of this group, 144 had diabetes: 79 were randomly assigned to CABG and 65 to PCI. Survival at 30 days, six months and 36 months was not significantly different with CABG or PCI. In this trial, 54% of patients received stents and 11% glycoprotein inhibitors. The use of drug-eluting stents may further improve this situation, as it is suggested by data of the ARTS II registry showing a reduced risk of revascularisation with drug-eluting stents (29,31).

Given the current use of stents, particularly drug-eluting stents, and GP IIb/IIIa inhibitors, PCI seems a reasonable first choice in patients with appropriate anatomy who do not have heart failure. In the light of the recently observed higher number of late thrombosis of drug-eluting stents, particularly if clopidogrel is not taken anymore, long-term results are needed in this respect (32).

THERAPY OF ACUTE CORONARY SYNDROMES Antiplatelet Drugs

All patients with an acute MI are given aspirin indefinitely and clopidogrel for at least nine months. Intravenous glycoprotein (GP) IIb/IIIa inhibitors are used in both ST elevation and non-ST elevation acute coronary syndromes. In a meta-analysis of six randomized trials that enrolled 6458 diabetic patients, therapy with the GP IIb/IIIa inhibitors was associated with a significant reduction in the 30-day mortality (6.2 vs. 4.6% for placebo, odds ratio 0.74) (33). A significant reduction in 30-day mortality was also seen in those undergoing a percutaneous coronary intervention (4.0 vs. 1.2%, odds ratio 0.3).

Beta Blockers

Beta blocker therapy after MI reduces the infarct size, the incidence of reinfarction, and cardiac mortality. This benefit was clearly shown in a report from the National Cooperative Cardiovascular Project, which reviewed the records of 45,308 patients 65 years of age or older, 26% of whom had diabetes (34). The multivariate analysis showed that the use of beta blockers was associated with lower one-year mortality (relative risk reduction between 13 and 27%).

ACE Inhibitors

After acute myocardial infarction, ACE inhibitors reduce infarct size, limit ventricular remodelling, and reduce mortality. ACE inhibitors may be of particular benefit in diabetic patients, as illustrated by data from the GISSI-3 trial. The GISSI-3 trial of patients with acute MI included 2790 diabetic patients, showed that six weeks of treatment with lisinopril reduced the six-month mortality among diabetics (12.9 vs. 16.1% for no lisinopril) (Fig. 2) (35).

Glycemic Control

Suboptimal glycemic control in diabetics and stress hyperglycemia in non diabetics are associated with worse in-hospital outcomes after acute MI. Intense glycemic control may be beneficial (show Fig. 3). Hence, the 2004 ACC/AHA guidelines on STEMI, which should also be applicable to non-ST elevation MI (NSTEMI), gave a Class I recommendation to the use of an insulin infusion to normalize blood glucose in patients with a complicated course (36). A Class IIa recommendation was given to the use of an insulin infusion in all MI patients with hyperglycemia.

Interventional Therapy

Immediate coronary reperfusion is recommended in all patients with an acute ST elevation MI, which is usually achieved by primary PCI. Whenever possible PCI should be attempted, as it has a lower incidence of side effects and complications compared to thrombolytic therapy. In patients with NSTEMI, coronary angiography should be performed within 48 hours as long-term outcome improves with early coronary angiography. Limited data are consistent with diabetics having a better outcome with primary PCI (37,38). This was shown in the GUSTO-IIb angioplasty substudy in which patients with an acute STEMI were randomly assigned to primary PCI or accelerated alteplase; the study included 1138 patients including 177 diabetic patients (37). Diabetics undergoing PCI, compared to those receiving thrombolysis, had the same relative reduction in the 30-day incidence of cardiovascular endpoints as the non diabetics (0.70 vs. 0.62). The value of primary PCI with stenting compared to PTCA alone was analyzed in the CADILLAC trial in which 2082 patients with acute STEMI (almost 17% diabetic) were randomly assigned to PCI alone, PCI and abciximab, stenting alone, or stenting and abciximab (39). The outcomes were significantly better with stenting and the relative benefit was similar in diabetics and non diabetics (odds ratio 0.56 and 0.52, respectively). However, at six months, the rate of the primary combined cardiovascular end-point was higher in diabetic patients (e.g., 14.1 vs. 9.7% with stenting).

FIGURE 2 Mortality curves up to 6 weeks in diabetic and nondiabetic patients treated (solid line; L) and not treated (dotted line; No L) with lisinopril.
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