Clinical Outcome of Patients with Diabetes Mellitus and Chronic Total Occlusion Treated with Drug-Eluting Stents

ABSTRACT: Objectives. The prognosis of patients with chronic total occlusion (CTO) and diabetes mellitus treated with percutaneous coronary intervention (PCI) and drug-eluting stent (DES) implantation is unknown. Methods. We compared the 12-month outcomes of 52 diabetic patients with CTO after successful PCI who underwent DES implantation with that of 47 patients with diabetes and CTO previously treated with bare-metal stents (BMS). Death, myocardial infarction and repeat PCI or coronary artery bypass surgery were considered as a combined primary endpoint. Results. At 1-year follow up, the primary endpoint occurred in 6% (n = 3) of patients treated with DES and 23% (n = 11) of the patients treated with BMS (p = 0.01). One patient in the DES group and 3 patients in the BMS group died during follow up (p = 0.26). Stepwise logistic regression analysis identified DES (odds ratio [OR] = 12.9, 95% confidence interval [CI] 2.90–57.5; p = 0.0004) and final minimal lumen diameter (odds ratio [OR] = 10.1, 95% CI 1.81–56.4; p = 0.01) as independent correlates of major adverse cardiac events (MACE) at follow up. Conclusions. In patients with chronic total occlusion, DES were superior to bare-metal stents in reducing the MACE and should be considered a preferred treatment strategy for patients with diabetes and CTO undergoing PCI. J INVASIVE CARDIOL 2008;20:651–654 Percutaneous coronary intervention (PCI) is an important strategy to treat chronic coronary total occlusion (CTO). Patients with successful recanalization of CTO with PCI have a better clinical outcome and improved left ventricular function compared with patients in whom the attempt to successfully recanalize CTO has failed.1­–4 Although the high restenosis rate has limited the benefits of PCI with plain-old balloon angioplasty, the implantation of bare-metal stents (BMS) has contributed to lower repeat target lesion revascularization (TLR). The recent introduction of sirolimus- and paclitaxel-eluting stents has resulted in an important reduction of restenosis in patients with CTO compared to BMS,5–8 with durable benefits.9 Diabetes mellitus represents a risk factor for a worse outcome after PCI. Since diabetic patients show a two-fold increase in the coronary occlusion rate compared to non-diabetics,10 patients with diabetes are frequently found among patients with CTO, and the number of patients with both diabetes and CTO is increasing.11 Although drug-eluting stents (DES) appear to be effective in reducing restenosis in patients with diabetes mellitus12 in comparison to BMS,13 there are no data available for the high-risk cohort of patients with both diabetes mellitus and CTO. The present study aimed to evaluate the clinical outcomes of successful recanalization of CTO with DES implantation compared with BMS in diabetic patients. Methods Study population. The study population consisted of 99 consecutive diabetic patients with CTO and evidence of related myocardial ischemia or viability who underwent successful revascularization with implantation of DES or BMS in lesions located in native coronary vessels. Diabetic patients with CTO of the left main coronary artery or occlusion of a previously stented coronary artery were not included in the study. The DES group included 52 consecutive patients with CTO who received sirolimus- or paclitaxel-eluting stents between December 2002 and December 2005. The BMS group included 47 consecutive diabetic patients with CTO who received BMS in the 3 years before the introduction of DES at our hospital. There was no temporal overlap in the two groups with regard to stent placement. The study was conducted in a large-volume laboratory where more than 1000 PCIs are performed each year during both BMS and DES time frames. Procedures were performed by 3 skilled physicians, each performing with a minimum of 50 CTO cases per year. Diabetes was considered to be present if patients were receiving a prescribed treatment (insulin or an oral hypoglycemic drug) before coronary angioplasty or on the basis of elevated levels (> 140 mg/dl) of fasting and non-stressed blood glucose on at least two separate occasions during the hospital stay corresponding to the procedure. Angiographic analysis. A CTO was defined as a complete obstruction of the vessel with thrombolysis in myocardial infarction (TIMI) flow grade 0 and an estimated duration of > 3 months. The age of the occlusion was determined by the interval from the last episode of acute coronary syndrome or myocardial infarction (MI) consistent with the location of the occlusion. A successful PCI was defined as final TIMI flow grade ≥ 2 and a residual stenosis Results Study population. Baseline characteristics are shown in Table 1. The mean age was 67.7 ± 9.4 years (range 42–85 years); 76 patients were males. A diagnosis of previous MI had been made in 68 patients, while 12 had undergone previous revascularization. Among patients with diabetes mellitus, 17 had insulin-requiring diabetes. Angiographic and procedural variables. Angiographic and procedural variables are shown in Table 2. Target vessel revascularization was represented by the left anterior descending coronary artery (LAD) in 59 patients, the circumflex artery (Cx) in 16, and the right coronary artery (RCA) in 24. Forty-five patients had single-vessel disease, while 54 had multi-vessel disease. One vessel was treated in 56 patients, 2 vessels were treated in 36 patients and 3 vessels were treated in 7 patients. Glycoprotein IIb/IIIa inhibitors were used in 26 cases. Patients treated with DES (38 patients with sirolimus- and 14 patients with paclitaxel-eluting stents) had a statistically significant longer lesion length, longer stented length and a greater number of stents implanted than the BMS group. Clinical follow up. Clinical events are described in Table 3. All patients had an uneventful hospital stay. At 1-year follow up (100% of patients), 3 events occurred in 3 (6%) patients treated who received DES, and 12 events in 11 (23%) of the patients treated with BMS (p = 0.01). One patient in the DES group and 3 patients in the BMS group died from a cardiac etiology during follow up (p = 0.26). One patient in each group suffered a MI, after which the patient in the BMS group underwent coronary bypass surgery. Two patients treated with DES and 6 with BMS underwent TLR. The following variables entered into the logistic regression model: DES, age, sex previous bypass, previous angioplasty, diabetes, hypercholesterolemia, ejection fraction, target vessel, treated segment, number of diseased vessels, number of treated vessels, glycoprotein IIb/IIIa inhibitors, lesion length, stent length, number of stents per lesion, reference vessel diameter, final minimal lumen diameter, and residual stenosis. A stepwise logistic regression model identified the DES (odds ratio [OR] = 12.9, 95% confidence interval [CI] 2.90–57.5; p = 0.0004) and the final minimal lumen diameter (odds ratio [OR] = 10.1, 95% CI 1.81–56.4; p = 0.01) as independent correlates of the primary endpoint (Figure 1). Discussion Randomized trials and retrospective analyses demonstrated the effectiveness of DES in diabetic patients.13,14 These studies, however, included lesions at low risk for restenosis or reocclusion. Patients with CTO represent a very high-risk group. Balloon angioplasty of CTOs is characterized by frequent acute vessel reocclusion and high rates of restenosis. Although stent implantation has almost abolished the occurrence of abrupt vessel closure, its impact on restenosis reduction has been less pronounced.3,4 Recently, both sirolimus- and paclitaxel-eluting stents have been shown to be safe and effective and have markedly reduced the incidence of restenosis and the need for TLR in patients with CTO.5–9 However, the efficacy and safety of DES in patients with CTO and diabetes have never been assessed. We compared the clinical outcomes of 52 diabetic patients with CTO after successful PCI with DES implantation to that of 47 patients with diabetes and CTO previously treated with BMS during a follow-up period of 12 months. The results of the present study show that the incidence of MACE is markedly reduced among patients with diabetes mellitus and CTO treated with DES compared to BMS. Although patients treated with DES had less favorable characteristics, including longer occlusions and stented lengths — traditionally recognized as predictors of an increased risk of restenosis — the use of DES was associated with significantly better outcomes than was the case for patients with BMS. The difference in MACE between the groups was statistically significant only during the first 6 months, but the benefits were maintained at 1-year follow up. This finding seems to confirm that the beneficial effects of DES are achieved through a reduction of restenosis and target vessel revascularization,5–9 even in the subgroup of patients with diabetes and CTO. Our results are in agreement with recent findings which show the superiority of DES over BMS in patients with CTO7–9 or diabetes.12,13 In addition, our findings suggest that DES may extend their benefits to patients with diabetes and CTO considered to be a very high-risk subset for restenosis. At multivariate analysis, we found that, apart from DES, final minimal lumen diameter was also an independent correlate of MACE. This finding has been previously described in patients with CTO treated with BMS.15,16 It is interesting to note that the number of MACE in the DES group is low when the final minimal lumen diameter is > 2 mm; patients with BMS experience a low number of events when the final minimal lumen diameter is > 3 mm (Figure 1). This finding seems to suggest that: a) one must try to obtain the best minimal lumen diameter after stent deployment; b) DES should be preferred when the expected final minimal lumen diameter is small. Study limitations. Our report presents some limitations. First, the study was not randomized: operator selection and inclusion criteria may have influenced the final results. Secondly, follow-up angiography was not routinely performed, and only patients with evidence of spontaneous inducible ischemia underwent repeat coronary angiography. Moreover, the sample size was relatively small. Finally, the duration of clopidogrel prescription was different between the two study groups; it cannot be excluded that this difference may have contributed to the reduction of major cardiovascular adverse events observed in the DES group. Despite these limitations, our study describes a real-world cohort of patients who had never been analyzed before. Conclusion In conclusion, DES implantation should be considered a preferred treatment strategy for patients with diabetes and CTO undergoing PCI. Efforts should be made to obtain the largest final minimal lumen diameters after stent deployment in this subgroup of patients.

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