End-Stage Renal Disease and Drug-Eluting Stents: One Small Step Forward?

Cardiovascular disease is the main cause of death at all stages of chronic renal failure and end-stage renal disease on hemodialysis (ESRD) in adults; it accounts for almost 50% of the mortality of these patients, with an annual mortality rate of 18–20%.^1–6 Although atherosclerosis seems to be accelerated in these patients, it does not seem to be secondary to the dialysis itself. Half of all dialysis patients have evidence of coronary artery disease before the initiation of hemodialysis.^10–12 The high prevalence of coronary artery disease in these patients has not been completely elucidated, but seems to be related to multiple concomitant risk factors, such as hypertension and diabetes, high levels of triglycerides and homocysteine and low levels of high-density lipoproteins. Invasive management of coronary artery disease has been routinely performed in these patients in an attempt to reduce the likelihood of subsequent cardiac events. Previous studies in a limited number of patients have examined the outcomes of patients with ESRD who undergo coronary artery bypass graft surgery. These studies demonstrated that although bypass surgery is feasible, the overall risks of morbidity and mortality exceeded by far those of patients without renal dysfunction.^7–9 Even a mild degree of renal insufficiency is associated with significantly higher in-hospital mortality rates. Percutaneous coronary intervention has shown disappointing results, even in patients with mild renal insufficiency. In-hospital and long-term morbidity and mortality after percutaneous coronary revascularization with stents is increased when compared to patients with normal renal function.¹³ Despite an initially successful procedure, these patients have a higher incidence of periprocedural complications (vascular and bleeding complications and increased all-cause and cardiac-related mortality rates). The 1-year survival is also less favorable in these patients, with increased myocardial infarction and overall mortality rates.¹³ Unfortunately, neither bypass surgery nor percutaneous coronary intervention has significantly improved the long-term outcomes of patients with ESRD, as 1-year mortality rates are not much below 50%.^13,14 Furthermore, high rates of repeat revascularization procedures following balloon angioplasty have been a source of continuous concern in this fragile population. Restenosis in dialysis patients can be explained by various factors, such as a greater degree of diffuse disease, coronary calcification, prothrombotic state with increased fibrin and platelet deposition, and a higher prevalence of diabetes mellitus. The introduction of stents has shown conflicting results regarding the beneficial effect on restenosis rates or mortality rates in this patient population. Drug-eluting stents (DES) have markedly reduced the incidence of restenosis and therefore of target lesion revascularization procedures. However, the majority of the studies that assessed the performance of these stents usually excluded patients with impaired renal function because of the aforementioned reasons. In this issue of the Journal, the authors¹⁵ report the results of a prospective analysis of 89 end-stage renal disease patients who underwent coronary artery stenting, 24 with a DES and 65 with a bare-metal stent (BMS). The primary endpoint of the study was target vessel revascularization at 9 months and the secondary endpoint was the combined endpoint of death, myocardial infarction or target vessel revascularization. Although both groups were similar regarding baseline clinical characteristics, patients treated with DES were given a longer stent (20.4 ± 4.4 mm vs. 17.3 ± 4.2 mm; p = 0.006) of smaller diameter (2.9 ± 0.4 mm vs. 3.1 ± 0.5 mm; p = 0.008), both strong independent predictors of restenosis, and therefore of repeat revascularization procedures in BMS. Target vessel revascularization rates at 9-month follow up were significantly lower in patients treated with DES, only 4% compared to 26% in patients treated with a BMS. Although the secondary combined endpoint was also significantly lower in patients treated with a DES, it was driven by high rates of repeat revascularization procedures, as mortality and myocardial infarction rates were similar in both groups. The authors understood that the main limitations of the study were the lack of randomization, the small number of patients and the duration of clopidogrel therapy, and concluded that DES are effective in reducing the incidence of target vessel revascularization in ESRD patients. Data on the impact of DES in ESRD patients are very scant. A recent manuscript by Lemos and colleagues¹⁶ described the outcomes of patients with impaired renal function (creatinine clearance 50 ml/minute) treated with either BMS or DES. In this study there was a significant reduction in the need for target vessel revascularization in those patients treated with DES (Figure 1). Although these patients were not on dialysis replacement therapy, it provides us with a reference for the possible beneficial effects of DES in patients with impaired renal function. Given the results of the present study,¹⁵ what have we learned? First, as in patients with normal renal function, DES have decreased the risk of repeat revascularization procedures compared to BMS in ESRD patients. Second, despite the clear impact of DES on repeat revascularization procedures, they did not have a significant effect on mortality or myocardial infarction in this patient population. Third, we are still missing critical data on the best treatment for patients with impaired renal function, as these patients are systematically excluded from major clinical trials. Although DES may not change the grim prognosis of ESRD patients with overt coronary artery disease, they obviously ameliorate their suffering by avoiding needless repeat revascularization procedures. Unfortunately, these patients also seem to be at a higher risk for late stent thrombosis, especially after undergoing DES implantation. Nonetheless, the lack of data prevents one to reach any conclusions on this issue which must be resolved in larger, well-controlled clinical trials.

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