Fig. 19.1
Impact of renal impairment on cardiovascular outcomes
Patients with CKD are predisposed towards more complex CAD, with a higher prevalence of multivessel disease, proximal or left main disease and heavy calcification [14, 15]. In addition, renal failure compromises oxygen supply to the myocardium through processes such as anemia, metabolic imbalance and microvascular disease leading to depressed coronary reserve [16].
The oxidative and metabolic processes associated with dialysis, which include renal anemia, uremia, cytokine excess, endothelial dysfunction and accumulation of pro-inflammatory products, render the vasculature more vulnerable to accelerated atherosclerosis [12, 13, 17]. Indeed, it is estimated that approximately 40 % of all patients on dialysis suffer CAD, with a recent case series reporting that over 60 % of non-selected dialysis patients had CAD with >75 % stenosis, and an average of 3.3 lesions per patient [18–20]. A significant proportion of patients who start on dialysis already have an extensive risk factor profile for CAD, with large numbers of patients suffering diabetes, dyslipidemia, hypertension and left ventricular dysfunction prior to initiation of therapy [7]. As a result, there is a high rate of de novo CVD development in patients on dialysis, and the co-existence of risk factors also confounds the hazard of poor outcomes following revascularization [21]. Exposure to the dialysis membrane increases the already heightened platelet reactivity seen in patients with severe renal impairment, as well as inflammation and corresponding thrombotic biomarkers [22–24]. Paradoxically, however, platelet reactivity is reduced at the end of dialysis and hemostatic changes are partially corrected for with the reduction of uremic toxins [25].
The risk of myocardial infarction (MI) in patients on dialysis is five-fold higher than that of the general population, and the 1-year mortality rate post-MI approaches 60 % in patients with ESRD [26]. These statistics are compounded by the high rates of silent myocardial infarction in patients with dialysis [27–29]. Symptoms of MI, such as dyspnea and angina, may be mistaken as a manifestation of fluid overload, which is a common complication of dialysis, leading to delayed diagnosis and misidentification or repeat ischemic symptoms. Detection is further complicated by the reduced sensitivity of the ECG for detecting ischemia in patients with ESRD due to a high prevalence of baseline ST-changes and left ventricular hypertrophy [30].
Percutaneous Coronary Intervention Verses Coronary Artery Bypass Grafting
The National Kidney Foundation guidelines indicate that percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) are both viable options for the treatment of obstructive CAD in severe renal impairment, but that CABG should be preferred in the management of triple vessel and left main disease [31]. However, these recommendations are only a Class C level of evidence as they stem from post-hoc observation studies and/or consensus opinion. As in patients without ESRD, the ACCF/AHA/SCAI guidelines indicate that patients with complex multivessel disease or severe disease involving the left main segment should be risk stratified according to the SYNTAX score to determine optimal mode of revascularization [32, 33]. Given these pathologies are more common in ESRD, it is logical that these patients have better survival when undergoing CABG, which has been demonstrated to confer a lower risk of long-term mortality [34].
The Arterial Revascularization Therapies Study (ARTS) trial randomized patients with CKD, defined as creatinine clearance ≤60 mL/min, and multivessel disease to either PCI or CABG. Although survival outcomes at 3 years were similar between patient groups, CABG was associated with a significant reduction in the need for repeat revascularization [35]. However, it is important to note that PCI techniques utilized in ARTS do not reflect contemporary methods and therefore these findings may not be generalizable to contemporary management of PCI patients. Significantly, the risk of poor outcomes conferred by even a mild reduction in renal function persisted at 3 years after intervention. Currently, there is no randomized data on patients with severe renal impairment, but several observational trials have indicated that the long-term benefit of CABG becomes increasingly apparent with greater reductions in renal function [36–40].
PCI and advanced renal disease
The consensus of several meta-analyses comparing invasive management of CAD in patients with severe renal disease has been that PCI is associated with better short-term survival, but confers a higher risk of myocardial infarction, repeat revascularization and long-term mortality compared to CABG. Table 19.1 summarizes the major comparisons between the methods.
Table 19.1
Direct comparison between PCI and CABG for patients with severe renal impairment
PCI | CABG | |
|---|---|---|
Short–term mortality | Worse | |
Repeat revascularization | Worse | |
Re–infarction | Worse | |
Long–term mortality | Worse | |
Triple–vessel disease | Worse | Better [43] |
Diabetics | Worse | |
Length of hospitalization | Shorter | |
Stroke rate | Higher |
Mortality and Ischemic Events
Studies have concluded that PCI is associated with superior short term survival, effectively halving the 30-day mortality rate of CABG [34, 41, 42]. However, this risk reverses at 1-year, with CABG patients experiencing substantially lower long-term mortality rates than those receiving PCI. The survival and adverse event benefit derived from CABG over PCI appears most marked in patients with ESRD [42], and long term mortality rates continue to be superior to 8-year follow-up [38]. It is worth remembering that patients have a poor 1-year survival rate regardless of revascularization strategy, and so choice should be individualized, based on a patient’s individual prognosis and baseline profile, as well as operator experience [41]. As well as conferring better long-term survival rates, CABG is associated with an increased duration of vessel patency, with significantly lower rates of repeat revascularization, MI and composite ischemic events [34, 42, 49].
Acute Coronary Syndromes
Among patients with severe renal impairment, mortality following acute myocardial infarction is 16–19 fold higher than that of the general population, approaching 70 % at 1 year following the index event [50, 51]. Both the National Kidney Foundation and European Society of Cardiology guidelines indicate that treatment for dialyzed and ESRD patients should be the same as those without renal impairment, which extends to the use of all drugs and interventional procedures [31, 52]. Emergent PCI is preferred over the use of thrombolysis in patients with STEMI, and care should be given to dose adjustment of drugs with altered clearance in kidney failure [31].
The efficacy of early invasive strategy in patients with severe renal impairment presenting with NSTEACS remains controversial. There is substantial bias presiding over the treatment of this patient group, who are more likely to be treated medically rather than invasively, or undergo revascularization with much greater delay [53]. The current ACC/AHA guidelines for NSTEACS do not specifically define a management protocol for patients with severe renal impairment, but indicate that patients deemed high risk, which generally includes this subset, should undergo an early invasive strategy (Class I) [54].
Several observational trials have attempted to define the role of invasive strategy in NSTEACS with conflicting results. Both the TACTICS-TIMI 18 and SWEDEHEART trials found a reduction in rates of adverse events at 6 months and 1 year, respectively, with an early invasive strategy in patients with mild-moderate renal impairment [55]. However, SWEDEHEART identified that as renal function declined, the survival benefit diminished, and as such patients with ESRD and dialysis derived no benefit from an early invasive strategy [53]. Recently, an analysis pooling data from the FRISC II [56] and ICTUS [57] studies indicated that there was a significant reduction in 5-year rates of cardiac death and MI in patients with moderate-severe renal impairment who underwent early invasive strategy for NSTEACS [58]. However, this subgroup included patients with eGFR <60 and did not conduct a separate analysis on those with ESRD or on dialysis. The risk of stroke and bleeding increases as renal function worsens [59, 60], which is further increased with interventional management. Potentially, the greater bleeding risk coupled with a more modest benefit in ischemic event reduction might favor a more conservative approach in otherwise stable NSTE-ACS patients with advanced renal disease.
The use of early coronary angiography in patients with severe renal function is also an area of contention, as there is an increased risk of cholesterol embolism and AKI in patients with marked reductions in renal function [61]. In patients with more severe (Stage 4–5) renal disease, 1-year mortality is reduced with angiography, but the risk of recurrent MI is higher. Thus, if delaying PCI is feasible, it is recommended to reduce the risk of contrast induced nephropathy [62].
Factors Complicating an Invasive Strategy in Advanced Renal Disease
Percutaneous Coronary Intervention
Studies have demonstrated that there is a dose-dependent increase in peri- and post-procedural cardiac death and ischemic complications with decreasing renal function in patients undergoing PCI [63]. Indeed, in patients with ESRD, PCI may have no benefit over medical management [64]. Factors responsible for complicating PCI in this patient subset are summarized in Table 19.2. Dialysis is an independent predictor of target lesion revascularization, which is driven by the high rates of in-stent restenosis [65–67]. Furthermore, in-stent restenosis is more likely to result in fatality as silent myocardial ischemia is frequent in patients undergoing dialysis in whom fluid overload in common and may mask a timely diagnosis. As a result, some physicians advocate the routine assessment for stent patency using dobutamine stress echocardiography [31, 68]. This modality is preferred as it does not require physical exertion and the sensitivity is not compromised by the presence of left ventricular hypertrophy, which is a limitation of EKG-based assessment in patients with ESRD.
Table 19.2
Factors complicating PCI in ESRD
Factors complicating PCI in ESRD |
|---|
Co-morbidities e.g. diabetes, hypertension [69] |
Increased rates of restenosis due to [70]: |
Accelerated atherosclerosis |
Poor responsiveness to statin therapy, clopidogrel |
Inflammatory processes [71] |
Stent hypo-expansion due to calcification [71] |
Increased bleeding risk, limiting duration of dual antiplatelet therapy |
Peripheral vascular disease complicating access |
Problems with stent delivery due to heavy calcification |
Increased need for rotablation [66] |
Silent ischemia delaying detection of restenosis |
Reduced efficacy of drug eluting stents |
Additional modifications to the PCI procedure must be taken into consideration for ESRD patients. A transradial approach, although shown to reduce bleeding risk, may be contraindicated in patients with ESRD due to the need to preserve the radial artery for the possibility of creating an arteriovenous fistula in the future. Low dose iso-osmolar contrast (such as iodixanol), at a minimum dose, is recommended [31, 32].
A major limitation of PCI is the need for repeat revascularization, which has been partially addressed by the newer generation drug eluting stents (DES). DES have reduced the rates of restenosis and target lesion revascularization in patients on dialysis, but this does not translate to the survival benefit seen in those with normal renal function [67, 73]. Patients on dialysis receiving DES have higher rates of TLR and stent thrombosis than those not on dialysis [74]. A recent analysis comparing stenting with DES to CABG found that in-hospital mortality was lower with DES but the chance of repeat revascularization was still higher [8], indicating that the clinical results still favor CABG [75].
Patients on dialysis are at an increased risk of bleeding and so consideration needs to be made with regards to dual antiplatelet therapy (DAPT) selection and duration [76]. Guidelines indicate that DAPT should be continued for a minimum 12 months but the duration may be reduced under physician guidance if the patient experiences bleeding complications. This additive risk of bleeding may render CABG more attractive for some patients. In addition, anticoagulation medications with complete or substantial renal elimination need to be used with care during PCI, either through down-titration or complete contra-indication. Such medications include low molecular weight heparin, bivalirudin, and small molecule glycoprotein IIb/IIIa inhibitors tirofiban and eptifabtide [52]. Despite this, a recent study indicated that the use of contraindicated antithrombotic agents in patients with severe renal impairment remains unacceptably high [77]. The use of these medications was associated with an increased risk of in-hospital major bleeding in a propensity-matched analysis. Renal insufficiency was found to be an independent predictor of excess dosing of glycoprotein IIb/IIIa inhibitors and unfractionated heparin, which may also contribute to the increased bleeding risk seen in PCI [78].
Coronary Artery Bypass Grafting
The majority of evidence suggests that CABG confers better long-term survival and lower ischemic adverse event rates than PCI in patients with ESRD. However, the procedural complexity and adverse outcomes of CABG are increased significantly in the presence of ESRD.
The short-term mortality of CABG in dialysis patients is higher than the general population [79], as are the rates of stroke, bleeding, and peri-procedural complications [79]. However, the use of the internal mammary artery as the bypass conduit has improved mortality rates markedly in this patient subset [47]. There is a short-term benefit in dialysis patients undergoing off-pump vs. on-pump CABG, but this requires further verification [80–82]. In addition, a greater survival advantage is noted in patients with triple vessel disease, which is a common feature of patients with ESRD and CAD [8, 82]. Factors complicating CABG in ESRD patients are summarized in Table 19.3. Patients undergoing CABG on dialysis have a higher risk of systemic infection, longer duration of surgery, greater need for mechanical ventilation, increased duration of cardiopulmonary bypass and greater need for balloon pump [47, 83, 84].
Table 19.3
Factors complicating CABG in ESRD
Factors complicating CABG in ESRD |
|---|
Co-morbidities e.g. diabetes, hypertension [69] |
Left ventricular hypertrophy and conduction abnormalities [85] |
Fluid and electrolyte disturbances [86] |
Increased medial vascular calcification complicating anastomoses [87] and surgical manipulation of the aorta |
Increased O2 demands from renal anemia, AV fistula |
Decreased patency of vein grafts [88] |
Altered platelet activity |
Complex coronary anatomy: severe distal disease [89], multivessel disease, calcified lesion < div class='tao-gold-member'>
Only gold members can continue reading. Log In or Register to continue
 Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
Get Clinical Tree app for offline access
|