REVIEW URRENT C OPINION
Early-invasive strategies for the management of coronary heart disease in chronic kidney disease: is acute kidney injury a consideration? Matthew T. James a,b and Neesh Pannu c
Purpose of review People with chronic kidney disease (CKD) are less likely to receive early-invasive management of acute coronary syndrome (ACS). The purpose of this article is to review the risks and outcomes of early-invasive versus conservative strategies, and to consider how contrast-induced acute kidney injury (CI-AKI) should factor in treatment decisions for people with CKD. Recent findings Numerous observational studies have characterized the prognostic importance of CI-AKI. However, recent studies illustrate that compared to the risk of AKI in individuals treated conservatively, the additional risk of kidney injury associated with invasive coronary procedures is relatively modest. Despite the risk of CI-AKI, early-invasive management of ACS has been associated with important long-term benefits. Summary These findings illustrate that the additional short-term risk of AKI associated with invasive management should be considered alongside long-term treatment effects on other clinical outcomes and should not act as a deterrent to their use. Strategies to increase the uptake of an invasive management approach, accompanied by the use of CI-AKI prevention strategies, could benefit high-risk individuals with CKD. Keywords cardiac catheterization, chronic kidney disease, contrast-induced acute kidney injury
INTRODUCTION Chronic kidney disease (CKD) affects more than one in ten adults and is a major public health problem, not only because of the risk of progression to endstage renal disease (ESRD), but also because it carries a high risk of cardiovascular morbidity and mortality. Importantly, more patients with CKD will die of cardiovascular disease than reach ESRD [1,2]. Improved management of cardiovascular disease therefore has the potential to significantly improve health and outcomes of people with CKD, and substantial efforts have been invested into raising awareness and promoting medical interventions to lower cardiovascular risk in CKD populations. Acute coronary syndrome (ACS), including unstable angina and non-ST elevation myocardial infarction, are common in people with CKD, who make up between 25 and 40% of patients hospitalized with non-ST elevation ACS [3,4]. The risk of both future cardiovascular events and mortality increases steeply with lower estimated glomerular filtration rate (eGFR) [5,6], and people with CKD are
much more likely to die following a cardiovascular event than those with normal kidney function, even after taking into account the additional comorbidities that are known to adversely affect survival [7,8]. Despite these risks, people with CKD are 20–50% less likely to receive invasive management, including coronary angiography or percutaneous revascularization, following an ACS [3,4]. Acute kidney injury (AKI) is common in people with CKD following invasive coronary procedures, and the fear of precipitating contrast-induced AKI (CI-AKI) may underlie the lower use of invasive procedures in people with a Department of Medicine, bDepartment of Community Health Sciences, University of Calgary, Calgary, Alberta and cDepartment of Medicine, University of Alberta, Edmonton, Alberta, Canada
Correspondence to Matthew T. James, MD, PhD, FRCPC, Room C201C, Foothills Medical Centre, 1402 29th Street, NW, Calgary, AB, Canada, T2N 2T9. Tel: +1 403 944 3960; fax: +1 403 944 2876; e-mail: [email protected] Curr Opin Nephrol Hypertens 2014, 23:283–290 DOI:10.1097/01.mnh.0000444819.03121.4b
1062-4821 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
www.co-nephrolhypertens.com
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Epidemiology and prevention
KEY POINTS Patients with CKD are often managed less invasively despite higher mortality after ACS. An underestimation of cardiovascular risk and fear of CI-AKI are thought to be barriers to the use of invasive treatment approaches in chronic kidney disease. In propensity score-matched analyses, patients who received early-invasive management were modestly more likely to have an episode of AKI than those managed conservatively; however, early-invasive management was not associated with either a significant increase in the short-term risk of dialysis or long-term risk of ESRD, but was associated with better long-term survival. Pooled results from five randomized trials illustrate nonstatistically significant reductions in death and recurrent myocardial infarction, and a significant reduction in rehospitalization in patients with CKD randomized to an early-invasive strategy, suggesting that broader use of an invasive strategy accompanied by CI-AKI prevention strategies targeted at patients with CKD might improve the outcomes of ACS.
CKD [9]. This article will review the differences in the use of invasive coronary procedures in people with and without CKD, and emphasize the recent knowledge concerning risks and outcomes of earlyinvasive versus conservative strategies for ACS in people with CKD. We focus this discussion on the implications of CI-AKI for the management of ACS in people with CKD and highlight the key areas requiring further investigation to inform decision-making for people with CKD.
USE OF INVASIVE-MANAGEMENT STRATEGIES FOR ACUTE CORONARY SYNDROME IN PEOPLE WITH CHRONIC KIDNEY DISEASE ACS can be managed invasively, with coronary angiography and percutaneous coronary intervention (PCI) to identify and open occluded vessels, or conservatively, employing medical therapies and reserving invasive procedures only for people with signs of ongoing cardiac ischemia in spite of medical management. Randomized trials in the general population have shown that early-invasive management reduces the risk of recurrent myocardial infarction, re-hospitalization, and improves long-term survival in appropriately selected high-risk individuals compared with conservative management for ACS [10–14]. Accordingly, current guidelines recommend early-invasive management for high-risk 284
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individuals with ACS [15], although observational studies suggest that not all eligible high-risk individuals receive these interventions [16,17]. A number of studies suggest a risk–treatment paradox in ACS management, in which patients with CKD are less likely to receive invasive management, even though they are among those at highest risk with the greatest potential to benefit [18]. One cohort study of elderly patients with acute myocardial infarction in the United States found that, compared with patients without CKD, those with an eGFR less than 30 ml/min/1.73 m2 were a third as likely to undergo coronary angiography, whereas patients with an eGFR 30–59 ml/min/1.73 m2 were 40% less likely to receive a coronary angiogram. Importantly, multivariable adjustment for demographic features, comorbidities, and other clinical features of presentation could not completely account for the lower use of invasive management in individuals with CKD. Similar findings were reported in a nationwide registry of ACS from Sweden, where the use of invasive management declined from 62% in those with an eGFR greater than 90 ml/min/1.73 m2 to only 15% in those with an eGFR of 15–29 ml/min/1.73 m2 (Fig. 1) [4]. Using data from three ACS registries, including 51 centers across Canada from 1999 to 2007, Wong et al. [19] observed that the use of coronary angiography in people with CKD has fallen behind other groups, driven by a 22% increase in the use of angiography among people with an eGFR greater than 60 ml/min/1.73 m2, but a corresponding increase of only 7.5% among those with an eGFR less than 30 ml/min/1.73 m2 over the same time period. There is limited information about the barriers to invasive management that underlie this treatment disparity in patients with CKD. One Canadian registry reported the most common reason cited by physicians for foregoing an invasive management strategy among people with CKD was that the patient was ‘not high risk’, provided as an explanation in 38% of cases [19]. However, Global Registry of Acute Coronary Events (GRACE) risk scores for this group were paradoxically high (median 140, interquartile range 119–163), suggesting that underrecognition of the poor prognosis of patients with CKD may be a major contributor. Overestimation of treatment-associated mortality and morbidity may also be a barrier to invasive management, driven by the concerns about precipitating CI-AKI and the downstream clinical outcomes that have been associated with this condition [9]. It has been hypothesized that these risks, and a desire to do no harm, may feature more prominently than the potential for improvement in long-term outcomes Volume 23 Number 3 May 2014
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Invasive management of coronary heart disease James and Pannu
100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0%
7%
9%
9%
29%
2%
3%
12%
12%
10%
9%
76%
76%
46%
53%
19%
21% 20%
45% 23%
18% eGFR ≥ 90
eGFR 60-89
eGFR 30-59
eGFR 15-29
eGFR
Early-invasive strategies for the management of coronary heart disease in chronic kidney disease: is acute kidney injury a consideration? Matthew T. James a,b and Neesh Pannu c
Purpose of review People with chronic kidney disease (CKD) are less likely to receive early-invasive management of acute coronary syndrome (ACS). The purpose of this article is to review the risks and outcomes of early-invasive versus conservative strategies, and to consider how contrast-induced acute kidney injury (CI-AKI) should factor in treatment decisions for people with CKD. Recent findings Numerous observational studies have characterized the prognostic importance of CI-AKI. However, recent studies illustrate that compared to the risk of AKI in individuals treated conservatively, the additional risk of kidney injury associated with invasive coronary procedures is relatively modest. Despite the risk of CI-AKI, early-invasive management of ACS has been associated with important long-term benefits. Summary These findings illustrate that the additional short-term risk of AKI associated with invasive management should be considered alongside long-term treatment effects on other clinical outcomes and should not act as a deterrent to their use. Strategies to increase the uptake of an invasive management approach, accompanied by the use of CI-AKI prevention strategies, could benefit high-risk individuals with CKD. Keywords cardiac catheterization, chronic kidney disease, contrast-induced acute kidney injury
INTRODUCTION Chronic kidney disease (CKD) affects more than one in ten adults and is a major public health problem, not only because of the risk of progression to endstage renal disease (ESRD), but also because it carries a high risk of cardiovascular morbidity and mortality. Importantly, more patients with CKD will die of cardiovascular disease than reach ESRD [1,2]. Improved management of cardiovascular disease therefore has the potential to significantly improve health and outcomes of people with CKD, and substantial efforts have been invested into raising awareness and promoting medical interventions to lower cardiovascular risk in CKD populations. Acute coronary syndrome (ACS), including unstable angina and non-ST elevation myocardial infarction, are common in people with CKD, who make up between 25 and 40% of patients hospitalized with non-ST elevation ACS [3,4]. The risk of both future cardiovascular events and mortality increases steeply with lower estimated glomerular filtration rate (eGFR) [5,6], and people with CKD are
much more likely to die following a cardiovascular event than those with normal kidney function, even after taking into account the additional comorbidities that are known to adversely affect survival [7,8]. Despite these risks, people with CKD are 20–50% less likely to receive invasive management, including coronary angiography or percutaneous revascularization, following an ACS [3,4]. Acute kidney injury (AKI) is common in people with CKD following invasive coronary procedures, and the fear of precipitating contrast-induced AKI (CI-AKI) may underlie the lower use of invasive procedures in people with a Department of Medicine, bDepartment of Community Health Sciences, University of Calgary, Calgary, Alberta and cDepartment of Medicine, University of Alberta, Edmonton, Alberta, Canada
Correspondence to Matthew T. James, MD, PhD, FRCPC, Room C201C, Foothills Medical Centre, 1402 29th Street, NW, Calgary, AB, Canada, T2N 2T9. Tel: +1 403 944 3960; fax: +1 403 944 2876; e-mail: [email protected] Curr Opin Nephrol Hypertens 2014, 23:283–290 DOI:10.1097/01.mnh.0000444819.03121.4b
1062-4821 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
www.co-nephrolhypertens.com
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Epidemiology and prevention
KEY POINTS Patients with CKD are often managed less invasively despite higher mortality after ACS. An underestimation of cardiovascular risk and fear of CI-AKI are thought to be barriers to the use of invasive treatment approaches in chronic kidney disease. In propensity score-matched analyses, patients who received early-invasive management were modestly more likely to have an episode of AKI than those managed conservatively; however, early-invasive management was not associated with either a significant increase in the short-term risk of dialysis or long-term risk of ESRD, but was associated with better long-term survival. Pooled results from five randomized trials illustrate nonstatistically significant reductions in death and recurrent myocardial infarction, and a significant reduction in rehospitalization in patients with CKD randomized to an early-invasive strategy, suggesting that broader use of an invasive strategy accompanied by CI-AKI prevention strategies targeted at patients with CKD might improve the outcomes of ACS.
CKD [9]. This article will review the differences in the use of invasive coronary procedures in people with and without CKD, and emphasize the recent knowledge concerning risks and outcomes of earlyinvasive versus conservative strategies for ACS in people with CKD. We focus this discussion on the implications of CI-AKI for the management of ACS in people with CKD and highlight the key areas requiring further investigation to inform decision-making for people with CKD.
USE OF INVASIVE-MANAGEMENT STRATEGIES FOR ACUTE CORONARY SYNDROME IN PEOPLE WITH CHRONIC KIDNEY DISEASE ACS can be managed invasively, with coronary angiography and percutaneous coronary intervention (PCI) to identify and open occluded vessels, or conservatively, employing medical therapies and reserving invasive procedures only for people with signs of ongoing cardiac ischemia in spite of medical management. Randomized trials in the general population have shown that early-invasive management reduces the risk of recurrent myocardial infarction, re-hospitalization, and improves long-term survival in appropriately selected high-risk individuals compared with conservative management for ACS [10–14]. Accordingly, current guidelines recommend early-invasive management for high-risk 284
www.co-nephrolhypertens.com
individuals with ACS [15], although observational studies suggest that not all eligible high-risk individuals receive these interventions [16,17]. A number of studies suggest a risk–treatment paradox in ACS management, in which patients with CKD are less likely to receive invasive management, even though they are among those at highest risk with the greatest potential to benefit [18]. One cohort study of elderly patients with acute myocardial infarction in the United States found that, compared with patients without CKD, those with an eGFR less than 30 ml/min/1.73 m2 were a third as likely to undergo coronary angiography, whereas patients with an eGFR 30–59 ml/min/1.73 m2 were 40% less likely to receive a coronary angiogram. Importantly, multivariable adjustment for demographic features, comorbidities, and other clinical features of presentation could not completely account for the lower use of invasive management in individuals with CKD. Similar findings were reported in a nationwide registry of ACS from Sweden, where the use of invasive management declined from 62% in those with an eGFR greater than 90 ml/min/1.73 m2 to only 15% in those with an eGFR of 15–29 ml/min/1.73 m2 (Fig. 1) [4]. Using data from three ACS registries, including 51 centers across Canada from 1999 to 2007, Wong et al. [19] observed that the use of coronary angiography in people with CKD has fallen behind other groups, driven by a 22% increase in the use of angiography among people with an eGFR greater than 60 ml/min/1.73 m2, but a corresponding increase of only 7.5% among those with an eGFR less than 30 ml/min/1.73 m2 over the same time period. There is limited information about the barriers to invasive management that underlie this treatment disparity in patients with CKD. One Canadian registry reported the most common reason cited by physicians for foregoing an invasive management strategy among people with CKD was that the patient was ‘not high risk’, provided as an explanation in 38% of cases [19]. However, Global Registry of Acute Coronary Events (GRACE) risk scores for this group were paradoxically high (median 140, interquartile range 119–163), suggesting that underrecognition of the poor prognosis of patients with CKD may be a major contributor. Overestimation of treatment-associated mortality and morbidity may also be a barrier to invasive management, driven by the concerns about precipitating CI-AKI and the downstream clinical outcomes that have been associated with this condition [9]. It has been hypothesized that these risks, and a desire to do no harm, may feature more prominently than the potential for improvement in long-term outcomes Volume 23 Number 3 May 2014
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Invasive management of coronary heart disease James and Pannu
100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0%
7%
9%
9%
29%
2%
3%
12%
12%
10%
9%
76%
76%
46%
53%
19%
21% 20%
45% 23%
18% eGFR ≥ 90
eGFR 60-89
eGFR 30-59
eGFR 15-29
eGFR
