Antiplatelet agents for chronic kidney disease.

BACKGROUND: Antiplatelet agents are widely used to prevent cardiovascular events. The risks and benefits of antiplatelet agents may be different in people with chronic kidney disease (CKD) for whom occlusive atherosclerotic events are less prevalent, and bleeding hazards might be increased. This is an update of a review first published in 2013. OBJECTIVES: To evaluate the benefits and harms of antiplatelet agents in people with any form of CKD, including those with CKD not receiving renal replacement therapy, patients receiving any form of dialysis, and kidney transplant recipients. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 13 July 2021 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We selected randomised controlled trials of any antiplatelet agents versus placebo or no treatment, or direct head-to-head antiplatelet agent studies in people with CKD. Studies were included if they enrolled participants with CKD, or included people in broader at-risk populations in which data for subgroups with CKD could be disaggregated. DATA COLLECTION AND ANALYSIS: Four authors independently extracted data from primary study reports and any available supplementary information for study population, interventions, outcomes, and risks of bias. Risk ratios (RR) and 95% confidence intervals (CI) were calculated from numbers of events and numbers of participants at risk which were extracted from each included study. The reported RRs were extracted where crude event rates were not provided. Data were pooled using the random-effects model. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: We included 113 studies, enrolling 51,959 participants; 90 studies (40,597 CKD participants) compared an antiplatelet agent with placebo or no treatment, and 29 studies (11,805 CKD participants) directly compared one antiplatelet agent with another. Fifty-six new studies were added to this 2021 update. Seven studies originally excluded from the 2013 review were included, although they had a follow-up lower than two months. Random sequence generation and allocation concealment were at low risk of bias in 16 and 22 studies, respectively. Sixty-four studies reported low-risk methods for blinding of participants and investigators; outcome assessment was blinded in 41 studies. Forty-one studies were at low risk of attrition bias, 50 studies were at low risk of selective reporting bias, and 57 studies were at low risk of other potential sources of bias. Compared to placebo or no treatment, antiplatelet agents probably reduces myocardial infarction (18 studies, 15,289 participants: RR 0.88, 95% CI 0.79 to 0.99, I² = 0%; moderate certainty). Antiplatelet agents has uncertain effects on fatal or nonfatal stroke (12 studies, 10.382 participants: RR 1.01, 95% CI 0.64 to 1.59, I² = 37%; very low certainty) and may have little or no effect on death from any cause (35 studies, 18,241 participants: RR 0.94, 95 % CI 0.84 to 1.06, I² = 14%; low certainty). Antiplatelet therapy probably increases major bleeding in people with CKD and those treated with haemodialysis (HD) (29 studies, 16,194 participants: RR 1.35, 95% CI 1.10 to 1.65, I² = 12%; moderate certainty). In addition, antiplatelet therapy may increase minor bleeding in people with CKD and those treated with HD (21 studies, 13,218 participants: RR 1.55, 95% CI 1.27 to 1.90, I² = 58%; low certainty). Antiplatelet treatment may reduce early dialysis vascular access thrombosis (8 studies, 1525 participants) RR 0.52, 95% CI 0.38 to 0.70; low certainty). Antiplatelet agents may reduce doubling of serum creatinine in CKD (3 studies, 217 participants: RR 0.39, 95% CI 0.17 to 0.86, I² = 8%; low certainty). The treatment effects of antiplatelet agents on stroke, cardiovascular death, kidney failure, kidney transplant graft loss, transplant rejection, creatinine clearance, proteinuria, dialysis access failure, loss of primary unassisted patency, failure to attain suitability for dialysis, need of intervention and cardiovascular hospitalisation were uncertain. Limited data were available for direct head-to-head comparisons of antiplatelet drugs, including prasugrel, ticagrelor, different doses of clopidogrel, abciximab, defibrotide, sarpogrelate and beraprost. AUTHORS' CONCLUSIONS: Antiplatelet agents probably reduced myocardial infarction and increased major bleeding, but do not appear to reduce all-cause and cardiovascular death among people with CKD and those treated with dialysis. The treatment effects of antiplatelet agents compared with each other are uncertain.

Antiplatelet agents for chronic kidney disease.

BACKGROUND: Antiplatelet agents are widely used to prevent cardiovascular events. The risks and benefits of antiplatelet treatment may be different in people with chronic kidney disease (CKD) for whom occlusive atherosclerotic events are less prevalent, and bleeding hazards might be increased. OBJECTIVES: To summarise the effects of antiplatelet treatment (antiplatelet agent versus control or other antiplatelet agent) for the prevention of cardiovascular and adverse kidney outcomes in individuals with CKD. SEARCH METHODS: In January 2011 we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Cochrane Renal Group's Specialised Register without language restriction. SELECTION CRITERIA: We selected randomised controlled trials of any antiplatelet treatment versus placebo or no treatment, or direct head-to-head antiplatelet agent studies in people with CKD. Studies were included if they enrolled participants with CKD, or included people in broader at-risk populations in which data for subgroups with CKD could be disaggregated. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data from primary study reports and any available supplementary information for study population, interventions, outcomes, and risks of bias. Risk ratios (RR) and 95% confidence intervals (CI) were calculated from numbers of events and numbers of participants at risk which were extracted from each included study. The reported RRs were extracted where crude event rates were not provided. Data was pooled using the random-effects model. MAIN RESULTS: We included 50 studies, enrolling 27,139 participants; 44 studies (21,460 participants) compared an antiplatelet agent with placebo or no treatment, and six studies (5679 participants) directly compared one antiplatelet agent with another. Compared to placebo or no treatment, antiplatelet agents reduced the risk of myocardial infarction (17 studies; RR 0.87, 95% CI 0.76 to 0.99), but not all-cause mortality (30 studies; RR 0.93, 95% CI 0.81 to 1.06), cardiovascular mortality (19 studies; RR 0.89, 95% CI 0.70 to 1.12) or stroke (11 studies; RR 1.00, 95% CI 0.58 to 1.72). Antiplatelet agents increased the risk of major (27 studies; RR 1.33, 95% CI 1.10 to 1.65) and minor bleeding (18 studies; RR 1.49, 95% CI 1.12 to 1.97). In terms of dialysis access outcomes, antiplatelet agents reduced access thrombosis or patency failure but had no effect on suitability for dialysis. Meta-regression analysis indicated no differences in the relative benefit or harms of treatment (risk of all-cause mortality, myocardial infarction, or major bleeding) by type of antiplatelet agent or stage of CKD. Limited data were available for direct head-to-head comparisons of antiplatelet drugs, treatment in kidney transplant recipients, primary prevention, or risk of ESKD. AUTHORS' CONCLUSIONS: Antiplatelet agents reduce myocardial infarction but increase major bleeding. Risks may outweigh harms among people with low annual risks of cardiovascular events, including those with early stages of CKD who do not have clinically-evident occlusive cardiovascular disease.

Effect of a vascular access surveillance program on service provision and access thrombosis.

Establishing and maintaining hemodialysis access are major challenges in dialysis patient care. The impact of implementing guideline recommendations around vascular access surveillance, which lacks strong evidence, is poorly understood. We report the results of a vascular access surveillance and early intervention program upon hemodialysis thrombosis rates for all patients hemodialyzing in a single center between January 2005 and March 2011. Data were derived from hospital records and the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA). Data were collected of 227 prevalent patients over the 6-year period. Crude ultrasound and angiography intervention rates increased from 23 and 57 per 100 prevalent patients per quarter (/100 pts/qtr) to 31 and 83/100 pts/qtr, respectively, during the study. Crude thrombosis rates fell from 21 to 2/100 pts/qtr during the study. After adjustment for comorbidities, mean ultrasound use increased by 4.6% per quarter (95% CI: 2.4-6.9, p<0.001), mean interventional angiography increased by 2.6% per quarter (95% CI: 1.1-4.2, p=0.001), and the predicted mean of the number of thromboses decreased by 8.4% per quarter (95% CI: 5.6-11.1, p<0.001). Implementation of a vascular access surveillance increases service utilization and is associated with a reduction in vascular access thrombosis.

Antiplatelet therapy to prevent hemodialysis vascular access failure: systematic review and meta-analysis.

BACKGROUND: Hemodialysis vascular access failure occurs often and increases morbidity for people on hemodialysis therapy. Antiplatelet agents may prevent hemodialysis vascular access failure, but potentially may be hazardous in people with end-stage kidney disease who have impaired hemostasis. STUDY DESIGN: Systematic review and meta-analysis of randomized controlled trials. SETTING & POPULATION: Adults on long-term hemodialysis therapy. SELECTION CRITERIA: Trials evaluating hemodialysis vascular access outcomes identified by searches in Cochrane CENTRAL and Renal Group Trial Registers and Embase, without language restriction. INTERVENTION: Antiplatelet therapy. OUTCOMES: Hemodialysis vascular access failure (thrombosis or loss of patency), failure to attain vascular access suitable for dialysis, need for intervention to attain patency or assist maturation, major bleeding, minor bleeding, and antiplatelet treatment withdrawal. Treatment effects were summarized as RRs with 95% CIs using random-effects meta-analysis. RESULTS: 21 eligible trials (4,826 participants) comparing antiplatelet treatment with placebo or no treatment were included. 12 trials (3,118 participants) started antiplatelet therapy around the time of dialysis vascular access surgery and continued treatment for approximately 6 months. Antiplatelet treatment reduced fistula failure (thrombosis or loss of patency) by one-half (6 trials, 1,222 participants; RR, 0.49; 95% CI, 0.30-0.81) but had uncertain effects on graft patency and attaining fistula or graft function suitable for dialysis. Overall, antiplatelet treatment had uncertain effects on major bleeding. LIMITATIONS: Unclear or high risk of bias in most trials and few trial data, particularly for antiplatelet effects on graft function and vascular access suitability for dialysis. CONCLUSIONS: Antiplatelet treatment protects fistula from thrombosis or loss of patency, but has little or no effect on graft patency and uncertain effects on vascular access maturation for dialysis and major bleeding. Interventions that demonstrably improve vascular access suitability for dialysis are needed.

Antioxidants for chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is a significant risk factor for premature cardiovascular disease and death. Increased oxidative stress in people with CKD has been implicated as a potential causative factor for some cardiovascular diseases. Antioxidant therapy may reduce cardiovascular mortality and morbidity in people with CKD. OBJECTIVES: To examine the benefits and harms of antioxidant therapy on mortality and cardiovascular events in people with CKD stages 3 to 5; dialysis, and kidney transplantation patients. SEARCH METHODS: We searched the Cochrane Renal Group's specialised register (July 2011), CENTRAL (Issue 6, 2011), MEDLINE (from 1966) and EMBASE (from 1980). SELECTION CRITERIA: We included all randomised controlled trials (RCTs) investigating the use of antioxidants for people with CKD, or subsets of RCTs reporting outcomes for participants with CKD. DATA COLLECTION AND ANALYSIS: Titles and abstracts were screened independently by two authors who also performed data extraction using standardised forms. Results were pooled using the random effects model and expressed as either risk ratios (RR) or mean difference (MD) with 95% confidence intervals (CI). MAIN RESULTS: We identified 10 studies (1979 participants) that assessed antioxidant therapy in haemodialysis patients (two studies); kidney transplant recipients (four studies); dialysis and non-dialysis CKD patients (one study); and patients requiring surgery (one study). Two additional studies reported the effect of an oral antioxidant inflammation modulator in patients with CKD (estimated glomerular filtration rate (eGFR) 20 to 45 mL/min/1.73 m²), and post-hoc findings from a subgroup of people with mild-to-moderate renal insufficiency (serum creatinine ≥125 µmol/L) respectively. Interventions included different doses of vitamin E (two studies); multiple antioxidant therapy (three studies); co-enzyme Q (one study); acetylcysteine (one study); bardoxolone methyl (one study); and human recombinant superoxide dismutase (two studies).Compared with placebo, antioxidant therapy showed no clear overall effect on cardiovascular mortality (RR 0.95, 95% CI 0.70 to 1.27; P = 0.71); all-cause mortality (RR 0.93, 95% CI 0.76 to 1.14; P = 0.48); cardiovascular disease (RR 0.78, 95% CI 0.52 to 1.18; P = 0.24); coronary heart disease (RR 0.71, 95% CI 0.42 to 1.23; P = 0.22); cerebrovascular disease (RR 0.91, 95% CI 0.63 to 1.32; P = 0.63); or peripheral vascular disease (RR 0.54, 95% CI 0.26 to 1.12; P = 0.10). Subgroup analyses found no evidence of significant heterogeneity based on proportions of males (P = 0.99) or diabetes (P = 0.87) for cardiovascular disease. There was significant heterogeneity for cardiovascular disease when studies were analysed by CKD stage (P = 0.003). Significant benefit was conferred by antioxidant therapy for cardiovascular disease prevention in dialysis patients (RR 0.57, 95% CI 0.41 to 0.80; P = 0.001), although no effect was observed in CKD patients (RR 1.06, 95% CI 0.84 to 1.32; P = 0.63).Antioxidant therapy was found to significantly reduce development of end-stage of kidney disease (ESKD) (RR 0.50, 95% CI 0.25 to 1.00; P = 0.05); lowered serum creatinine levels (MD 1.10 mg/dL, 95% CI 0.39 to 1.81; P = 0.003); and improved creatinine clearance (MD 14.53 mL/min, 95% CI 1.20 to 27.86; P = 0.03). Serious adverse events were not significantly increased by antioxidants (RR 2.26, 95% CI 0.74 to 6.95; P = 0.15).Risk of bias was assessed for all studies. Studies that were classified as unclear for random sequence generation or allocation concealment reported significant benefits from antioxidant therapy (RR 0.57, 95% CI 0.41 to 0.80; P = 0.001) compared with studies at low risk of bias (RR 1.06, 95% CI 0.84 to 1.32; P = 0.63). AUTHORS' CONCLUSIONS: Although antioxidant therapy does not reduce the risk of cardiovascular and all-cause death or major cardiovascular events in people with CKD, it is possible that some benefit may be present, particularly in those on dialysis. However, the small size and generally suboptimal quality of the included studies highlighted the need for sufficiently powered studies to confirm this possibility. Current evidence suggests that antioxidant therapy in predialysis CKD patients may prevent progression to ESKD; this finding was however based on a very small number of events. Further studies with longer follow-up are needed for confirmation. Appropriately powered studies are needed to reliably assess the effects of antioxidant therapy in people with CKD.

Effects of antiplatelet therapy on mortality and cardiovascular and bleeding outcomes in persons with chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: Antiplatelet agents are used to prevent cardiovascular events; however, treatment effects may differ in persons with chronic kidney disease (CKD) because atherosclerotic disease is less prevalent, whereas bleeding hazards may be increased in this population. PURPOSE: To summarize the effects of antiplatelet treatment on cardiovascular events, mortality, and bleeding in persons with CKD. DATA SOURCES: Embase and Cochrane databases through November 2011 without language restriction. STUDY SELECTION: Randomized trials that included adults with CKD and compared antiplatelet agents with standard care, placebo, or no treatment. DATA EXTRACTION: Data for populations, interventions, outcomes, and risk for bias were extracted. Quality of evidence for treatment effects on myocardial infarction, death, and bleeding was summarized by using Grading of Recommendations Assessment, Development, and Evaluation guidelines. DATA SYNTHESIS: Nine trials (all post hoc subgroup analyses for CKD) involving 9969 persons who had acute coronary syndromes or were undergoing percutaneous coronary intervention and 31 trials involving 11,701 persons with stable or no cardiovascular disease were identified. Low-quality evidence has found that in persons with acute coronary syndromes, glycoprotein IIb/IIIa inhibitors or clopidogrel plus standard care compared with standard care alone had little or no effect on all-cause or cardiovascular mortality or on myocardial infarction but increased serious bleeding. Compared with placebo or no treatment in persons with stable or no cardiovascular disease, antiplatelet agents prevented myocardial infarction but had uncertain effects on mortality and increased minor bleeding according to generally low-quality evidence. LIMITATIONS: Data for antiplatelet agents in persons with CKD are frequently derived from post hoc analyses of trials of broader populations. Definitions for bleeding outcomes and trial duration were heterogeneous. CONCLUSION: Benefits for antiplatelet therapy among persons with CKD are uncertain and are potentially outweighed by bleeding hazards. PRIMARY FUNDING SOURCE: None.

Cardiovascular risk management in chronic kidney disease in general practice (the AusHEART study).

BACKGROUND: Chronic kidney disease (CKD) is common and increasing in prevalence. Adverse outcomes of CKD can be prevented through early detection and treatment. There is limited data on the awareness of CKD and the quality of care offered to patients with CKD in the primary care setting. The objectives of this study were to assess the prevalence, general practitioner (GP) awareness and extent of current evidence-practice gaps in the management of CKD in Australian primary care. METHODS: The Australian Hypertension and Absolute Risk Study (AusHEART) was a nationally representative, cluster stratified, cross-sectional survey among 322 GPs. Each GP was asked to provide data for 15-20 consecutive patients (age ≥ 55 years) who presented between April and June, 2008. The main outcome measures were CKD prevalence based on proteinuria and decreased estimated glomerular filtration rate. Evidence-practice gaps in management of patients with CKD were identified. RESULTS: Among a total of 4966 patients with kidney function test data, 1845 (37%) had abnormal kidney function. Of the 1312 patients with abnormal kidney function known to the GP at the time of visit, only 235 were correctly identified as having CKD. GPs under-estimated cardiovascular (CV) risks in patients with CKD when compared with the prevailing guidelines at the time of survey and the recent national guidelines, particularly in later stages of CKD. Among CKD patients not prescribed blood pressure-lowering agents or lipid-lowering agents, treatment was indicated as per relevant guidelines in 51 and 46%, respectively. For CKD patients who were already prescribed blood pressure-lowering and lipid-lowering agents, 61 and 50%, respectively, did not meet the treatment targets recommended by the relevant guidelines. CONCLUSIONS: CKD is common, significantly under-recognized and under-treated in primary care. Effort to increase awareness and provide opportunities for improved screening and assessment should improve the management and outcome of these patients at high risk of CV disease.