Benefits and Harms of Statin Therapy for Persons With Chronic Kidney Disease

University of Otago, Christchurch, 2 Riccarton Avenue, PO Box 4345, Christchurch 8041, New Zealand.
Annals of internal medicine (Impact Factor: 17.81). 08/2012; 157(4):263-75. DOI: 10.7326/0003-4819-157-4-201208210-00007
Source: PubMed


Statins have uncertain benefits in persons with chronic kidney disease (CKD) because individual trials may have insufficient power to determine whether treatment effects differ with severity of CKD.
To summarize the benefits and harms of statin therapy for adults with CKD and examine whether effects of statins vary by stage of kidney disease.
Cochrane and EMBASE databases (inception to February 2012).
Randomized trials comparing the effects of statins with placebo, no treatment, or another statin on mortality and cardiovascular outcomes.
Two independent reviewers extracted data and assessed risk of bias.
Eighty trials comprising 51099 participants compared statin with placebo or no treatment. Treatment effects varied with stage of CKD. Moderate- to high-quality evidence indicated that statins reduced all-cause mortality (relative risk [RR], 0.81 [95% CI, 0.74 to 0.88]), cardiovascular mortality (RR, 0.78 [CI, 0.68 to 0.89]), and cardiovascular events (RR, 0.76 [CI, 0.73 to 0.80]) in persons not receiving dialysis. Moderate- to high-quality evidence indicated that statins had little or no effect on all-cause mortality (RR, 0.96 [CI, 0.88 to 1.04]), cardiovascular mortality (RR, 0.94 [CI, 0.82 to 1.07]), or cardiovascular events (RR, 0.95 [CI, 0.87 to 1.03]) in persons receiving dialysis. Effects of statins in kidney transplant recipients were uncertain. Statins had little or no effect on cancer, myalgia, liver function, or withdrawal from treatment, although adverse events were evaluated systematically in fewer than half of the trials.
There was a reliance on post hoc subgroup data for earlier stages of CKD.
Statins decrease mortality and cardiovascular events in persons with early stages of CKD, have little or no effect in persons receiving dialysis, and have uncertain effects in kidney transplant recipients.

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    • "Therefore, preventive measures for CVD are of great importance in patients with CKD. Previous studies have demonstrated that efforts to lower blood pressure [2], [3] and lipid levels [4] are effective for reducing the risk of CVD in patients with CKD. However, the importance of other potential preventive therapies, such as antiplatelet agents, remains controversial. "
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    ABSTRACT: Background Chronic kidney disease (CKD) is a major risk factor for the development of cardiovascular disease (CVD). Previous trials have investigated the effects of low-dose aspirin on CVD prevention in patients with diabetes; however, patients with CKD were not examined. The role of aspirin in diabetics is controversial, and the available literature is contradictory. Therefore, we studied whether low-dose aspirin would be beneficial for patients with CKD, a group that is at high risk for CVD. Method From a total of 25340 patients with CKD, 1884 recipients of low-dose aspirin (100 mg/day) were paired 1∶1 with non-recipients for analysis using propensity score matching. The primary endpoint was the development of atherosclerotic CVD, including coronary arterial disease, stroke, and peripheral arterial disease. Secondary endpoints included death from any cause, bleeding events, doubling of serum creatinine, and renal death. Results The incidence of a primary endpoint of any atherosclerotic CVD was significantly higher in the aspirin users than in the non-users (P<0.001). Secondary endpoints, including all-cause mortality and composite bleeding events, were not significantly different between the aspirin users and the non-users. However, the doubling of serum creatinine levels (P = 0.001) and renal death (P = 0.042) were significantly associated with the use of aspirin. Conclusion These results suggest that the use of low-dose aspirin in patients with CKD may have harmful consequences related to the development of CVD and renal progression.
    Full-text · Article · Aug 2014 · PLoS ONE
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    • "No increased risk of renal disease attributable to statin treatment was found in our review. Recent systematic reviews of trials have demonstrated lower mortality and cardiovascular events in persons with early stages of chronic kidney disease (CKD) on statins, but little or no effect in persons receiving dialysis, and uncertain effects in kidney transplant recipients [135,136]. "
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    ABSTRACT: Efficacy of statins has been extensively studied, with much less information reported on their unintended effects. Evidence from randomized controlled trials (RCTs) on unintended effects is often insufficient to support hypotheses generated from observational studies. We aimed to systematically assess unintended effects of statins from observational studies in general populations with comparison of the findings where possible with those derived from randomized trials. Medline (1998 to January 2012, week 3) and Embase (1998 to 2012, week 6) were searched using the standard BMJ Cohort studies filter. The search was supplemented with reference lists of all identified studies and contact with experts in the field. We included prospective studies with a sample size larger than 1,000 participants, case control (of any size) and routine health service linkage studies of over at least one year duration. Studies in subgroups of patients or follow-up of patient case series were excluded, as well as hospital-based cohort studies. Ninety studies were identified, reporting on 48 different unintended effects. Statins were associated with lower risks of dementia and cognitive impairment, venous thrombo-embolism, fractures and pneumonia, but these findings were attenuated in analyses restricted to higher quality studies (respectively: OR 0.74 (95% CI 0.62 to 0.87); OR 0.92 (95% CI 0.81 to 1.03); OR 0.97 (95% CI 0.88 to 1.05); OR 0.92 (95% CI 0.83 to 1.02)); and marked heterogeneity of effects across studies remained. Statin use was not related to any increased risk of depression, common eye diseases, renal disorders or arthritis. There was evidence of an increased risk of myopathy, raised liver enzymes and diabetes (respectively: OR 2.63 (95% CI 1.50 to 4.61); OR 1.54 (95% CI 1.47 to 1.62); OR 1.31 (95% CI 0.99 to 1.73)). Our systematic review and meta-analyses indicate that high quality observational data can provide relevant evidence on unintended effects of statins to add to the evidence from RCTs. The absolute excess risk of the observed harmful unintended effects of statins is very small compared to the beneficial effects of statins on major cardiovascular events.
    Full-text · Article · Mar 2014 · BMC Medicine
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    • "Although few studies enrolled CKD only subjects to test the statin efficacy, statins were shown to effectively lower LDL and be safe in CKD population 8, 14. Statins can decrease mortality and cardiovascular events in CKD persons without dialysis 8, 15. Therefore, ESC guideline suggests that LDL lowering with statin to reduce cardiovascular disease should be considered 5. "
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    ABSTRACT: Background: Patients with chronic kidney disease (CKD) is a very high risk cardiovascular disease population and should be treated aggressively. We investigated lipid management in CKD patients with atherosclerosis in Taiwan. Methods: 3057 patients were enrolled in a multi-center study (T-SPARCLE). Lipid goal are defined as total cholesterol (TC) < 160mg/dl, low-density lipoprotein (LDL) <100 mg/dl, high-density lipoprotein (HDL) > 40 mg/dl in men, HDL > 50 mg/dl in women, non-HDL cholesterol < 130mg/dl, and triglyceride < 150 mg/dl. Results: Compared with those without CKD (n=2239), patients with CKD (n=818) had more co-morbidities (hypertension, glucose intolerance, stroke and heart failure) and lower HDL but higher triglyceride levels. Overall 2168 (70.5%) patients received lipid-lowering agents. There was similar equivalent statin potency between CKD and non-CKD groups. The goal attainment is lower in HDL and TG in the CKD group as compared with non-CKD subjects (47.1 vs. 51.9% and 63.2 vs. 68.9% respectively, both p < 0.02). Analysis of sex and CKD interaction on goals attainment showed female CKD subjects had lower non-HDL and TG goals attainment compared with non-CKD males (both p < 0.019). Conclusion: Although presenting with more comorbidities, the CKD population had suboptimal lipid goal attainment rate as compared with the non-CKD population. Further efforts may be required for better lipid control especially on the female CKD subjects.
    Full-text · Article · Feb 2014 · International journal of medical sciences
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