Effect of Statin Therapy on Outcomes in Patients With CKD
Effect of Statin Therapy on Outcomes in Patients With CKD
Aims The effects of statin therapy in patients with chronic kidney disease (CKD) remain uncertain. We undertook a systematic review and meta-analysis to investigate the effects of statin on major clinical outcomes.
Methods and results We systematically searched MEDLINE, Embase, and the Cochrane Library for trials published between 1970 and November 2011. We included prospective, randomized, controlled trials assessing the effects of statins on cardiovascular outcomes in people with kidney disease. Summary estimates of relative risk (RR) reductions were calculated with a random effects model. Thirty-one trials that include at least one event were identified, providing data for 48 429 patients with CKD, including 6690 major cardiovascular events and 6653 deaths. Statin therapy produced a 23% RR reduction (16–30) for major cardiovascular events (P<0.001), an 18% RR reduction (8–27) for coronary events, and 9% (1–16) reduction in cardiovascular or all-cause deaths, but had no significantly effect on stroke (21%, –12 to 44) or no clear effect on kidney failure events (5%, −1 to 10). Adverse events were not significantly increased by statins, including hepatic (RR 1.13, 95% CI 0.92–1.39) or muscular disorders (RR 1.02, 95% CI 0.95–1.09). Subgroup analysis demonstrated the relative effects of statin therapy in CKD were significantly reduced in people with advanced CKD (P < 0.001) but that the absolute risk reductions were comparable.
Conclusion Statin therapy reduces the risk of major cardiovascular events in patients with chronic kidney disease including those receiving dialysis.
Chronic kidney disease (CKD) is a major public health problem. Cardiovascular disease (CVD) continues to be the leading cause of morbidity and mortality among people with CKD worldwide, with rates of cardiovascular events and mortality consistently increasing as kidney function declines. Dialysis patients have mortality rates up to 40-fold higher than the general population, with CVD being responsible for up to 50% of these deaths. Patients with CKD have higher prevalence of a number of risk factors for CVD, including lipid abnormalities, hypertension, obesity, and diabetes.
Kidney Disease Outcome Quality Initiative (K/DOQI) clinical practice guidelines have recommended statin therapy for the prevention of CVD in patients with CKD and high-LDL cholesterol (LDL-C) levels. However, the value of this approach continues to be debated, particularly in those with the most advanced kidney dysfunction. Levels of cholesterol in patients with kidney disease do not always have the same log-linear relationship with cardiovascular events observed in the general population. Indeed, a 'U'-shaped or inverse relationship has been described in cohort studies of dialysis patients where people with the lowest levels of LDL-C have the worst outcomes. The burden of CVD may not be predominantly due to atherosclerotic disease in people with severely decreased GFR when compared with people with normal renal function. Emerging data suggest the pattern of cardiovascular pathology may be different in advanced CKD, with vascular stiffness and calcification, structural heart disease, and sympathetic overactivity contributing to an increasing risk of cardiac arrhythmia and heart failure. Thus, the effect of statin therapy may be less compared with the general population. In the past few years, several large-scale trials of statin therapy in people with CKD have been completed, including the recent large SHARP (Study of Heart and Renal Protection) trial. Although some of these trials have shown benefit, others have shown no effect, leading to uncertainty about the presence and magnitude of cardiovascular protective effects and therefore difficulties for clinicians in the interpretation of the results.
Two recent overviews have investigated the effect of statin in patients with CKD. However, both have not evaluated the effect of kidney function on the statin therapy. In this systematic review, we sought to synthesize all the available clinical trial data and define better the balance of risks and benefits of statin in patients with CKD and also the effect of kidney function on statin use.
Abstract and Introduction
Abstract
Aims The effects of statin therapy in patients with chronic kidney disease (CKD) remain uncertain. We undertook a systematic review and meta-analysis to investigate the effects of statin on major clinical outcomes.
Methods and results We systematically searched MEDLINE, Embase, and the Cochrane Library for trials published between 1970 and November 2011. We included prospective, randomized, controlled trials assessing the effects of statins on cardiovascular outcomes in people with kidney disease. Summary estimates of relative risk (RR) reductions were calculated with a random effects model. Thirty-one trials that include at least one event were identified, providing data for 48 429 patients with CKD, including 6690 major cardiovascular events and 6653 deaths. Statin therapy produced a 23% RR reduction (16–30) for major cardiovascular events (P<0.001), an 18% RR reduction (8–27) for coronary events, and 9% (1–16) reduction in cardiovascular or all-cause deaths, but had no significantly effect on stroke (21%, –12 to 44) or no clear effect on kidney failure events (5%, −1 to 10). Adverse events were not significantly increased by statins, including hepatic (RR 1.13, 95% CI 0.92–1.39) or muscular disorders (RR 1.02, 95% CI 0.95–1.09). Subgroup analysis demonstrated the relative effects of statin therapy in CKD were significantly reduced in people with advanced CKD (P < 0.001) but that the absolute risk reductions were comparable.
Conclusion Statin therapy reduces the risk of major cardiovascular events in patients with chronic kidney disease including those receiving dialysis.
Introduction
Chronic kidney disease (CKD) is a major public health problem. Cardiovascular disease (CVD) continues to be the leading cause of morbidity and mortality among people with CKD worldwide, with rates of cardiovascular events and mortality consistently increasing as kidney function declines. Dialysis patients have mortality rates up to 40-fold higher than the general population, with CVD being responsible for up to 50% of these deaths. Patients with CKD have higher prevalence of a number of risk factors for CVD, including lipid abnormalities, hypertension, obesity, and diabetes.
Kidney Disease Outcome Quality Initiative (K/DOQI) clinical practice guidelines have recommended statin therapy for the prevention of CVD in patients with CKD and high-LDL cholesterol (LDL-C) levels. However, the value of this approach continues to be debated, particularly in those with the most advanced kidney dysfunction. Levels of cholesterol in patients with kidney disease do not always have the same log-linear relationship with cardiovascular events observed in the general population. Indeed, a 'U'-shaped or inverse relationship has been described in cohort studies of dialysis patients where people with the lowest levels of LDL-C have the worst outcomes. The burden of CVD may not be predominantly due to atherosclerotic disease in people with severely decreased GFR when compared with people with normal renal function. Emerging data suggest the pattern of cardiovascular pathology may be different in advanced CKD, with vascular stiffness and calcification, structural heart disease, and sympathetic overactivity contributing to an increasing risk of cardiac arrhythmia and heart failure. Thus, the effect of statin therapy may be less compared with the general population. In the past few years, several large-scale trials of statin therapy in people with CKD have been completed, including the recent large SHARP (Study of Heart and Renal Protection) trial. Although some of these trials have shown benefit, others have shown no effect, leading to uncertainty about the presence and magnitude of cardiovascular protective effects and therefore difficulties for clinicians in the interpretation of the results.
Two recent overviews have investigated the effect of statin in patients with CKD. However, both have not evaluated the effect of kidney function on the statin therapy. In this systematic review, we sought to synthesize all the available clinical trial data and define better the balance of risks and benefits of statin in patients with CKD and also the effect of kidney function on statin use.
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