Effect of statin therapy on cardiovascular and renal outcomes in patients with chronic kidney disease: a systematic review and meta-analysis.

Hou W, Lv J, Perkovic V, et al.
Eur Heart J. 2013 Mar 6. [Epub]

Background:

Cardiovascular disease (CVD) is 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 [1,2]. Patients with CKD have higher prevalence of a number of risk factors for CVD, such as 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 [3]. However, 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 [4]. 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. 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 [5] Thus, the effect of statin therapy may be less compared with the general population. In this systematic review, available clinical trial data were analyzed to define the balance of risks and benefits of statin in patients with CKD and also the effect of kidney function on statin use. 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.

Main results:

• Statin therapy produced a 23% reduction in the risk of cardiovascular events (RR 0.77, 95% CI 0.70–0.85, P<0.001); statin effect was significantly modified by kidney function
• Statin therapy reduced the risk of coronary events by 22% (RR 0.78, 95% CI 0.69–0.88)
• There was no effect of statin therapy on the risk of stroke (RR 0.79, 95% CI 0.56–1.12)
• Statin therapy reduced all-cause death (RR 0.92, 95% CI 0.85–0.99) and also cardiovascular death (RR 0.91, 95% CI 0.84–0.99)
• There was no clear evidence that statins reduced the risk of kidney failure (RR 0.95, 95% CI 0.90–1.01)
• 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).
• The relative effects of statin therapy in CKD were significantly reduced in people with advanced CKD (P<0.001) but the absolute risk reductions were comparable.

Conclusion:

Statin therapy reduces the risk of major vascular events, as well as cardiovascular and all-cause death in patients with CKD, across a broad range of kidney functions, including patients with dialysis. Although
the relative vascular protection of statins is significantly modified by kidney function, meaningful reductions in absolute risk might be achieved in every stage of CKD.

References:

1. Go AS, Chertow GM, Fan D, et al. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004;351:1296–1305.
2. Yach D, Leeder SR, Bell J, et al. Global chronic diseases. Science 2005;307:317.
3. Snyder JJ, Collins AJ. KDOQI hypertension, dyslipidemia, and diabetes care guidelines and current care patterns in the United States CKD population: National Health and Nutrition Examination Survey 1999–2004. Am J Nephrol 2009;30:44–54.
4. Liu Y, Coresh J, Eustace JA, et al. Association between cholesterol level and mortality in dialysis patients: role of inflammation and malnutrition. JAMA 2004;291:451–459.
5. Foley RN, Parfrey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis 1998;32(5 Suppl. 3):S112–S119.

 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.