Annals of Internal Medicine: Renal Replacement Therapy Topic Collection

Review: Statins decrease mortality and major CV events in adults with CKD not receiving dialysis

Ramesh Prasad GV. — Tue, 20 Nov 2012 00:00:00 GMT

Questions

What is the efficacy of statin therapy in adults with chronic kidney disease (CKD)? Do effects differ by CKD stage?

Review scope

Included studies compared statin therapy with placebo or no treatment in adults with CKD and had ≥ 8 weeks of follow-up. Outcomes included all-cause and cardiovascular (CV) mortality and major CV events as defined in individual studies.

Review methods

EMBASE/Excerpta Medica, Cochrane Central Register of Controlled Trials, and Cochrane Renal Group Specialised Register to Feb 2012; and a 2008 systematic review* were searched for randomized controlled trials (RCTs). 80 RCTs (86 comparisons, n = 51 099, mean age range 23 to 73 y, 24% to 89% men, follow-up range 2 mo to 5.5 y) met inclusion criteria: 48 comparisons were done in patients not having dialysis (n = 39 820), 21 in those having dialysis (n = 7982), and 17 in kidney transplant recipients (n = 3297). Subgroup analyses by dialysis and kidney transplant status were preplanned. 15 RCTs had adequate allocation concealment, 36 used blinding in patients or investigators and 17 in outcome assessors, 18 used intention-to-treat analysis, and 19 had adequate follow-up. Results of 9 RCTs that compared statin therapy with the same or other statins are not reported in this abstract.

Main results

Meta-analysis showed that statin therapy reduced all-cause and CV mortality and major CV events more than placebo or no treatment (Table). In subgroup analyses, statins reduced all outcomes in patients not receiving dialysis at study entry but not in those receiving dialysis or with a history of kidney transplant at study entry (all-cause mortality, Pinteraction = 0.009; CV mortality, Pinteraction = 0.08; CV events, Pinteraction < 0.001) (Table).

Conclusion

Statin therapy decreases all-cause mortality and major cardiovascular events in adults with chronic kidney disease who are not receiving dialysis.Statin therapy vs placebo or no treatment in adults with CKD†PatientsOutcomes (quality of evidence‡)Number of trials (n)Weighted event ratesRRR (95% CI)NNT (CI)All§All-cause mortality32 (45 154)14% vs 16%11% (3 to 18)57 (35 to 209)CV mortality27 (35 417)7.3% vs 8.5%14% (5 to 22)85 (54 to 236)Major CV events20 (45 362)15% vs 19%22% (15 to 28)24 (19 to 36)NondialysisAll-cause mortality (high)11 (28 276)7.3% vs 9.0%19% (12 to 26)59 (43 to 93)CV mortality (high)8 (19 059)4.7% vs 6.0%22% (11 to 32)76 (53 to 152)Major CV events (moderate)14 (36 033)14% vs 19%24% (20 to 27)22 (20 to 27)DialysisAll-cause mortality (moderate)13 (4705)40% vs 42%4% (−4 to 12)NSCV mortality (moderate)13 (4623)19% vs 21%||6% (−7 to 18)NSMajor CV events (high)4 (7084)24% vs 25%5% (−3 to 13)NSKidney transplantCV mortality (low)4 (2322)3.3% vs 4.8%32% (−2 to 55)NSMajor CV events (low)1 (2102)11% vs 13%16% (−6 to 34)NSRRI (CI)Kidney transplantAll-cause mortality (low)6 (2760)11% vs 10%5% (−16 to 31)NS†CKD = chronic kidney disease; CV = cardiovascular; NS = not significant; other abbreviations defined in Glossary. Weighted event rates, RRR, RRI, NNT, and CI calculated from risk ratios and control event rates in article using a random-effects model.‡Grading of Recommendations Assessment, Development, and Evaluation criteria (grades: very low, low, moderate, and high).§Interactions for treatment by CKD status (nondialysis, dialysis, or kidney transplantation): all-cause mortality, P = 0.009; CV mortality, P = 0.08; major CV events, P < 0.001.||Revised control event rate (477/2312) provided by author.

Review: Lipid-lowering drugs decrease all-cause and cardiac mortality and CV events in CKD

Ramesh Prasad GV. — Tue, 20 Nov 2012 00:00:00 GMT

Question

What is the efficacy of lipid-lowering therapy for clinical outcomes in chronic kidney disease (CKD)?

Review scope

Included studies compared ≥ 1 lipid-lowering agent (statins, ezetimibe, niacin, colestipol, or cholestyramine) with placebo, no treatment, or other lipid-lowering treatment in patients with CKD; had ≥ 6 months of follow-up; and included ≥ 100 adults or ≥ 25 children with CKD in each treatment group. Trials of dietary supplements, phosphate binders, apheresis, stanols, or sterols were excluded. Outcomes included all-cause, cardiovascular (CV), and cardiac mortality; and a composite of CV events.

Review methods

MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews (2000 to Nov 2011); a 2003 systematic review*; and reference lists were searched for peer-reviewed, randomized, controlled trials (RCTs) and systematic reviews. 18 RCTs met inclusion criteria: 5 were done in patients with CKD (n = 15 603, mean age range 50 to 66 y, 54% to 69% men) and 13 in the general population with subgroup analyses reported in patients with CKD (n = 20 926 with CKD, mean age range 52 to 70 y, 35% to 82% men). All RCTs were done in adults. 16 RCTs evaluated statins, and 2 evaluated simvastatin plus ezetimibe. 13 trials compared lipid-lowering therapy with placebo, 2 with usual care, 2 with another statin or statin dose, and 1 with diet modification. Subgroup analyses by dialysis status were preplanned.

Main results

Meta-analysis in all CKD patients showed that lipid-lowering therapy decreased all-cause and cardiac mortality and CV events, including revascularization, more than control treatment; groups did not differ for CV mortality (Table). In CKD patients not receiving maintenance dialysis, lipid-lowering therapy decreased all-cause and cardiac mortality and CV events (Table); in those having dialysis, lipid-lowering therapy decreased cardiac mortality (Table).

Conclusion

Lipid-lowering drugs decrease all-cause and cardiac mortality and cardiovascular events more than control treatment in adults with chronic kidney disease.Lipid-lowering drugs vs control treatment in adults with CKD†PatientsOutcomesNumber of trials (n)Weighted event ratesRRR (95% CI)NNT (CI)All‡All-cause mortality15 (31 555)10% vs 11%9% (1 to 17)100 (53 to 893)CV mortality§4 (13 211)10% vs 11%4% (−6 to 13)NSCardiac mortality6 (14 247)4.8% vs 5.9%18% (9 to 26)95 (66 to 189)CV events||9 (19 924)10% vs 13%22% (14 to 29)36 (28 to 57)NondialysisAll-cause mortality11 (18 054)NR17% (2 to 30)NRCV mortality§2 (1168)NR0% (−295 to 75)NSCardiac mortality3 (2991)NR33% (6 to 52)NRCV events||9 (16 683)NR23% (17 to 29)NRDialysisAll-cause mortality2 (4028)NR4% (−2 to 10)NSCV mortality§1 (2773)NR0% (−14 to 13)NSCardiac mortality2 (1986)NR22% (11 to 32)NRCV events||1 (2527)NR4% (−15 to 20)NS†CKD = chronic kidney disease; CV = cardiovascular; NR = not reported; NS = not significant; other abbreviations defined in Glossary. Weighted event rates, RRR, NNT, and CI calculated from risk ratios and either raw control event rates (CV mortality) or pooled control rate estimates per 1000 (all-cause mortality, cardiac mortality, and CV events) reported in article using a random-effects model.‡Strength of evidence for all patients was moderate (all-cause mortality and CV events) or high (CV and cardiac mortality) using modified Grading of Recommendations Assessment, Development, and Evaluation criteria (grades: very low, low, moderate, and high).§Cardiac or stroke.||Including revascularization procedures.