Download 4D Trial (Statin in Dialysis)

Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis
4D Trial N Engl J Med 2005;353:238-48 (July 21)
Study Type: POEM
Purpose: Does atorvastatin benefit the diabetic patient with renal disease receiving hemodialysis?
Study Duration: 5-year trial
Trial Design: double-blinded, placebo-controlled, intention-to-treat, multicenter (178 dialysis centers in Germany), 4-week
run-in placebo, then randomization to 20 mg atorvastatin vs placebo
Patients: 1255 patients, mean age ~66, ~46% female, 18 years of diabetes (HbA1c 6.8), 8 months on dialysis, BP = 145/76,
9% smokers, Most had some history of cardiovascular disease, Baseline TC 220, LDL 126 (~20% < 100), HDL 36, TG 267
Medications: ACEI 48%, ARB 12%, Beta-blockers 38%, CCB 40%, Antiplatelet 50%
Inclusion: age 18 to 80, hemodialysis for less than 2 years
Exclusion: LDL < 80 or > 190, TG > 1000, LFT’s > 3 times normal, hematopoietic disease, HF or MI within 3 months,
unsuccessful kidney transplant, resistant hypertension
Outcome Scores:
Primary end point: composite of death from cardiac causes, fatal stroke, nonfatal stroke, nonfatal MI, whichever occurred first,
only one was reported
Secondary measures: all-cause death, all cardiac events combined, all cerebrovascular events
1.
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•
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2.
Are the results valid?
randomized? yes
double-blinded? yes
were groups similar? yes
allocation concealment? ?
all patients accounted for? yes
What were the results?
Outcome
Primary
Death from
cardiac causes
Nonfatal MI
Fatal stroke
Nonfatal stroke
Secondary
All cardiac
events
All CV events
All-cause death
Fatal cancer
LDL
Placebo
38%
23%
Atorvastatin
37%
20%
p-value
NS
NS
ARR
NNT
12%
2%
5%
11%
4%
5%
NS
.04
NS
2% (ARI)
50 (NNH)
39%
33%
.03
6%
17
11%
50%
3%
120
13%
48%
3%
72
NS
NS
NS
Adverse Event
•
Patients on hemodialysis generally have many side effects, but there were no cases of rhabdomyolysis or severe
liver disease
3.
•
Will the results help me?
The results are surprising, especially in these patients that have significant disease (secondary prevention).
Conclusion: In diabetic patients on hemodialysis, the use of 20 mg of atorvastatin did not reduce the composite endpoint of
death from cardiac causes, fatal stroke, nonfatal stroke, and nonfatal MI, despite the pronounced LDL-lowering effect to 72.
For every 100 patients treated, 2 would have a stroke as a result of treatment. The benefit of atorvastatin in diabetic patients
utilizing hemodialysis is of no value.
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