New guidelines on managing cholesterol were published in
Circulation this month by the ACC/AHA task force.
As we spend much of our time in CKD clinic managing cardiovascular risk factors
such as blood pressure, diabetes, lifestyle factors and cholesterol I think it
is important we are up to date on the latest guidelines.
The task force based their recommendations based on
randomized controlled trials based on fixed doses of statins in those at risk
for atherosclerotic cardiovascular disease. The authors also emphasize the
continuing importance of lifestyle modification for the reduction of ASCVD.
Those who benefit from statins are (Task Force Summary):
1. Individuals with clinical ASCVD
2. Individuals with primary elevations of LDL–C ≥190 mg/dL
3. Individuals 40 to 75 years of age with diabetes and LDL–C
70 to189 mg/dL without clinical ASCVD
4. Individuals without clinical ASCVD or diabetes who are 40
to 75 years of age with LDL–C 70 to 189 mg/dL and have an estimated 10-year
ASCVD risk of 7.5% or higher.
The Caveats; no evidence for statin therapy in these
Primary prevention in over 75s unless clinically evident
Those with NYHA HF class II – IV
Those on hemodialysis
Significant changes to note:
No specific LDL-C and non-HDL-C targets recommended once on
The de-emphasis of surrogate markers such as CRP and calcium
Cautious use and clinical judgment in those over 75 years
without clinical ASCVD
What about renal
The Task Force
Authors looked at the TNT trial and the subgroup analysis from Shepard et al.
The guidelines do not explicitly recommend the use of statins in CKD patients
but they do highlight the beneficial findings of high dose (80mg) atorvastatin.
Shepard et al did a
subgroup analysis of the TNT trial looking at secondary prevention of major
cardiovascular events in patients with an MDRD eGFR less than 60. In the
original TNT study patients were age 35 to 75 and patients on long-term immunosuppression
or with nephrotic syndrome were excluded. At baseline patients already had an
LDL-C of less than 130mg/dl. Shepard showed that 80mg of atorvastatin reduced
the RR of a major CV by 32% compared with 10mg of atorvastatin.
My impression is
that we should use statins in our CKD patients but remain cautious with respect
to drug interactions and side effects.
Cholesterol RCTs in renal patients (a refresher on the
This German trial looked at 18 to 80 year olds with type 2
DM on hemodialysis for less than 2 years. Patients with LDL-C outside the 80 to
190 range were excluded as were failed kidney transplant patients. After a 4
week lipid-med free wash out patients were assigned to atorvastatin 20mg or
placebo. The primary outcome was a composite of cardiovascular death. About
1200 patients were enrolled for a mean of nearly 4 years. In this trial statin
did reduce LDL-C levels but there was no significant difference in the primary
or secondary outcomes.
Were the 4D study focused on the high risk diabetic
population on HD this trial investigated the efficacy of statin therapy in the
general dialysis population. Patients were 50 to 80 years and on regular
hemodialysis or filtration for 3 months. Expected transplantation within the
next year or statin therapy within the last 6 months excluded patients. Randomization
was to rosuvastatin 10mg or placebo and the primary endpoint was cardiovascular
death or non-fatal stroke or MI. Again, statin therapy reduced cholesterol
levels significantly but there was no difference in primary or secondary outcomes.
Further more, there was no correlation between primary outcome and baseline
LDL-C or 3 month LDL-C.
This trial attempted to look at the effects of simvastatin
20mg + ezetimibe 10mg versus placebo on major atherosclerotic events in
patients with CKD with no previous MI or revascularization3. About 3000 of the
9000 patients were on dialysis. The authors concluded that combination therapy
produced a relative risk reduction of 17% for major ASCVD outcomes. This trial
came in for a lot of criticism mainly because the authors appeared to
extrapolate their results by assuming all patients actually took their assigned
meds. 2700 patients were enrolled for a mean trial length of over 3 years.
ALERT (Assessment of LEscol in Renal Transplantation)
Lancet, 361 (2003), pp. 2024–2031
This study assessed the use
of statin therapy on transplant patients. Enrolled patients were between 30 and
75 and had a kidney or KP transplant for more than 6 months with stable renal
function. All patients were on ciclosporin and had total cholesterol levels
between 4 and 8 mmol/l. Patients were excluded if they had rejection in the
last 3 months or were already on statin therapy. 2100 patients were enrolled
and followed for a mean of 5 years. Randomization was to fluvastatin 40mg or placebo.
The primary end point was cardiac death, non-fatal MI or coronary
revascularization. Fluvastatin lowered LDL-C by 32% but there was no
significant difference in the primary endpoints. Interestingly in this study
only about 13% in each group had diabetic nephropathy and about 5% had
‘hypertensive nephrosclerosis’ as a cause of their primary renal failure. This
study was conducted in Canada and Europe.