the kidney & statin therapy: friend or foe? - pace-cme kidney & statin therapy: friend or...

The kidney & statin therapy: Friend or Foe?

Raul Santos, MD Sao Paulo Medical School

Sao Paolo, Brazil

The kidney & Statin Therapy: Friend or Foe?

Raul D. Santos MD, PhD

Lipid Clinic InCor University of São Paulo

Brazil

2

Disclosure

• Consulting and speakers honoraria : Merck, Astra Zeneca, ISIS-Genzyme, Novo-Nordisk, BMS, Biolab, Pfizer, Lilly, Boehringer-Ingelheim, Amgen, Aegerion & Sanofi

Summary: The kidney & statin therapy: Friend or Foe?

• Friend

– Kidney disease and

CVD

– Prevention of CVD and death

– Reduction of CKD progression?

• Foe

– Can cause renal

failure?

Latin American Registry : 1992-2005 End

Stage Renal Disease Treatment

SLANH 2006

129 131

147 173 174

199

258 278 335

352 387

424 443

478

0

100

200

300

400

500

600

700 1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

Pre

va

len

ce p

//m

year

Last 10 years : 276% increase

Since 1992: 370% increase

Aprox.

630 ppm

in 2010

CKD Stages :

Stage Description GFR

(ml/min/1.73 m2)

1 Kidney Damage with

Normal or GFR 90

2 Kidney Damage with

Mild GFR 60-89

3 Moderate GFR 30-59

4 Severe GFR 15-29

5 Kidney Failure < 15 or Dialysis

* GFR estimated from serum creatinine using MDRD Study equation based on age, gender, race and calibration for serum

creatinine. For Stage 1 and 2, kidney damage estimated by spot albumin-to-creatinine ratio 17 mg/g in men or 25 mg/g in

women in two measurements.

Age-Standardized Rates of Death from Any Cause (Panel A) and Cardiovascular Events (Panel B),

According to the Estimated GFR among 1,120,295 Ambulatory Adults

Go A et al. NEJM 200; 351: 1296-305

Causes of death in renal failure patients : studies with statins

Lewis D et al. J Ren Care. 2010;36 Suppl 1:27-33

Clin J Am Soc Nephrol 6: 1456–1462, 2011

Friend: Can statins reduce CVD in subjects with CKD?

Wanner, C. et al. N Engl J Med 2005;353:238-248 Fellstrom et al. NEJM 2009;360:1395-407

Pro

po

rtio

nal

red

uct

ion

in

ath

ero

scle

roti

c ev

ent

rate

(9

5%

CI)

0%

5%

10%

15%

20%

25%

30% Statin vs control (21 trials)

Mean LDL cholesterol difference between treatment groups (mg/dL)

More vs Less (5 trials)

SHARP 32 mg/dL

0 20 40 10 30

SHARP 17% risk reduction

SHARP and CTT : Major atherosclerorotic events by LDL-C reduction

Lancet 2011; 377: 2181-2192

Summary of the effects of statin therapy on major

cardiovascular events stratified by kidney function.

Hou W et al. Eur Heart J 2013;34:1807-1817

Overall 23% reduction 18% per mmol/L

48 429 patients with CKD, including 6690 major

cardiovascular events and 6653 deaths.

Statins and cardiovascular outcomes in CKD according to

dialysis or not


Impact of Statin Treatment According to Renal Status


Friend: Can statins reduce renal function loss?

1

7 17

Effects of atorvastatin on kidney outcomes and cardiovascular disease in patients with diabetes

“A modest beneficial effect of atorvastatin on eGFR, particularly in those with albuminuria, was observed.

Atorvastatin did not influence albuminuria incidence. Atorvastatin was effective at decreasing CVD in those with and

without a moderately decreased eGFR and achieved a high absolute benefit.”

American Journal of Kidney Diseases 2009: 54: 810-819

This slide deck is intended for medical to medical communications and not for promotional use.


Proportion of patients with decline or improvement from baseline eGFR:TNT

9.2%

37.8%

6.6%

45.6%

0%

10%

20%

30%

40%

50%

Atorvastatin 10mg Atorvastatin 80mg

eGFR improvement from

<60mL/min/1.73m2

eGFR decline from

≥60mL/min/1.73m2

P<0.0001

P<0.0001

% o

f p

atie

nts

with

ch

an

ge

in e

GF

R

(n = 3,324) (n = 3,225) (n = 1,505) (n = 1,602)

American Journal of Kidney Diseases 2009: 54: 810-819

Are all statins similar regarding renal function?



PLANET I: Prospective evaLuation of proteinuriA and reNal function in diabETic patients with progressive renal disease

Primary end point:

Change in urinary/creatinine ratio from

baseline to Week 52

Ongoing, report date unknown

Key secondary end points:

Assessment of relationship between renal

effects and lipid parameters from baseline to

weeks 26 and 52

Change in GFR from baseline to

weeks 26 and 52

Rosuvastatin 20mg

Atorvastatin 40mg

Rosuvastatin 10mg

Rosuvastatin 40mg

Atorvastatin 80mg

Weeks 0 4 52

353 patients

Type 1 or 2 diabetes

Mild hypercholesterolemia

Fasting LDL-C ≥90mg/dL

Moderate proteinuria

Receiving ACE inhibitor and/or

ARB treatment for >3 months Period 1 Period 2

de Zeeuw D. 2010European Renal Association-European Dialysis and Transplant Association Congress; June 27, 2010; Munich, Germany



Planet 1: change in eGFR

-2.73

-3.7

-5.46

-7.29

-10

-8

-6

-4

-2

0

Week 26 Week 52

RSV 10/10 RSV 20/40 ATV 40/80

*eGFR data not provided These results have not been published and have not been peer-reviewed

Ch

an

ge

in

eG

FR

(m

L/m

in)

Week 26 Week 52

Mean change in eGFR significantly different between RSV 20/40 and ATV 40/80 at Week 26 (P=0.04) and Week 52 (P=0.01)

P=0.03

P=0.0001

P=0.01

P=0.0002

NS NS

*




Planet II: prospective evaluation of proteinuria and renal function in non-

diabetic patients with progressive renal disease

Primary end point:

Change in urinary/creatinine ratio from

baseline to 52 weeks

Key secondary end points:

Assessment of relationship between renal

effects and lipid parameters from baseline to

26 and 52 weeks

Change in GFR from baseline to 26 and

52 weeks

Rosuvastatin 20mg

Atorvastatin 40mg

Rosuvastatin 10mg

Rosuvastatin 40mg

Atorvastatin 80mg

Weeks 0 4 52

237 patients

Mild hypercholesterolemia

Fasting LDL-C ≥90mg/dL

Moderate proteinuria

Receiving ACE inhibitor and/or

ARB treatment for >3 months

Period 1 Period 2




Planet 2: change in eGFR

-4

-3

-2

-1

0

1

2

Week 26 Week 52

RSV 10/10 RSV 20/40 ATV 40/80

*P 0.03, †P=NS vs. baseline

Cha

ng

e in

eG

FR

(m

L/m

in)

Week 26 Week 52

†NS

1.39

-3.41*

-1.61

†NS

-2.71

†NS -3.30*

-1.74

†NS


Foe: Can statins damage the kidney?

CTT meta-analysis: muscle damage with

statins

• Myopathy: 0.5/1,000

• Rhabdomyolysis :0.1/1,000

Lancet 2012;380:581-590

High dose statins increased hospitalization for acute renal damage in

non-CKD patients: retrospective analysis

Dormuth C R et al. BMJ 2013;346:bmj.f880

Admission within 120 days

and persists for 2 years

OR 1.34 ( 1.25 to 1.43)

NNH= 1/1,700

N=2,008,003 Admission Low dose: 1-4/1,000

Dormuth C R et al. BMJ 2013;346:bmj.f880

High dose statins did not increase hospitalization for acute renal

damage in CKD patients: retrospective analysis

HR 1.10 (0.99 to 1.23)

n=59,000 Admission : Low dose: 23-45/1,000

Adverse events of statin reported in the trials with chronic

kidney disease.


Conclusions: Friend of foe?

• CKD

– is increasing in Latin America

– raises CVD risk

• Statins reduce CVD and mortality in CKD

– Benefit proportional do LDL-C lowering

– Less benefit in those with more advanced disease

• Statins are safe in CKD

• Improvement in GFR (Atorva trials)

the kidney & statin therapy: friend or foe? - pace-cme kidney & statin therapy: friend or...

Documents