the lipid management is very important for treatment of peripheral arterial disease

1. Lipid management in
PAD
DR ASHWANI MEHTA
SENIOR CONSULTANT CARDIOLOGIST
SIR GANGA RAM HOSPITAL
NEW DELHI

2. PERIPHERAL ARTERIAL DISEASE
• Peripheral artery disease (PAD) is a manifestation of
systemic atherosclerosis and is associated with high
mortality due to cardiovascular events.Includes renal and
carotid disease also.
• As lipid-lowering therapy has proven its efficiency in the
treatment of patients with atherosclerosis including -
PAD.
• There is a need for disseminating information to improve
adherence to the lipid reduction protocols specially in
India .

3. Typical vs Atypical Symptoms
in Patients With Symptomatic PAD
33%2
>50%2
Atypical Symptoms1
• Exertional leg pain that
– may involve areas other
than the calves
– may not stop the patient
from walking
– may not resolve within
10 minutes of rest
Typical Symptoms1
Intermittent claudication
• Exertional calf pain that
– causes the patient to
stop walking
– resolves within 10
minutes of rest
1. McDermott MM et al. JAMA. 2001;286:1599-1606.
2. Hiatt WR. N Engl J Med. 2001;344:1608-1621.
Other nonspecific
leg symptoms
that may be
indicative of PAD

4. Prevalence of PAD in At-Risk Patients
• The PARTNERS* program evaluated 6,979 patients in
physicians’ offices.
• Patient criteria:
≥70 years, or
– 50–69 years with a history of smoking and/or diabetes
* PARTNERS=PAD Awareness, Risk, and Treatment: New Resources for Survival.
Hirsch AT, et al. JAMA. 2001;286:1317-1324.
29%29% of patients were
diagnosed with PAD
29%

5. *
Kaplan-Meier survival curves based on mortality from all causes.
†
Large-vessel PAD.
Adapted from Criqui MH et al. N Engl J Med. 1992;326:381-386.
Normal Subjects
Asymptomatic LV-PAD†
Symptomatic LV-PAD†
Severe Symptomatic LV-PAD†
1.00
0.75
0.50
0.25
0.00
0 2 4 6 8 10 12
Survival
Year
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
Impact of PAD on Mortality

6. Event-free survival by PAD status at 5 years for 6880
patients
Kaplan–Meier estimates showing all-cause mortality or
severe vascular events
Curt Diehm, Circulation November 24, 2009

7. Natural History of PAD
Age > 50 years
Limb
Morbidity
Cardiovascular
Morbidity /
Mortality
Worsening
Claudication
10-20%
Critical
Limb
Ischemia
1-2%
Nonfatal
CV Events
20%
Mortality
15-30%
Stable
Claudication
70-80%
CV Causes
75%
Non CV Causes
25%

8. Values of plasma lipid and lipoprotein
concentrations in male cases with PAD and
healthy controls
B.F. Mowat et al. : Atherosclerosis 131 (1997) 161–166

9. Lipoprotein(a) and PAD in a Community-Based Sample of Older Men and
Women (the InCHIANTI Study)
Am J Cardiol 2010;105:1825–1830

10. Heart Protection Study: Vascular Events by
Baseline Disease
Baseline feature
Simvastatin
(n=10,269)
Placebo
(n=10,267)
Previous MI 1007 1255
Other CHD (not MI) 914 1234
No prior CHD
CVD 182 215
PVD 332 427
Diabetes 279 369
All patients
2042
(19.9%)
2606
(25.4%)
Collins R. Presented at AHA, Anaheim, California, 13 November 2001.
Risk ratio and 95% CI
Statin
better
Statin
worse
↓ 24 ± 2.6%
(2P <0.00001)
0.4 0.6 0.8 1.0 1.2 1.4

13. The effect of intensified lipid-lowering therapy on long-term
prognosis in patients with peripheral arterial disease (1374 patients,
followed for 6.4 ± 3.6 years)
J Vasc Surg 2007;45:936-43

14. Prospective trial
Journal of vascular surgery 2007
INTERPRETATION:
Pravastatin given for 3 years reduced the risk of coronary
disease in elderly individuals. PROSPER therefore extends to
elderly individuals the treatment strategy currently used in
middle aged people

15. Risk Reduction with ACE-inhibitors, Statins,
and Antiplatelet Therapy in PAD
APTC Antiplatelet Trialists’ Collaboration. BMJ. 1994;308:81-106.
CAPRIE Steering Committee. Lancet. 1996;348:1329-1339.
HOPE Study Investigators. N Engl J Med. 2000;342:145-153.
Heart Protection Study Collaborative Group. Lancet. 2002;360:7-22.
placebo 6.0%
CAPRIE* clopidogrel
4.9%
3.7%
0 1 2 3 4 5 6 7
HOPE* ramipril
4.4%
3.4%
placebo
HPS*
placebo
simvastatin
6.1%
4.9%
aspirin
Event Rate (% per year)
APTC*
No. of Patients
(>9000)
(>6000)
(4051)
(2701)
P < 0.001
P < 0.001
*PAD subgroups only.

16. 1. Kannel WB. J Cardiovasc Risk. 1994;1:333-339.
2. Criqui MH et al. N Engl J Med. 1992;326:381-386.
Stroke1
Fatal MI or
CHD Death2
Death
from
CVD2
0
2
4
6
8
10
IncreasedRisk
ofCVMortality
4x
2–3x
6x
Patients with
symptomatic PAD
face up to 6x
greater risk of
death from CVD,
including MI and
stroke
Cardiovascular Events with PAD

17. IMPROVEMENT OF QUALITY OF LIFE
• Regarding functional capacity, lipid-lowering therapy has also proved to be beneficial,
multiple studies showing an improvement of walking performance and claudication.
• The same Cochrane meta-analysis mentioned above showed the impact of different
lipid-lowering drugs on PAD symptoms [4]. Although there was not a significant
change of ABI after lipid-lowering treatment, an improvement in the total walking
distance and pain-free walking distance was observed.
• The results of POSCH (Program on the Surgical Control of the Hyperlipidemias)
showed that cholesterol reduction by partial ileal bypass surgery leads to a reduction
in the development of clinically evident PAD and of ABI values, although no changes
were observed in the peripheral arteriograms after a mean follow-up period of 10
years.

18. IMPROVEMENT OF QUALITY OF LIFE
• The Scandinavian Simvastatin Survival Study demonstrated a
reduction by 38% of the risk of new or worsening intermittent
claudication in the simvastatin group vs the placebo group, over a
follow-up period of 5.4 years .
• This study demonstrated the beneficial effects of statins in slowing
the process of atherosclerosis, no matter its location, by also
reducing the incidence of carotid bruits and of new or worsening
angina.

19. Cholesterol Reduction and the
Development of Intermittent Claudication
Scandinavian Simvastatin
Survival Study Pedersen et al. Am J
Card 1998;81:333-5.
Placebo
38%
Simvastatin
]

20. What should we do?
1. Treat as CAD
2. Statins in all PAD patients

21. Patients with statin use had significantly less
inflammatory activity in 515 patients with severe PAD
European Heart Journal (2004) 25, 742–748

22. Effect of Atorvastatin of Maximum Walking
Time in PAD
Mohler E R et al. Circulation 2003;108:1481-1486

23. Non Statin therapy
• Fibrates
• Ezetimibe
• PCSK 9 antibodies

24. NON-STATIN LIPID-LOWERING
THERAPY
• Although data from the Framingham Study indicated that
the lipid profile of patients with PAD is that of metabolic
syndrome (high level of triglycerides and low level of
high-density lipoprotein) .
• No Conclusive evidence to show benefit.

25. PLEIOTROPIC EFFECTS OF STATINS
• The beneficial impact of statins in patients with PAD is
explained not only by their lipid-lowering properties, but
also by their pleiotropic effects.
• Statins play an important role in stabilization and
regression of atherosclerotic lesions, a fact supported by
studies that used imaging methods.

26. Patients with statin use had significantly less
inflammatory activity in 515 patients with severe PAD
European Heart Journal (2004) 25, 742–748

27. Statin therapy improves cardiovascular outcome of
patients with severe PAD
European Heart Journal
(2004) 25, 742–748

28. Peripheral Arterial Disease (PAD)
• Studies of patients with atherosclerotic PAD
support the concept that PAD, regardless of
diagnosis by ABI, lower limb blood flow
studies, or clinical symptoms, is a CHD risk
equivalent

29. Guidelines for Lipid Management in PAD
Guideline
source
LDL-C HDL-C Triglycerides
ACCF/AHA
Class 1: LDL <100 mg/dl, for all patients with PAD
using HMG-CoA reductase inhibitor (statin)
Class 2a: LDL <70 mg/dl, for those at high risk of
ischemic events
Class 2a: low HDL,
consider treatment with
fibric acid derivative
Class 2a: elevated
triglycerides, consider
treatment with fibric acid
derivative
TASC II
LOE A: LDL <100 mg/dl, for all patients with PAD
LOE B: LDL <70 mg/dl, for patients with
atherosclerosis in other territories
LOE A: statin drugs should be the primary agent used
LOE B: low HDL,
consider treatment with
niacin or fibrates
LOE B: elevated
triglycerides, consider
treatment with fibrates
ESC
Class 1: LDL <2.5 mmol/l (100 mg/dl), for all patients
with PAD
Class 1: Optimal LDL <1.8 mmol/l (<70 mg/dl)
Class 1: Goal >50% LDL reduction, if target level
cannot be reached
Not addressed in
guidelines
Not addressed in
guidelines

30. Date of download: 4/29/2016 Copyright © The American College of Cardiology. All rights reserved.
From: 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A
Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines
J Am Coll Cardiol. 2014;63(25_PA):2889-2934. doi:10.1016/j.jacc.2013.11.002

31. HOW LOW IS LOW ENOUGH?
• Although a threshold for LDL-C is recommended by the guidelines,
there are still questions about the optimal treatment regimen that
should be adopted in patients with PAD.
• How intensive should statin therapy be ? What is the threshold at
which the possible benefits of statin therapy are outweighed by their
adverse effects?
• Evidence : A study that included over 1,300 patients over a period of
15 years showed that higher doses of statins and lower LDL-C
levels are both independently associated with improved outcome in
patients with PAD.
• ( The effect of intensified lipid-lowering therapy on long-term prognosis in patients with peripheral arterial disease.
Feringa HH, Karagiannis SE, van Waning VH, Boersma E, Schouten O, Bax JJ, et al.J Vasc Surg.2007
May;45(5):936-43.)

32. To conclude : Statins are beneficial
• In preventing cardiovascular events
• Pleiotropic effects, can also increase the
functional capacity and lower the risk of adverse
limb outcomes.
• Recent data indicate a major paradigm shift:
targeting atherosclerotic cardiovascular disease
risk instead of LDL-levels applies also to
patients of peripheral vascular disease.

33. THANK YOU
STATINS FOR ALL