- 2nd Amiri Diabetes Conference 2014

Report
Hyperlipidemia Management in T2DM
Changing Diabetes Mellitus to
Diabetes Lipidus
Dr.Wehad ALTourah
Consultant Internist, Assistant Director
Internal Medicine Residency training Program
FRCP(London),KBIM
Amiri Hospital
Outline
Cases
Epidemiology and cardiovascular risk
Lipid pattern & Target in T2DM
Screening
CV Risk Stratification
Treatment Options:
Statins,Fibrates,Niacin,Ezetimibe,Omega-3 FA
Combination Treatment
Drug Monitoring
Statin and DM
Future Research
Conclusion
Case 1
45 years-old gentleman
T2DM for 3 years,
No other significant history
Med.: Metformin 1gm /BID
BMI 30
Bp 120/80
Total Cholesterol 7mmol/L
LDL-C:2.6 mmol/L
HDL-C:1.0 mmol/L
TG: 2.0 mmol/L
Case1
What will be your primary
lipid target :
LDL-C?
HDL-C?
TG?
Case 2
45 years- old gentleman
Current smoker,T2DM for 5 years, hypertension for 10 years
He is on lisonpril 10mg OD, metformin 1 gm BID
BMI 28
Blood pressure: 135/85 mmHg
HA1C 6.5%
Total cholesterol: 5 mmol/L
LDL-cholesterol: 2.6 mmol/L
HDL-cholesterol: 1.2 mmol/L
Triglycerides: 2.0 mmol/L
Case 2
Would You Initiate a lipid
lowering agent in This
Patient?
OR
Would you advise nonpharmacological
Treatment?
Case 3
50 years-old lady
T2DM for 12 years, Hypertension, non-smoker
Meds: metformin 1gm BID, lisinopril 20mg/day,
simvastatin10mg/day
BMI 26.5
Bp: 135/85 mmHg
Total cholesterol: 4.7 mmol/l
LDL-cholesterol: 2.7 mmol/L
HDL-cholesterol: 1.0 mmol/L
Triglycerides: 2.4 mmol/L
Case 3
Would you Intensify This
Patient’s Statin?
OR
Would you change her
statin to more potent
agent?
Case 4
65year-old lady,
T2DM, PCI for STEMI 6 months ago
no current CV symptoms
Meds: ASA, clopidogrel, lisinopril, atorvastatin 80 mg/day
BMI 29.0
Blood pressure: 125/85 mmHg
Total cholesterol: 3.1 mmol/L
LDL-cholesterol: 0.9 mmol/L
HDL-cholesterol: 0.9 mmol/L
Triglycerides: 3.4 mmol/L
Case 4
Would you decrease this
patient’s statin dose?
OR
Would you add a fibrate?
Case 5
50 year-old lady
T2DM 5 years, Hypertension 5 years
Had pain in her arms and legs for 6 months
Meds: Lisinopril 10mg/d, atorvastatin 20mg/d, aspirin
75mg/d
LFT:N
CK:700 (40-176 IU/L)
Total cholesterol:4.0mmol/L
LDL-C:1.8mmol/L
HDL-C:0.9mmolL
TG:2.0mmol/L
Case 5
What will be your Approach to
Solve this patient’s problem?
DM is a Huge Burden
IDF Diabetes Atlas, 6th edition
Top 10 countries/territories
for prevalence(%) of diabetes
(20-79),2013
Dm and CVD
IDF 2013
Dm is Strong risk Factor for CAD:DM=CHD
T2DM is associated with a marked
risk of CVD. Individuals with DM
have an absolute risk of major
coronary events similar to that on
nondiabetic individuals with
established coronary heart disease
Medescape.Treating Dyslipidemia: Recommendations
for T2DM 27/9/13
The risk for CVS death is ↑2-3 fold in T2DM.
Prevalence of Dyslipidemia
is high in Type 2 Diabetes
Control of Lipids
LDL-C
> 100 mg/dL
HDL-C
< 40 mg/dL (men)
< 50 mg/dL (women)
Triglycerides
> 150 mg/dL
Patients With
Diabetes, %
Patients Without
Diabetes, %
P Value
74.7
75.7
NS
63.7
40.0
< .001
61.6
25.5
< .001
N = 498 adults (projected to 13.4 million) aged > or = 18 years with diabetes representative
of the US population and surveyed within the cross-sectional National Health and
Nutrition Examination Survey 1999-2000. Diabetes Res Clin Pract;70:263-269.2005
Lipid Pattern in Diabetes
UKPDS
Lipid Pattern in Diabetes
UKPDS
Clinical Diabetes.Vol.24,no.1,2006
The relationship between
LDL-C,HDL-C and CVD
UKPDS,0.1mmol/L
↑HDL-C was
associated with
15% ↓in CVD events
UKPDS,1mmol/L
↑LDL-C was
associated with
57% ↑risk MI
adapted from Gordon T. et al, American Journal of Medicine, 1977;62;707-714
Lipid Pattern in Diabetes
Low
HDL- C
High
Small
dense
LDL
High
TG
Lipoprotein Pattern in
Diabetes
Diabetes Care.16:434-444.1994
Whom to Screen?
How often?
ADA Guidelines 2014
-In most adult patients with DM, measure fasting
LIPID PROFILE AT LEAST ANNUALLY. (LEVEL B)
-In adults with low risk lipid values(LDL-C <2.6mmol/L,
HDL-C>1.3mmol/L, and TG<1.7mmol/L),LIPID
ASSESSMENT MAY BE REPEATED EVERY
2 YEARS.(Level E)
Diabetes Care,volume 37,Supp 1,January 2014
What are the additional
predictors beyond LDL and
HDL To be assessed?
1-Apo lipoprotein B:
No evidence yet for regular screening.
Very strong predictor for cardiovascular disease in DM.
Has less biologic variation, reliable measures.
Non fasting sample.
High cost.
ESC/EAS 2011
What are the additional
predictors beyond LDL and
HDL to be assessed?
2-Highly sensitive CRP
-These additional inflammatory markers are helpful in
intermediate risk patients but proven to be unhelpful
for the very high risk patients.
Risk Stratification?
Is it important?
What are the risk scoring
systems?
Total cardiovascular risk
estimation
1- Framingham Risk Score.
2- Systemic Coronary Risk Estimation(SCORE).
3- Atherosclerotic cardiovascular disease risk
(ASCVD).(ACC/AHA)
4- QRISK Lifetime cardiovascular risk
(Joint British Societies in 2014).
SCORE
Framingham Risk
Score
Total cardiovascular risk
estimation
Very High
Risk
Risk Level
SCORE
10yrs CVD
Risk
≥ 10%
CVD/PAD/
Stroke
+
T2DM
+
CKD
+
Risk Factors
(FH/Severe
HTN)
ESC/EAS Guidelines 2011
High Risk
Moderate
Risk
≤10% - ≥5%
≤5% - ≥1%
++
+++
Low Risk
≤1%
ASCVD 10-year Risk
ACC/AHA Guidelines 2013
Cumulative Incidence of CVD Adjusted for the Competing
Risk of Death According to Risk Factor Burden at Age 50
Lloyd-Jones DM et al, Circulation 2006;113:791
Management of
Hyperlipidemia in DM?
Management Of
Hyperlipidemia in T2DM?
1-Whom should we treat?
2-What are the important targets?
3-What are the target Levels?
4-What are the treatment
Strategies?
Q1: Whom Should we
Treat?
Whom Should we Treat?
ADA Guidelines 2014
1-Diabetic patients <40years,without CVD,LDL
cholesterol>2.6mmol/L(low risk) after failure of life
style modifications, or with multiple CVD risk
factors(level C).
ADA Guidelines, January 2014
Whom Should we Treat?
ADA Guidelines 2014
2- Patients without CVD,>40years,having one or more
other CVD risk factors(family history of CVD,
hypertension,smoking,albuminuria) regardless of the
LDL(level A).
3-Diabetic patients with overt CVD, regardless of the
LDL level(High risk patients),(level A).
ADA Guidelines,January 2014
Q2:Which target is the
most important?
LDL
Othe
rs
HDL
TG
UKPDS
- LDL cholesterol was the strongest independent predictor
of CHD, followed by HDL.TG level did not predict CHD
events.
Clinical Diabetes.Vol.24,no. 1,2006
Q3: What Are the Lipid’s
Target Level?
ADA Guidelines 2014
In individuals without overt CVD, the goal is LDL-C
<2.6mmol/L.(Level B)
Individuals with overt CVD, a lower LDL-C
goal of < 1.8mmol/L with a high dose statin.
(Level B)
If maximum tolerated statin therapy, a reduction in
LDL-C of 30-40-% from baseline is an alternative
goal.(Level B)
Diabetes Care,vol.37,Supp 1,January 2014
ADA Guidelines 2014
TG <1.7mmol/L and HDL cholesterol>1.0mmo/L in
men and > 1.3mmo/L in women.
LDL-C -targeted statin therapy remains the preferred
strategy.(Level A)
ADA Guidelines,January 2014
Q4:What are the Treatment
Options or Strategies?
Treatment Options
Life Style
Exercise
Diet
Pharmacological Lipid Management
Statins Fibrates
Niacin Ezetimibe
Non-Lipid Interventions
Intensive Glycemic
Control
Intensive Blood
Pressure Control
Life style modification is
critical component
Weight Loss
Exercise
Diet
Life Style Intervention
ESC/EAS 2011
>5% weight loss
if BMI>25
Level I
30min.moderate
physical activity
on most days/
wk. Level II
Serves up 8,000
calorie burger
meal... the
equivalent of
FIVE DAYS worth
of food
Life Style Intervention
Diet
1-High polyunsaturated fatty acids diet – saturated fat< 7% of
daily calories +↓intake of cholesterol to 200mg/day(Level II).
2-↑the amount of soluble dietary fibers to 10-25g/day(level II).
→associated with 5-15% ↓in the LDL-C.
3- limits the carbohydrates to <60% in individuals with ↑TG/
↓HDL→ short term effect /OR replace the saturated fat with
carbohydrates /monosaturated fat(Level I).
National Evidence Based Guidelines for the Management of Type 2 Diabetes
Mellitus. the Australian Centre for Diabetes Strategies.Part7.2004
ADA.2014
Dietary Recommendation
to TC and LDL-C
ESC,EAS Guidelines2011
Effects of Drug Therapy and
Diet on Lipids
Pre-drug
Drug
Drug + diet
325
300
275
250
TC 225
(mg/dL)
200
175
150
125
100
1° Prevention (n=40)
* 84% reached NCEP LDL target (<130 mg/dL)
† 63% reached NCEP LDL-C target (<100 mg/dL)
Barnard RJ, et al. Exerpta Medica Brief Reports. 1997;1112-1114.
2° Prevention (n=53)
Pharmacological Lipid
Management
Statins
Combina
tions
Fibrates
Ezetimibe
Niacin
Use Statins To Treat
the Risk Not
Cholesterol
Clinical Trial Evidence
Primary
Prevention
Secondary
Prevention
Study
Intervention
Baseline
LDLcholesterol
(mg/dl)
Number
Diabetes/
Total
CVD
Out
come
RRR
Diabetes
(%)
RRR
NonDiabetes
(%)
Primary
Prevention
CARDS
Atorvastatin
10mg
117
2838
Acute Coronary
Events
Stroke
36*
-
Primary
secondary
Prevention
HPS
ALLHAT
Primary Prevention
CARDS
Simvastatin
20mg
5963/20536
Major CHD event
Primary&124Secondary
Prevention
Any major CVS
event
HPS
Pravastatin
129
3635/10357
Major CHD event
48*
27*
22*
27*
24*
11
8
16
23*
44*
20*
Total mortality
Major CHD event
43
55*
29*
23*
10mg
ASCOT-LLA
Atorvastatin
10mg
Secondary
Prevention
128
2532/10305
Major CHD event
Secondary
Prevention
Total CVS events
and procedures
4S
4S
Simvastatin
10-40mg
186
202/4444
CTT
CARE
Pravastatin
40mg
136
586/4159
Major CHD
Expanded endpoint
13
25*
26*
23*
LIPID
Pravastatin
40mg
143
1077/9014
Major CHD event
Any CVS event
19
21*
23*
13*
Clinical Diabetes.Vol.24.no.1,2006
Collaborative Atorvastatin
Diabetes Study(CARDS)
First RCT statin trial conducted only in diabetic subjects
2838 patients
40-75 yrs
T2DM
1428
Atorvastatin
10mg
1410 placebo
LDL-C <4.4
+at least one
risk factor
Primary endpoint
Time to first CV event/revascularization/stroke
FU 3.9 yrs
Lancet.364:685-696.2004
CARDS
The trial was terminated 2 years earlier than expected
40% reduction LDL-C
CARDS
Conclusion:
Atorvastatin 10 mg daily is safe and efficacious in
reducing the risk of first cardiovascular disease
events, including stroke, in patients with T2DM
without high LDL-cholesterol.
Lancet.364:685-696.2004
Heart Protection Study(HPS)
The Largest sub-analysis of statins in patients with DM
( 2912 T2DM )
Composite primary end point 33
Effect of Statins in the 4S trial
in patients with and without
Diabetes
*There was 55%reduction in the
incidence of CVD events(P0.002)
CTT Meta-analysis
18686 patients with diabetes from 14 RCTs primary&
secondary CVD prevention, follow-up 4.3 years
21%reduction in
the incidence of
major vascular
events/1mmol
LDL-C reduction
Lancet.366.1267-1278.2005
Is intensive Lipid Lowering
Beneficial?
Is intensive Lipid Lowering
Beneficial?
Treating to New Targets Study (TNT)
Pravastatin or Atorvastatin Evaluation
and Infection Therapy- Thrombolysis in
Myocardial Infarction 22
(PROVE IT-TIMI22)
Incremental Decrease in Endpoints Through
Aggressive Lipid Lowering(IDEAL)
:103 patients :80mg/D,135 :10mg/D
*Significant differences in favour of atorvastatin
80 mg were also observed for time to CVA
event (P 0.037) and any CV event (P 0.044).
*LDL cholesterol levels were
significantly lowered in patients
receiving atorvastatin 80mg
(P <0.0001).
Diabetes Care,Vol.29,no.6,January2006
-No significant difference between the treatment groups in
the rate of treatment related adverse events and
persistent elevation in liver enzymes.
Diabetes Care,Vol.29,no.6,January2006
Diabetes Care,Vol.29,no.6,January2006
PROVE IT –TIMI 22
To determine the impact of intensive lipid lowering therapy versus
standard therapy with statins on the outcome in acute coronary
syndrome(ACS) patients with diabetes.
4162 patients
739 DM
ACS
Atorvastatin
80mg
Pravastatin
40mg
FU
18-36months
Primary endpoint
death, MI, unstable angina requiring hospitalization,
revascularization with PCI or CABG at least 30 days following
randomization or stroke,
Triple endpoint:
acute cardiac events(death, MI, unstable angina requiring
hospitalization)
PROVE IT –TIMI 22
PROVE IT-TIMI 22
*Rate of events was higher in diabetic patients and the rate of acute
cardiac events was reduced with the intensive therapy
P(0.03)
PROVE IT –TIMI 22
Conclusion:
In ACS patients with DM, intensive statins therapy
reduces the acute cardiac events as it does in those
without DM.
Despite intensive therapy, the majority of diabetics did
not reach the dual goal of LDL-C< 1.8mmol/L.
Statins?
Which Dose?
ADA Guidelines 2014
Maximum tolerated drug dose that will lead to the
target LDL,OR 30-40%rduction in LDL-C from baseline.
(Level B)
ACC/AHA Guideline 2013
ACC/AHA Guidelines 2013
Are All Statin the Same?
Which Statin?
The CURVES Trial
Comparison of LDL-C among
Statins
*At doses of 10, 20, and 40 mg,
atorvastatin produced reductions in
LDL-C of -38%, -46%, and -51%,
respectively (P>0.01).
Am J Cardiol.81:582-587.1998
Residual CV Risk
Remains?
Treatment Beyond
LDL-Cholesterol?
Beyond LDL-Cholesterol:
Triglyceride(TG)
HDL-Cholesterol
(Guidelines for the HDL-C target levels were not established)
What are the target levels
According to the
Guidelines?
ADA 2014:
TG level<150mg/dl(1.7mmol/L) and HDL-Cholesterol
>40mg/dl(1.0mmol/L)in men and >50mg/dl(1.3mmol/L)
in women are desirable.(Level C).
HDL-C raising strategies may be considered in high-risk
individuals with HDL-C < 40mg/dl(<50mg/dl in women).
What are the available agents?
Fibrates
Niacin
Ezetimibe
Omega 3
What is the evidence from
the trials?
Fibrates
FIELD
VA-HIT
ACCORD
Fenofibrate Intervention and
Event Lowering in DM study
(FIELD)
-FIELD is primary prevention , double-blind, placebocontrolled trial in 63 centres in 3 countries.
-Examining the effects of long-term fibrate therapy
on coronary heart disease (CHD) event rates in
patients with T2DM regardless of the lipid profile.
Lancet,366:1849.2005
FIELD
Primary end
point:
CAD death,
non-fatal MI
Significant reduction in all
CV death& secodary end
point (P0.035).Effect is more
in mixed lipidemia.
ADA Guidelines 2014
- Hypertriglyceridemia
dietary and life style changes.
-Severe hypertriglyceridemia is absent
therapy targeting HDL-C or TG lacks the strong evidence
base of statin therapy.
- Severe hypertriglyceridemia <1000mg/dl(11mmol/L)
immediate pharmacological therapy may be warranted with
fibtares, niacin or fish oil.
Is Combination therapy
Beneficial?
The Action to Control
Cardiovascular Risk in
Diabetes-Lipid trial(ACCORD)
ACCORD
-Investigated whether combination therapy with a statin
plus a fibrate, as compared with statin monotherapy,
would reduce the risk of cardiovascular disease in
patients with T2DM at high risk for CVD.
NEJM. Vol. 362. no.17.April 29,2010
ACCORD
5518
patients
T 2 DM
2765received
fenofibrate
&simvastatin
2753 received
Simvastatin&
placebo
Secondary
outcomes included the
combination of the
primary outcome plus
revascularization or
hospitalization
for congestive heart
failure
FU 4.7 years
primary outcome
was the first
occurrence of a
major cardiovascular
event
NEJM.vol.362no.17.April 29.2010
ACCORD: Results
NEJM.vol.362.no.17.April 29.2010
ACCORD: Results
NEJM.vol.362.no.17.April 29.2010
ACCORD
“The combination of fenofibrate and simvatatin did not
reduce the rate of fatal cardiovascular events, non-fatal MI
or non-fatal stroke, as compared with simvatatin alone.”
NEJM, April 29,2010.vol.362no.17
ADA Guidelines 2014
Combination therapy with statin and fibrates maybe
efficacious for treatment for all three lipid fractions, but
this combination is associated with an increased risk of
abnormal transaminase levels, myositis or
rhabdomyolysis and does not provide additional CVS
benefit. Hence, combination therapy can not be
broadly recommended.(Level A)
*Gemfibrozil is not preferably combined with statins
ACC/AHA 2013 Guidelines
Niacin:
-Niacin is the most effective drug for raising HDL-C.
-Niacin Trials:
ARBITER 6-HALTSNIA-Plaque,AIM-HIGH,
-HPS2-THRIVE showed disappointing results.
Diabetes&Vascular Disease Research.10(2) 99-114.2012
Niacin:
-NO COMPLETED RCT with clinical endpoints are
available yet to guide practice on addition of niacin to
statin therapy.
-Until the results of the ongoing trials are reported,
a consensus suggested to add niacin to statin in very high
risk group.
Medescape .15.3.2011
ADA Guidelines 2014
If the HDL-C<1mmol/L and the LDL-C between
2.6mmol/L and 3.3mmol/L , a fibrate or niacin might
be used especially if a patient is intolerant to statins.
Ezetimibe
The Improved Reduction of Outcomes: Vytorin Efficacy
International Trial:
IMPROVE-IT Trial:
-The trial is investigating the effect of simvastatin 40mg/d
with or without ezetimibe 10mg/d in patients with ACS.
Outcome:
-Effect of treatment on CVD death, non-fatal stroke and
mom-fatal MI
-The results will be released in September 2014
Diabetes&Vascular Disease Research.10(2) 99-114.2012
Omega- 3 Fatty Acids
- Omega-3 PUFAs can be used to ↓ TG levels.
Trials:
ORIGIN
GISSI-P
JELIS
-There were differences in the outcomes seen in the
various PUFA studies.
-Further studies are needed to confirm the benefit of omega
-3 FA in patients with DM and dyslipidemia.
Pharmacotherapy.24(12):1692-1713.2004
How would you monitor
Lipid Lowering Therapy?
How Would You Treat
Intolerability to Lipid
Lowering Agents?
ESC/EAS Guidelines 2011
Statins are safe but nothing is without risk:
Review of 35 statin therapy trials
FDA-approved statin* monotherapy vs placebo (N = 74,102)
Outcome
Statin Placebo
(%)
(%)
RD
P value
Myalgias
15.4
18.7
2.7
0.37
CK elevations
0.9
0.4
0.2
0.64
Rhabdomyolysis
0.2
0.1
0.4
0.13
LFT elevation
1.4
1.1
4.2
<0.01
AE
discontinuation
5.6
6.1
-0.5
0.80
*Atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, simvastatin.AE:adverse events.
Circulation;114:2788-97.2006
ESC/EAS Guidelines 2011
Statin Diabetogenicity
Remaining Question
-JUPITER Trial: 26% higher incidence of DM in the
rosuvastatin group.
-A meta-analysis of 13 RC statin trials with 91140
participants showed that treatment of 255 patients with
statins for 4 years resulted in one additional case of DM
while preventing 5.4 vascular events among 255 patients.
-Future studies should continue to assess the effects of end
organ dysfunction related to long-term hyperglycemia from
statin therapy.
Am J Cardiovasc Drugs.14:79-87(2014)
Curr Opin Cardio.28:554-560.2013/ Lancet.375:75-742.2010.
Future Research
New LDL-C lowering drugs Phase III trials:
1-Microsomal transfer protein inhibitors(MTP).
2-Thyroid hormone mimetics with liver selectivity.
3-Oligonucleotides suppressing Apo B.
ESC/EAS Guidelines 2011
CASES
Case 1
What will be your primary lipid target :
LDL-C? HDL-C? TG?
45 years-old gentleman
T2DM for 3 years,
No other significant history
Med.: Metformin 1gm /BID
BMI30
Bp 120/80
Total Cholesterol 7mmol/L
LDL-C:2.6 mmol/L
HDL-C: 1 mmol/L
TG: 2 mmol/L
Case 1
UKDP: LDL cholesterol was the strongest independent
predictor of CHD, followed by HDL.TG level did not predict
CHD events.
-LDL-C remains the primary goal in the treatment of
dyslipidemia according to ADA,ACC,ESC and NCEP.
-Targeting HDL-C may be useful in high risk patients but
still the evidence is lacking.
Diabetes&Vascular Disease Research.10(2).99-114.2012
British Journal of Diabetes and Vascular Disease.Vol.5.issue2.56-62.2005
Case 2: Would You Initiate a lipid lowering agent in
This Patient? OR
Would you advise non-pharmacological Treatment
45 years- old gentleman
Current smoker, 10 year history of hypertension
He is on lisonpril 10mg OD
BMI 28
Blood pressure: 135/85 mmHg
HA1C 6.5%
Total cholesterol: 5 mmol/L
LDL-cholesterol: 2.6 mmol/L
HDL-cholesterol: 1.2 mmol/L
Triglycerides: 2.0 mmol/L
Whom Should we Treat?
ADA Guidelines 2014
1-Diabetic patients <40years,without CVD,LDL
cholesterol>2.6mmol/L(low risk) after failure of life
style modifications, or with multiple CVD risk
factors(level C).
ADA Guidelines, January 2014
Whom Should we Treat?
ADA Guidelines 2014
2- Patients without CVD,>40years,having one or more
other CVD risk factors(family history of CVD,
hypertension,smoking,albuminuria) regardless of the
LDL(level A).
3-Diabetic patients with overt CVD, regardless of the
LDL level(High risk patients),(level A).
ADA Guidelines,January 2014
Case 3: Would you Intensify This Patient’s Statin?
OR
Would you change her statin to more potent agent
50 years-old lady
T2DM for 12 years, Hypertension, non-smoker
Meds: metformin 1gm BID, lisinopril 20mg/day,
simvastatin10mg/day
BMI 26.5
Bp: 135/85 mmHg
Total cholesterol: 6 mmol/l
LDL-cholesterol: 2.7 mmol/L
HDL-cholesterol: 1.0 mmol/L
Triglycerides: 2.4 mmol/L
Case 3
DM, age 40-75,LDL-C
1.8-4.9mmol/L:
Framingham
CV Risk Score=
3.44% moderate
intensityrisk=
statin
unless score>7.5%,then high –intensity
SCORE
1%
statin
The patient will be in the moderate risk group
Case 4: Would you decrease this patient’s statin
dose? OR Would you add a fibrate?
65year-old lady,
T2DM, PCI for STEMI 6 months ago
no current CV symptoms
Meds: ASA, clopidogrel, lisinopril, atorvastatin 80 mg/day
BMI 29.0
Blood pressure: 125/85 mmHg
Total cholesterol: 3.1 mmol/L
LDL-cholesterol: 0.9 mmol/L
HDL-cholesterol: 0.9 mmol/L
Triglycerides: 3.4 mmol/L
Total cardiovascular risk
estimation
Risk Level
Very High
Risk
SCORE
10yrs CVD
Risk
≥ 10%
CVD/PAD/
Stroke
+
T2DM
+
CKD
+
Risk Factors
(FH/Severe
HTN)
ESC/EAS Guidelines 2011
High Risk
Moderate
Risk
≤10%≥5%
≤5%≥1%
++
+++
Low Risk
≤1%
Case 4: ADA Guidelines 2014
Combination therapy with statin and fibrates or statin and niacin
maybe efficacious for treatment for all three lipid fractions, but this
combination is associated with an increased risk of abnormal
transaminase levels, myositis or rhabdomyolysis and does not
provide additional CVS benefit. Hence, combination therapy can
not be broadly recommended.(Level A)
ACC/AHA Guidelines 2013
Case 5: What will be your Approach to Solve this
patient problem?
50 year-old lady
T2DM 5 years, Hypertension 5 years
Had pain in her arms and legs for 6 months
Meds: Lisinopril 10mg/d, atorvastatin 20mg/d,aspirin
75mg/d
LFT:N
CK:700 (40-176 IU/L)
Total cholesterol:4.0mmol/L
LDL-C:1.8mmol/L
HDL-C:0.9mmolL
TG:2.0mmol/L
Case5:ESC/EASGuidelines 2011
Conclusion
-The prevalence of T2DM is continuing to rise.
- Diabetes increases the risk of CVD which is the major
cause of death in this population, and is treated as CVD
equivalent.
-Dyslipidemia should be the key management target.
-There is little evidence for any threshold below which the
lower LDL-C is not associated with lower risk.
Conclusion
- Life style measures are an important cornerstone in the
management.
-Glycemic Control can also beneficially modify plasma lipid
levels particularly in patients with very high TG.
-Statin therapy is highly effective at reducing the risk of
CVD in primary & secondary prevention trials.
Conclusion
-Combination therapy of statins and other lipid lowering
agents can not be broadly recommended.
-Despite statin therapy, high CVD risk persists suggesting
that further intervention in addition to intensive statin
therapy are needed in the very high-risk diabetic patients.
Thank you

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