hyperlipidemia management in t2dm changing diabetes mellitus to diabetes lipidus dr.wehad altourah...

Hyperlipidemia Management in T2DMChanging Diabetes Mellitus to

Diabetes Lipidus

Dr.Wehad ALTourahConsultant Internist, Assistant Director

Internal Medicine Residency training ProgramFRCP(London),KBIM

Amiri Hospital

OutlineCases

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 245 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

Would You Initiate a lipid lowering agent in This

Patient?

OR

Would you advise non-pharmacological

Treatment?

Case 2

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

Would you Intensify This Patient’s Statin?

OR

Would you change her statin to more potent

agent?

Case 3

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?

ORWould 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

Dm is Strong risk Factor for CAD:DM=CHD

IDF 2013

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 Patients With Diabetes, %

Patients Without Diabetes, %

P Value

LDL-C > 100 mg/dL 74.7 75.7 NS

HDL-C < 40 mg/dL (men)< 50 mg/dL (women) 63.7 40.0 < .001

Triglycerides> 150 mg/dL 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

adapted from Gordon T. et al, American Journal of Medicine, 1977;62;707-714

UKPDS,1mmol/L ↑LDL-C was associated with 57% ↑risk MI

UKPDS,0.1mmol/L ↑HDL-C was associated with 15% ↓in CVD events

LowHDL- C

HighTG

HighSmall dense LDL

Lipid Pattern in Diabetes

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

Risk Level Very High Risk

High Risk Moderate Risk

Low Risk

SCORE 10yrs CVD Risk

≥ 10% ≤10% - ≥5% ≤5% - ≥1% ≤1%

CVD/PAD/Stroke

+

T2DM +

CKD +

Risk Factors(FH/Severe HTN)

++ +++

ESC/EAS Guidelines 2011

ASCVD 10-year Risk

ACC/AHA Guidelines 2013

Lloyd-Jones DM et al, Circulation 2006;113:791

Cumulative Incidence of CVD Adjusted for the Competing Risk of Death According to Risk Factor Burden at Age 50

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

HDL

TG

Others

- 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

UKPDS

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 modification is critical component

Weight Loss

Exercise

Diet

Life Style Intervention

>5% weight loss if BMI>25Level I

30min.moderate physical activity on most days/ wk. Level II

ESC/EAS 2011

Life Style

Intervention

Serves up 8,000 calorie burger meal... the equivalent of FIVE DAYS worth of food

Life Style InterventionDiet

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.Part7.2004ADA.2014

Dietary Recommendationto TC and LDL-C

ESC,EAS Guidelines2011

Effects of Drug Therapy and Diet on Lipids

100

125

150

175

200

225

250

275

300

325 Pre-drugDrug

Drug + diet

* 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.

TC (mg/dL)

1° Prevention (n=40) 2° Prevention (n=53)

Pharmacological Lipid Management

Statins

Fibrates

NiacinEzetimibe

Combinations

Use Statins To Treat the Risk Not Cholesterol

Clinical Trial Evidence

Primary Prevention

Secondary Prevention

Study Intervention Baseline LDL-

cholesterol(mg/dl)

NumberDiabetes/

Total

CVDOut

come

RRRDiabetes

(%)

RRRNon-

Diabetes(%)

Primary Prevention

CARDS

Atorvastatin 10mg

117 2838 Acute Coronary EventsStroke

36*

48*

--

Primary secondary Prevention

HPS Simvastatin 20mg

124 5963/20536 Major CHD eventAny major CVS

event

27*22*

27*24*

ALLHAT Pravastatin10mg

129 3635/10357 Major CHD event 11 8

ASCOT-LLA Atorvastatin 10mg

128 2532/10305 Major CHD eventTotal CVS events and procedures

16 23*

44*20*

Secondary Prevention

4S Simvastatin10-40mg

186 202/4444 Total mortalityMajor CHD event

43 55*

29*23*

CARE Pravastatin40mg

136 586/4159 Major CHDExpanded endpoint

13 25*

26*23*

LIPID Pravastatin 40mg

143 1077/9014 Major CHD eventAny CVS event

19 21*

23*13*

Clinical Diabetes.Vol.24.no.1,2006

Primary PreventionCARDS

Primary& Secondary Prevention HPS

Secondary Prevention4S

CTT

Collaborative Atorvastatin Diabetes Study(CARDS)

First RCT statin trial conducted only in diabetic subjects2838 patients 40-75 yrs

T2DM1428Atorvastatin 10mg

1410 placebo

Primary endpointTime to first CV event/revascularization/stroke

FU 3.9 yrs

Lancet.364:685-696.2004

CARDSThe trial was terminated 2 years earlier than expected

40% reduction LDL-C

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

CARDS

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

Lancet.366.1267-1278.2005

21%reduction in the incidence of major vascular events/1mmol LDL-C reduction

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

*LDL cholesterol levels were significantly lowered in patients receiving atorvastatin 80mg (P <0.0001).

Diabetes Care,Vol.29,no.6,January2006

*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).

-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

4162 patients 739 DM

ACSAtorvastatin 80mg

Pravastatin 40mg

FU18-36months

PROVE IT –TIMI 22To determine the impact of intensive lipid lowering therapy versusstandard therapy with statins on the outcome in acute coronary

syndrome(ACS) patients with diabetes.

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)

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.

PROVE IT –TIMI 22

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?

*At doses of 10, 20, and 40 mg, atorvastatin produced reductions in LDL-C of -38%, -46%, and -51%, respectively (P>0.01).

The CURVES TrialComparison of LDL-C among

Statins

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

Omega 3

Ezetimibe

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, placebo-controlled trial in 63 centres in 3 countries.

-Examining the effects of long-term fibrate therapy on coronary heart disease (CHD) event rates inpatients 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.

- 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.

ADA Guidelines 2014

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

2765received fenofibrate &simvastatin

2753 receivedSimvastatin&

placebo FU 4.7 years

primary outcome was the first occurrence of a major cardiovascular event

ACCORD

5518 patients T 2 DM

Secondaryoutcomes included the

combination of theprimary outcome plus revascularization or

hospitalizationfor congestive heart

failure

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

“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

ACCORD

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

-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

Niacin:

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

OutcomeStatin(%)

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

Statins are safe but nothing is without risk: Review of 35 statin therapy trials

FDA-approved statin* monotherapy vs placebo (N = 74,102)

*Atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, simvastatin.AE:adverse events.

Circulation;114:2788-97.2006

ESC/EAS Guidelines 2011

Statin DiabetogenicityRemaining 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 1What 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

Framingham CV Risk Score= 3.44%

SCORE risk= 1%

The patient will be in the moderate risk group

DM, age 40-75,LDL-C 1.8-4.9mmol/L: moderate intensity statin unless score>7.5%,then high –intensity statin

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

High Risk Moderate Risk

Low Risk

SCORE 10yrs CVD Risk

≥ 10% ≤10%≥5% ≤5%≥1% ≤1%

CVD/PAD/Stroke

+

T2DM +

CKD +

Risk Factors(FH/Severe HTN)

++ +++

ESC/EAS Guidelines 2011

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.

- 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.

Conclusion

Thank you