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GO! Diabetes Train the Trainer Program. Cardiovascular Disease Prevention Blood Pressure, Dyslipidemia, Antiplatelet Therapy. Diabetes and Hypertension Key Questions. Why should we pay so much attention? What parameters? Non Drug Recommendations Which drugs and how many?

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Go diabetes train the trainer program

GO! DiabetesTrain the Trainer Program


Cardiovascular disease prevention blood pressure dyslipidemia antiplatelet therapy

Cardiovascular Disease PreventionBlood Pressure, Dyslipidemia, Antiplatelet Therapy


Diabetes and hypertension key questions
Diabetes and Hypertension Key Questions

  • Why should we pay so much attention?

  • What parameters?

  • Non Drug Recommendations

  • Which drugs and how many?

  • What do others besides the ADA say?

  • What about resistant cases?


Diabetes and hypertension why
Diabetes and HypertensionWhy?

  • Volume Expansion

    • Increased insulin levels

      • Higher sympathetic activity

    • Increased glucose level

      • Increased sodium resorption with hyperglycemia

  • Decreased arterial compliance

  • Obesity


Hot trial effect of diastolic target on cvd events 4 years
HOT Trial: Effect Of Diastolic Target On CVD Events - 4 Years

48%

RiskReduction

30

24.4

18.6

20

Events/

1000

Pt-Yrs

11.9

10.0

9.9

9.3

10

0

<90

<85

<80

<90

<85

<80

DiabeticPatients

n=1,501; P=0.016

Non-DiabeticPatients

n=18,790; P=NS

Lancet 1998;351:1755


Ukpds blood pressure study tight vs less tight control
UKPDS Blood Pressure Study: YearsTight vs. Less Tight Control

  • 1148 type 2 patients

  • BP lowered to avg. 144/82 (controls-154/87); 9 yr follow-up

    Endpoint Risk Reduction(%) P Value

    Any diabetes related endpoint 24 0.0046

    Diabetes related deaths 32 0.019

    Heart failure 56 0.0043

    Stroke 44 0.013

    Myocardial infarction 21 NS

    Microvascular disease 37 0.0092

UKPDS. BMJ. 317: 703-713. 1998.


Diabetes treatment goals for blood pressure
Diabetes Treatment Goals Yearsfor Blood Pressure

  • Control blood pressure

    • 130/80 mmHg for most patients

    • 125/75 mmHg for patients who have proteinuria>1 g/day and renal insufficiency

  • Reduce the risk of end-organ failure

  • Reduce the risk of cardiovascular events

    • Myocardial infarction

    • Cardiovascular death

  • Delay or prevent the progression to heart failure

JNC 7 Report. JAMA 2003;289:2560; Bakris GL et al. Am J Kidney Dis 2000;36:646

ADA. Diabetes Care 2007;30(suppl 1):S15


Ada guidelines for the treatment of hypertension

Initial therapy Years

Lifestyle modification

Smoking cessation

Weight reduction

Increase physical activity

Sodium restriction

Pharmacologic therapy

Albuminuria - ACEI/ARB, thiazide, β-blocker, CCB

Albuminuria + ACEI/ARB

Multiple drugs generally required

ADA Guidelines for the Treatment of Hypertension

Goal of therapy

BP <130/80 mmHg

Diabetes Care 2007;30 (Suppl 1):S15


Number of medications to achieve goal bp in 5 trials of dm and or renal disease
Number of Medications to Achieve Goal YearsBP In 5 Trials of DM and/or Renal Disease

UKPDS (<150/85 mmHg)

2.7

ABCD (<75 mmHg DBP)

2.8

MDRD (<92 mmHg MAP)

3.6

HOT (<80 mmHg DBP)

3.3

AASK (<92 mmHg MAP)

3.8

0

1

2

3

4

Number Of BP Meds

Bakris. J Clin Hypertens 1999;1:141


Ukpds blood pressure study tight vs less tight control1
UKPDS Blood Pressure Study: YearsTight vs. Less Tight Control

  • 1148 type 2 patients

  • BP lowered to avg. 144/82 (controls-154/87); 9 yr follow-up

    Endpoint Risk Reduction(%) P Value

    Any diabetes related endpoint 24 0.0046

    Diabetes related deaths 32 0.019

    Heart failure 56 0.0043

    Stroke 44 0.013

    Myocardial infarction 21 NS

    Microvascular disease 37 0.0092

UKPDS. BMJ. 317: 703-713. 1998.


Nkf recommendations on treatment of hypertension and diabetes
NKF Recommendations On Treatment YearsOf Hypertension And Diabetes

  • Blood pressure goal: ≤130/80 mmHg

  • BP-lowering medications should reduce both BP + proteinuria

  • Lower goal has been recommended to reduce renal disease progression and incidence of ischemic heart disease

  • Antihypertensive drug classes shown to reduce proteinuria and cardiovascular events

    • ACE inhibitors

    • --blocker (carvedilol)

    • -blockers

    • CCBs

    • Diuretics

Bakris GL et al. Am J Kidney Dis 2000;36:646


Acc aha practice guidelines recommendations for patients at high risk for hf hypertensive patients
ACC/AHA Practice Guidelines YearsRecommendations For Patients At High Risk For HF: Hypertensive Patients

  • Control of systolic and diastolic HTN in accordance with recommended guidelines

  • Appropriate antihypertensive regimen frequently consists of several drugs used in combination

  • Drugs that are useful for the treatment of both HTN and HF are preferred (e.g., diuretics, ACE inhibitors, -blockers)

Hunt SA et al. J Am Coll Cardiol 2001;38:2101


Clinical trials of anti hypertensive agents in diabetes

Clinical Trials Of YearsAnti-Hypertensive Agents In Diabetes


Ukpds ace inhibitor vs blocker aggregate clinical endpoints
UKPDS: ACE Inhibitor Vs Years-Blocker Aggregate Clinical Endpoints

Relative Risk & 95% CI

RR

P

0.5

1

2

Any diabetes-related endpoint

1.10

0.43

1.27

Diabetes-related deaths

0.28

1.14

All-cause mortality

0.44

1.20

Myocardial infarction

0.35

1.29

Microvascular disease

0.30

1.12

Stroke

0.74

FavorsACE Inhibitor

Favors-Blocker

UKPDS Group. BMJ 1998;317:713


Superior drugs variable results
Superior Drugs? Variable Results Years

Thiazide, ACE, CCB, BB

BB = ACE

ACE > CCB

ACE + CCB > ACE > CCB

ARB > BB

ACE > ARB

Thiazide > ARB

Thiazide ≥ ACE

Thiazide ≥ CCB

ACE > Thiazide

Vs Placebo

UKPDS:

ABCD:

FACET:

LIFE:

CONSENSUS:

ALLHAT:

ALLHAT:

ALLHAT:

AUSTRALIAN:


Which class of agents should be added second line
Which Class Of Agents Should Be Added Second-Line? Years

  • Thiazide diuretics

    • Complementary mechanism to ACEs or ARBs

    • ALLHAT showed benefit

    • Particularly effective in African American patients

    • BUT slightly higher deterioration of glucose metabolism

  • Beta blockers

    • Good evidence of benefit particularly for those with coronary heart disease or congestive heart failure

    • BUT mechanism of action may not complement ACEs or ARBs


Treatment Algorithm - Hypertension Years

BP >130/80 mmHg

Lifestyle Intervention

Smoking Cessation

Quarterly to semi-annual follow-up

Monthly to quarterly follow-up

SBP <130 and DBP <80?

Yes

No

Coronary Disease

Albuminuria/CVD Risk Factors

β-blocker

Thiazide

ACE/ARB

Virtually all two drug combinations should include a thiazide diuretic

The third drug could (should) be a calcium channel blocker

In the setting of kidney disease and significant proteinuria, consider combined ACE/ARB therapy

In the setting of kidney or heart disease, consider adding a furosemide bid or torsemide


Additional bp recommendations
Additional BP Recommendations Years

  • Lower blood pressure gradually in the elderly

  • If unable to achieve goal, don’t hesitate to discuss with peers

  • Check for orthostasis in some patients when clinically indicated

  • If angiotensin modifying drugs or diuretics are used, monitor renal function and potassium

  • Use as many medicines as necessary to achieve blood pressure target

    • 130/80 mmHg

    • 125/75 mmHg if proteinuria is found

  • Begin with an angiotensin modifying drug

  • Add a thiazide in African American patients

  • Add a Beta blocker in patients with heart disease

ADA. Diabetes Care 2007;30(Suppl1):16


Causes of resistant hypertension
Causes Of Resistant Hypertension Years

  • Improper blood pressure measurement

  • Excess sodium intake

  • Inadequate diuretic therapy

  • Medication

    • Inadequate doses

    • Drug actions and interactions (e.g. nonsteroidal anti-inflammatory drugs (NSAIDs), illicit drugs, sympathomimetics, oral contraceptives)

    • Over-the-counter (OTC) drugs and herbal supplements

  • Excess alcohol intake

  • Identifiable causes of hypertension


Lipids Years

American Diabetes Association

LDL <100 mg/dL

(<70 mg/dL in patients at “highest risk”)

HDL >40 mg/dL (>50 mg/dL in females)

TG <150 mg/dL

National Cholesterol Education Program

LDL <100 mg/dL

(<70 mg/dL in patients at “highest risk”)

Non-HDL <130 mg/dL


Statins primary and secondary prevention

4S Years

LIPID

CARE

PROVE-IT

HPS(estimated)

WOSCOPS

CARDS

TNT

TNT

HPS(estimated)

AFCAPS

Statins:Primary And Secondary Prevention

25

20

% With

CVD

Event

15

10

5

0

50

70

90

110

130

150

170

190

210

LDL-C (mg/dL)

Adapted from Illingworth. Med Clin North Am 2000;84:23 and LaRosa. N Engl J Med 2005;352 (e-pub) and Colhoun. Lancet 2004;364:685


Ada standards 2007 dyslipidemia
ADA Standards 2007 YearsDyslipidemia

  • Fasting lipid profile annually

  • Without overt CVD

    • LDL<100

    • At age 40 start on statin regardless of LDL to reduce LDL 30-40%

  • With overt CVD

    • Start statin to reduce LDL 30-40%

    • LDL<70 is an option

    • Normalizing triglycerides and raising HDL with fibrates reduces CV events


Ada standards 2007 dyslipidemia1
ADA Standards 2007 YearsDyslipidemia

  • High LDL, High triglycerides, Low HDL

    • Consider statin + fibric acid

      • Remember the increased risk of rhabdomyolysis

    • Consider statin + niacin

      • Remember niacin can increase glucose levels

      • moderate doses = mild changes in glycemia


Statin fibrate combination therapy pharmacokinetic interactions
Statin-Fibrate Combination Therapy: Pharmacokinetic Interactions

GemfibrozilFenofibrate

Atorvastatin Not available Not available

Pravastatin  in Cmax by 2-fold No effect

Fluvastatin No effect Not available

Simvastatin  Cmax by 112% No effect

Cerivastatin  Cmax by 2 to 3-fold No effect

Rosuvastatin  in Cmax by 2-fold No effect

Cmax =peak concentration

Pan W-J et al. J Clin Pharmacol 2000;40:316; Backman JT et al. Clin Pharmacol Ther 2000;68:122

Kyrklund C et al. Clin Pharmacol Ther 2001;69:340; Backman JT et al. Clin Pharmacol Ther 2002;72:685; Davidson MH. Am J Cardiol. 2002;90(suppl):50K; Prueksaritanont T et al. Drug Metab Dispos 2002;30:1280; Martin PD et al. Clin Ther 2003;25:459


Statin fibrate combination therapy retrospective analysis of adverse events
Statin-Fibrate Combination Therapy: InteractionsRetrospective Analysis Of Adverse Events

Number No. Cases

No. Cases Prescriptions Reported

MedicationReported1Dispensed2,3Per Million

Gemfibrozil + any Statin 590 6,757,000 87.3

Gemfibrozil + Cerivastatin 533 116,000 4,590

Gemfibrozil + other Statins 57 6,641,000 8.58

Fenofibrate + any Statin 16 3,519,000 4.55

Fenofibrate + Cerivastatin 14 100,000 140

Fenofibrate + other Statins 2 3,419,000 0.58

1Adverse Event Reporting System, U.S. Food and Drug Administration

2National Prescription Audit Plus report, IMS Health

3Concomitancy Report, VERISPAN, LLC


Anti platelet therapy ada standards
Anti-platelet Therapy InteractionsADA Standards

  • Recommendations for Aspirin

    • ASA 75-162 mg/day for 2o prevention

    • ASA 75-162 mg/day for 1o prevention

      • Age > 40

      • Any age with CV risk factors (htn, hyperlipidemia, renal disease, family history, smoking)

    • Not recommended ages < 21 (Reye’s syndrome)

  • Clopidogrel

    • Very high risk diabetics; intolerance to ASA


Questions
Questions? Interactions


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