GO Diabetes Train the Trainer Program

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GO! DiabetesTrain the Trainer Program
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Cardiovascular Disease PreventionBlood
Pressure, Dyslipidemia, Antiplatelet Therapy
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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?

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Diabetes and HypertensionWhy?

• Volume Expansion
• Increased insulin levels
• Higher sympathetic activity
• Increased glucose level
• Increased sodium resorption with hyperglycemia
• Decreased arterial compliance
• Obesity

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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
lt90
lt85
lt80
lt90
lt85
lt80
Diabetic Patients n1,501 P0.016
Non-Diabetic Patients n18,790 PNS
Lancet 19983511755
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UKPDS Blood Pressure StudyTight 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.
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Diabetes Treatment Goalsfor Blood Pressure

• Control blood pressure
• 130/80 mmHg for most patients
• 125/75 mmHg for patients who have proteinuriagt1
  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 20032892560 Bakris GL et
al. Am J Kidney Dis 200036646 ADA. Diabetes
Care 200730(suppl 1)S15
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ADA Guidelines for the Treatment of Hypertension

• Initial therapy
• Lifestyle modification
• Smoking cessation
• Weight reduction
• Increase physical activity
• Sodium restriction

• Pharmacologic therapy
• Albuminuria - ACEI/ARB, thiazide, ß-blocker,
  CCB
• Albuminuria ACEI/ARB
• Multiple drugs generally required

Goal of therapy BP lt130/80 mmHg
Diabetes Care 200730 (Suppl 1)S15
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Number of Medications to Achieve Goal BP In 5
Trials of DM and/or Renal Disease
UKPDS (lt150/85 mmHg)
2.7
ABCD (lt75 mmHg DBP)
2.8
MDRD (lt92 mmHg MAP)
3.6
HOT (lt80 mmHg DBP)
3.3
AASK (lt92 mmHg MAP)
3.8
0
1
2
3
4
Number Of BP Meds
Bakris. J Clin Hypertens 19991141
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UKPDS Blood Pressure StudyTight 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.
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NKF Recommendations On TreatmentOf 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 200036646
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ACC/AHA Practice GuidelinesRecommendations 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 2001382101
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Clinical Trials Of Anti-Hypertensive Agents In
Diabetes
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UKPDS ACE Inhibitor Vs ?-Blocker Aggregate
Clinical Endpoints
Relative Risk 95 CI
0.5
1
2
P
RR
Any diabetes-related endpoint
1.10
0.43
Diabetes-related deaths
1.27
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 1998317713
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Superior Drugs? Variable Results
Thiazide, ACE, CCB, BB BB ACE ACE gt CCB ACE
CCB gt ACE gt CCB ARB gt BB ACE gt ARB Thiazide gt
ARB Thiazide ACE Thiazide CCB ACE gt Thiazide
Vs Placebo UKPDS ABCD FACET LIFE CONSENSUS AL
LHAT ALLHAT ALLHAT AUSTRALIAN
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Which Class Of Agents Should Be Added Second-Line?

• 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

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Treatment Algorithm - Hypertension
BP gt130/80 mmHg
Lifestyle Intervention Smoking Cessation
Quarterly to semi-annual follow-up
Monthly to quarterly follow-up
SBP lt130 and DBP lt80?
Yes
No
Coronary Disease
Albuminuria/CVD Risk Factors
Thiazide
ACE/ARB
ß-blocker
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
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Additional BP Recommendations

• Lower blood pressure gradually in the elderly
• If unable to achieve goal, dont 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 200730(Suppl1)16
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Causes Of Resistant Hypertension

• 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

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Lipids
American Diabetes Association LDL lt100 mg/dL (lt70
mg/dL in patients at highest risk) HDL gt40
mg/dL (gt50 mg/dL in females) TG lt150 mg/dL
National Cholesterol Education Program LDL lt100
mg/dL (lt70 mg/dL in patients at highest
risk) Non-HDL lt130 mg/dL
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StatinsPrimary And Secondary Prevention
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With CVD Event
15
10
5
0
50
210
70
190
170
150
130
110
90
LDL-C (mg/dL)
Adapted from Illingworth. Med Clin North Am
20008423 and LaRosa. N Engl J Med 2005352
(e-pub) and Colhoun. Lancet 2004364685
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ADA Standards 2007Dyslipidemia

• Fasting lipid profile annually
• Without overt CVD
• LDLlt100
• At age 40 start on statin regardless of LDL to
  reduce LDL 30-40
• With overt CVD
• Start statin to reduce LDL 30-40
• LDLlt70 is an option
• Normalizing triglycerides and raising HDL with
  fibrates reduces CV events

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ADA Standards 2007Dyslipidemia

• 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

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Statin-Fibrate Combination Therapy
Pharmacokinetic Interactions

• Gemfibrozil Fenofibrate
• 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 200040316
Backman JT et al. Clin Pharmacol Ther
200068122 Kyrklund C et al. Clin Pharmacol Ther
200169340 Backman JT et al. Clin Pharmacol
Ther 200272685 Davidson MH. Am J Cardiol.
200290(suppl)50K Prueksaritanont T et al. Drug
Metab Dispos 2002301280 Martin PD et al.
Clin Ther 200325459
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Statin-Fibrate Combination TherapyRetrospective
Analysis Of Adverse Events

• Number No. Cases
• No. Cases Prescriptions Reported
• Medication Reported1 Dispensed2,3 Per
  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
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Anti-platelet TherapyADA Standards

• Recommendations for Aspirin
• ASA 75-162 mg/day for 2o prevention
• ASA 75-162 mg/day for 1o prevention
• Age gt 40
• Any age with CV risk factors (htn,
  hyperlipidemia, renal disease, family history,
  smoking)
• Not recommended ages lt 21 (Reyes syndrome)
• Clopidogrel
• Very high risk diabetics intolerance to ASA

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Questions?