Download Lisinopril post MI diabetes

115th Annual Convention of Indiana Osteopathic
Association
Diabetes and Cardiovascular Disease
Dr. Bradley Weinberg, FACC
Community Hospital Network
Indianapolis, Indiana
May 5, 2012
DIABETES
IS
A CORONARY HEART DISEASE
RISK EQUIVALENT
Cardiovascular disease is the major cause of
morbidity and mortality in diabetics
It is the largest contributor to direct and indirect cost
Hypertension, Dyslipidemia and Smoking
commonly coexist with Diabetes
Large benefits are seen when these risk factors for
Cardiovascular disease are addressed concurrently
PREVENTING HEART DISEASE IN DIABETES
BLOOD PRESSURE CONTROL
A goal SBP <130 is the guideline recommendation.
I target a SBP < 140
The goal DBP is less than 80 mm Hg
HOT TRIAL
Study design
19,000 pts with diastolic pressures of 100-115
Randomized to target diastolic of < 90 or < 85
or < 80
3,000 patients had diabetes
Initial drug felodipine, then ACE-inhibitor, then
beta blocker then diuretic
Achieved diastolics lowered 20.3 mm vs 22.3
mm vs 24.3 mm
ACCORD TRIAL BLOOD PRESSURE ARM
4400 DIABETICS WITH SBP of 130-180
RANDOMIZED TO SYSTOLIC BP
<120 mm Hg vs <140 mm Hg
ACCORD Mean SBP at each study visit
ACCORD Outcomes by level of BP control
Blood pressure treatment in Diabetes
Start with an ACE-I or ARB
I like to add Tenoretic. (Atenolol + Chlorthalidone)
It is a 4$/mo drug and chlorthalidone has data
Next I will change the ACE-I to Lotrel generic
which is Amlodipine + Benazepril or an
ARB- Amlodipine combination drug.
Finally if indicated and K and renal function OK, I
add spironolactone (a secret weapon!)
Most pts are controlled on 2 or 3 pills (5 drugs!)
A Few Practical BP tips
Use home BP monitoring
DASH diet
½ hr of exercise 5 days per week
Treat sleep apnea
For GFR < 30 ml/min, use a loop diuretic in place of
thiazides and spironolactone. I like once daily
torsemide. It is twice as potent as furosemide.
Monitor electrolytes and renal function.
Preventing Heart Disease in Diabetes
Lipid Management
I target an LDL < 100 mg/dl or a reduction of
30-40% below baseline.
If possible, I choose a one of the two highest
doses of either atorvastatin or rosuvastatin.
Avoid 80 mg simvastatin daily
In high risk pts a target of LDL <70 mg/dl is
reasonable
Lipid Management in Diabetes
The data supporting targeting triglycerides and HDL
are thin.
Triglycerides will often remain high until glycemic
control is achieved.
I believe fenofibrate is overused.
My blood pressure and lipid approaches are colored
by cost considerations and pill burden issues.
Smoking Cessation in Diabetes
Advise all smokers to quit
Chantix bid taken with meals
Nicotine replacement (without Chantix)
Bupropion
1-800-QUIT-NOW
Freedom from Smoking classes
Preventing Heart Disease in Diabetes
Antiplatelet Agents
Aspirin should be used in those with known
vascular disease.
Aspirin 81 mg daily is reasonable in those with
multiple additional risk factors or over age 50 in
men or over age 60 in women.
Clopidogrel is reasonable in similar patients who
cannot take aspirin.
The decision can be balanced by bleeding risks.
Screening for Coronary Disease in Diabetics
In asymptomatic patients, routine screening for
coronary artery disease IS NOT recommended
as it does not improve outcomes and it adds
cost (and potential risks) to care without benefit
Glycemic Goals in non-pregnant Adults
A Cardiologist’s Perspective
Blood Glucose / A1C
And the Relationship to
Macrovascular Complications
A1C = Average Glucose
28.7 x A1C – 41.7 = estimated average glucose
A1C
Average Glucose
6
126
6.5
140
7
154
7.5
169
8
183
8.5
197
9
212
10
240
11
269
12
298
Targets for Glycemic
Control in Most
Non-Pregnant Adults
A1C
Fasting Glucose
Post-prandial Glucose
<7.0
70-130
<180
Type 2 Diabetes UKPDS
1% A1C decreases Complications
Amputation
↓
43%
Microvasc
Cataract
Surgery
↓
↓
37%
19%
Heart
Failure
Myocardial
Infarction
↓
↓
16%
14%
Stroke
↓
12%
Blood Sugar Control and Cardiovascular Disease
ACCORD, ADVANCE and VADT did not show improved
cardiovascular outcomes with A1C under 6.5%
Other data suggest post-prandial glucose which is
difficult to target may contribute to adverse
cardiovascular outcomes
A1C and Cardiovascular Outcomes
So What Now?
A1C and Complications
Data suggest lower A1Cs earlier in the
course of diabetes is beneficial
Long term poor control may not benefit from
stringent control later, particularly with
reference to coronary heart disease.
Optimal A1Cs for patients with known heart
disease is unclear but < 7.5 may be adequate
and even < 8.0 in older and sicker patients.
COURAGE STUDY 2007
2287 patients (1999-2004)
• 70% proximal narrowing in 1 or more coronaries
• Objective evidence of ischemia or typical angina with an
80%+ narrowing in one or more coronaries
• Suitable for PCI (percutaneous coronary intervention)
EXCLUSIONS
Class IV angina
LVEF < 30%
Prior revascularization
PCI + OMT (optimal medical therapy) vs OMT alone
What is Optimal Medical Therapy?
•
•
•
•
•
•
•
•
•
•
Aspirin or clopidogrel
LDL < 85, HDL >40, Triglycerides < 150
BP < 130/85
A1C < 7.0
30 minutes or more of exercise 5 + days per wk
Step II AHA diet
Smoking cessation
BMI <25
ACE-inhibitor or ARB
Long acting metoprolol, amlodipine, and long acting
nitrates titrated to angina
COURAGE Study
Thus, unstable coronary lesions that lead to
myocardial infarction are not necessarily severely
stenotic, and severely stenotic lesions are not
necessarily unstable. Focal management of even
severely stenotic coronary lesions with PCI in our
study did not reduce the rate of death and
myocardial infarction, presumably because the
treated stenoses were not likely to trigger an acute
coronary event. Furthermore, our lower-thanprojected event rate in the medical-therapy group
may be explained by systemic therapy that reduced
plaque vulnerability through aggressive intervention
for multiple risk factors and evidence-based use of
medication
What are the implications of the COURAGE
study?
• PCI added to medical therapy did not reduce
the risk of death, MI or other major
cardiovascular events compared to optimal
medical therapy alone
• In patients with stable coronary artery
disease, OMT and aggressive management of
multiple treatment targets without initial
revascularization can be safely initiated in the
majority of patients with chronic stable angina
COURAGE study
• It is reasonable to reserve revascularization for
patients with unacceptable symptoms on
optimal medial therapy or judged to be at very
high risk based on non-invasive testing.
BARI 2D Study
Bypass Angioplasty Revascularization
2 Diabetes Study
• What is the optimal treatment for patients
with diabetes and angiographically defined
stable ischemic heart disease?
• 2368 type II diabetics with either a positive
stress test and a > 50% stenosis in a major
coronary artery or a >70% stenosis and
typical angina pectoris
BARI 2D Treatment Strategies
• First a cardiologist determined whether CABG
or PCI (percutaneous revascularization) would
be preferred if revascularization was done.
• Then 2x2 randomization was done.
• Optimal medical therapy alone vs Optimal
medical therapy plus revascularization
• Insulin sensitization initially vs. initial insulin
provision (sulfonylurea or insulin or both)
BARI 2D RESULTS
BARI 2D RESULTS
BARI 2D RESULTS
• Prompt revascularization in patients treated with
intensive medical therapy for diabetes and ischemic
heart disease did not reduce the rate of death or
major cardiovascular events
• Insulin sensitization and insulin provision had similar
event rates
• Among patients for who CABG was deemed
appropriate, prompt revascularization reduced the
rate of major cardiovascular events compared to
medical therapy
• Over 5 years, 42% of patients had to cross-over to
revascularization because of symptom progression.
Patients meeting target values at 3 yrs in BARI 2D
• A1C < 7.0%
• LDL < 100 mg/dl
• BP < 130/80
48%
83%
71%
• All 3 targets
28%
Diabetes and Heart Failure
Diabetes increases the risk of CHF independent of
coronary artery disease and hypertension
The risk of CHF is 2.5 x higher in men and 5 x
higher in women with diabetes.
Among patients hospitalized with heart failure in
the US about 42% are diabetic
Independent of BMI and BP, diabetics have higher
LV mass, more LVH, stiffer arteries and worse
systolic function than non-diabetics.
Diabetes and Heart Failure
Diabetics commonly have diastolic dysfunction.
In diabetes increased myocardial fibrosis and
collagen is seen.
Autonomic neuropathy may play a role in left
ventricular dysfunction with impaired vagal tone
and abnormal sympathetic tone.
The vascular bed may have decreased
capacitance due to impaired endothelial function.
Diabetes and Heart Failure
Diabetics with heart failure have poorer
survival then non-diabetics with heart failure.
Age, low LVEF and diabetes are the strongest
predictors of the development of worsening
heart failure among patients with coronary
disease.
Thiazolidinediones (TZDs) and Heart Failure
TZDs cause fluid retention and increase the risk of CHF
They activate PPAR gamma receptors in the kidney (like
aldosterone) and increase renal sodium retention.
This is resistant to loop diuretics but may respond to
aldosterone antagonists like spironolactone and
eplerenone
Weight gain and edema occur more often with
concomitant TZDs and insulin therapy
AHA and ADA guidelines on TZD use
In patients with NYHA class III or IV CHF, TZDs
should not be used.
If patients with risks for CHF such as Cr > 2,
longstanding DM, age over 70, history of CHF,
prior MI, significant valvular heart disease, LVH,
hypertension, or edema or weight gain with
TZDs, only low doses should be used and the
patient followed carefully for heart failure.
If edema or weight gain occur on TZDs, the
patient should be assessed for heart failure.
METFORMIN USE
Hemodynamically unstable patients or those with liver
disease, significant renal insufficiency or sepsis are at
increased risk of potentially fatal lactic acidosis with
metformin.
However with stable heart failure with a creatinine less
than 1.5 it is relatively safe.
In fact in the European Society of Cardiology’s heart
failure guidelines it is recommended as a first line agent in
overweight diabetic patients with a GFR over 30 ml/min
Prevention is the Best Medicine
Possible Mechanisms for Increased
Atherosclerosis in Type II Diabetes Mellitus
 Dyslipidemia
 Hypertension
 Hyperinsulinemia/insulin
resistance
 Hemostatic abnormalities
 Hyperglycemia
 AGE proteins
 Oxidative stress
 Endothelial Dysfunction
 Inflammation
National Diabetes Education Program (NDEP)
Control Your Diabetes for Life The ABCs
A A1C (blood glucose) less than 7 percent
B Blood pressure less than 130/80
C Cholesterol – LDL less than 100 mg/dl
Free educational material 1-800-438-5383
Or visit www.ndep.nih.gov
THANK YOU!