Treat Everyone to an LDLC of 70mgdl

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Treat Everyone to an LDL-C of 70mg/dl?

• Daniel Edmundowicz, MS, MD, FACC
• Associate Professor Of Medicine
• Director, Preventive Cardiology
• UPMC Cardiovascular Institute

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Dyslipidemia and CHD LDL-C
ARIC Study (Men)
4.50
2.85
Relative risk of CHD
1.80
Adjusted for age and race 10-year follow-up
N5432
1.15
0.75
91
110
130
149
168
188
LDL-C (mg/dL)
LDL low-density lipoprotein LDL-C LDL
cholesterol ARIC Atherosclerosis Risk in
Communities. Adapted from Sharrett et al.
Circulation. 20011041108.
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HMG-CoA Reductase Inhibitor Secondary Prevention
Relationship between LDL Levels and Event Rates
in Secondary Prevention Trials of Patients with
Stable CHD
Statin Placebo
LDL-CLow density lipoprotein cholesterol
TNTTreating to New Targets HPSHeart Protection
Study CARECholesterol and Recurrent Events
Trial LIPIDLong-term Intervention with
Pravastatin in Ischaemic Disease 4SScandinavian
Simvastatin Survival Study.
LaRosa JC et al. NEJM. 20053521425-1435
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LDL approx. 50 - 70 mg/dl
LDL approx. 130 mg/dl
OKeefe JH, et al. JACC 2004432142
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Vascular endothelium modification in
atherosclerosis
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Although the LDLC mantra lower is better has
been popularized in advertising and continuing
medical education the precise target level for
LDLC for optimal treatment has not been
rigorously defined.
William Isley, MD Mayo Clinic
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Intention to treat LDL-C levels and CHD
riskCholesterol Treatment Trialists
Collaborators90,056 participants in 14
randomized trials of Statins
Am J Cardiol 20069814051408
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Estimates of risk and NNT to prevent one event
with additional 30mg/dl LDL lowering
Am J Cardiol 20069814051408
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Intention to treat LDL-C levels and CHD risk by
presence of risk factors risk curve approach
to LDL therapy
LDL Therapy
Alternative Risk Factor Therapy
Am J Cardiol 20069814051408
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Many advocates of lower is better seem
oblivious to the potential downsides of more
aggressive lipid-lowering therapy.
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PROVE-IT and A to Z

• No significant reduction in non-fatal MI/CHD
  death
• 30 drop-out rates
• Prove-It Prior statin use or those with baseline
  LDL treatment
• NNT to cause significant LFT abnl similar to NNT
  to prevent CV event

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TNT and IDEAL

• Adverse events and treatment related drug
  discontinuation 40 more common in high dose
  atorvastatin
• Over twice as many subjects in the atorva 80mg
  group stopped therapy related to side effects
  compared to simva 20/40.

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LDL goal attainment among Kaiser Permanente
Northwest patients over the age of 65
Am Heart J 2007154554
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Aggressive vs. Conventional Lipid lowering in 235
patient with CHD
Simvastatin 40 mg daily
Atorvastatin 40 mg daily
Cardiovasc Drugs Ther (2007) 2191
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While LDL was lower, no change in levels of
oxidative stress or inflammatory markers with
more intensive statin therapy
Cardiovasc Drugs Ther (2007) 2191
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LDL-C Lowering According to Statin and Dose A
Meta-analysis of 164 Trials
Standardized to LDL-C 186 mg/dL (mean
concentration in trials) before treatment.
Independent of pretreatment LDL-C.Maximum
dose of 80 mg/d administered as two 40-mg
tablets. Not FDA approved at 80 mg/d.
Law MR et al. BMJ. 20033261423-1427.
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Statin Titration Yields Minimal Incremental LDL-C
Reduction
1stdoubling of statin dose
2nddoubling
3rddoubling
Starting dose of statin
20-46
3-7
3-7
3-7
LDL-C reduction
Jones et al. Am J Cardiol. 200392152.
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Mechanism ofIntestinal-Acting Agents
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47
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53
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Cost Effectiveness

• First three available statins available
  generically
• Difference in drug acquisition costs is marked
  (plus monitoring of high dose Rx)
• Doubtful that the incremental cost would be worth
  the benefit of more aggressive LDLC lowering in
  the majority of patients

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Cost of CVD in the United States
Lost productivity/ mortality
Hospital/nursing home
Total direct and indirect costs 286.5 billion
Lost productivity/ morbidity
Home health/ other medical durables
Physicians/other professionals
Drugs
American Heart Association. 1999 Heart and Stroke
Statistical Update. 1998.
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Ideal Lipid Lowering Drug

• Drive LDLC below 70
• Live Longer

• Aphrodisiac
• Tax Deductible
• Ozone Friendlier

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Conclusion

• LDL-C of 70mg/dl or less is a reasonable goal for
  the highest risk patients (i.e. CHD and
  diabetes).
• An individualized clinical management strategy
  that takes into account the patients absolute
  benefit from further LDL-C reduction as well as
  from shifting the risk curve downward through non
  lipid interventions.

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Conclusion (cont.)

• Moderate dose statin therapy can lower CHD risk
  in primary and secondary prevention with minimal
  side effects and, with the availability of
  several generic statins, with great
  cost-effectiveness.