Statins are NOT good or fast Statins are NOT good or fast enough; they are enough; they are

overrated!overrated!

Ward Casscells, MDWard Casscells, MDUniversity of Texas-Houston HSC &University of Texas-Houston HSC &Texas heart instituteTexas heart institute

Vulnerable Plaques:Vulnerable Plaques:Multifocal vs. SystemicMultifocal vs. Systemic

Vulnerable Plaque: A Multifocal DiseaseVulnerable Plaque: A Multifocal Disease

Autopsy series:Autopsy series: A second occlusive thrombus in 6-16% of MI victims A second occlusive thrombus in 6-16% of MI victims

Angiography:Angiography: Second progressive lesion: 0-14%Second progressive lesion: 0-14% Second vulnerable lesions 2.6 per U/A patientSecond vulnerable lesions 2.6 per U/A patient IVUS:IVUS: 2 or more plaque ruptures in 50-79% of ACS patients2 or more plaque ruptures in 50-79% of ACS patients

Vulnerable Plaque: A Multifocal DiseaseVulnerable Plaque: A Multifocal Disease

Angioscopy:Angioscopy: Almost always reveals only one thrombus in MI Almost always reveals only one thrombus in MI

patientspatients Yellow plaques in some patients with stable anginaYellow plaques in some patients with stable angina Yellow plaques in most patients with unstable angina Yellow plaques in most patients with unstable angina Yellow plaques in nearly all patients with AMIYellow plaques in nearly all patients with AMI

Thermal heterogeneity found in: Thermal heterogeneity found in: Some patients with stable anginaSome patients with stable angina In almost all patients with unstable anginaIn almost all patients with unstable angina Two or even three hot plaques in AMITwo or even three hot plaques in AMI

What to do with vulnerable plaques What to do with vulnerable plaques once we find them? once we find them?

Do statins work fast enough? Do statins work fast enough?

None of the 6 large clinical trails showed None of the 6 large clinical trails showed any significant decrease in mortality in the any significant decrease in mortality in the first year of statin therapyfirst year of statin therapy

4S

WOSCOPS CARE

AFCAPS/TexCAPS

HPS

Do statins protect enough?Do statins protect enough?

On average, 42% of deaths in statin trials On average, 42% of deaths in statin trials happened in their statin arms. happened in their statin arms.

Coronary Death in the Statin Arm Coronary Death in the Statin Arm of Clinical Trialsof Clinical Trials

TrialTrial % Coronary Death% Coronary Death

4S4S 3737

LIPIDLIPID 4343

WOSCOPSWOSCOPS 4242

CARECARE 4444

MRC/BHFMRC/BHF 4545

AFCAPS/TEXCAPSAFCAPS/TEXCAPS 4242

PROSPERPROSPER 4343

Why protection is delayed?Why protection is delayed?

Lipid-lowering and anti-inflammatory Lipid-lowering and anti-inflammatory effects of statins begin by 6 weeks. effects of statins begin by 6 weeks.

However, death rate is delayed for at least However, death rate is delayed for at least 12 months.12 months.

Is there a hidden increase in risk which Is there a hidden increase in risk which counters the benefits in the first year? counters the benefits in the first year?

Q: How the macrophages exit the plaque? Q: How the macrophages exit the plaque? Do they weaken the fibrous cap on exit? Do they weaken the fibrous cap on exit?

What should be done? What should be done?

Use multiple therapies:Use multiple therapies:Various combinations of Various combinations of

Aspirin with warfarin or clopidogrelAspirin with warfarin or clopidogrel ACE inhibitors with beta-adrenergic blockersACE inhibitors with beta-adrenergic blockers statins with niacin, fibrates, and resinsstatins with niacin, fibrates, and resins Mediterranean diet Mediterranean diet Fight triggersFight triggers Flu shotFlu shot Etc. Etc.

Local therapy to buy timeLocal therapy to buy time

Since statins may not reduce mortality in Since statins may not reduce mortality in time, the most vulnerable plaques may time, the most vulnerable plaques may merit stenting or some other form of local merit stenting or some other form of local therapy to “buy time”. therapy to “buy time”.