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Prevention of a “Broken Heart”. Prevention of a “Broken Heart”. February 16 2005 Mario L Maiese DO FACC FACOI Associate Professor UMDNJSOM S outh J ersey H eart G roup www.sjhg.org Email @ maiese1@comcast.net. Hidden Overlap of Atherothrombotic Disease.
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Prevention of a “Broken Heart” February 16 2005 Mario L Maiese DO FACC FACOI Associate Professor UMDNJSOM South Jersey Heart Group www.sjhg.org Email @ maiese1@comcast.net
Hidden Overlap of Atherothrombotic Disease CoronaryArteryDisease CerebrovascularDisease 40% 15% 16% 9% 11% 3% 6% 38% overlap (³ 2 vascular beds) Peripheral Arterial Disease Patients with one manifestationoften have coexistent disease in other vascular beds Ness J, Aronow WS. JAGS. 1999;47(10):1255-56.
Dyslipidemia: Identify high-risk patients and determine benefits of treatment. Strategy and recommendations for obtaining safe optimal aggressive treatment goals.
Atherothrombosis: A Progressive Process PlaqueRupture/Fissure &Thrombosis Occlusive AtheroscleroticPlaque Unstable Angina FattyStreak FibrousPlaque Normal MI Coronary Death Stroke Effort Angina Claudication Clinically Silent Critical Leg Ischemia Increasing Age Courtesy of P Ganz.
Thrombotic occlusion Final Result Normal blush
“To a man with a hammer every nail looks like it needs driving”. …Mark Twain
“If prevention is your goal focus on the donut, not the hole”.
It is this "hidden disease" – the presence of vulnerable plaques throughout the coronary tree – that is the target of long-term treatment with high-dose statins, aspirin, ACE inhibitors.
ABCs of CVD Risk Management CVD=cardiovascular disease; ACE=angiotensin converting enzyme; ARB=angiotensin receptor blocker; BP=blood pressure; EF=ejection fraction; MI=myocardial infarction. Braunstein JB et al. Cardiol Rev. 2001;9:96-105.
ABCs of CVD Risk Management Braunstein JB et al. Cardiol Rev. 2001;9:96-105.Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497. * Circulation July 13 2004; 110: 227-239.
ABCs of CVD Risk Management BMI=body mass index; HbA1c=glycosylated hemoglobin;CAD=coronary artery disease. Braunstein JB et al. Cardiol Rev. 2001;9:96-105. *JAMA Nov 2004;2442-2490.
PRIMARY GOAL: LDL-C SECONDARY GOAL: Non HDL-C JAMA 2001; 285: 2486-2497. Cholesterol Management…per NCEP III Guidelines
Non-HDL-C • Provides a measure of all the cholesterol in atherogenic particles including LDL-C, Apo B, LP(a) and TG-rich particles in VLDL,VLDL remnants and intermediately dense lipoproteins. • Introduced as the secondary target of therapy in patients with high TG (> 200mg/dL) per NCEP ATP III. JAMA 2001; 285: 2486-2497.
NCEP III Non HDL-C Goal • Non-HDL-C = TC - HDL-C • Goal Non-HDL-C is 30mg > LDL-C goal Must be remembered that LDL-C and non HDL-C goals are surrogates for the number 1 lipid risk factor which is Apo B (a marker of atherogenic lipoproteins).
Modifications to NCEP III • TLC was re-emphasized. • Use of the Framingham CAD risk calculator was recommended. Circulation July 13 2004; 110: 227-239
NCEP III Update Based on 5 Clinical Trials Trial Name Statin Therapy Summary
Safety Analysis of Intensive Tx • Among subjects treated with intensive statin therapy following ACS, there were lower rates of clinical events in those patients who achieved LDL-C < 60 mg/dL (or < 40 mg/dL) compared with those in the > 80-100 mg/dL range. • Lipid levels well below the current guidelines were not associated with worse safety outcomes. • Therefore, there is no need to reduce statin dosage if the LDL-C levels are below target goal. Circulation 2004;110:III-498. Abstract 2340.
“Very High Risk” Patients The updated NCEP III definition of “high risk” requires established CVD plus: • Multiple risk factors (especially diabetes). • Severe and poorly controlled risk factors (especially continued cigarette smoking). • Multiple risk factors for MetS (especially high TG >200 plus non HDL-C > 130mg/dL with low HDL-C [< 40mg/dL]). • Patients with ACS.
The Forgotten Cardiac Risk Factor: Noncompliance With Lipid-Lowering Therapy • Before NCEP ATP III Update. • Will be even more difficult reaching LDL-C goals post update.
The CARDS data strongly demonstrateas the safety and benefits of statin therapy in T2DM regardless of baseline LDL-C. Conclusion:
Comparative Efficacy of Available Statins Available Statins % LDL-C reduction Rosuvastatin 5mg Atorvastatin10mg 33-39% Simvastatin 20mg Lovastatin 40mg Pravastatin 40mg Fluvastatin 80mg Roberts WC. Am J Cardiol. 1997; 80: 106-107. Stein E et al. J Cardiovasc Pharmacol Therapeut. 1997; 2: 7-16.
Even with optimal statin treatment: ----30- 40% reduction in CV events with statins. “There is 50% to 60% risk we’re not addressing”.
Preliminary data suggests that combination therapy is much more efficacious in ↓ CV events (> 75%) - not surprising given that the lipid lowering effect is much greater.
Be aggressive with combination therapies. In insulin resistant patients with abnormalities of the TG/HDL-C axis statin/Zetia/TriCor would solve the overwhelming majority of lipoprotein abnormalities seen in most patients (getting to LDL-C and non-HDL-C goals (apoB surrogate markers).
Efficacy of HDL-C Increasing Compounds • Fibrates reduce major coronary events and increase HDL-C without significant toxicity. • Niacin has a more potent effect on HDL-C levels, but data on CV event reduction are limited. • HDL-C will probably be the “next target” over the next 10 years. J Am Coll Cardiol January 18 2005; 45: 185-197.
AFREGS: Armed Forces Regression Study A combination of 3 drugs aimed at increasing HDL-C (niacin, fibrates and cholestyramine): • Improves cholesterol profiles. • Helps halt angiographic progression of coronary stenosis. • May help prevent CV events. Ann Intern Med January 18 2005; 142: 95-104.
Adverse Effects of Statins • Myalgias (muscle pains), which is seen in 2% to 4% of patients. • Myopathy (10x NL CPK) including rhabdomyolysis (> 10,000 CPK) is very rare: Incidence =0.5-1 in 10,000 patients. • Increased values in liver function tests (LFTs) in ~ 1% of patients, significant elevations > than 3x NL up to 2% or 2.5% with the highest doses of statins.
Adverse Effects of Therapy • Risk usually increases with dose escalation. • Risk is higher in women, older age (> 60), dehydration or those with underlying renal or liver disease. • Risk increases with combination therapy. • Risk is not directly proportional to cholesterol-lowering efficacy.
Management • Listen to the patient first (muscle pain weakness or stiffness). • Negative placebo situation Balance Positive placebo effect • Temporarily stop, reduce the dose or switch (every other day dosing is frequently as effective with reduced side effcts).