Primary and Secondary Prevention of Dyslipidemia: Established Therapies
and Emerging Paradigms
Sidney C. Smith, Jr. MD
Professor of Medicine Director, Center for Cardiovascular Science and Medicine
When to Start Cholesterol Lowering Therapy in Patients with Coronary Heart Disease
“ The cardiovascular specialist or attending physician should be responsible for starting some form of cholesterol lowering therapy in patients upon discharge from the hospital after acute coronary events……….The cardiovascular specialist thus should insure that appropriate therapy is initiated and maintained.”
4S: Treatment Benefit in Subgroup With
Impaired Fasting Glucose (FG 110-125mg/dL)
Total mortality 0
Coronary mortality
Major coronary
events
Revascularizations
University of North Carolina at Chapel Hill
Most MIs Arise From Smaller, Non flow-limiting Stenoses
80
68%
60
Percent of MI 40
Patients
20
18%
PCI CABG
14%
0 <50%
-10
-20
in events -30 (%)
-40
-50
-46
-60
-56
P=0.005
Haffner SM et al. Diabetes. 1998;(suppl 1):A54. Abstract.
-40 P=0.001
-43 P=0.010
Clinical Trial Findings: The Statins
0
%
-10
-20
-30
-30 * -40
-33 *
-29 †
-28 ‡
-22 §
*Confidence interval (CI) not reported. †95% CI, 14%-41%. ‡95% CI, 16%-37%. §95% CI, 12%-31%.
Hebert PR et al. JAMA. 1997;278:313-321.
cardiovascular mortality in 1° prevention • Studies support treatment in various patient groups
– women – elderly – diabetics
Lipid Lowering Therapy for the Prevention of Vascular Disease
1. When Should Lipid Lowering Therapy be started?
2. What should be the Treatment Goal? Findings of the HPS Study.
3. Should HDL – Cholesterol be a Target?
0
Diabetic, simvastatin
Diabetic, placebo
- P=0.002
Nondiabetic, simvastatin
Nondiabetic, placebo
- P=0.0001
1
2
3
4
5
Yr since randomization
32% 55%
6
Pyörälä K et al. Diabetes Care. 1997;20:614-620.
CARE LIPID
LDL LDL Rx RRR ARR NNT 188 122(-35%) 34%* 8.5% 12 139 98(-32%) 24%* 3.0% 34 150 113(-25%) 23%* 3.4% 30
WSCPS 192 159(-26%) 29%* 2.2% 46 AFCAPS 150 113(-25%) 36%^ 1.8% 56
4S: Major CHD Event Reduction in a Subgroup of Patients With Diabetes
15.00
04..9000
Proportion without
major CHD event
03..8000
0.70 2.00
0.60 1.00 0.50 0.00
50%–70%
% Stenosis
>70%
Adapted from Falk et al. Circulation 1995; 92:657–671.
Effects of Statins on Coronary Disease: Primary & Secondary Prevention
Study 4S
• Statins LDL-C by 25%-35% • Benefits at various LDL-C levels; evident soon after therapy • in LDL-C required for in CHD morbidity/mortality • in all-cause mortality in 2° prevention and in
* = NFMI/CHD mort. ^ring LDL-C on CVD Events and Total Mortality
Nonfatal/
CVD
Total
LDL-C fatal CHD Stroke mortality mortality