A high level of LDL cholesterol (160 mg/dL and above) reflects an increased risk of heart disease. Patients with a diagnosis of heart disease should aim for a target LDL cholesterol of less than 100 mg/dL. The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) issued an evidence-based set of guidelines on cholesterol management in 2001 (Grundy, 2004) Since the publication of the ATP III, five major clinical trials of statin therapy with clinical endpoints have been published: - HPS: Heart Protection Study (Collins, 2004)
o Simvastatin significantly reduced the first event rate of stroke versus placebo (444 versus 585, P<0.0001)
o There was no significant difference in strokes attributed to hemorrhage (51 versus 53, P=0.8)
o Simvastatin also reduced the number of patients having TIAs alone compared with placebo (2.0% versus 2.4%, P=0.02) or requiring CEA or angioplasty (0.4% versus 0.8%, P=0.0003) - PROSPER: Prospective Study of Pravastatin in the Elderly (Shepherd, 2002)
o Statistically significant reduction in major vascular events in patients using pravastatin versus placebo (408 versus 473, P=0.014)
o Death from CHD and nonfatal MI was significantly reduced by 24% (P=0.043) and CHD events were reduced by 19% in patients receiving active therapy (P=0.006)
o Stroke risk was unaffected by pravastatin (P=0.8) and TIAs were decreased by 25% (P=0.51) - ALLHAT: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial—Lipid Lowering Trial (ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group, 2002)
o Patients treated with chlorthalidone had a 15% lower risk for stroke (P=0.02) and a 10% lower risk of combined CVD (P=0.001) - ASCOT-LLA: Anglo-Scandinavian Cardiac Outcomes—Lipid Lowering Arm (Sever, 2003)
o The trial was stopped early because atorvastatin had resulted in a statistically significant reduction in CVD events: stroke (89 versus 121, P=0.024); total CV events (389 versus 486, P=0.0005); total coronary events compared with placebo (178 versus 247, P=0.0005) - PROVE IT-TIMI 22: Pravastatin or Atorvastatin Evaluation and Infection—Thrombolysis in Myocardial Infarction 22 (Rouleau, 2005)
o Standard treatment (statin) with a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductants receiving active therapy (P=0.006)
o Stroke risk was unaffected by pravastatin (P=0.8) and TIAs were decreased by 25% (P=0.51) - ALLHAT: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial—Lipid Lowering Trial (ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group, 2002)
o Patients treated with chlorthalidone had a 15% lower risk for stroke (P=0.02) and a 10% lower risk of combined CVD (P=0.001) - ASCOT-LLA: Anglo-Scandinavian Cardiac Outcomes—Lipid Lowering Arm (Sever, 2003)
o The trial was stopped early because atorvastatin had resulted in a statistically significant reduction in CVD events: stroke (89 versus 121, P=0.024); total CV events (389 versus 486, P=0.0005); total coronary events compared with placebo (178 versus 247, P=0.0005) - PROVE IT-TIMI 22: Pravastatin or Atorvastatin Evaluation and Infection—Thrombolysis in Myocardial Infarction 22 (Rouleau, 2005)
o Standard treatment (statin) with a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (pravastatin 40 mg/d) resulted in a 22% reduction in LDL cholesterol levels at 30 days compared with a 51% reduction with intensive therapy (atorvastatin 80 mg/d)
o At two years, a relative risk reduction of 16% (95% CI, 5%-26%; P = 0.005) in the primary endpoint rate (death, MI, documented unstable angina requiring hospitalization, coronary revascularization, or stroke) was seen in patients receiving intensive statin treatment compared with standard statin therapy
These trials addressed issues that were not examined in previous clinical trials of cholesterol-lowering therapy. The trials confirmed the benefit of cholesterol-lowering therapy in high-risk patients and support the following: - ATP III treatment goal of LDL cholesterol <100 mg/dL
- Inclusion of patients with diabetes in the high-risk category and confirm the benefits of LDL cholesterol lowering therapy in these patients
- Inclusion of older persons benefiting from therapeutic lowering of LDL cholesterol
More recently, tn) with a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (pravastatin 40 mg/d) resulted in a 22% reduction in LDL cholesterol levels at 30 days compared with a 51% reduction with intensive therapy (atorvastatin 80 mg/d)
o At two years, a relative risk reduction of 16% (95% CI, 5%-26%; P = 0.005) in the primary endpoint rate (death, MI, documented unstable angina requiring hospitalization, coronary revascularization, or stroke) was seen in patients receiving intensive statin treatment compared with standard statin therapy These trials addressed issues that were not examined in previous clinical trials of cholesterol-lowering therapy. The trials confirmed the benefit of cholesterol-lowering therapy in high-risk patients and support the following: - ATP III treatment goal of LDL cholesterol <100 mg/dL
- Inclusion of patients with diabetes in the high-risk category and confirm the benefits of LDL cholesterol lowering therapy in these patients
- Inclusion of older persons benefiting from therapeutic lowering of LDL cholesterol
More recently, the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial demonstrated that when compared with placebo, atorvastatin 80 mg/d significantly reduced the risk of recurrent stroke in patients with recent stroke or TIA and no history of CHD, while substantially decreasing the risk of major coronary and CHD events and revascularization procedures (Welch, 2006). Table 7 provides the updated ATP III guidelines for cholesterol management (Grundy, 2004). Therapeutic lifestyle changes remain an essential modality in clinical management. Lifestyle changes, which include a healthy diet and exercise, must be an integral part of risk reduction therapy. When an LDL-cholesterol-lowering drug is employed in a person at high risk or moderately high risk, a reduction in LDL cholesterol levels of at least 30% to 40% beyond dietary therapy should be achieved, if feasible.
Very high risk patients consider LDL <> If HDL is low consider niacin or gemfibrozil |
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