The primary and secondary prevention and atherosclerosis regression studies below in aggregate suggest that for optimal effects, LDL cholesterol should be lowered well below 100 mg/dl, to levels around 75-80 mg/dl.
An increasing amount of data from primary prevention, secondary prevention, and atherosclerosis regression studies suggest that to provide optimal results in terms of lowering coronary heart disease events and /or stopping the progression of or reversing atherosclerotic lesions, LDL cholesterol should be lowered to well under 100 mg/dl, and optimally to <80 mg/dl.
Heart Protection Study (HPS)1
Lower LDL cholesterol is associated with a lower risk of cardiovascular disease. The purpose of the Heart Protection Study (HPS) was to investigate whether lowering LDL cholesterol with simvastatin (brand name Zocor®) reduced the development of vascular disease irrespective of initial LDL concentrations. The researchers studied 20,536 patients in the United Kingdom with coronary disease, other occlusive arterial disease, or diabetes. Patients were randomly assigned to receive either 40mg of simvastatin per day or a placebo. The average compliance was 85%, and 17% of the patients were already taking statins not related to the study.
Among the findings was that patients taking simvastatin showed in a first non-fatal or fatal stroke compared to the placebo group (444 [4.3%] vs 585 [5.7%]; p<0.0001). Additionally, patients taking simvastatin showed a lower frequency of first non-fatal or fatal heart attack (8.7% vs 11.8%, p<.0001). Overall, patients taking simvastatin had a 24% reduction in the first occurrence of any of the studied major vascular events. Importantly, patients who entered the study with LDL cholesterol < 100 mg/dl before receiving Zocor had a reduction in cardiovascular events which was essentially as great as patients whose baseline LDL cholesterol was 130 or 160 mg/dl. This focused attention on lowering LDL cholesterol to ~80 mg/dl (as in this group) for optimal prevention of cardiovascular events.
This reduction in major vascular events was not significant in the first year of the study, but it was significant in each of the following four years. Furthermore, this reduction was seen in each subcategory (based on the type of vascular disease in their history) of patients studied.
There are several important messages from this study. Adding simvastatin to an existing treatment (17% were already on statins) safely produces large additional benefits over a wide range of cholesterol ranges. Taking 40 mg of simvastatin daily reduced the rates of heart attack, stroke, and revascularization by roughly 25%.Because of 15% non-compliance in this study, the true reduction could be as large as 33%. Although treatment with simvastatin produced significant benefits, the size of the five-year benefit depends on the overall risk for vascular disease rather than only cholesterol concentrations. That is, lowering cholesterol is likely to decrease the risk of a vascular event but the amount of reduction depends largely on other factors such as smoking, obesity, and genetic predisposition, rather than cholesterol concentrations alone.
During the early time after an acute coronary syndrome—unstable angina (chest pain due to a blockage in the heart) or sudden heart attack—patients have the highest rate of death or recurrent ischemic (blockage) events. This study investigated whether 80 mg daily of atorvastatin (brand name Lipitor®), started 1-4 days after an acute coronary event, reduced the risk of death or non-fatal ischemic events. Patients at 122 clinical centers in Europe, North America, South Africa, and Australasia (n =3086) were randomly divided into two groups, receiving either 80 mg of atorvastatin per day or a placebo. Patients were followed for 16 weeks after the occurrence of an acute coronary syndrome. The significant finding was that patients in the atorvastatin group had a lower occurrence of recurrent ischemic events in the first 16 weeks after the appearance of acute coronary syndrome.
Anglo-Scandinavian Clinical Outcomes Trial (ASCOT)3
Hypertension (high blood pressure) and elevated cholesterol are two of the most common risk factors for heart disease and stroke, which are major causes of death worldwide. Lowering blood pressure and cholesterol are important in controlling these conditions. The ASCOT study included 19,342 patients randomized into one of two antihypertensive regimens. A total of 10,305 patients were randomly selected from these groups and placed in a lipid-lowering group which consisted of 10 mg of atorvastatin daily or placebo. The atorvastatin and placebo groups of the lipid-lowering arm had identical initial cholesterol levels and blood pressure. Patients were followed for a median of 3.3 years. The atorvastatin group had a 35% relative reduction in the LDL compared to the placebo group. Fatal heart attack and fatal coronary heart disease were 36% lower in the atorvastatin group. There were also significant (29%) reductions in total coronary events and a 27% reduction in fatal and non-fatal strokes. In the atorvastatin group, LDL cholesterol levels were about 80 mg/dl on therapy, again providing emphasis on lowering LDL to well below 100 mg/dl.
Reversing Atherosclerosis with Aggressive Lipid Lowering (REVERSAL)4
This recent study compared the effectiveness of atorvastatin and pravastatin in the reversal in atherosclerosis. Five hundred and two patients diagnosed with coronary heart disease and with LDL cholesterol around 150 mg/dl were treated with either atorvastatin or pravastatin (brand name Pravachol®). Intravascular ultrasound was used to assess atherosclerotic plaque status at pre-treatment baseline and after 18 months on therapy. The group treated with atorvastatin showed a median 0.4% reduction in plaque volume (the total plaque in a given section of an artery) while the pravastatin group had a median 2.7% increase in total plaque volume. Additionally, 97% of the patients taking atorvastatin reached the recommended LDL levels (=100 mg/dL) while 67% of pravastatin patients reached this level. On atorvastatin, LDL cholesterol was lowered to around 80 mg/dl, while on pravastatin, to 110 mg/dl.