Intensive Lipid Lowering with Atorvastatin in Coronary Disease
http://www.100md.com
《新英格兰医药杂志》
To the Editor: LaRosa and colleagues (April 7 issue)1 report that among patients with stable coronary heart disease (CHD), an intensive statin regimen provides a 22 percent reduction in the risk of cardiovascular events when compared with a standard regimen. However, despite the 20 percent reduction in the risk of death from CHD in the group that received 80 mg of atorvastatin per day, there was no significant difference between the groups in overall mortality. This finding reflects an increase in the risk of death from noncardiovascular causes, which is undoubtedly a matter of concern.
In patients with an acute coronary syndrome, high-dose atorvastatin, as compared with standard-dose pravastatin, was associated with reductions of 28 and 30 percent in overall mortality and mortality related to CHD, respectively, by two years.2 The benefit of high-dose atorvastatin emerged as early as 30 days after the start of treatment with the statin.2 A lower cardiovascular risk among patients with stable CHD than among patients with an acute coronary syndrome, together with longer exposure to the potential toxicity of high-dose atorvastatin (2.0 vs. 4.9 years), may explain the difference in the effect on overall mortality in the Treating to New Targets (TNT) study1 and the Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22 (PROVE IT–TIMI 22) trial.2 Thus, when treatment with very high statin doses is considered, the selection of patients whose risk of cardiovascular events is high enough to outweigh the potential risk of toxic drug-related effects is of utmost importance.
Johann Auer, M.D.
Gudrun Lamm, M.D.
Bernd Eber, M.D.
General Hospital Wels
A-4600 Wels, Austria
johann.auer@klinikum-wels.at
References
LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005;352:1425-1435.
Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004;350:1495-1504.
To the Editor: In his editorial on the study by LaRosa and colleagues, Pitt1 expresses concern regarding the nonsignificant difference in mortality from noncardiovascular causes between high-dose and low-dose statin treatment. This difference, however, may be due to the play of chance. To evaluate all available data, we performed a meta-analysis of the three trials comparing intensive and standard lipid lowering to date with respect to mortality from cardiovascular and noncardiovascular causes. As for mortality from noncardiovascular causes, the trial reported by LaRosa et al. (TNT, in which 10 mg of atorvastatin per day was compared with 80 mg of atorvastatin per day in a population of 10,001 patients) showed a nonsignificantly higher rate with high-dose statin therapy; the second trial (PROVE IT–TIMI 22, in which 40 mg of pravastatin per day was compared with 80 mg of atorvastatin per day in a population of 4162 patients) showed a lower rate with high-dose therapy2; and in the third (Aggrastat-to-Zocor [A-to-Z], in which 20 mg of simvastatin per day was compared with 80 mg of simvastatin in a population of 4497 patients), the difference in dose had no effect.3 On the other hand, mortality from cardiovascular causes in the three trials was significantly reduced, by 24 percent (P=0.004), adding further support to the trend toward reduced mortality from cardiovascular causes seen with intensive statin therapy in the individual trials. This analysis should provide reassurance that intensive lipid lowering does not appear to have any adverse effect on mortality from noncardiovascular causes and in fact that it is associated with a substantial benefit in preventing morbidity and mortality from cardiovascular causes.
Christopher P. Cannon, M.D.
Sabina A. Murphy, M.P.H.
Eugene Braunwald, M.D.
Brigham and Women's Hospital
Boston, MA 02115
cpcannon@partners.org
Dr. Cannon reports having received research grant support from AstraZeneca, Bristol-Myers Squibb, Merck, Merck/Schering-Plough, and Sanofi-Aventis and having served on paid advisory boards for AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Merck/Schering-Plough Partnership, Merck, Pfizer, and Sanofi-Aventis. Dr. Braunwald reports having received research grant support from Sanofi-Aventis, Bristol-Myers Squibb, and Merck/Schering Plough.
References
Pitt B. Low-density lipoprotein cholesterol in patients with stable coronary heart disease -- is it time to shift our goals? N Engl J Med 2005;352:1483-1484.
Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004;350:1495-1504.
de Lemos JA, Blazing MA, Wiviott SD, et al. Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. JAMA 2004;292:1307-1316.
To the Editor: When a drug designed to prevent cardiovascular disease fails to lower overall mortality rates, as in the TNT study, it is mandatory to report meticulously the number, nature, and severity of adverse effects, because the benefits from reductions in the incidence of coronary events may be outweighed by such complications.
A nonfatal heart attack or stroke may have few sequelae; the consequences of aggressive statin treatment, including rhabdomyolysis, polyneuropathy,1 aggressive or suicidal behavior,2 amnesia,3 or serious congenital defects4 could be much more catastrophic for patients. Although such adverse effects of statins have been rare, there can be little doubt that their incidence would rise with an increase in dosage by a factor of eight. We are therefore concerned about the cursory manner in which the authors dealt with this important issue; in particular, we object to the arbitrary exclusion of adverse effects that they considered unrelated to treatment (e.g., five cases of rhabdomyolysis). What other untoward effects not reported did they consider unrelated to treatment?
Uffe Ravnskov, M.D., Ph.D.
Magle Stora Kyrkogata 9
Lund S-22350, Sweden
ravnskov@tele2.se
Paul J. Rosch, M.D.
New York Medical College
New York, NY 10703
Morley C. Sutter, M.D.
University of British Columbia
Vancouver, BC V6T 1Z3, Canada
References
Gaist D, Jeppesen U, Andersen M, Garcia Rodriguez LA, Hallas J, Sindrup SH. Statins and risk of polyneuropathy: a case-control study. Neurology 2002;58:1333-1337.
Golomb BA, Kane T, Dimsdale JE. Severe irritability associated with statin cholesterol-lowering drugs. QJM 2004;97:229-235.
Wagstaff LR, Mitton MW, Arvik BM, Doraiswamy PM. Statin-associated memory loss: analysis of 60 case reports and review of the literature. Pharmacotherapy 2003;23:871-880.
Edison RJ, Muenke M. Central nervous system and limb anomalies in case reports of first-trimester statin exposure. N Engl J Med 2004;350:1579-1582.
To the Editor: The study by LaRosa et al. adds to the growing literature indicating that the lower the low-density lipoprotein (LDL) cholesterol level, the better the outcome among patients with known coronary artery disease. It would be useful clinically to have two further analyses of their data. First, what were the clinical outcomes of the patients stratified according to their achieved LDL cholesterol levels? Statins have many pleiotropic effects in addition to their direct lipid-lowering effect.1 However, if the actual LDL cholesterol level achieved were in fact a predictor of future events, as found in the PROVE IT trial,2 then clinicians could use the lowest dose of atorvastatin necessary to achieve that goal, thereby minimizing medication-related side effects and costs.
Second, what role does high-density lipoprotein (HDL) cholesterol play? For example, a target LDL cholesterol level of 100 mg per deciliter in a patient with an HDL cholesterol level of 55 mg per deciliter might be clinically superior to an LDL cholesterol target of 70 mg per deciliter in a patient with an HDL cholesterol level of 25 mg per deciliter. There are abundant examples in the literature suggesting that the ratio of LDL (or total) cholesterol to HDL cholesterol is a better predictor of clinical outcomes than the LDL cholesterol level itself.3,4
Geoffrey A. Modest, M.D.
Boston University School of Medicine
Boston, MA 02118
gmodest@partners.org
References
Rosenson RS, Tangney CC. Antiatherothrombotic properties of statins: implications for cardiovascular event reduction. JAMA 1998;279:1643-1650.
Ridker PM, Cannon CP, Morrow D, et al. C-reactive protein levels and outcomes after statin therapy. N Engl J Med 2005;352:20-28.
Kinosian B, Glick H, Garland G. Cholesterol and coronary heart disease: predicting risks by levels and ratios. Ann Intern Med 1994;121:641-647.
Mediene-Benchekor S, Brousseau T, Richard F, Benhamamouch S, Amouyel P. Blood lipid concentrations and risk of myocardial infarction. Lancet 2001;358:1064-1065.
To the Editor: LaRosa et al. report a 22 percent relative reduction in the risk of major cardiovascular events with 80 mg of atorvastatin per day as compared with a dose of 10 mg per day. The cohort assigned to the higher dose also had a lower mean LDL cholesterol level (77 mg per deciliter vs. 101 mg per deciliter). According to the data presented, changing the target of statin therapy from an LDL cholesterol level of 100 mg per deciliter to a level of 70 mg per deciliter is not warranted. In PROVE IT–TIMI 22, the benefit of intensive lipid-lowering therapy was driven primarily by the subgroup (27 percent of the population) with an LDL cholesterol level greater than 125 mg per deciliter at randomization.1 It would be interesting to see a similar subgroup analysis in the current study, given that substantial numbers of patients had an LDL cholesterol level above 100 mg per deciliter at randomization. It is entirely possible that the benefit of the higher dose of atorvastatin is attributable to the subgroup of patients whose baseline LDL cholesterol levels were greater than 100 mg per deciliter. If that is the case, then no change in existing guidelines is warranted.
William Southern, M.D.
Albert Einstein College of Medicine
Bronx, NY 10461
wsouther@montefiore.org
References
Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004;350:1495-1504.
The authors reply: Dr. Southern and Dr. Modest both suggest the examination of clinical benefits in groups stratified according to LDL cholesterol levels during treatment. In addition, Dr. Modest asks about the relationship between HDL cholesterol levels during treatment and cardiovascular risk. We have not yet performed these analyses.
Dr. Ravnskov and colleagues attribute conditions to statins in what are, at best, associations that have not been demonstrated in this or previous statin trials. The increased incidence they speculate would be present with the higher dose was not confirmed in this large study, which was conducted over a five-year period (with almost 25,000 patient-years of atorvastatin therapy at a dose of 80 mg per day). With regard to the cases of rhabdomyolysis, none of the on-site investigators believed they could be attributed to statin use, and none met American College of Cardiology–American Heart Association–National Heart, Lung, and Blood Institute criteria for rhabdomyolysis. The decision as to whether an adverse event was considered unrelated to treatment was made by the investigator with direct responsibility for the patient, and not by the authors. Even if Dr. Ravnskov and colleagues disagree, they cannot deny that the incidence is extremely low and unrelated to the dose of atorvastatin used.
The comparison of data from the TNT, PROVE IT–TIMI 22, and A-to-Z trials by Dr. Cannon and colleagues is reassuring, although we acknowledge, as do Dr. Auer and colleagues, that the mechanisms underlying the benefit from high-dose statin therapy in acute coronary syndromes may not be exactly the same as they are in stable CHD.
We concur with Dr. Cannon and colleagues that the play of chance could be driving the observed results in the TNT study. TNT was not powered to detect a treatment effect on death from any cause. Previous large-scale secondary-prevention studies in which death from any cause was not the primary end point have also failed to find a significant effect on overall mortality. We cannot draw definitive conclusions about mortality from noncardiovascular causes on the basis of a study substantially underpowered to study it; we can only repeat that no single cause of death explains what is most likely a chance observation.
We will face a similar challenge in designing future LDL-lowering studies focusing on clinical outcomes. Since placebo-controlled trials involving patients with stable disease are no longer ethical, we will be challenged to power controlled studies around events with a low incidence, such as death from any cause. We estimated in TNT that a sample size of roughly 35,000 patients (17,500 in each group) would have been necessary to detect a treatment effect on overall mortality.
Previous studies, adequately powered to detect differences in mortality, have clearly demonstrated the mortality benefits associated with the use of statins. We are now in an era in which randomized, comparative clinical studies are likely only to demonstrate benefits in terms of reductions in morbidity. In TNT, mortality from any cause in both treatment groups was lower than that in the treatment group in all previous trials of statins in secondary prevention. In this new era, TNT found significant reductions in morbidity from cardiovascular causes (including a highly significant reduction in the risk of stroke) with the use of 80 mg of atorvastatin per day to lower LDL cholesterol levels substantially below the current LDL cholesterol goals.
John C. LaRosa, M.D.
State University of New York Health Sciences Center
Brooklyn, NY 11203
jclarosa@downstate.edu
Scott M. Grundy, M.D., Ph.D.
University of Texas Southwestern Medical Center
Dallas, TX 75390
David D. Waters, M.D.
San Francisco General Hospital
San Francisco, CA 94110
In patients with an acute coronary syndrome, high-dose atorvastatin, as compared with standard-dose pravastatin, was associated with reductions of 28 and 30 percent in overall mortality and mortality related to CHD, respectively, by two years.2 The benefit of high-dose atorvastatin emerged as early as 30 days after the start of treatment with the statin.2 A lower cardiovascular risk among patients with stable CHD than among patients with an acute coronary syndrome, together with longer exposure to the potential toxicity of high-dose atorvastatin (2.0 vs. 4.9 years), may explain the difference in the effect on overall mortality in the Treating to New Targets (TNT) study1 and the Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22 (PROVE IT–TIMI 22) trial.2 Thus, when treatment with very high statin doses is considered, the selection of patients whose risk of cardiovascular events is high enough to outweigh the potential risk of toxic drug-related effects is of utmost importance.
Johann Auer, M.D.
Gudrun Lamm, M.D.
Bernd Eber, M.D.
General Hospital Wels
A-4600 Wels, Austria
johann.auer@klinikum-wels.at
References
LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005;352:1425-1435.
Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004;350:1495-1504.
To the Editor: In his editorial on the study by LaRosa and colleagues, Pitt1 expresses concern regarding the nonsignificant difference in mortality from noncardiovascular causes between high-dose and low-dose statin treatment. This difference, however, may be due to the play of chance. To evaluate all available data, we performed a meta-analysis of the three trials comparing intensive and standard lipid lowering to date with respect to mortality from cardiovascular and noncardiovascular causes. As for mortality from noncardiovascular causes, the trial reported by LaRosa et al. (TNT, in which 10 mg of atorvastatin per day was compared with 80 mg of atorvastatin per day in a population of 10,001 patients) showed a nonsignificantly higher rate with high-dose statin therapy; the second trial (PROVE IT–TIMI 22, in which 40 mg of pravastatin per day was compared with 80 mg of atorvastatin per day in a population of 4162 patients) showed a lower rate with high-dose therapy2; and in the third (Aggrastat-to-Zocor [A-to-Z], in which 20 mg of simvastatin per day was compared with 80 mg of simvastatin in a population of 4497 patients), the difference in dose had no effect.3 On the other hand, mortality from cardiovascular causes in the three trials was significantly reduced, by 24 percent (P=0.004), adding further support to the trend toward reduced mortality from cardiovascular causes seen with intensive statin therapy in the individual trials. This analysis should provide reassurance that intensive lipid lowering does not appear to have any adverse effect on mortality from noncardiovascular causes and in fact that it is associated with a substantial benefit in preventing morbidity and mortality from cardiovascular causes.
Christopher P. Cannon, M.D.
Sabina A. Murphy, M.P.H.
Eugene Braunwald, M.D.
Brigham and Women's Hospital
Boston, MA 02115
cpcannon@partners.org
Dr. Cannon reports having received research grant support from AstraZeneca, Bristol-Myers Squibb, Merck, Merck/Schering-Plough, and Sanofi-Aventis and having served on paid advisory boards for AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Merck/Schering-Plough Partnership, Merck, Pfizer, and Sanofi-Aventis. Dr. Braunwald reports having received research grant support from Sanofi-Aventis, Bristol-Myers Squibb, and Merck/Schering Plough.
References
Pitt B. Low-density lipoprotein cholesterol in patients with stable coronary heart disease -- is it time to shift our goals? N Engl J Med 2005;352:1483-1484.
Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004;350:1495-1504.
de Lemos JA, Blazing MA, Wiviott SD, et al. Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. JAMA 2004;292:1307-1316.
To the Editor: When a drug designed to prevent cardiovascular disease fails to lower overall mortality rates, as in the TNT study, it is mandatory to report meticulously the number, nature, and severity of adverse effects, because the benefits from reductions in the incidence of coronary events may be outweighed by such complications.
A nonfatal heart attack or stroke may have few sequelae; the consequences of aggressive statin treatment, including rhabdomyolysis, polyneuropathy,1 aggressive or suicidal behavior,2 amnesia,3 or serious congenital defects4 could be much more catastrophic for patients. Although such adverse effects of statins have been rare, there can be little doubt that their incidence would rise with an increase in dosage by a factor of eight. We are therefore concerned about the cursory manner in which the authors dealt with this important issue; in particular, we object to the arbitrary exclusion of adverse effects that they considered unrelated to treatment (e.g., five cases of rhabdomyolysis). What other untoward effects not reported did they consider unrelated to treatment?
Uffe Ravnskov, M.D., Ph.D.
Magle Stora Kyrkogata 9
Lund S-22350, Sweden
ravnskov@tele2.se
Paul J. Rosch, M.D.
New York Medical College
New York, NY 10703
Morley C. Sutter, M.D.
University of British Columbia
Vancouver, BC V6T 1Z3, Canada
References
Gaist D, Jeppesen U, Andersen M, Garcia Rodriguez LA, Hallas J, Sindrup SH. Statins and risk of polyneuropathy: a case-control study. Neurology 2002;58:1333-1337.
Golomb BA, Kane T, Dimsdale JE. Severe irritability associated with statin cholesterol-lowering drugs. QJM 2004;97:229-235.
Wagstaff LR, Mitton MW, Arvik BM, Doraiswamy PM. Statin-associated memory loss: analysis of 60 case reports and review of the literature. Pharmacotherapy 2003;23:871-880.
Edison RJ, Muenke M. Central nervous system and limb anomalies in case reports of first-trimester statin exposure. N Engl J Med 2004;350:1579-1582.
To the Editor: The study by LaRosa et al. adds to the growing literature indicating that the lower the low-density lipoprotein (LDL) cholesterol level, the better the outcome among patients with known coronary artery disease. It would be useful clinically to have two further analyses of their data. First, what were the clinical outcomes of the patients stratified according to their achieved LDL cholesterol levels? Statins have many pleiotropic effects in addition to their direct lipid-lowering effect.1 However, if the actual LDL cholesterol level achieved were in fact a predictor of future events, as found in the PROVE IT trial,2 then clinicians could use the lowest dose of atorvastatin necessary to achieve that goal, thereby minimizing medication-related side effects and costs.
Second, what role does high-density lipoprotein (HDL) cholesterol play? For example, a target LDL cholesterol level of 100 mg per deciliter in a patient with an HDL cholesterol level of 55 mg per deciliter might be clinically superior to an LDL cholesterol target of 70 mg per deciliter in a patient with an HDL cholesterol level of 25 mg per deciliter. There are abundant examples in the literature suggesting that the ratio of LDL (or total) cholesterol to HDL cholesterol is a better predictor of clinical outcomes than the LDL cholesterol level itself.3,4
Geoffrey A. Modest, M.D.
Boston University School of Medicine
Boston, MA 02118
gmodest@partners.org
References
Rosenson RS, Tangney CC. Antiatherothrombotic properties of statins: implications for cardiovascular event reduction. JAMA 1998;279:1643-1650.
Ridker PM, Cannon CP, Morrow D, et al. C-reactive protein levels and outcomes after statin therapy. N Engl J Med 2005;352:20-28.
Kinosian B, Glick H, Garland G. Cholesterol and coronary heart disease: predicting risks by levels and ratios. Ann Intern Med 1994;121:641-647.
Mediene-Benchekor S, Brousseau T, Richard F, Benhamamouch S, Amouyel P. Blood lipid concentrations and risk of myocardial infarction. Lancet 2001;358:1064-1065.
To the Editor: LaRosa et al. report a 22 percent relative reduction in the risk of major cardiovascular events with 80 mg of atorvastatin per day as compared with a dose of 10 mg per day. The cohort assigned to the higher dose also had a lower mean LDL cholesterol level (77 mg per deciliter vs. 101 mg per deciliter). According to the data presented, changing the target of statin therapy from an LDL cholesterol level of 100 mg per deciliter to a level of 70 mg per deciliter is not warranted. In PROVE IT–TIMI 22, the benefit of intensive lipid-lowering therapy was driven primarily by the subgroup (27 percent of the population) with an LDL cholesterol level greater than 125 mg per deciliter at randomization.1 It would be interesting to see a similar subgroup analysis in the current study, given that substantial numbers of patients had an LDL cholesterol level above 100 mg per deciliter at randomization. It is entirely possible that the benefit of the higher dose of atorvastatin is attributable to the subgroup of patients whose baseline LDL cholesterol levels were greater than 100 mg per deciliter. If that is the case, then no change in existing guidelines is warranted.
William Southern, M.D.
Albert Einstein College of Medicine
Bronx, NY 10461
wsouther@montefiore.org
References
Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004;350:1495-1504.
The authors reply: Dr. Southern and Dr. Modest both suggest the examination of clinical benefits in groups stratified according to LDL cholesterol levels during treatment. In addition, Dr. Modest asks about the relationship between HDL cholesterol levels during treatment and cardiovascular risk. We have not yet performed these analyses.
Dr. Ravnskov and colleagues attribute conditions to statins in what are, at best, associations that have not been demonstrated in this or previous statin trials. The increased incidence they speculate would be present with the higher dose was not confirmed in this large study, which was conducted over a five-year period (with almost 25,000 patient-years of atorvastatin therapy at a dose of 80 mg per day). With regard to the cases of rhabdomyolysis, none of the on-site investigators believed they could be attributed to statin use, and none met American College of Cardiology–American Heart Association–National Heart, Lung, and Blood Institute criteria for rhabdomyolysis. The decision as to whether an adverse event was considered unrelated to treatment was made by the investigator with direct responsibility for the patient, and not by the authors. Even if Dr. Ravnskov and colleagues disagree, they cannot deny that the incidence is extremely low and unrelated to the dose of atorvastatin used.
The comparison of data from the TNT, PROVE IT–TIMI 22, and A-to-Z trials by Dr. Cannon and colleagues is reassuring, although we acknowledge, as do Dr. Auer and colleagues, that the mechanisms underlying the benefit from high-dose statin therapy in acute coronary syndromes may not be exactly the same as they are in stable CHD.
We concur with Dr. Cannon and colleagues that the play of chance could be driving the observed results in the TNT study. TNT was not powered to detect a treatment effect on death from any cause. Previous large-scale secondary-prevention studies in which death from any cause was not the primary end point have also failed to find a significant effect on overall mortality. We cannot draw definitive conclusions about mortality from noncardiovascular causes on the basis of a study substantially underpowered to study it; we can only repeat that no single cause of death explains what is most likely a chance observation.
We will face a similar challenge in designing future LDL-lowering studies focusing on clinical outcomes. Since placebo-controlled trials involving patients with stable disease are no longer ethical, we will be challenged to power controlled studies around events with a low incidence, such as death from any cause. We estimated in TNT that a sample size of roughly 35,000 patients (17,500 in each group) would have been necessary to detect a treatment effect on overall mortality.
Previous studies, adequately powered to detect differences in mortality, have clearly demonstrated the mortality benefits associated with the use of statins. We are now in an era in which randomized, comparative clinical studies are likely only to demonstrate benefits in terms of reductions in morbidity. In TNT, mortality from any cause in both treatment groups was lower than that in the treatment group in all previous trials of statins in secondary prevention. In this new era, TNT found significant reductions in morbidity from cardiovascular causes (including a highly significant reduction in the risk of stroke) with the use of 80 mg of atorvastatin per day to lower LDL cholesterol levels substantially below the current LDL cholesterol goals.
John C. LaRosa, M.D.
State University of New York Health Sciences Center
Brooklyn, NY 11203
jclarosa@downstate.edu
Scott M. Grundy, M.D., Ph.D.
University of Texas Southwestern Medical Center
Dallas, TX 75390
David D. Waters, M.D.
San Francisco General Hospital
San Francisco, CA 94110