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Statins, High-Density Lipoprotein Cholesterol, and Regression of Coronary Atherosclerosis


Stephen J. Nicholls, MBBS, PhD; E. Murat Tuzcu, MD; Ilke Stephen J. Nicholls, MBBS, PhD; E. Murat Tuzcu, MD; Ilke Sipahi, MD; Adam W. Grasso, MD; Paul Schoenhagen, MD; Sipahi, MD; Adam W. Grasso, MD; Paul Schoenhagen, MD;

Tingfei Hu, MS; Kathy Wolski, MPH; Tim Crowe, BS; Tingfei Hu, MS; Kathy Wolski, MPH; Tim Crowe, BS; Milind Y. Desai, MD; Stanley L. Hazen, MD, PhD; Milind Y. Desai, MD; Stanley L. Hazen, MD, PhD;

Samir R. Kapadia, MD; Steven E. Nissen, MDSamir R. Kapadia, MD; Steven E. Nissen, MD

Published in JAMAPublished in JAMA

February 7, 2007February 7, 2007




Statins, High-Density Lipoprotein Cholesterol, and Regression of Coronary Atherosclerosis: Background

Statins, High-Density Lipoprotein Cholesterol, and Regression of Coronary Atherosclerosis: Background

• Statins reduce low-density lipoprotein cholesterol Statins reduce low-density lipoprotein cholesterol (LDL-C) levels and slow progression of coronary (LDL-C) levels and slow progression of coronary atherosclerosis.atherosclerosis.

• Statins have been reported to increase high-Statins have been reported to increase high-density lipoprotein cholesterol (HDL-C) levels by density lipoprotein cholesterol (HDL-C) levels by 5% to 15%, but it has never been established that 5% to 15%, but it has never been established that these small statin-induced increases in HDL-C these small statin-induced increases in HDL-C translate into a meaningful clinical benefit.translate into a meaningful clinical benefit.

• Statins reduce low-density lipoprotein cholesterol Statins reduce low-density lipoprotein cholesterol (LDL-C) levels and slow progression of coronary (LDL-C) levels and slow progression of coronary atherosclerosis.atherosclerosis.

• Statins have been reported to increase high-Statins have been reported to increase high-density lipoprotein cholesterol (HDL-C) levels by density lipoprotein cholesterol (HDL-C) levels by 5% to 15%, but it has never been established that 5% to 15%, but it has never been established that these small statin-induced increases in HDL-C these small statin-induced increases in HDL-C translate into a meaningful clinical benefit.translate into a meaningful clinical benefit.

Nicholls SJ, et al. JAMA. 2007 Feb; 297(5): 499-508. Nicholls SJ, et al. JAMA. 2007 Feb; 297(5): 499-508.


Statins, High-Density Lipoprotein Cholesterol, and Regression of Coronary Atherosclerosis: Background (cont.)

Statins, High-Density Lipoprotein Cholesterol, and Regression of Coronary Atherosclerosis: Background (cont.)

• This study investigated the relationship between This study investigated the relationship between changes in lipoprotein levels and atheroma volume changes in lipoprotein levels and atheroma volume in patients with coronary artery disease (CAD) who in patients with coronary artery disease (CAD) who were treated with statins.were treated with statins.

• The principal objective was to determine the The principal objective was to determine the relative contribution of statin-induced reductions in relative contribution of statin-induced reductions in atherogenic lipoproteins and increases in HDL-C atherogenic lipoproteins and increases in HDL-C on the rate of atheroma progression.on the rate of atheroma progression.

• This study investigated the relationship between This study investigated the relationship between changes in lipoprotein levels and atheroma volume changes in lipoprotein levels and atheroma volume in patients with coronary artery disease (CAD) who in patients with coronary artery disease (CAD) who were treated with statins.were treated with statins.

• The principal objective was to determine the The principal objective was to determine the relative contribution of statin-induced reductions in relative contribution of statin-induced reductions in atherogenic lipoproteins and increases in HDL-C atherogenic lipoproteins and increases in HDL-C on the rate of atheroma progression.on the rate of atheroma progression.



Statins, High-Density Lipoprotein Cholesterol, and Regression of Coronary Atherosclerosis: Study Design

Statins, High-Density Lipoprotein Cholesterol, and Regression of Coronary Atherosclerosis: Study Design

Primary Endpoint: Relationship between changes in LDL-C and Primary Endpoint: Relationship between changes in LDL-C and

HDL-C levels and atheroma burden.HDL-C levels and atheroma burden.

Primary Endpoint: Relationship between changes in LDL-C and Primary Endpoint: Relationship between changes in LDL-C and

HDL-C levels and atheroma burden.HDL-C levels and atheroma burden.

REVERSAL

n=502

REVERSAL

n=502

1455 patients from 4 trials (REVERSAL, CAMELOT, ACTIVATE, ASTEROID) with CAD undergoing serial intravascular ultrasonography while receiving statin treatment.

Post-hoc analysis of raw data from the four prospective, randomized trials. Follow-up at 18 or 24 months.Exclusion criteria: Target segment selected was required to have no greater than 50% lumen narrowing for

a length of at least 30 mm and target vessel required to have not previously undergone percutaneous coronary intervention.

1455 patients from 4 trials (REVERSAL, CAMELOT, ACTIVATE, ASTEROID) with CAD undergoing serial intravascular ultrasonography while receiving statin treatment.

Post-hoc analysis of raw data from the four prospective, randomized trials. Follow-up at 18 or 24 months.Exclusion criteria: Target segment selected was required to have no greater than 50% lumen narrowing for

a length of at least 30 mm and target vessel required to have not previously undergone percutaneous coronary intervention.

18 or 24 mos. follow-up 18 or 24 mos. follow-up

CAMELOT

n=240

CAMELOT

n=240

ACTIVATE

n=364

ACTIVATE

n=364

ASTEROID

n=349

ASTEROID

n=349



CharacteristicCharacteristic REVERSALREVERSAL(n=502)(n=502)

CAMELOTCAMELOT(n=240)(n=240)

ACTIVATEACTIVATE(n=364)(n=364)

ASTEROIDASTEROID(n=349)(n=349)

Length of study, Length of study, momo 1818 2424 1818 2424

Age, mean (SD)Age, mean (SD) 56.2 (9.5)56.2 (9.5) 56.7 (9.9)56.7 (9.9) 59.4 (9.6)59.4 (9.6) 58.5 (10.0)58.5 (10.0)

MenMen 362 (72.1)362 (72.1) 187 (77.9)187 (77.9) 261 (71.7)261 (71.7) 245 (70.2)245 (70.2)

White raceWhite race 444 (88.4)444 (88.4) 223 (92.9)223 (92.9) 327 (89.8)327 (89.8) 338 (96.8)338 (96.8)

Body mass index, Body mass index, mean (SD)mean (SD) 30.5 (6.1)30.5 (6.1) 30.2 (4.9)30.2 (4.9) 30.7 (5.6)30.7 (5.6) 29.1 (4.9)29.1 (4.9)

DiabetesDiabetes 95 (18.9)95 (18.9) 39 (16.3)39 (16.3) 94 (25.8)94 (25.8) 46 (13.2)46 (13.2)

HypertensionHypertension 348 (69.3)348 (69.3) 152 (63.3)152 (63.3) 271 (74.5)271 (74.5) 335 (96.0)335 (96.0)

Metabolic Metabolic SyndromeSyndrome 292 (58.2)292 (58.2) 107 (44.6)107 (44.6) 179 (49.2)179 (49.2) 165 (47.3)165 (47.3)

Current SmokerCurrent Smoker 132 (26.3)132 (26.3) 56 (23.5)56 (23.5) 74 (20.3)74 (20.3) NANA

Statins, High-Density Lipoprotein Cholesterol, and Regression of Coronary Atherosclerosis: Baseline Characteristics

Statins, High-Density Lipoprotein Cholesterol, and Regression of Coronary Atherosclerosis: Baseline Characteristics



CharacteristicCharacteristic REVERSALREVERSAL(n=502)(n=502)




Previous event or Previous event or procedureprocedure MIMI PCIPCI CABG surgeryCABG surgery

181 (36.1)181 (36.1)357 (71.1)357 (71.1) 15 (3.0)15 (3.0)

81 (33.8)81 (33.8)71 (29.6)71 (29.6)

9 (3.8)9 (3.8)

114 (31.3)114 (31.3)297 (81.5)297 (81.5)

20 (5.5)20 (5.5)

107 (30.7)107 (30.7)

NANA NANA

Baseline Baseline medication usemedication use StatinStatin ββ-blocker-blocker ACE inhibitorACE inhibitor AspirinAspirin

144 (28.7)144 (28.7)361 (72.0)361 (72.0)240 (47.8)240 (47.8)471 (93.8)471 (93.8)

113 (47.1)113 (47.1)198 (82.5)198 (82.5)

15 (6.4)15 (6.4)231 (96.2)231 (96.2)

321 (88.2)321 (88.2)273 (74.9)273 (74.9)211 (58.1)211 (58.1)355 (97.5)355 (97.5)

00

278 (79.6)278 (79.6)177 (50.7)177 (50.7)331 (94.8)331 (94.8)

Statins, High-Density Lipoprotein Cholesterol, and Regression of Coronary Atherosclerosis: Baseline Characteristics (cont.)

Statins, High-Density Lipoprotein Cholesterol, and Regression of Coronary Atherosclerosis: Baseline Characteristics (cont.)



REVERSALREVERSAL(n=502)(n=502)




Baseline LevelBaseline Level Cholesterol, Cholesterol, mg/dLmg/dL TotalTotal LDLLDL HDLHDL

232.2 (34.2)232.2 (34.2)150.2 (26.9)150.2 (26.9)42.6 (10.7)42.6 (10.7)

179.9 (37.8)179.9 (37.8)102.8 (31.6)102.8 (31.6)40.4 (11.8)40.4 (11.8)

170.1 (35.2)170.1 (35.2)94.3 (30.3)94.3 (30.3)43.3 (10.9)43.3 (10.9)

204.0 (41.2)204.0 (41.2)130.4 (34.3)130.4 (34.3)43.1 (11.1)43.1 (11.1)

Triglycerides, Triglycerides, mg/dLmg/dL††

175.0 (130.0 175.0 (130.0 to 237.0)to 237.0)

141.6 (106.2 141.6 (106.2 to 221.3)to 221.3)

144.0 (105.0144.0 (105.0to 199.0)to 199.0)

135.0 (97.0135.0 (97.0to 187.0)to 187.0)

CRP, mg/dLCRP, mg/dL†† 2.9 (1.4 to 6.1)2.9 (1.4 to 6.1) NANA 2.7 (1.1 to 5.9)2.7 (1.1 to 5.9) NANA

Percent atheroma Percent atheroma volumevolume 38.9 (11.0)38.9 (11.0) 41.1 (9.8)41.1 (9.8) 39.8 (9.1)39.8 (9.1) 39.6 (8.5)39.6 (8.5)

Total atheroma Total atheroma volume, mmvolume, mm33 190.3 (83.5)190.3 (83.5) 198.2 (80.9)198.2 (80.9) 172.7 (78.1)172.7 (78.1) 188.6 (72.3)188.6 (72.3)

Statins, High-Density Lipoprotein Cholesterol, and Regression of Coronary Atherosclerosis: Laboratory Values and Atheroma Volume

Statins, High-Density Lipoprotein Cholesterol, and Regression of Coronary Atherosclerosis: Laboratory Values and Atheroma Volume


Laboratory Values and Atheroma Volume of Patients Stratified by Study*Laboratory Values and Atheroma Volume of Patients Stratified by Study*

*Values are expressed as mean (SD) unless otherwise indicated

††Values are expressed as median (interquartile range)Values are expressed as median (interquartile range)


REVERSALREVERSAL(n=502)(n=502)




Change from Change from baselinebaseline Cholesterol, Cholesterol, mg/dLmg/dL TotalTotal LDLLDL HDLHDL

-65.2 (37.6)-65.2 (37.6)-58.7 (32.5)-58.7 (32.5)

1.9 (6.0)1.9 (6.0)

0.6 (35.7)0.6 (35.7)-2.6 (28.9)-2.6 (28.9)1.7 (8.0)1.7 (8.0)

-0.4 (26.8)-0.4 (26.8)-0.6 (24.0)-0.6 (24.0)1.2 (5.5)1.2 (5.5)

-63.2 (30.9)-63.2 (30.9)-63.9 (27.8)-63.9 (27.8)

5.7 (6.8)5.7 (6.8)

Triglycerides, Triglycerides, mg/dLmg/dL††

-34.9 (-72.5 -34.9 (-72.5 to -5.7)to -5.7)

6.6 (-42.0 6.6 (-42.0 to 46.5)to 46.5)

-1.8 (-28.3 -1.8 (-28.3 to 21.8)to 21.8)

-19.3 (-49.5 -19.3 (-49.5 to 6.7)to 6.7)

CRP, mg/dLCRP, mg/dL†† -0.4 (-1.8 to 0.9)-0.4 (-1.8 to 0.9) NANA -0.2 (-2.0 to 0.8)-0.2 (-2.0 to 0.8) NANA

Percent Percent atheroma atheroma volumevolume

1.3 (5.1)1.3 (5.1) 0.5 (3.0)0.5 (3.0) 0.5 (3.5)0.5 (3.5) -0.7 (2.4)-0.7 (2.4)

Total Total atheroma atheroma volume, mmvolume, mm33

2.5 (30.4)2.5 (30.4) 0.3 (18.5)0.3 (18.5) -3.8 (18.6)-3.8 (18.6) -9.8 (17.1)-9.8 (17.1)

Statins, High-Density Lipoprotein Cholesterol, and Regression of Coronary Atherosclerosis:

Laboratory Values and Atheroma Volume (cont.)

Statins, High-Density Lipoprotein Cholesterol, and Regression of Coronary Atherosclerosis:

Laboratory Values and Atheroma Volume (cont.)


Laboratory Values and Atheroma Volume of Patients Stratified by Study (cont.)Laboratory Values and Atheroma Volume of Patients Stratified by Study (cont.)


Level, Mean (SD) [Median]*Level, Mean (SD) [Median]*

At BaselineAt Baseline During TreatmentDuring Treatment Mean (SD)Mean (SD) P ValueP Value

Cholesterol, Cholesterol, mg/dL (n=1455)mg/dL (n=1455) LDLLDL HDLHDL

124.0 (38.3) [126.0]124.0 (38.3) [126.0]42.5 (11.0) [41.0]42.5 (11.0) [41.0]

87.5 (28.8) [85.6]87.5 (28.8) [85.6]45.1 (11.4) [43.7]45.1 (11.4) [43.7]

-36.7 (41.1)-36.7 (41.1)2.6 (6.7)2.6 (6.7)

<0.001<0.001<0.001<0.001

LDL/HDL ratio LDL/HDL ratio (n=1455)(n=1455) 3.0 (1.1) [3.0]3.0 (1.1) [3.0] 2.1 (0.9) [1.9]2.1 (0.9) [1.9] -1.0 (1.1)-1.0 (1.1) <0.001<0.001

Percent Percent atheroma atheroma volumevolume

39.7 (9.8) [40.0]39.7 (9.8) [40.0] 40.1 (9.7) [40.1]40.1 (9.7) [40.1] 0.5 (3.9)0.5 (3.9) 0.0010.001

Total atheroma Total atheroma volume, mmvolume, mm33 186.8 (79.5) [176.2]186.8 (79.5) [176.2] 184.4 (78.2) [174.3]184.4 (78.2) [174.3] -2.4 (23.6)-2.4 (23.6) <0.001<0.001

Statins, High-Density Lipoprotein Cholesterol, and Regression of Coronary Atherosclerosis: Pooled Data for Atheroma Change in Biochemical

Parameters and Atheroma Volume in Patients Receiving Statin Therapy

Statins, High-Density Lipoprotein Cholesterol, and Regression of Coronary Atherosclerosis: Pooled Data for Atheroma Change in Biochemical

Parameters and Atheroma Volume in Patients Receiving Statin Therapy


Pooled Data for Change in Biochemical Parameters and Atheroma Volume in Patients Receiving Statin Therapy (n=1455)Pooled Data for Change in Biochemical Parameters and Atheroma Volume in Patients Receiving Statin Therapy (n=1455)


Statins, High-Density Lipoprotein Cholesterol, and Regression of Coronary Atherosclerosis: Results

Statins, High-Density Lipoprotein Cholesterol, and Regression of Coronary Atherosclerosis: Results

• In univariate analysis, mean levels and treatment-In univariate analysis, mean levels and treatment-mediated changes in LDL-C, total cholesterol, non-mediated changes in LDL-C, total cholesterol, non-HDL-cholesterol, apolipoprotein B, and ratio of HDL-cholesterol, apolipoprotein B, and ratio of apolipoprotein B to apolipoprotein A-I were apolipoprotein B to apolipoprotein A-I were significantly correlated with the rate of significantly correlated with the rate of atherosclerotic progression, whereas treatment-atherosclerotic progression, whereas treatment-mediated changes in HDL-C were inversely mediated changes in HDL-C were inversely correlated with atheroma progression. correlated with atheroma progression.

• In univariate analysis, mean levels and treatment-In univariate analysis, mean levels and treatment-mediated changes in LDL-C, total cholesterol, non-mediated changes in LDL-C, total cholesterol, non-HDL-cholesterol, apolipoprotein B, and ratio of HDL-cholesterol, apolipoprotein B, and ratio of apolipoprotein B to apolipoprotein A-I were apolipoprotein B to apolipoprotein A-I were significantly correlated with the rate of significantly correlated with the rate of atherosclerotic progression, whereas treatment-atherosclerotic progression, whereas treatment-mediated changes in HDL-C were inversely mediated changes in HDL-C were inversely correlated with atheroma progression. correlated with atheroma progression.



Statins, High-Density Lipoprotein Cholesterol, and Regression of Coronary Atherosclerosis: Results (cont.)


• In multivariate analysis, mean levels of LDL-C (In multivariate analysis, mean levels of LDL-C (ββ coefficient, 0.11 [95% confidence interval, 0.07-coefficient, 0.11 [95% confidence interval, 0.07-0.15]) and increases in HDL-C (0.15]) and increases in HDL-C (ββ coefficient, coefficient, -0.26 [95% confidence interval, -0.41-0.10]) -0.26 [95% confidence interval, -0.41-0.10]) remained independent predictors of atheroma remained independent predictors of atheroma regression.regression.

• In multivariate analysis, mean levels of LDL-C (In multivariate analysis, mean levels of LDL-C (ββ coefficient, 0.11 [95% confidence interval, 0.07-coefficient, 0.11 [95% confidence interval, 0.07-0.15]) and increases in HDL-C (0.15]) and increases in HDL-C (ββ coefficient, coefficient, -0.26 [95% confidence interval, -0.41-0.10]) -0.26 [95% confidence interval, -0.41-0.10]) remained independent predictors of atheroma remained independent predictors of atheroma regression.regression.





• Substantial atheroma regression (Substantial atheroma regression (≥≥5% reduction 5% reduction in atheroma volume) was observed in patients in atheroma volume) was observed in patients with levels of LDL-C less than the mean (87.5 with levels of LDL-C less than the mean (87.5 mg/dL) during treatment and percentage mg/dL) during treatment and percentage increases of HDL-C greater than the mean (7.5%; increases of HDL-C greater than the mean (7.5%; P<0.001).P<0.001).

• No significant differences were found with regard No significant differences were found with regard to clinical events. to clinical events.

• Substantial atheroma regression (Substantial atheroma regression (≥≥5% reduction 5% reduction in atheroma volume) was observed in patients in atheroma volume) was observed in patients with levels of LDL-C less than the mean (87.5 with levels of LDL-C less than the mean (87.5 mg/dL) during treatment and percentage mg/dL) during treatment and percentage increases of HDL-C greater than the mean (7.5%; increases of HDL-C greater than the mean (7.5%; P<0.001).P<0.001).

• No significant differences were found with regard No significant differences were found with regard to clinical events. to clinical events.



Statins, High-Density Lipoprotein Cholesterol, and Regression of Coronary Atherosclerosis: Limitations

Statins, High-Density Lipoprotein Cholesterol, and Regression of Coronary Atherosclerosis: Limitations

• This study was a post-hoc analysis that incorporated This study was a post-hoc analysis that incorporated the data from patients who participated in 4 different the data from patients who participated in 4 different clinical trials. clinical trials.

• The individual studies differed in length of time The individual studies differed in length of time between baseline and follow-up ultrasound evaluations between baseline and follow-up ultrasound evaluations and required adjustment in both univariate and and required adjustment in both univariate and multivariate analysis; it remains to be determined multivariate analysis; it remains to be determined whether atheroma progression with time is linear.whether atheroma progression with time is linear.

• This study was a post-hoc analysis that incorporated This study was a post-hoc analysis that incorporated the data from patients who participated in 4 different the data from patients who participated in 4 different clinical trials. clinical trials.

• The individual studies differed in length of time The individual studies differed in length of time between baseline and follow-up ultrasound evaluations between baseline and follow-up ultrasound evaluations and required adjustment in both univariate and and required adjustment in both univariate and multivariate analysis; it remains to be determined multivariate analysis; it remains to be determined whether atheroma progression with time is linear.whether atheroma progression with time is linear.



Statins, High-Density Lipoprotein Cholesterol, and Regression of Coronary Atherosclerosis: Limitations (cont.)


• The findings are derived from patients with CAD The findings are derived from patients with CAD diagnosed at angiography performed for a clinical diagnosed at angiography performed for a clinical indication and cannot be extrapolated to the indication and cannot be extrapolated to the setting of primary prevention. setting of primary prevention.

• The requirement for an invasive catheterization The requirement for an invasive catheterization procedure for a clinical indication, variable lipid procedure for a clinical indication, variable lipid inclusion criteria, and differences between studies inclusion criteria, and differences between studies in terms of the statin being the active treatment or in terms of the statin being the active treatment or background therapy may have allowed for background therapy may have allowed for sampling biases.sampling biases.

• The findings are derived from patients with CAD The findings are derived from patients with CAD diagnosed at angiography performed for a clinical diagnosed at angiography performed for a clinical indication and cannot be extrapolated to the indication and cannot be extrapolated to the setting of primary prevention. setting of primary prevention.

• The requirement for an invasive catheterization The requirement for an invasive catheterization procedure for a clinical indication, variable lipid procedure for a clinical indication, variable lipid inclusion criteria, and differences between studies inclusion criteria, and differences between studies in terms of the statin being the active treatment or in terms of the statin being the active treatment or background therapy may have allowed for background therapy may have allowed for sampling biases.sampling biases.





• Intravascular ultrasonography provides a Intravascular ultrasonography provides a suboptimal characterization of plaque components. suboptimal characterization of plaque components. Thus, it remains uncertain whether simultaneous Thus, it remains uncertain whether simultaneous lowering of LDL-C and raising of HDL-C has an lowering of LDL-C and raising of HDL-C has an incremental beneficial effect on plaque stabilization incremental beneficial effect on plaque stabilization with statins.with statins.

• Intravascular ultrasonography provides a Intravascular ultrasonography provides a suboptimal characterization of plaque components. suboptimal characterization of plaque components. Thus, it remains uncertain whether simultaneous Thus, it remains uncertain whether simultaneous lowering of LDL-C and raising of HDL-C has an lowering of LDL-C and raising of HDL-C has an incremental beneficial effect on plaque stabilization incremental beneficial effect on plaque stabilization with statins.with statins.





• While the results demonstrate a favorable effect While the results demonstrate a favorable effect of increasing levels of HDL-C, the relationship of increasing levels of HDL-C, the relationship between statin-induced changes in HDL between statin-induced changes in HDL subclasses and the rate of progression of subclasses and the rate of progression of atherosclerotic plaque remains to be investigated.atherosclerotic plaque remains to be investigated.

• Similarly, the effect of differing duration of statin Similarly, the effect of differing duration of statin use prior to enrollment and potential lifestyle use prior to enrollment and potential lifestyle changes by subjects remains uncertain.changes by subjects remains uncertain.

• While the results demonstrate a favorable effect While the results demonstrate a favorable effect of increasing levels of HDL-C, the relationship of increasing levels of HDL-C, the relationship between statin-induced changes in HDL between statin-induced changes in HDL subclasses and the rate of progression of subclasses and the rate of progression of atherosclerotic plaque remains to be investigated.atherosclerotic plaque remains to be investigated.

• Similarly, the effect of differing duration of statin Similarly, the effect of differing duration of statin use prior to enrollment and potential lifestyle use prior to enrollment and potential lifestyle changes by subjects remains uncertain.changes by subjects remains uncertain.





• Smoking and revascularization data were not Smoking and revascularization data were not collected in the ASTEROID study.collected in the ASTEROID study.

• Given the limited evidence correlating favorable Given the limited evidence correlating favorable changes in plaque progression with a reduction in changes in plaque progression with a reduction in clinical events, it remains to be demonstrated that clinical events, it remains to be demonstrated that simultaneous lowering of LDL-C and elevation of simultaneous lowering of LDL-C and elevation of HDL-C translates to less clinical events.HDL-C translates to less clinical events.

• Smoking and revascularization data were not Smoking and revascularization data were not collected in the ASTEROID study.collected in the ASTEROID study.

• Given the limited evidence correlating favorable Given the limited evidence correlating favorable changes in plaque progression with a reduction in changes in plaque progression with a reduction in clinical events, it remains to be demonstrated that clinical events, it remains to be demonstrated that simultaneous lowering of LDL-C and elevation of simultaneous lowering of LDL-C and elevation of HDL-C translates to less clinical events.HDL-C translates to less clinical events.



Statins, High-Density Lipoprotein Cholesterol, and Regression of Coronary Atherosclerosis: SummaryStatins, High-Density Lipoprotein Cholesterol, and Regression of Coronary Atherosclerosis: Summary

• Statin therapy is associated with regression of Statin therapy is associated with regression of coronary atherosclerosis when LDL-C is coronary atherosclerosis when LDL-C is substantially reduced and HDL-C is increased by substantially reduced and HDL-C is increased by more than 7.5%.more than 7.5%.

• These findings suggest that statin benefits are These findings suggest that statin benefits are derived from both reductions in atherogenic derived from both reductions in atherogenic lipoprotein levels and increases in HDL-C.lipoprotein levels and increases in HDL-C.

• Statin therapy is associated with regression of Statin therapy is associated with regression of coronary atherosclerosis when LDL-C is coronary atherosclerosis when LDL-C is substantially reduced and HDL-C is increased by substantially reduced and HDL-C is increased by more than 7.5%.more than 7.5%.

• These findings suggest that statin benefits are These findings suggest that statin benefits are derived from both reductions in atherogenic derived from both reductions in atherogenic lipoprotein levels and increases in HDL-C.lipoprotein levels and increases in HDL-C.



Statins, High-Density Lipoprotein Cholesterol, and Regression of Coronary Atherosclerosis: Summary (cont.)

Statins, High-Density Lipoprotein Cholesterol, and Regression of Coronary Atherosclerosis: Summary (cont.)

• However, it remains to be determined whether the However, it remains to be determined whether the atherosclerotic regression associated with these atherosclerotic regression associated with these changes in lipid levels will translate to meaningful changes in lipid levels will translate to meaningful reductions in clinical events and improved clinical reductions in clinical events and improved clinical outcomes.outcomes.

• However, it remains to be determined whether the However, it remains to be determined whether the atherosclerotic regression associated with these atherosclerotic regression associated with these changes in lipid levels will translate to meaningful changes in lipid levels will translate to meaningful reductions in clinical events and improved clinical reductions in clinical events and improved clinical outcomes.outcomes.


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