Trial Outcomes & Findings for Reduction in YEllow Plaque by Aggressive Lipid LOWering Therapy (NCT NCT01567826)

NCT ID: NCT01567826

Last Updated: 2017-05-19

Results Overview

The regression of yellow plaque content from the atherosclerotic lipid pool after statin therapy by utilizing NIR spectroscopy as compared from baseline to 6-8 weeks after intervention. Spectroscopic information obtained from raw spectra was transformed into a probability of lipid core that was mapped to a red-to-yellow color scale, with the low probability of lipid shown as red and the high probability of lipid shown as yellow. Analyses were performed offline using the Matlab-based software, as previously published. Yellow pixels within the analyzed segment were divided by all viable pixels to generate the lipid-core burden index (LCBI). The maximal value of LCBI for each nonculprit obstructive lesion was recorded and used for comparison.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

87 participants

Primary outcome timeframe

at baseline and at 6-8 weeks after intervention

Results posted on

2017-05-19

Participant Flow

779 patients consecutive patients with chronic stable angina presenting for elective coronary angiography were screened from May 21, 2010 until Jan 10, 2012. 87 participants met criteria and were randomized.

Participant milestones

Participant milestones
Measure
Standard of Care Lipid Therapy
standard-care lipid-lowering therapy: Zocor or Lipitor standard of care lipid therapy: Patients will be randomized in a 1:1 fashion to receive either A) Rosuvastatin (Crestor) 40mg daily, or B) standard-care lipid-lowering therapy. Zocor, Lipitor \[any dose\] and Crestor \[less than 40mg\]
Aggressive Lipid Therapy
aggressive lipid therapy: Crestor Aggressive lipid therapy: Patients will be randomized in a 1:1 fashion to receive either A) Rosuvastatin (Crestor) 40mg daily, or B) standard-care lipid-lowering therapy.
Overall Study
STARTED
43
44
Overall Study
COMPLETED
40
42
Overall Study
NOT COMPLETED
3
2

Reasons for withdrawal

Reasons for withdrawal
Measure
Standard of Care Lipid Therapy
standard-care lipid-lowering therapy: Zocor or Lipitor standard of care lipid therapy: Patients will be randomized in a 1:1 fashion to receive either A) Rosuvastatin (Crestor) 40mg daily, or B) standard-care lipid-lowering therapy. Zocor, Lipitor \[any dose\] and Crestor \[less than 40mg\]
Aggressive Lipid Therapy
aggressive lipid therapy: Crestor Aggressive lipid therapy: Patients will be randomized in a 1:1 fashion to receive either A) Rosuvastatin (Crestor) 40mg daily, or B) standard-care lipid-lowering therapy.
Overall Study
Lost to Follow-up
3
2

Baseline Characteristics

Reduction in YEllow Plaque by Aggressive Lipid LOWering Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Standard of Care Lipid Therapy
n=43 Participants
standard-care lipid-lowering therapy: Zocor or Lipitor standard of care lipid therapy: Patients will be randomized in a 1:1 fashion to receive either A) Rosuvastatin (Crestor) 40mg daily, or B) standard-care lipid-lowering therapy. Zocor, Lipitor \[any dose\] and Crestor \[less than 40mg\]
Aggressive Lipid Therapy
n=44 Participants
aggressive lipid therapy: Crestor Aggressive lipid therapy: Patients will be randomized in a 1:1 fashion to receive either A) Rosuvastatin (Crestor) 40mg daily, or B) standard-care lipid-lowering therapy.
Total
n=87 Participants
Total of all reporting groups
Age, Continuous
62.9 years
STANDARD_DEVIATION 9.8 • n=5 Participants
64.4 years
STANDARD_DEVIATION 9.29 • n=7 Participants
63.6 years
STANDARD_DEVIATION 9.5 • n=5 Participants
Sex: Female, Male
Female
12 Participants
n=5 Participants
9 Participants
n=7 Participants
21 Participants
n=5 Participants
Sex: Female, Male
Male
31 Participants
n=5 Participants
35 Participants
n=7 Participants
66 Participants
n=5 Participants
Current tobacco use
yes
4 participants
n=5 Participants
9 participants
n=7 Participants
13 participants
n=5 Participants
Current tobacco use
no
39 participants
n=5 Participants
35 participants
n=7 Participants
74 participants
n=5 Participants
Hypertension
yes
40 participants
n=5 Participants
40 participants
n=7 Participants
80 participants
n=5 Participants
Hypertension
no
3 participants
n=5 Participants
4 participants
n=7 Participants
7 participants
n=5 Participants
Hypercholesterolemia
yes
40 participants
n=5 Participants
39 participants
n=7 Participants
79 participants
n=5 Participants
Hypercholesterolemia
no
3 participants
n=5 Participants
5 participants
n=7 Participants
8 participants
n=5 Participants
Diabetes mellitus
yes
3 participants
n=5 Participants
5 participants
n=7 Participants
8 participants
n=5 Participants
Diabetes mellitus
no
40 participants
n=5 Participants
39 participants
n=7 Participants
79 participants
n=5 Participants
Prior CVA/TIA
yes
3 participants
n=5 Participants
2 participants
n=7 Participants
5 participants
n=5 Participants
Prior CVA/TIA
no
40 participants
n=5 Participants
42 participants
n=7 Participants
82 participants
n=5 Participants
Previous MI
yes
8 participants
n=5 Participants
8 participants
n=7 Participants
16 participants
n=5 Participants
Previous MI
no
35 participants
n=5 Participants
36 participants
n=7 Participants
71 participants
n=5 Participants
Previous PCI
yes
20 participants
n=5 Participants
16 participants
n=7 Participants
36 participants
n=5 Participants
Previous PCI
no
23 participants
n=5 Participants
28 participants
n=7 Participants
51 participants
n=5 Participants
Statin Use
yes
35 participants
n=5 Participants
37 participants
n=7 Participants
72 participants
n=5 Participants
Statin Use
no
8 participants
n=5 Participants
7 participants
n=7 Participants
15 participants
n=5 Participants
Beta-blocker use
yes
30 participants
n=5 Participants
33 participants
n=7 Participants
63 participants
n=5 Participants
Beta-blocker use
no
13 participants
n=5 Participants
11 participants
n=7 Participants
24 participants
n=5 Participants
ACE-I/ARB use
yes
19 participants
n=5 Participants
16 participants
n=7 Participants
35 participants
n=5 Participants
ACE-I/ARB use
no
24 participants
n=5 Participants
28 participants
n=7 Participants
52 participants
n=5 Participants
Creatinine
1.1 mg/dl
STANDARD_DEVIATION 1.3 • n=5 Participants
1.0 mg/dl
STANDARD_DEVIATION 0.3 • n=7 Participants
1.04 mg/dl
STANDARD_DEVIATION 0.96 • n=5 Participants
LAD Coronary vessel
yes
17 participants
n=5 Participants
20 participants
n=7 Participants
37 participants
n=5 Participants
LAD Coronary vessel
no
26 participants
n=5 Participants
24 participants
n=7 Participants
50 participants
n=5 Participants
LCx coronary vessel
yes
14 participants
n=5 Participants
14 participants
n=7 Participants
28 participants
n=5 Participants
LCx coronary vessel
no
29 participants
n=5 Participants
30 participants
n=7 Participants
59 participants
n=5 Participants
RCA coronary vessel
yes
13 participants
n=5 Participants
10 participants
n=7 Participants
23 participants
n=5 Participants
RCA coronary vessel
no
30 participants
n=5 Participants
34 participants
n=7 Participants
64 participants
n=5 Participants

PRIMARY outcome

Timeframe: at baseline and at 6-8 weeks after intervention

Population: Data were not available in 17 patients because of loss to follow-up (n = 5), incorrect image formatting that could not be recovered at the time of core laboratory analysis (n = 5), NIRS console/catheter malfunction at the time of index PCI (n = 3), and loss of disc integrity or corruption before core laboratory analysis (n = 4).

The regression of yellow plaque content from the atherosclerotic lipid pool after statin therapy by utilizing NIR spectroscopy as compared from baseline to 6-8 weeks after intervention. Spectroscopic information obtained from raw spectra was transformed into a probability of lipid core that was mapped to a red-to-yellow color scale, with the low probability of lipid shown as red and the high probability of lipid shown as yellow. Analyses were performed offline using the Matlab-based software, as previously published. Yellow pixels within the analyzed segment were divided by all viable pixels to generate the lipid-core burden index (LCBI). The maximal value of LCBI for each nonculprit obstructive lesion was recorded and used for comparison.

Outcome measures

Outcome measures
Measure
Standard of Care Lipid Therapy
n=34 Participants
standard-care lipid-lowering therapy: Zocor or Lipitor standard of care lipid therapy: Patients will be randomized in a 1:1 fashion to receive either A) Rosuvastatin (Crestor) 40mg daily, or B) standard-care lipid-lowering therapy. Zocor, Lipitor \[any dose\] and Crestor \[less than 40mg\]
Aggressive Lipid Therapy
n=36 Participants
aggressive lipid therapy: Crestor Aggressive lipid therapy: Patients will be randomized in a 1:1 fashion to receive either A) Rosuvastatin (Crestor) 40mg daily, or B) standard-care lipid-lowering therapy.
Lipiscan - Lipid Core Burden Index (LCBI)
Baseline LCBI, lesion
95.4 ratio
Interval 29.6 to 174.6
132.4 ratio
Interval 99.0 to 201.2
Lipiscan - Lipid Core Burden Index (LCBI)
Follow-up LCBI, lesion
99.9 ratio
Interval 38.2 to 204.3
99.8 ratio
Interval 64.2 to 159.3

PRIMARY outcome

Timeframe: at baseline and at 6-8 weeks after intervention

Population: Data were not available in 17 patients because of loss to follow-up (n = 5), incorrect image formatting that could not be recovered at the time of core laboratory analysis (n = 5), NIRS console/catheter malfunction at the time of index PCI (n = 3), and loss of disc integrity or corruption before core laboratory analysis (n = 4).

LCBI4mm max = change in lipid-core burden index at the 4-mm maximal segment. Spectroscopic information obtained from raw spectra was transformed into a probability of lipid core that was mapped to a red-to-yellow color scale, with the low probability of lipid shown as red and the high probability of lipid shown as yellow. Yellow pixels within the analyzed segment were divided by all viable pixels to generate the lipid-core burden index (LCBI). The maximal value of LCBI for each nonculprit obstructive lesion was recorded and used for comparison.

Outcome measures

Outcome measures
Measure
Standard of Care Lipid Therapy
n=34 Participants
standard-care lipid-lowering therapy: Zocor or Lipitor standard of care lipid therapy: Patients will be randomized in a 1:1 fashion to receive either A) Rosuvastatin (Crestor) 40mg daily, or B) standard-care lipid-lowering therapy. Zocor, Lipitor \[any dose\] and Crestor \[less than 40mg\]
Aggressive Lipid Therapy
n=36 Participants
aggressive lipid therapy: Crestor Aggressive lipid therapy: Patients will be randomized in a 1:1 fashion to receive either A) Rosuvastatin (Crestor) 40mg daily, or B) standard-care lipid-lowering therapy.
LCBI4mm Max
Baseline LCBI4mm max
356.7 ratio
Interval 145.2 to 509.2
490.6 ratio
Interval 363.8 to 689.7
LCBI4mm Max
Follow-up LCBI4mm max
385.7 ratio
Interval 139.2 to 510.9
336.1 ratio
Interval 252.3 to 479.9

PRIMARY outcome

Timeframe: at baseline and at 6-8 weeks after intervention

Population: Data were not available in 17 patients because of loss to follow-up (n = 5), incorrect image formatting that could not be recovered at the time of core laboratory analysis (n = 5), NIRS console/catheter malfunction at the time of index PCI (n = 3), and loss of disc integrity or corruption before core laboratory analysis (n = 4).

Change in LCBI4mm max at 6-8 weeks after intervention as compared to baseline. LCBI4mm max = change in lipid-core burden index at the 4-mm maximal segment.

Outcome measures

Outcome measures
Measure
Standard of Care Lipid Therapy
n=34 Participants
standard-care lipid-lowering therapy: Zocor or Lipitor standard of care lipid therapy: Patients will be randomized in a 1:1 fashion to receive either A) Rosuvastatin (Crestor) 40mg daily, or B) standard-care lipid-lowering therapy. Zocor, Lipitor \[any dose\] and Crestor \[less than 40mg\]
Aggressive Lipid Therapy
n=36 Participants
aggressive lipid therapy: Crestor Aggressive lipid therapy: Patients will be randomized in a 1:1 fashion to receive either A) Rosuvastatin (Crestor) 40mg daily, or B) standard-care lipid-lowering therapy.
Change in LCBI4mm Max
2.4 ratio
Interval -36.1 to 44.7
-149.1 ratio
Interval -210.9 to -42.9

PRIMARY outcome

Timeframe: at baseline and at 6-8 weeks post intervention

Population: Data were not available in 17 patients because of loss to follow-up (n = 5), incorrect image formatting that could not be recovered at the time of core laboratory analysis (n = 5), NIRS console/catheter malfunction at the time of index PCI (n = 3), and loss of disc integrity or corruption before core laboratory analysis (n = 4).

Change in LCBI at 6-8 weeks after intervention as compared to baseline

Outcome measures

Outcome measures
Measure
Standard of Care Lipid Therapy
n=34 Participants
standard-care lipid-lowering therapy: Zocor or Lipitor standard of care lipid therapy: Patients will be randomized in a 1:1 fashion to receive either A) Rosuvastatin (Crestor) 40mg daily, or B) standard-care lipid-lowering therapy. Zocor, Lipitor \[any dose\] and Crestor \[less than 40mg\]
Aggressive Lipid Therapy
n=36 Participants
aggressive lipid therapy: Crestor Aggressive lipid therapy: Patients will be randomized in a 1:1 fashion to receive either A) Rosuvastatin (Crestor) 40mg daily, or B) standard-care lipid-lowering therapy.
Change in LCBI, Lesion
8.0 ratio
Interval -7.7 to 22.1
-22.5 ratio
Interval -59.2 to -3.5

SECONDARY outcome

Timeframe: at baseline and at 6-8 weeks after intervention

Change in atheroma volume and lumen CSA on IVUS as related to change in yellow plaque index as compared from baseline to 6-8 weeks after intervention. Data not analyzed. Data not available.

Outcome measures

Outcome measures
Measure
Standard of Care Lipid Therapy
n=43 Participants
standard-care lipid-lowering therapy: Zocor or Lipitor standard of care lipid therapy: Patients will be randomized in a 1:1 fashion to receive either A) Rosuvastatin (Crestor) 40mg daily, or B) standard-care lipid-lowering therapy. Zocor, Lipitor \[any dose\] and Crestor \[less than 40mg\]
Aggressive Lipid Therapy
n=44 Participants
aggressive lipid therapy: Crestor Aggressive lipid therapy: Patients will be randomized in a 1:1 fashion to receive either A) Rosuvastatin (Crestor) 40mg daily, or B) standard-care lipid-lowering therapy.
Intravascular Ultrasound (IVUS) Parameters
Baseline Total atheroma volume
193.7 mm^2
Standard Deviation 61.7
195.8 mm^2
Standard Deviation 63.3
Intravascular Ultrasound (IVUS) Parameters
6-8 weeks Total atheroma volume
199.6 mm^2
Standard Deviation 63.9
209.6 mm^2
Standard Deviation 74.1
Intravascular Ultrasound (IVUS) Parameters
Baseline Lumen CSA
2.4 mm^2
Standard Deviation 0.6
2.5 mm^2
Standard Deviation 0.8
Intravascular Ultrasound (IVUS) Parameters
6-8 weeks Lumen CSA
2.4 mm^2
Standard Deviation 0.7
2.5 mm^2
Standard Deviation 0.7

SECONDARY outcome

Timeframe: at baseline and at 6-8 weeks after intervention

Change in FFR as related to change in yellow plaque index as compared from baseline to 6-8 weeks after intervention. Fractional flow reserve (FFR), defined as the ratio of maximum flow in the presence of a stenosis to normal maximum flow, is a lesion-specific index of stenosis severity that can be calculated by simultaneous measurement of mean arterial, distal coronary, and central venous pressure.

Outcome measures

Outcome measures
Measure
Standard of Care Lipid Therapy
n=43 Participants
standard-care lipid-lowering therapy: Zocor or Lipitor standard of care lipid therapy: Patients will be randomized in a 1:1 fashion to receive either A) Rosuvastatin (Crestor) 40mg daily, or B) standard-care lipid-lowering therapy. Zocor, Lipitor \[any dose\] and Crestor \[less than 40mg\]
Aggressive Lipid Therapy
n=44 Participants
aggressive lipid therapy: Crestor Aggressive lipid therapy: Patients will be randomized in a 1:1 fashion to receive either A) Rosuvastatin (Crestor) 40mg daily, or B) standard-care lipid-lowering therapy.
Fractional Flow Reserve (FFR) Value
Baseline
0.73 ratio
Standard Deviation 0.1
0.73 ratio
Standard Deviation 0.1
Fractional Flow Reserve (FFR) Value
Follow-up
0.73 ratio
Standard Deviation 0.1
0.75 ratio
Standard Deviation .01

SECONDARY outcome

Timeframe: Baseline and 6-8 weeks post intervention

Percentage stenosis of vessel diameter in the analysis segment of nontarget lesions as measured by angiography that remained \>70%, after successful PCI of the target lesion.

Outcome measures

Outcome measures
Measure
Standard of Care Lipid Therapy
n=43 Participants
standard-care lipid-lowering therapy: Zocor or Lipitor standard of care lipid therapy: Patients will be randomized in a 1:1 fashion to receive either A) Rosuvastatin (Crestor) 40mg daily, or B) standard-care lipid-lowering therapy. Zocor, Lipitor \[any dose\] and Crestor \[less than 40mg\]
Aggressive Lipid Therapy
n=44 Participants
aggressive lipid therapy: Crestor Aggressive lipid therapy: Patients will be randomized in a 1:1 fashion to receive either A) Rosuvastatin (Crestor) 40mg daily, or B) standard-care lipid-lowering therapy.
Diameter Stenosis
Baseline
79.9 percentage of lesions
79.6 percentage of lesions
Diameter Stenosis
Follow-up
83 percentage of lesions
79.4 percentage of lesions

SECONDARY outcome

Timeframe: at 6-8 weeks after intervention

Correlation of yellow plaque index with post procedure CK-MB, Troponin-I release.

Outcome measures

Outcome measures
Measure
Standard of Care Lipid Therapy
n=43 Participants
standard-care lipid-lowering therapy: Zocor or Lipitor standard of care lipid therapy: Patients will be randomized in a 1:1 fashion to receive either A) Rosuvastatin (Crestor) 40mg daily, or B) standard-care lipid-lowering therapy. Zocor, Lipitor \[any dose\] and Crestor \[less than 40mg\]
Aggressive Lipid Therapy
n=44 Participants
aggressive lipid therapy: Crestor Aggressive lipid therapy: Patients will be randomized in a 1:1 fashion to receive either A) Rosuvastatin (Crestor) 40mg daily, or B) standard-care lipid-lowering therapy.
Post PCI Cardiac Enzymes
Troponin-I
0.4 ng/mL
Standard Deviation 1.0
0.3 ng/mL
Standard Deviation 5.1
Post PCI Cardiac Enzymes
CK-MB
5.1 ng/mL
Standard Deviation 9.0
3.7 ng/mL
Standard Deviation 0.3

SECONDARY outcome

Timeframe: at 6-8 weeks after intervention

MACE defined as a combined clinical endpoint of death, MI (Q wave or non Q-wave with CK-MB \>3 times above the upper normal limit (48 U/L), urgent revascularization or stroke at 30 days and 1 year. Details reported in adverse events section.

Outcome measures

Outcome measures
Measure
Standard of Care Lipid Therapy
n=43 Participants
standard-care lipid-lowering therapy: Zocor or Lipitor standard of care lipid therapy: Patients will be randomized in a 1:1 fashion to receive either A) Rosuvastatin (Crestor) 40mg daily, or B) standard-care lipid-lowering therapy. Zocor, Lipitor \[any dose\] and Crestor \[less than 40mg\]
Aggressive Lipid Therapy
n=44 Participants
aggressive lipid therapy: Crestor Aggressive lipid therapy: Patients will be randomized in a 1:1 fashion to receive either A) Rosuvastatin (Crestor) 40mg daily, or B) standard-care lipid-lowering therapy.
Major Adverse Cardiac Events (MACE)
2 participants
3 participants

SECONDARY outcome

Timeframe: at baseline and at 6-8 weeks after intervention

Correlation of yellow plaque index with changes in levels of blood HsCRP as compared from baseline to 6-8 weeks after intervention

Outcome measures

Outcome measures
Measure
Standard of Care Lipid Therapy
n=43 Participants
standard-care lipid-lowering therapy: Zocor or Lipitor standard of care lipid therapy: Patients will be randomized in a 1:1 fashion to receive either A) Rosuvastatin (Crestor) 40mg daily, or B) standard-care lipid-lowering therapy. Zocor, Lipitor \[any dose\] and Crestor \[less than 40mg\]
Aggressive Lipid Therapy
n=44 Participants
aggressive lipid therapy: Crestor Aggressive lipid therapy: Patients will be randomized in a 1:1 fashion to receive either A) Rosuvastatin (Crestor) 40mg daily, or B) standard-care lipid-lowering therapy.
Blood Chemistry - HsCRP
Baseline
1.7 mg/l
Interval 0.7 to 3.4
1.7 mg/l
Interval 0.8 to 3.5
Blood Chemistry - HsCRP
Follow-Up
1.9 mg/l
Interval 0.7 to 4.7
1.2 mg/l
Interval 0.7 to 2.5

Adverse Events

Standard of Care Lipid Therapy

Serious events: 2 serious events
Other events: 9 other events
Deaths: 0 deaths

Aggressive Lipid Therapy

Serious events: 3 serious events
Other events: 7 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Standard of Care Lipid Therapy
n=43 participants at risk
standard-care lipid-lowering therapy: Zocor or Lipitor
Aggressive Lipid Therapy
n=44 participants at risk
aggressive lipid therapy: Crestor
Cardiac disorders
Hospitalization
4.7%
2/43
6.8%
3/44

Other adverse events

Other adverse events
Measure
Standard of Care Lipid Therapy
n=43 participants at risk
standard-care lipid-lowering therapy: Zocor or Lipitor
Aggressive Lipid Therapy
n=44 participants at risk
aggressive lipid therapy: Crestor
Vascular disorders
Unplanned revascularization
4.7%
2/43 • Number of events 2
0.00%
0/44
Injury, poisoning and procedural complications
Periprocedural complications
2.3%
1/43 • Number of events 1
6.8%
3/44 • Number of events 3
Blood and lymphatic system disorders
Any bleeding
4.7%
2/43 • Number of events 2
0.00%
0/44
Hepatobiliary disorders
AST > 3x ULN
0.00%
0/43
0.00%
0/44
Hepatobiliary disorders
ALT > 3x ULN
0.00%
0/43
0.00%
0/44
Renal and urinary disorders
Creatine kinase-MB > 5x ULN
4.7%
2/43 • Number of events 2
2.3%
1/44 • Number of events 1
Renal and urinary disorders
Creatine kinase-MB >10x ULN
4.7%
2/43 • Number of events 2
0.00%
0/44
General disorders
Statin discontinuation
0.00%
0/43
0.00%
0/44
General disorders
Statin dose reduction
0.00%
0/43
6.8%
3/44 • Number of events 3

Additional Information

Dr. Pedro R. Moreno

Icahn School of Medicine at Mount Sinai

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place