atorvastatin versus revascularization treatments (avert) trial

TM

© 1999 Professional Postgraduate Services®

Patients recommended for angioplastyCAD 1 lesion 50% stenosis

LDL-C 115 mg/dL (3.0 mmol/L)TG 500 mg/dL (5.6 mmol/L); LVEF 40%Bruce protocol treadmill test or 20-W/min

bicycle exercise test 4 min

Atorvastatin 80 mg/d+

usual medical therapy (n=164)

Angioplasty+

usual care, including lipid lowering (n=177)

18 months• Occurrence of ischemic events (death from cardiac causes, nonfatal MI, CVA, CABG,

angioplasty, worsening angina verified by objective evidence resulting in hospitalization, resuscitation after cardiac arrest)

• Time to first ischemic event

• Change in lipid parameters

• Safety

Pitt B et al. N Engl J Med. 1999;341:70-76.

AVERT: Study Design and Inclusion Criteria

TM


Pitt B et al. N Engl J Med. 1999;341:70-76. McCormick LS et al. Am J Cardiol. 1997;80:1130-1133.

AVERT: Major Exclusion Criteria• Left main disease or

3-vessel disease

• Unstable angina

• MI within previous 14 days

• Known ejection fraction <40% or NYHA Class III or IV heart failure

• Previous CABG, unless grafts were patent and patient did not have 3-vessel disease

• CABG recommended based on current angiogram

• Percutaneous revascularization in previous 6 months

• Known hypersensitivity to HMG-CoA reductaseinhibitors

• AST/ALT >2 x ULN

• CPK >3 x ULN or unexplained elevations

TM



AVERT: Overview of Study Procedures

Treatment phase

• Patients randomized to atorvastatin

– discontinued other lipid-lowering medication and immediately began atorvastatin 80 mg/d

• Patients randomized to angioplasty/usual care (UC)

– underwent angioplasty followed by “usual care”

• usual care may or may not have included lipid-lowering therapy (eg, diet, behavior modification, or medication)

• angioplasty may or may not have included stenting

• usual care was determined by investigator or patient’s primary physician

TM

© 1999 Professional Postgraduate Services®Pitt B et al. N Engl J Med. 1999;341:70-76.

– angioplasty (other than the original procedure in angioplasty/usual care group)

– worsening angina verified by objective evidence resulting in hospitalization

CVA=cerebrovascular accident.

AVERT: Primary Efficacy Assessment

• Incidence of an ischemic event in each treatment group

• Ischemic event was defined as occurrence of one of the following:

– cardiac death

– resuscitation aftercardiac arrest

– nonfatal MI

– CVA

– CABG

TM



AVERT: Secondary Efficacy Assessments• Time from randomization to ischemic event

• Percent change from baseline in TC, LDL-C, HDL-C, TG, apo A1, apo B, and Lp(a)

• All-cause mortality

• Change from baseline in angina class

• Worsening angina with objective evidence

• Change in quality of life

• Economic assessment

TM


Atorvastatin (n=164) Angioplasty/UC (n=177)

Age (yr), mean 59 58Gender

Male 130 (79%) 157 (89%) Female 34 (21%) 20 (11%)

Mean ejection fraction 61% 61%Nature of CHDSingle vessel 94 (57%) 99 (56%)Double vessel 70 (43%) 78 (44%)

Mean % stenosis 80% 81%Mean no. of risk factors 2.5 2.5Prior MI 73 (45%) 70 (40%)Patients with target lesionLAD 70 (43%) 53 (30%)LCX 59 (36%) 63 (36%)RCA 59 (36%) 64 (36%)

CCS Angina ClassAsymptomatic 29 (18%) 27 (15%)Class I 74 (45%) 70 (40%)Class II 60 (37%) 77 (44%)Class III 1 (1%) 2 (1%)Class IV 0 (0%) 1 (1%)


AVERT: Baseline Patient Characteristics

TM


Number (%) of patients experiencing an ischemic event

Atorvastatin Angioplasty/UCn=164 n=177 %

Any Ischemic event 22 (13) 37 (21) -36*

Death 1 (0.6) 1 (0.6)Resuscitated cardiac arrest 0 (0.0) 0 (0.0)Nonfatal MI 4 (2.4) 5 (2.8)CVA 0 (0.0) 0 (0.0)CABG 2 (1.2) 9 (5.1)Revascularization 18 (11.0) 21 (11.9)Worsening angina with objectiveevidence & hospitalization 11 (6.7) 25 (14.1)

*P=0.048 vs an adjusted significance level of 0.045.


AVERT: Ischemic Events

TM


* P=0.048 vs an adjusted significance level of 0.045 atorvastatin vs angioplasty/UC.Data from Pitt B et al. N Engl J Med. 1999;341:70-76.

0

5

10

15

20

25

Atorvastatin Angioplasty/UC

% of patientswith an

ischemic event

13%

21%

-36% difference*

(P=0.048)

n=22 of 164 n=37 of 177

AVERT: Ischemic Events

TM


0

5

10

15

20

25

0 6 12 18

P=0.03Cumulative incidence

(%)

Time since randomization (months)


Atorvastatin (n=164)

Angioplasty/UC (n=177)

AVERT: Time to First Ischemic Event

TM


*Significantly different from angioplasty/UC (P<0.05).† Baseline values represented patients at randomization without a washout period from existing lipid-lowering therapy.Note: 73% of angioplasty/UC-treated patients were on lipid-lowering medication.Pitt B et al. N Engl J Med. 1999;341:70-76.

mg/dL(mmol/L)

Atorvastatin end of studyAngioplasty/UC baseline†

Angioplasty/UC end of study

Atorvastatin baseline†

10%

0

50

100

150

200

250

LDL-C TC TG HDL-C

18%

31% *

46% *

10%

11% *

8% 11%

(6.5)

(2.6)

(3.9)

(5.2)

(1.3)

AVERT: Summary of Lipid Parameters

TM


0

5

10

15

20

0-6 months >6-18 months

Atorvastatin

Angioplasty/UC

24% difference46%

difference

% of patientswith an

ischemic event

7%6%

10%11%


AVERT: Incidence of First Ischemic Event by Time

TM

© 1999 Professional Postgraduate Services®Pitt B et al. N Engl J Med. 1999;341:70-76.

AVERT: Safety Evaluation

• Elevations in AST or ALT (consecutive elevations >3 x ULN)

– 4 (2.4%) atorvastatin-treated patients

– none in angioplasty/UC-treated patients

• Elevations in CPK (>10 x ULN)

– none in either treatment group

• There were no clinically significant differences in adverse event rates between the two treatment groups

– in this study, eight patients discontinued atorvastatin treatment due to an adverse event, seven of which remained in the study

TM


• Reduces ischemic events by 36%

• Delays the time to first event

• Is safe

• Can delay or prevent the need for percutaneous revascularization


Aggressive lipid lowering with atorvastatin in stable CAD patients:

AVERT: Conclusions

atorvastatin versus revascularization treatments (avert) trial

Documents