Association between Pre-Operative Statin use
and Major Cardiovascular Complications among
Patients undergoing Noncardiac Surgery
The
Study
Vascular events In noncardiac Surgery patIents cOhort evaluatioN study
(NCT00512109)
Otavio Berwanger, Yannick Lemanach, Erica Aranha Suzumura,
Bruce Biccard, Sadeesh Srinathan, Wojciech Szczeklik, Jose A Espirito
Santo, Eliana Santucci, Alexandre B Cavalcanti, Andrew Archbold,
PJ Devereaux for the VISION Investigators
Study organization
International Coordinating Centre
• Clinical Epidemiology & Biostatistics, McMaster University
(CLARITY Group) and the Population Health Research
Institute, Hamilton, ON, Canada
Principal Investigator and Chair
• Dr PJ Devereaux (McMaster University)
SC and National Leader (Brazil)
• Dr Otavio Berwanger (Research Institute HCor)
Participating centres
• 12 centres in eight countries
• North/South America, Africa, Asia, Australia, and Europe
Rationale
 Noncardiac surgery is common
– 200 Million adults worldwide annually
– ≥10 million will suffer major CV complication in first 30-days
after surgery
 Observational studies and small RCTs
– suggest statins may reduce risk of CV events
 VISION Study
– large international prospective cohort study of representative
sample of patients undergoing noncardiac surgery
 Objective of statin substudy
– assess effects of perioperative statin usage on CV events at
30-days
VISION Methods
 Prospective, international, cohort study
 Eligibility criteria
– >45 yrs undergoing in-hospital noncardiac
surgery
– received a general or regional anaesthetic
 Sampling method
– representative sample (consecutive patients)
 Quality Control
– On-site and central statistical monitoring
JAMA. 2012;307:2295-2304.
TnT drawn between 6 to 12 hours after surgery and on
the 1st, 2nd, and 3rd day after surgery
Sample size – 40,000 patients
After first 15,478 patients :
 event rate was >3 X expected  report results related to
4th generation Trop T
 switched from 4th gen Trop T to 5th gen (hs) Trop T
Outcomes
Primary outcome
Composite of all-cause mortality, myocardial injury after
noncardiac surgery (MINS), or stroke at 30-days
Secondary outcomes
MINS*: peak TnT ≥0.03 ng/ml due to myocardial ischaemia
Myocardial infarction (Third Universal Definition)
Cardiovascular and non-cardiovascular death
Stroke
All events centrally adjudicated
* Anesthesiology. 201;120:564-78
Study groups
 Patients who received statin in 7 days b/f surgery (Statin group)
 Patients who did not receive statin in 7 days b/f surgery (No statin
group)
Multivariable logistic model to estimate probability of
receiving statins pre-operatively (i.e. Propensity Score)
 27 pre-operative variables were included
Propensity score matching to correct for
confounding
 Nearest neighbor propensity score matching with caliper of 20% of
standard deviation of logit of probability of taking statin before
surgery
Pre-Operative Characteristics
Matched Population
PRE-OPERATIVE
VARIABLE
Male Sex
Age (years) +/- SD
Statin
N=2845
n
%
1392
48.9
68.8+/-10.2
No Statin
N=4492
n
%
2077
ASD
(%)
46.2
5.4
68.6+/-11.7
1.9
Hypertension
2061
72.4
3095
68.9
7.6
Stroke
295
10.4
401
8.9
5.1
Active cancer
369
13.0
587
13.1
0.3
Pre-op Beta-blocker use
721
25.3
981
21.8
8.5
ASD: absolute standardized difference; SD: standard deviation
Type of Surgery
Matched Population
Statin
N=2845
No Statin
N=4492
n
%
n
%
Urgent surgery
63
2.2
100
2.2
0.1
Emergent surgery
225
7.9
357
8.0
0.1
Orthopedic
736
25.9
1210
26.9
1.4
Vascular
139
4.9
135
3.0
4.8
Other
1097
38.5
1764
39.3
1.1
Low-risk surgeries
1034
36.3
1625
36.2
0.3
SURGERY
ASD
(%)
Variables with ASD>10%
Matched Population
Statin
N=2845
No Statin
N=4492
n
%
n
%
Coronary artery disease
560
19.7
609
13.6
17.9
Peripheral vascular
disease
220
7.7
233
5.2
11.5
Diabetes
852
30.0
1129
25.1
11.1
Pre-op Aspirin use
701
24.6
839
18.7
15.3
Pre-op ACEI/ARB use
1516
53.3
2162
48.1
10.3
PRE-OPERATIVE
VARIABLE
* Conditional Poisson Regression to compute RR and 95% CI
ASD
(%)
Outcomes at 30 Days
Outcome
Primary composite
outcome *
Frequency
in matched RR (95%CI)
cohort
11.8%
P
value
0.83 (0.73-0.95) 0.007
* Composite of all-cause mortality, myocardial injury after
noncardiac surgery (MINS), or stroke
Outcomes at 30 Days
Outcome
Primary composite
outcome
All-cause mortality
Frequency
in matched RR (95%CI)
cohort
P
value
11.8%
0.83 (0.73-0.95) 0.007
1.8%
0.58 (0.40-0.83) 0.003
CV mortality
0.8%
0.42 (0.23-0.76) 0.004
Non-CV mortality
0.9%
0.82 (0.50-1.36)
0.45
MINS
Myocardial
infarction
Stroke
10.6%
0.86 (0.73-0.98)
0.02
3.6%
0.88 (0.70-1.14)
0.35
0.5%
0.93 (0.48-1.81)
0.84
Survival at 30-days
Subgroup Analyses
Sensitivity Analyses
 Among 500 replications of main analyses, only
2 (0.4%) had P>0.05
 1653 patients who received statin b/f surgery
and first 3 days after surgery and 2847
matched controls
 Statin group had lower risk of primary outcome
(RR, 0.82; 95% CI, 0.68–0.98)
Limitations
 Observational study
 Use of statins may represent surrogate for
unmeasured confounders that relate to prognosis
 Despite matching, standardized differences
remained >10% in 5 pre-operative variables
 All of these variables were more frequently seen in
Statin group
 If optimal matching had been possible results might
have been even more pronounced
 Data on type and dosing of statins, liver and
muscle function not collected
Conclusions
 In large cohort of patients undergoing noncardiac
surgery, pre-operative statin use was associated
with a lower risk of 30-day major CV events
 Statins may represent a potentially beneficial
intervention to prevent cardiovascular
complications in this setting
 Our results require confirmation in large
perioperative statin RCT
doi: 10.1093/eurheartj/ehv456
eurheartj.oxfordjournals.org