Vascular events In noncardiac Surgery patIents cOhort evaluatioN study (NCT00512109) The Study Otavio Berwanger, Yannick Lemanach, Erica Aranha Suzumura,

Vascular events In noncardiac Surgery patIents cOhort evaluatioN study(NCT00512109)

TheThe Study Study

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

Association between Pre-Operative Statin use and Major Cardiovascular Complications among

Patients undergoing Noncardiac Surgery

Study organization

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

TnT drawn between 6 to 12 hours after surgery and on the 1st, 2nd, and 3rd day after surgery

Sample size – 40,000 patientsAfter 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

JAMA. 2012;307:2295-2304.

Outcomes Primary outcomeComposite of all-cause mortality, myocardial injury after noncardiac surgery (MINS), or stroke at 30-days

Secondary outcomesMINS*: 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

StatinN=2845

No StatinN=4492 ASD

(%)n % n %

Male Sex 1392 48.9 2077 46.2 5.4

Age (years) +/- SD 68.8+/-10.2 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

SURGERYStatin

N=2845No StatinN=4492 ASD

(%)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

Variables with ASD>10%

  Matched Population

PRE-OPERATIVE VARIABLE

StatinN=2845

No StatinN=4492 ASD

(%)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

* Conditional Poisson Regression to compute RR and 95% CI

Outcomes at 30 Days

OutcomeFrequency in matched

cohortRR (95%CI)

P value

Primary composite outcome *

11.8% 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

OutcomeFrequency in matched

cohortRR (95%CI)

P value

Primary composite outcome

11.8% 0.83 (0.73-0.95) 0.007

All-cause mortality 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 10.6% 0.86 (0.73-0.98) 0.02Myocardial infarction

3.6% 0.88 (0.70-1.14) 0.35

Stroke 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

eurheartj.oxfordjournals.orgdoi: 10.1093/eurheartj/ehv456