Vascular events In noncardiac Surgery patIents cOhort evaluatioN study (NCT ) The 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 1 st, 2 nd, and 3 rd day after surgery  Sample size – 40,000 patients After first 15,478 patients : event rate was >3 X expected  report results related to 4 th generation Trop T switched from 4 th gen Trop T to 5 th gen (hs) Trop T JAMA. 2012;307:

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 Statin N=2845 No Statin N=4492 ASD (%) n%n% Male Sex Age (years) +/- SD68.8+/ / Hypertension Stroke Active cancer Pre-op Beta-blocker use ASD: absolute standardized difference; SD: standard deviation

Type of Surgery Matched Population SURGERY Statin N=2845 No Statin N=4492 ASD (%) n%n% Urgent surgery Emergent surgery Orthopedic Vascular Other Low-risk surgeries

Variables with ASD>10% Matched Population PRE-OPERATIVE VARIABLE Statin N=2845 No Statin N=4492 ASD (%) n%n% Coronary artery disease Peripheral vascular disease Diabetes Pre-op Aspirin use Pre-op ACEI/ARB use * Conditional Poisson Regression to compute RR and 95% CI

Outcomes at 30 Days Outcome Frequency in matched cohort RR (95%CI) P value Primary composite outcome * 11.8%0.83 ( )0.007 * Composite of all-cause mortality, myocardial injury after noncardiac surgery (MINS), or stroke

Outcomes at 30 Days Outcome Frequency in matched cohort RR (95%CI) P value Primary composite outcome 11.8%0.83 ( )0.007 All-cause mortality1.8%0.58 ( )0.003 CV mortality0.8%0.42 ( )0.004 Non-CV mortality0.9%0.82 ( )0.45 MINS10.6%0.86 ( )0.02 Myocardial infarction 3.6%0.88 ( )0.35 Stroke0.5%0.93 ( )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: /eurheartj/ehv456