What we have noticed
Troponin elevation after surgery is associated with significant mortality at 30 days. In the recent large prospective study VISION, postoperative high sensitivity troponin T (ng/L) elevation between 20 to 65, and 65 to 1000, carries a 30-day mortality of 3.0% and 9.1%, respectively1. Furthermore, a 30 day mortality for patients with troponin greater than 1000 approaches 29.6%1. This is termed myocardial injury after non-cardiac surgery (MINS). This diagnosis is made after other causes of troponin elevation are ruled out, such as sepsis, rapid atrial fibrillation, pulmonary embolism or chronically elevated troponins. Up to 90% of patients with a troponin elevation postoperatively do not exhibit any symptoms, yet their outcomes are still poor, and comparable to those who are symptomatic with chest pain1,2. Because these events are missed unless systematic troponin screening are done, the 2017 Canadian Cardiovascular Society (CCS) Perioperative Guideline recommends routine serial troponin measuresments postoperatively on selected high-risk patients3.
When MINS is diagnosed, at least an antiplatelet and statin are recommended, with follow-up of the patient’s cardiovascular risk factors3. In a large observational cohort of 8351 patients, aspirin and statin have been shown to decrease mortality in patients who suffered MINS, with an adjusted odds ratio of 0.54, and 0.26 respectively4. Nevertheless, because these are not data from randomized control trial, some have questioned the validity of treating MINS and even the value of postoperative troponin surveillance. The MANAGE trial is the first randomized control trial looking at outcome-modifying therapy (dabigatran) for patients who have suffered MINS.
Data that answers these questions
The MANAGE trial randomized 1754 patients who suffered an episode of MINS after non-cardiac surgery to either dabigatran 110mg bid or placebo. Mean patient age was 70 years and 49% were female. Only 13% of the patient had a prior myocardial infarction, and 4% had a previous stroke. 39% of the surgeries were orthopedic, and 28% were general surgery. Patient with an eGFR < 35 or has indication for anticoagulation or high risk of bleeding (bleeding diathesis, prior intracranail, intraocular or spinal bleeding) are excluded. In addition to the treatment medications (dabigatran vs placebo), 74% of the patients continued to take aspirin, and 69% continue to take a statin. Mean follow-up for both groups was 16 months. 91% of MINS occurred without symptoms or signs of cardiac ischemia. All-cause mortality was 12% in the entire cohort. The primary outcome, which is a composite of vascular death, myocardial infarction, nonhemorrhagic stroke, peripheral arterial thrombosis, amputation, symptomatic venous thromboembolism, for dabigatran vs. placebo, was 11% vs. 15%, p = 0.012. Analysis of the individual secondary outcomes showed a statistically significant 80 percent reduced non-hemorrhagic stroke. Dabigatran group also had a 20% lower risk of MI and vascular mortality but it did not reach statistical significance. Furthermore, while there was a slightly higher risk of minor and lower GI bleeding, dabigatran did not cause any significant life-threatening major, and critical organ bleeding, even in the postsurgical state.
Limitations of the trial include high rates of discontinuation of the drug (>40%) in both treatment arms, low recruitment numbers, and broadening of the initial primary effiacy outcome to include amputation and symptomatic deep vein thrombosis after the trial was started.
In summary, the MANAGE trial informs us of two important points. First of all, consistent with previous studies, majority (90%) of MINS would have been missed without troponin screening, and these events are associated with increased mortality and vascular complications. The MANAGE trial adds to the growing body of evidence that we should not be complacent about MINS. Secondly, MANAGE provides evidence that the major vascular complications associated with MINS can be reduced. However, further studies are needed to confirm the benefit of anticoagulants in the management of MINS before it can be adopted into routine management.
What we recommend (practice tips)
The following has been implemented locally at St. Paul’s Hospital:
- As per the CCS Perioperative guideline, screen at-risk patient undergoing overnight, non-cardiac surgery for MINS. While not mentioned explicitly in the guideline, if postoperative troponin surveillance is done, having a baseline preoperative troponin would be helpful.
- Recognize that even without symptoms, postoperative troponin elevation carries significant elevated mortality and morbidity. This “troponitis” or “troponemia” is not benign.
- Consistent with the 2017 CCS Perioperative guideline, provided there is no bleeding concern, once MINS is diagnosed, start aspirin 81mg a day and also a statin.
- Until there is further data, we do not routinely use dabigatran specifically for MINS, unless there are other reasons for anticoagulation.
- Reassess these patients postoperatively in the clinic for optimization of cardiovascular risk factors.
Also, please refer to the earlier This Changed My Practice article for a summary on the Canadian guideline on perioperative cardiac risk assessment and management for patients undergoing non-cardiac surgery: https://thischangedmypractice.com/first-canadian-guideline-on-perioperative-cardiac-risk-in-non-cardiac-surgery/.
- Writing Committee for the VISION Study Investigators, Devereaux PJ, Biccard BM, et al. Association of postoperative high-sensitivity troponin levels with myocardial injury and 30-day mortality among patients undergoing noncardiac surgery. JAMA. 2017;317(16):1642-1651. DOI: 10.1001/jama.2017.4360. (Request with CPSBC or view with UBC)
- Puelacher C, Lurati Buse G, Seeberger D, et al. Perioperative myocardial injury after noncardiac surgery: Incidence, mortality, and characterization. Circulation. 2018;137(12):1221-1232. DOI: 10.1161/CIRCULATIONAHA.117.030114. (View)
- Duceppe E, Parlow J, MacDonald P, et al. Canadian Cardiovascular Society guidelines on perioperative cardiac risk assessment and management for patients who undergo noncardiac surgery. Can J Cardiol. 2017;33(1):17-32. DOI: 10.1016/j.cjca.2016.09.008. (View with CPSBC or UBC)
- Devereaux PJ, Xavier D, Pogue J, et al. Characteristics and short-term prognosis of perioperative myocardial infarction in patients undergoing noncardiac surgery: A cohort study. Ann Intern Med. 2011;154(8):523-528. DOI: 10.7326/0003-4819-154-8-201104190-00003. (View with CPSBC or UBC)