Statin Therapy with Major Vascular Surgery
Abstract & Commentary
By Michael H. Crawford, MD
Source: Feringa HHH, et al. Intensity of statin therapy in relation to myocardial ischemia, troponin t release, and clinical cardiac outcome in patients undergoing major vascular surgery. J Am Coll Cardiol. 2007;50:1649-1656.
Cardiac death and perioperative myocardial infarctions occur in 2-20% (mean 6) of major noncardiac vascular surgery. Statins have been shown to have a protective effect, but the exact mechanism of this benefit is unclear. Thus, Feringa and colleagues from the Netherlands and Wisconsin prospectively studied 359 patients undergoing major vascular surgery (aorta, carotid, peripheral arteries). Statin doses and cholesterol levels were noted preoperatively. Starting one day before surgery, 72-hour continuous ECG monitoring was performed, and troponin T was measured on days 1, 3, 7 and pre-discharge after surgery. The main cardiac events were cardiac death or Q wave infarction. Patients with ECG confounders, such as bundle branch block, atrial fibrillation, left ventricular hypertrophy, or who had had a myocardial infarction < 6 months prior, were excluded. Beta-blockers were advised for all patients to keep heart rate in the 60-65 range. Also, all patients had dobutamine stress echoes prior to surgery, and were managed accordingly. Revascularization was not mandated unless appropriate for reasons not related to the surgery. Propensity analysis was used to correct for selection biases.
Results: A total of 52% of the patients were receiving statins, most of them for > 3 months. These patients were more likely to have had a prior stroke and hypercholesterolemia, but there were no differences in the occurrence of coronary artery disease, diabetes, or a positive dobutamine stress echo. Ischemic episodes by 72-hour ECG occurred in 29% of the patients, and were significantly less in those on statins and those with lower LDL cholesterol levels. Troponin release occurred in 23% of the patients and was also less likely in those on statins and with lower LDL cholesterols. Deaths occurred in 3%, and Q wave infarctions in 1% of the patients in 30 days and were less frequent in those on statins and with low LDLs. Late events (mean 2.3 years) were also reduced by statins. Heart rate variability was greatest before surgery and least during surgery. Lower values before and during surgery predicted troponin leaks and ischemia. Higher statin doses were associated with fewer cardiac events and higher heart rate variability. Feringa et al concluded that higher statin doses and lower LDL cholesterol levels predict less perioperative myocardial ischemia, troponin release, and cardiac events with major vascular surgery.
This study supports previous observational studies which have suggested that statin therapy and lower LDL cholesterol values predict less cardiac events with major vascular surgery. This study adds some mechanistic data that seem to support beneficial non-lipid lowering effects of statins, or the so called pleotropic effects. The higher the statin dose, the more the heart rate variability even adjusted for cholesterol levels. This suggests that statins may affect the autonomic nervous system. Also, the observation that ECG myocardial ischemia was less on statins even adjusted for cholesterol levels suggests that effects of statins, such as reduction of inflammatory markers, increased nitric oxide, and improved endothelial function, may be important in the perioperative period. In addition, statins may stabilize plaques which would explain the lower incidence of troponin leakage, Q wave infarction, and death.
These results suggest that all vascular surgery patients should be treated with statins perioperatively regardless of their cholesterol levels. In this study, only 52 % were on stains. Also, the study suggests that doses > 50% of maximum recommended doses are more effective. Unfortunately, we don't have prospective, randomized trails to identify the best candidates for statins, the right dosage/agent, or the duration of therapy, especially preoperatively. In addition, this study has limitations. Although various statistical adjustments were made, the effect of selection biases in this observational study can never be fully elucidated. The inclusion of carotid surgery patients may have confounded the heart rate variability data, since carotid manipulation can affect autonomic tone. The observations in this study can only be applied to major vascular surgery and not necessarily in other high risk surgery or in other high-risk patients. Finally, about 75% of the patients in this study were on beta-blockers, which are recommended by the most recent guidelines for the management of high-risk perioperative patients. Thus, the results were seen on top of this therapy. The current guidelines do not recommend statins due to the lack of randomized trials, but also do not discourage their use (Circulation. 2007; 116:1971-1996).