In what sounds like a baffling negation of the previous meta-analyses vouching for the effectiveness of statin therapy, the recent STICS trial states that the perioperative use of statin does not prevent post-surgical complications in patients undergoing elective cardiac surgery. The findings were published in the New England Journal of Medicine on May 5, 2016.
In a clinical trial of 1,922 patients scheduled for elective cardiac surgery, the perioperative i.e., occurring during or at the time around surgery, use of Rosuvastatin did not confer benefit in terms of preventing post-operative atrial fibrillation or perioperative myocardial damage. In fact, if anything, Rosuvastatin increased the risk of acute kidney injury in such patients.
In past, statins have been shown to indirectly curb the incidence of atrial fibrillation by preventing inflammation and oxidative stress. Atrial fibrillation, a type of arrhythmia, is closely linked with a generalized inflammatory response that is common after surgery. For instance, in one of the trials, an initiation of statin therapy prior to cardiac surgery was linked with a decrease in the reactive oxygen species. While in the other trial, the pre-operative use of statins was able to restrict the production of C-reactive protein. C-reactive protein is a protein produced by the liver in a response to inflammation anywhere in the body.
The findings of the current trial clash with those of the earlier trials. The earlier trials, it seems, were small and had other limitations. The current trial, named the Statin Therapy in Cardiac Surgery (STICS), was not only large, randomized and placebo-controlled but also provides a definitive evidence about the perioperative use of statins and its postoperative effects.
Statin Therapy in Cardiac Surgery (STICS)
A total of 1,922 patients were enrolled in the trial, all aged 18 years and older. The patients had a cardiac complication and were scheduled to undergo an elective cardiac surgery that included coronary artery bypass graft (CABG) and surgical aortic valve replacement. Patients were eligible for enrollment if they were in sinus rhythm and were not taking anti-arrhythmic drugs, save beta-blockers.
Patients were made to undergo a number of diagnostic tests for the evaluation and assessment of left ventricular ejection fraction (LVEF) and left atrial size, as well as for the measurement of different proteins, stress- and bio-markers, LFTs and RFTs. The tests included, transthoracic echocardiography and laboratory evaluation of high sensitivity C-reactive protein, low-density lipoprotein (LDL) cholesterol, creatinine, and troponin I, N-terminal pro–brain natriuretic peptide (NT-proBNP).
Following the diagnostic evaluation, the patients were randomly assigned to statin therapy arm (n=960) or placebo arm (n=962). Patients in the drug therapy arm received rosuvastatin (20 mg) once a day for eight days prior to, and five days after the surgery.
The primary outcomes were postoperative atrial fibrillation and perioperative cardiac injury. While secondary outcomes entailed a plethora of cardiac complications other than the primary outcome.
Compared to the placebo arm, the postoperative concentrations of low-density lipoprotein cholesterol and C-reactive protein were lower in the statin arm i.e., 49.9 mg/dl VS 77.7 mg/dl. However, there was not much of a statistically significant difference in the primary outcome between the two arms i.e., rosuvastatin (21.1%) VS placebo group (20.5%).
While Rosuvastatin therapy did not confer beneficial effects on the secondary outcome, it was tied to an increased rate of postoperative acute kidney injury.
Study Strengths And Limitations
The prime limitation of the study was the short average duration of the drug regimen before surgery. In other trials, the average duration was long. Moreover, the study enrolled patients from only one ethnic background i.e., Chinese, which might be related to the lack of statin effectiveness in the patients. Previous studies have shown that statin therapy was beneficial in Southeast Asian and White patients.
The STICs study was stronger and more authentic than earlier trials based on statins, since it was randomized, placebo-controlled, and included a large number of patients.
Statins are a class of drugs, called anti-hyperlipidemics, that help to lower blood cholesterol levels. In patients with an abnormally high level of cholesterol, statins confer a survival benefit by preventing the risk of heart attacks and stroke. Studies and clinical trials have shown that statins can lower the risk of heart attack, stroke, and even death from heart disease by 25-35% in certain patients. Moreover, statins have also been shown to reduce the likelihood of recurrent strokes or heart attacks by about 40% in high-risk patients.
As per estimates, apart from people who are already on the statin therapy, an additional 15-20 million people are eligible for the drug therapy owing to their increased risk for a heart disease.
Linked with a high morbidity and mortality, heart disease is the number one killer in United States only. In 2011, it killed nearly 787,000 people.
Each year, around 720,000 people in the United States get a heart attack.