Key messages
– Taking statins may make little to no difference to death within 30 days of surgery, irregular heart rhythms and stroke (a serious life-threatening condition that happens when the blood supply to part of the brain is cut off); and probably results in little to no difference in heart attacks, length of intensive care unit stay and overall hospital stay. We are very uncertain about the effects of statins on kidney failure and harmful effects from statin treatment.
– Further studies are required to investigate whether statin treatment can help reduce the likelihood of death and other heart-related (cardiovascular) issues in this context.
What are the dangers of cardiac surgery and how may statins help?
Cardiac surgeries can effectively treat people with heart and circulation problems. However, undergoing cardiac surgery also increases the risk of death, heart attack, stroke (a serious life-threatening condition that happens when the blood supply to part of the brain is cut off), irregular heart rhythms and kidney failure. This is partly because more than half of people undergoing cardiac surgery are over 70 years of age. To reduce these risks, we should try to improve recovery rates by preventing these problems from occurring before, during and after surgery.
Statins are medications used throughout the world to lower blood cholesterol (a fatty substance found in the blood that may block blood vessels) levels and reduce the chances of cardiovascular issues becoming worse. Studies have shown that fewer people who had built up dangerous amounts of cholesterol in their blood vessels (arteries) died while taking statins. However, the potential benefits of taking statins in people undergoing cardiac surgery are unclear.
What did we want to find out?
We wanted to find out whether taking statins before undergoing cardiac surgery could help reduce the risk of:
– death occurring shortly after surgery; or
– developing other heart or kidney problems.
We also wanted to find out if there were any changes in the quality of care associated with cardiac surgeries for people who had been taking statins, such as reducing the length of hospital stay or intensive care unit stay, or if there were any harmful effects from statin treatment.
What did we do?
We searched for studies published up to September 2023 that compared treatment with statins to treatment with a placebo (a pretend medicine that looks or tastes identical to the medicine being tested) or usual care in people undergoing cardiac surgeries. Contrary to previous versions of this review, we only included trials that we were sure were approved by an ethical review board.
What did we find?
We found eight studies involving 5592 people with an average age of 63 years and 79% were men. Of these, 2798 people were treated with statins and 2794 people were not treated with statins before cardiac surgery. The smallest study included 57 people and the largest involved 2406 people. All studies were conducted in hospitals affiliated with universities in Asia, Europe and North America. Each study used different statin types (atorvastatin, fluvastatin, simvastatin, pravastatin or rosuvastatin) and doses (between 20 mg and 80 mg).
Main results
In people undergoing cardiac surgery, compared to no statin treatment, statin treatment:
– probably results in little to no difference in heart attacks (5 studies, 4645 people), length of intensive care unit stay (3 studies, 4528 people) and overall hospital stay (5 studies, 4788 people);
– may make little to no difference to death within 30 days of surgery (6 studies, 5260 people), irregular heart rhythm (8 studies, 5592 people) and stroke (4 studies, 5143 people).
We are very uncertain about the effects of statins on major harmful cardiac events (1 study, 2406 people) and kidney failure (4 studies, 4728 people).
What are the limitations of the evidence?
We are moderately confident in our findings that there were probably little to no differences in the risk of heart attack, length of hospital and intensive care unit stay. However, we have little to very little confidence about our other findings, namely the most important finding we were looking for, which was a reduction in death. This is because most of the studies had many differences between them, there were fewer comparative cases than expected, and the studies did not always provide information about the statin intervention or treatment outcomes we were interested in. In addition, all studies used a different approach to statin treatment, which made them difficult to compare. Overall, this lowered our confidence in the evidence.
Further studies are required to investigate whether statin treatment can help reduce the likelihood of death and other heart-related (cardiovascular) issues in this context.
How up to date is this evidence?
This is an update of a Cochrane review. The evidence is up to date to September 2023.
In this updated Cochrane review, we found no evidence that statin use in the perioperative period of elective cardiac surgery was associated with any clinical benefit or worsening, when compared with placebo or standard of care. Compared with placebo or standard of care, statin use probably results in little to no difference in MIs, length of ICU stay and overall hospital stay; and may make little to no difference to mortality, atrial fibrillation and stroke. We are very uncertain about the effects of statins on major harmful cardiac events and renal failure. The certainty of the evidence validating this finding varied from moderate to very low, depending on the outcome. Future trials should focus on assessing the impact of statin therapy on mortality and major adverse cardiovascular events.
Despite significant advances in surgical techniques and perioperative care, people undertaking cardiac surgery due to cardiovascular disease are more prone to the development of postoperative adverse events. Statins (5-hydroxy-3-methylglutaryl-co-enzyme A (HMG-CoA) reductase inhibitors) are well-known for their anti-inflammatory and antioxidant effects and are established for primary and secondary prevention of coronary artery disease. In addition, statins are thought to have clinical benefits in perioperative outcomes in people undergoing cardiac surgery. This review is an update of a review that was first published in 2012 and updated in 2015.
To evaluate the benefits and harms of preoperative statin therapy in adults undergoing cardiac surgery compared to standard of care or placebo.
We performed a search of the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 9, 2023), Ovid MEDLINE (1980 to 14 September 2023), and Ovid Embase (1980 to 2023 (week 36)). We applied no language restrictions.
We included all randomised controlled trials (RCTs) comparing any statin treatment before cardiac surgery, for any given duration and dose, versus no preoperative statin therapy (standard of care) or placebo. We excluded trials without a registered trial protocol and trials without approval by an institutional ethics committee.
We used standard Cochrane methodology. Primary outcomes were short-term mortality and major adverse cardiovascular events. Secondary outcomes were myocardial infarction, atrial fibrillation, stroke, renal failure, length of intensive care unit (ICU) stay, length of hospital stay and adverse effects related to statin therapy. We reported effect measures as risk ratios (RRs) or mean differences (MDs) with corresponding 95% confidence intervals (CIs). We used the RoB 1 tool to assess the risk of bias in included trials, and GRADE to assess the certainty of the evidence.
We identified eight RCTs (five new to this review) including 5592 participants. Pooled analysis showed that statin treatment before surgery may result in little to no difference in the risk of postoperative short-term mortality (RR 1.36, 95% CI 0.72 to 2.59; I2 = 0%; 6 RCTs, 5260 participants; low-certainty evidence; note 2 RCTs reported 0 events in both groups so RR calculated from 4 RCTs with 5143 participants). We are very uncertain about the effect of statins on major adverse cardiovascular events (RR 0.93, 95% CI 0.77 to 1.13; 1 RCT, 2406 participants; very low-certainty evidence). Statins probably result in little to no difference in myocardial infarction (RR 0.88, 95% CI 0.73 to 1.06; I2 = 0%; 5 RCTs, 4645 participants; moderate-certainty evidence), may result in little to no difference in atrial fibrillation (RR 0.87, 95% CI 0.72 to 1.05; I2 = 60%; 8 RCTs, 5592 participants; low-certainty evidence), and may result in little to no difference in stroke (RR 1.47, 95% CI 0.90 to 2.40; I2 = 0%; 4 RCTs, 5143 participants; low-certainty evidence). We are very uncertain about the effect of statins on renal failure (RR 1.04, 95% CI 0.80 to 1.34; I2 = 57%; 4 RCTs, 4728 participants; very low-certainty evidence). Additionally, statins probably result in little to no difference in length of ICU stay (MD 1.40 hours, 95% CI −1.62 to 4.41; I2 = 43%; 3 RCTs, 4528 participants; moderate-certainty evidence) and overall hospital stay (MD −0.31 days, 95% CI −0.64 to 0.03; I2 = 84%; 5 RCTs, 4788 participants; moderate-certainty evidence).
No study had any individual risk of bias domain classified as high. However, two studies were at high risk of bias overall given the classification of unclear risk of bias in three domains.