Perioperative statins: More than lipid-lowering?
ABSTRACTPreliminary evidence indicates that statin drugs may be beneficial when given in the perioperative period. Although more studies are needed to draw firm conclusions, the acute nonlipid pleiotropic effects of statins may improve patient outcomes, especially for patients at the highest risk.
KEY POINTS
- Experiments in animals suggest that statins, given shortly before or after a cardiovascular event, confer benefit before any changes in lipids are measurable.
- Retrospective and prospective studies indicate that patients with either acute myocardial infarction or acute coronary syndrome who are already receiving statins should not have them stopped, and those who had not been receiving statins should receive them immediately.
- Most patients undergoing coronary artery bypass grafting or noncardiac vascular surgery should already be receiving a statin. These drugs can also be considered in patients undergoing intermediate-risk nonvascular surgery. Patients who have been receiving statins prior to surgery should not have them stopped for surgery.
EFFECTS OF STATINS IN ACUTE CORONARY SYNDROME
The National Registry of Myocardial Infarction17 is a prospective, observational database of all patients with acute myocardial infarction admitted to 1,230 participating hospitals throughout the United States. In an analysis from this cohort, patients were divided into four groups: those receiving statins before and after admission, those receiving statins only before admission, those receiving statins only after admission, and those who never received statins.
Compared with those who never received statins, fewer patients who received them both before and after admission died while in the hospital (unadjusted odds ratio 0.23, 95% confidence interval [CI] 0.22–0.25), and the odds ratio for those who received statins for the first time was 0.31 (95% CI 0.29–0.33). Patients who stopped receiving a statin on admission were more likely to die than were patients who never received statins (odds ratio 1.09, 95% CI 1.03–1.15). These trends held true even when adjustments were made for potential confounding factors.
Comment. Unmeasured confounding factors (such as the inability to take pills due to altered mental status or the different practice styles of the providers who chose to discontinue statins) might have affected the results. Nevertheless, these results suggest that the protective effects of statins stop almost immediately when these drugs are discontinued, and that there may even be an adverse “rebound” effect when patients who have been taking these drugs for a long time stop taking them temporarily.
The Platelet Receptor Inhibition in Ischemic Syndrome Management trial,18 in a subgroup analysis, had nearly identical findings. In the main part of this trial, patients with coronary artery disease and chest pain at rest or accelerating pain in the last 24 hours were randomized to receive tirofiban (Aggrastat) or heparin. Complete data on statin use were available for 1,616 (50%) of the 3,232 patients in this trial, and the rate of the primary end point (death, myocardial infarction, or recurrent ischemia) was analyzed on the basis of statin therapy in this subgroup.
Comment. Together, these data lead to the conclusion that, when admitted for either acute myocardial infarction or acute coronary syndrome, patients already receiving statins should not have them stopped, and those who had not been receiving statins should receive them immediately. The safety of these medications in the acute setting appears excellent: in the Myocardial Ischemia Reduction With Acute Cholesterol Lowering (MIRACL)12 and the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT)11 trials, fewer than 5% of statin-treated patients had transient elevations in transaminase levels, and no cases of rhabdomyolysis were reported.
PERIOPERATIVE STATIN STUDIES
The data on perioperative statin use are mostly observational and retrospective and fall into essentially four surgical categories: coronary artery bypass grafting (CABG), carotid endarterectomy,19,20 noncardiac vascular surgery, and major noncardiac surgery. Two meta-analyses have also evaluated the data.21,22 The only randomized controlled trial (performed by Durazzo et al23) was small and was carried out at a single center in vascular surgery patients, and the event rate was low.
Current recommendations from the National Cholesterol Education Program (NCEP)24 say that patients who need CABG, have peripheral arterial disease, have an abdominal aortic aneurysm, or have cerebrovascular disease should already be on a statin to achieve an LDL-C goal level of less than 100 mg/dL, with an optional goal of less than 70 mg/dL, independent of surgery.
Since not all patients who should be on statins are actually on them, questions arise:
- Is it important (and safe) to start statin treatment preoperatively?
- Will patients with cardiovascular risk factors but without known cardiovascular disease benefit from statins perioperatively?
Noncardiac vascular surgery
Multiple retrospective studies have evaluated the effect of statins in patients undergoing major noncardiac vascular surgery.25–32
Kertai et al25 evaluated 570 patients in Holland who underwent elective open surgery for infrarenal abdominal aortic aneurysms between 1991 and 2001, looking for an association between statin use and the incidence of perioperative death from myocardial infarction. Only 162 of the 570 patients had been on long-term statin therapy before the surgery. The use of statins was only one of many known baseline characteristics that were significantly different between the two groups, including age, body mass index, known coronary artery disease, and use of angiotensin-converting enzyme inhibitors and beta-blockers. In univariate analysis, statins appeared to be protective: 6 (3.7%) of the patients in the statin group died of a myocardial infarction, compared with 45 (11%) of those in the nostatin group. A multivariate analysis yielded similar findings, with an odds ratio of 0.24 (95% CI 0.11–0.54).
Ward et al27 performed a very similar retrospective study, with similar findings. In 446 patients who underwent surgery for infrarenal abdominal aortic aneurysm, statin therapy was associated with a significantly lower incidence of the combined end point of death, myocardial infarction, stroke, and major peripheral vascular complications, with an adjusted odds ratio of 0.36 (95% CI 0.14–0.93).
Poldermans et al26 noted similar findings in a case-control study of noncardiac vascular surgery patients. Statin users had a much lower perioperative risk of death than did nonusers, with an adjusted odds ratio of 0.22 (95% CI 0.10–0.47).
O’Neil-Callahan et al,28 in a cohort study, found that statin users had fewer perioperative cardiac complications, with an adjusted odds ratio of 0.49 (95% CI 0.28–0.84, P = .009).
