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A peri‐operative statin update for non‐cardiac surgery. Part I: The effects of statin therapy on atherosclerotic disease and lessons learnt from statin therapy in medical (non‐surgical) patients
SummaryThe utility of peri‐operative statin therapy is currently considered to be inconclusive. To provide a platform for more meaningful peri‐operative statin literature in the future, this is the first of two review articles evaluating peri‐operative statin therapy. This review examines the predictors of cardiovascular outcome and therapeutic targets which are established in medical (non‐surgical) patients. In patients with stable coronary artery disease at least 4–6 weeks of standard statin therapy are required to realise most of the beneficial cellular and metabolic effects of statin therapy. Low‐density lipoprotein‐cholesterol reduction is associated with improved survival in these patients. In comparison, patients who sustain an acute coronary event require high‐dose statin therapy probably initiated within 24 h with a therapeutic target of C‐reactive protein reduction. Withdrawal of statin therapy results in a rapid return to endothelial dysfunction and amplification of the inflammatory process, which may increase cardiovascular risk.
Dexmedetomidine and cardiac protection for non‐cardiac surgery: a meta‐analysis of randomised controlled trials
SummaryWe conducted a systematic review of the effects of dexmedetomidine on cardiac outcomes following non‐cardiac surgery. We included prospective, randomised peri‐operative studies of dexmedetomidine that reported mortality, cardiac morbidity or adverse drug events. A PubMed Central and EMBASE search was conducted up to July 2007. The reference lists of identified papers were examined for further trials. Of 425 studies identified, 20 were included in the meta‐analysis (840 patients). Dexmedetomidine was associated with a trend towards improved cardiac outcomes; all‐cause mortality (OR 0.27, 95% CI 0.01–7.13, p = 0.44), non‐fatal myocardial infarction (OR 0.26, 95% CI 0.04–1.60, p = 0.14), and myocardial ischaemia (OR 0.65, 95% CI 0.26–1.63, p = 0.36). Peri‐operative hypotension (26%, OR 3.80, 95% CI 1.91–7.54, p = 0.0001) and bradycardia (17%, OR 5.45, 95% CI 2.98–9.95, p < 0.00001) were significantly increased. An anticholinergic did not reduce the incidence of bradycardia (p = 0.43). A randomised placebo‐controlled trial of dexmedetomidine is warranted.
Clinical risk predictors associated with cardiac mortality following vascular surgery in South African patients.
Clinical risk prediction is important in the prognostication of peri-operative cardiac complications and the management of high-risk cardiac patients for major non-cardiac surgery. However, the current pre-operative clinical risk indices have been derived in European and American patients and not validated in South African patients. The purpose of this study was to evaluate the utility of the clinical risk predictors identified in Lee's revised cardiac risk index and in the African arm of the INTERHEART study, in predicting cardiac mortality following vascular surgery in South African patients. A retrospective cohort study was conducted of all patients undergoing elective or urgent vascular surgery at Inkosi Albert Luthuli Central Hospital over a three-year period. All in-hospital deaths were identified and classified into cardiac or non-cardiac deaths by an investigator blinded to the patients' pre-operative clinical risk predicators. A second investigator blinded to the cause of death identified the following clinical risk predictors: history of ischaemic heart disease, congestive cardiac failure and cerebrovascular accident, presence of diabetes, hypertension and obesity (BMI > 30 kg.m(-2)), elevated serum creatinine (> 180 micromol.l(-1)), positive smoking history and ethnicity. The main finding was that a serum creatinine level of greater than 180 micromol.l(-1) and a positive smoking history were significantly associated with cardiac death (p = 0.012, p = 0.012, respectively). Multivariate analyses using a backward stepwise modeling technique found only a serum creatinine of > 180 micromol.l(-1) and a positive smoking history to be significantly associated with cardiac mortality (p = 0.038, 0.035, respectively) with an odds ratio and 95% confidence interval of 3.02 (1.06-8.59) and 3.40 (1.09-10.62), respectively. All other clinical predictors were not significantly different between the two groups. However, based on the sample size of this study, a type 2 or b error may have resulted in the other risk predictors not being identified as important clinical predictors of cardiac mortality. Therefore, until such time as a study of adequate power is conducted, a history of ischaemic heart disease, congestive cardiac failure, diabetes and cerebrovascular accidents should still be considered to be important clinical risk predictors in South African surgical patients. In conclusion, an elevated serum creatinine and a positive history for smoking are important clinical predictors of cardiac mortality in South African patients following elective or urgent vascular surgery.
The pharmaco-economics of peri-operative beta-blocker and statin therapy in South Africa.
We conducted a pharmaco-economic analysis of the prospective peri-operative studies of beta-blocker and statin administration for major elective non-cardiac surgery, using the Discovery Health claims costs for 2004. This analysis shows that acute peri-operative beta-blockade and statin therapy could result in a cost saving through a reduction in major perioperative cardiovascular complications in patients with an expected peri-operative major cardiovascular complication rate exceeding 10% following elective major non-cardiac surgery. The validity of these findings is dependent on whether the incidence of cardiovascular complications following major noncardiac surgery reported in the international literature is found to be similar in South Africa.
Acute peri‐operative beta blockade in intermediate‐risk patients
SummaryPeri‐operative beta‐blockade has been shown to reduce the incidence of postoperative cardio‐ vascular complications including cardiac death in high‐risk non‐cardiac surgical patients. However, the recent analysis by Lindenauer et al. suggests that it is inappropriate to administer beta‐blockers blindly to all surgical patients. In an attempt to determine the appropriateness of peri‐operative beta‐blocker administration across patients with a spectrum of cardiovascular risks, we have examined studies of intermediate‐risk patient groups (that is those undergoing intermediate risk surgery or those with a Lee Revised Cardiac Risk Score of≤2). We analysed data from randomised prospective studies of the effects of acute peri‐operative beta‐blockade on the incidence of peri‐operative myocardial ischaemia. By examining the demographics and surgical interventions in these patients, we have compared these studies with other studies of peri‐operative silent myocardial ischaemia representing patients of similar risk. We thus estimated the expected long‐term postoperative cardiovascular complication rate associated with myocardial ischaemia in these patients in terms of number needed to treat for ischaemia prevention and for prevention of major cardiovascular complications. Prevention of peri‐operative myocardial ischaemia with acute beta‐blockade in non‐cardiac surgical patients with 1–2 RCRI clinical risk factors can be achieved with a number needed to treat of 10. It is not associated with a significant increase in drug associated side‐effects. However, acute beta‐blockade shows no real benefit in the prevention of major cardiovascular complications in intermediate risk non‐vascular surgical patients with a number‐needed‐to‐treat of 833. Vascular surgical patients undergoing intermediate‐risk surgery may benefit from the protective effects of acute peri‐operative beta‐blockade, however, with a number‐needed‐to‐treat of 68 it would require a randomised clinical trial of over 24 000 patients to prove their efficacy.
The pharmacoeconomics of peri‐operative beta‐blocker therapy
SummaryIt is widely recommended that beta‐blockade be used peri‐operatively as it may reduce the incidence of postoperative cardiovascular complications including death. However, there are few data concerning the cost‐effectiveness of such strategies. We have analysed the pharmacoeconomics of acute beta‐blockade using data from eight prospective peri‐operative studies in which patients underwent elective non‐cardiac surgery, and in which the incidence of adverse side‐effects of treatment, as well as clinical outcomes, have been reported. The costs of treatment were based on the NHS reference costs for 2004. From these data, the number‐needed‐to‐treat (NNT) to prevent a major cardiovascular complication (including cardiovascular death) in high‐risk patients was 18.5. This is comparable to the NNT for peri‐operative statin therapy. The incremental cost of peri‐operative beta‐blockade (costs of drug acquisition and of treating associated adverse drug events) was £67.80 per patient. This results in a total cost of £1254.30 per peri‐operative cardiovascular complication prevented. However, there is evidence that in patients at lower cardiovascular risk, beta‐blockers may be potentially harmful, since their adverse effects (hypotension, bradycardia) may outweigh their potential cardioprotective effects.
Statin therapy: a potentially useful peri‐operative intervention in patients with cardiovascular disease
SummaryStatin cardiovascular protection is mediated by lipid lowering and pleiotropic effects. The efficacy of statins has been established in non‐surgical patients with cardiovascular disease and also more recently in non‐surgical patients who sustain an acute coronary event. Peri‐operative statin administration has been shown to improve both short‐term and long‐term cardiac outcome following non‐cardiac and coronary bypass graft surgery. This cardioprotection may be independent of peri‐operative haemodynamics due to a positive effect on plaque stability. Recommendations for the peri‐operative statin administration are suggested. These include indications for peri‐operative statin therapy, timing of administration, therapeutic targets, duration of administration, the adverse implications of peri‐operative statin withdrawal, safety and cost‐effectiveness.
The pharmaco‐economics of peri‐operative statin therapy
SummaryWe analysed the pharmaco‐economics of the prospective peri‐operative studies of statin administration for major elective vascular surgery, using the NHS reference costs for 2004. This analysis suggests that peri‐operative statin therapy for patients undergoing vascular surgery may present the most cost‐effective use of statin therapy yet described, with a number‐needed‐to‐treat of 15 and almost 60% of the total cost of atorvastatin therapy recovered through a reduction in peri‐operative adverse events.
Relationship between the inability to climb two flights of stairs and outcome after major non‐cardiac surgery: implications for the pre‐operative assessment of functional capacity
SummaryFunctional capacity is an integral component of the pre‐operative evaluation of the cardiac patient for non‐cardiac surgery. Stair climbing capacity has peri‐operative prognostic importance. It may predict survival after lung resection and complications after major non‐cardiac surgery. However, stair climbing cannot determine the aerobic metabolic capacity necessary to survive the peri‐operative stress response. The potential benefits and current limitations of cardiopulmonary exercise testing to determine peri‐operative aerobic capacity are discussed. Principles for the selection of an appropriate screening test of aerobic function are put forward.
Peri‐operative β‐blockade and haemodynamic optimisation in patients with coronary artery disease and decreasing exercise capacity presenting for major noncardiac surgery
SummaryPatients with coronary artery disease presenting for major noncardiac surgery may have indications for both peri‐operative β‐blockade and haemodynamic optimisation. The combination of peri‐operative cardiorespiratory failure and myocardial ischaemia has a grave prognosis. Recent investigations have shown that in patients with coronary artery disease, β‐blockade does not depress cardiac output as much as originally thought. There may, therefore, be a place for both peri‐operative β‐blockade and haemodynamic optimisation. The indications for peri‐operative β‐blockade and haemodynamic optimisation, the effect of acute β‐blockade on cardiac output in patients with coronary artery disease, and the interaction of peri‐operative β‐blockade and haemodynamic optimisation are discussed.
Phaeochromocytoma and Acute Myocardial Infarction
Phaeochromocytoma is uncommonly associated with myocardial infarction. We present a patient who, despite established alpha adrenoceptor blockade, sustained an acute myocardial infarction and was found to have coronary artery disease. Indications for coronary revascularization were not met, and adrenalectomy was successfully performed four weeks later. Factors contributing to the myocardial infarction, the role of beta adrenoceptor blockade, the timing of adrenalectomy and the place of coronary revascularization are discussed.