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.     

A peri-operative statin update for non-cardiac surgery. Part II: Statin therapy for vascular surgery and peri-operative statin trial design

This is the second of two review articles evaluating peri-operative statin therapy. In surgical patients, the utility of peri-operative statin therapy is strongly suggested by retrospective studies, although it is probably overestimated, as important confounding factors have not been controlled for and hence the literature is considered to be currently inconclusive. This review examines the potential mechanisms and indications for peri-operative statin protection, the efficacy of acute peri-operative beta-blockade in addition to statin therapy, the effect of peri-operative statin therapy withdrawal and the implications of comorbidities associated with peri-operative cardiovascular risk on statin therapy. Recommendations concerning appropriate dosing, duration, therapeutic targets and necessary investigations when prescribing peri-operative statins are made. Peri-operative study design recommendations are suggested, so that future meta-analyses may be more informative. Recommendations are made regarding retrospective reporting of statin studies to minimise the bias inherent in a number of the current retrospective studies on this subject.     

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

The 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.     

The pharmacoeconomics of peri-operative beta-blocker therapy

It 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 pounds sterling per patient. This results in a total cost of 1254.30 pounds sterling 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.     

Perioperative beta-blocker and statin therapy

PURPOSE OF REVIEW: Perioperative beta-blockade and statin therapy have been advocated to reduce cardiac risk of noncardiac surgery. This review evaluates recent articles published on the cardioprotective effects of perioperative therapy with these medications. RECENT FINDINGS: Initial studies evaluating beta-blocker therapy during the perioperative period suggested that beta-blockers may be beneficial in reducing cardiac deaths and myocardial infarctions. Later studies and recent meta-analyses, however, are less favorable and suggest that beta-blockers may be associated with increased incidence of bradycardia and hypotension. One randomized trial and several cohort studies have found a significant reduction in cardiovascular complications with perioperative statin therapy. Additionally, statin withdrawal is associated with increased postoperative cardiac risk. SUMMARY: Based upon the available evidence and guidelines, patients currently taking beta-blockers should continue these agents. Patients undergoing vascular surgery who are at high cardiac risk should also take beta-blockers. The question remains regarding the best protocol to initiate perioperative beta-blockade. Statins should be continued in patients already taking these agents prior to surgery. The optimal duration and time of initiation of statin therapy remains unclear.     

Cardiovascular protection by anti-inflammatory statin therapy

Statins are widely used in the prevention of atheromatous disease and its complications. While their lipid lowering effects are very important, there is increasing emphasis on the other effects of statins described as pleiotropic. These include atheromatous plaque stabilisation generally ascribed to their anti-inflammatory properties. It is increasingly clear that perioperative cardiac events relate to both haemodynamic perturbations (with imbalance between oxygen demand and oxygen supply to the myocardium), and rupture/disruption of atheromatous plaques. Thus, the effects of statins on perioperative cardiac outcome have been studied, mostly in observational studies. The majority of the studies have shown benefits of statin therapy. The reason for these reported benefits is the anti-inflammatory properties of statins in the face of the known release of such mediators during major surgery, leading to plaque disruption and major adverse cardiac events. To date there are too few randomised controlled studies to recommend the prophylactic administration of statins preoperatively, yet the cohort studies are suggestive of benefits.     

Monitoring of peri-operative fluid administration by individualized goal-directed therapy

Background:  In order to avoid peri-operative hypovolaemia or fluid overload, goal-directed therapy with individual maximization of flow-related haemodynamic parameters has been introduced. The objectives of this review are to update research in the area, evaluate the effects on outcome and assess the use of strategies, parameters and monitors for goal-directed therapy.
Methods:  A MEDLINE search (1966 to 2 October 2006) was performed to identify studies in which a goal-directed therapeutic strategy was used to maximize flow-related haemodynamic parameters in surgical patients, as well as studies referenced from these papers. Furthermore, methods applied in these studies and other monitors with a potential for goal-directed therapy are described.
Results:  Nine studies were identified pertaining to fluid optimization during the intra- and post-operative period with goal-directed therapy. Seven studies ( n = 725) found a reduced hospital stay. Post-operative nausea and vomiting (PONV) and ileus were reduced in three studies and complications were reduced in four studies. Of the monitors that may be applied for goal-directed therapy, only oesophageal Doppler has been tested adequately; however, several other options exist.
Conclusion:  Goal-directed therapy with the maximization of flow-related haemodynamic variables reduces hospital stay, PONV and complications, and facilitates faster gastrointestinal functional recovery. So far, oesophageal Doppler is recommended, but other monitors are available and call for evaluation.     

Coronary stents, dual antiplatelet therapy and peri-operative problems

Up to 90% of all percutaneous coronary interventions include coronary artery stenting. Dual antiplatelet therapy, usually involving acetylsalicyl acid combined with clopidogrel, is mandatory for patients with coronary artery stents. The duration of antiplatelet therapy for bare metal stents is 3-4 weeks, for drug eluting stents 6-12 months. Preoperative discontinuation of both drugs increases the risk of stent thrombosis, continuation the risk of relevant bleeding. According to the recommendations of anaesthesiological and cardiological societies, perioperative management has to balance the risk of bleeding vs stent thrombosis. Surgery involving a high risk of bleeding can require the discontinuance of both substances. In cases of high thrombosis risk, at least the acetylsalicyl acid should be continued until the day of surgery. For patients under antiplatelet therapy scheduled for local anaesthesia, national recommendations exist. A close collaboration between the anaesthesiologist, cardiologist and surgeon is essential for appropriate pre-, intra- and postoperative management.     

Meta-analysis of statin therapy in maintenance dialysis patients

Abstract

The effects of statin therapy in patients on maintenance dialysis remained uncertain. We conducted a meta-analysis to investigate the effects of statin on major clinical outcomes. We systematically searched Pubmed, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang and Chinese Technological Journal of Database for randomized controlled trials (RCTs). Criteria for inclusion were RCTs on statins therapy versus placebo, >3 months of follow-up. The outcomes were serum level of low density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglyceride (TG), high-sensitivity C-reactive protein (hs-CRP) and albumin (ALB), all cardiac events, cardiovascular deaths and all-cause mortality. Twenty-one trials were identified, providing data for 8186 patients on maintenance dialysis. Statin therapy reduced LDL-C (weighted mean difference [WMD]?=??0.74?mmol/L; 95%CI [?0.96,??0.52], p?<?0.00001), TG (WMD?=??0.36?mmol/L; 95%CI [?0.57,??0.14], p?=?0.001), and hs-CRP (WMD?=??3.98?mg/L; 95%CI [?5.24,??2.72], p?<?0.00001), elevated HDL-C (WMD?=?0.25?mmol/L; 95%CI [0.10,?0.39], p?=?0.0007) and ALB (WMD?=?1.70?g/L; 95%CI [0.19,?3.21], p?=?0.03) significantly comparing with placebo. Statin therapy also had benefit in reducing all cardiac events (relative risk [RR]?=?0.90; 95%CI [0.83,?0.97], p?=?0.006), but had no effect on cardiovascular deaths (RR?=?0.97; 95%CI [0.88,?1.07], p?=?0.54) or all-cause mortality (RR?=?0.98; 95%CI [0.93,?1.04], p?=?0.49). In conclusion, statins had no impact on all-cause or cardiovascular mortality, while there was an overall significant improvement for dyslipidemia, hs-CRP, hypoalbuminemia and cardiovascular events in dialysis patients.     

Management of vagus nerve stimulation therapy in the peri-operative period

Vagus nerve stimulation is a well-established treatment option for patients with drug-resistant epilepsy and has an expanding range of other clinical indications. Side effects of vagus nerve stimulation therapy include: cough; voice changes; vocal cord adduction; rarely, obstructive sleep apnoea; and arrhythmia. Patients with implanted vagus nerve stimulation devices may present for unrelated surgery and critical care to clinicians who are unfamiliar with their function and safe management. These guidelines have been formulated by multidisciplinary consensus based on case reports, case series and expert opinion to support clinicians in the management of patients with these devices. The aim is to provide specific guidance on the management of vagus nerve stimulation devices in the following scenarios: the peri-operative period; peripartum period; during critical illness; and in the MRI suite. Patients should be aware of the importance of carrying their personal vagus nerve stimulation device magnet with them at all times to facilitate urgent device deactivation if necessary. We advise that it is generally safer to formally deactivate vagus nerve stimulation devices before general and spinal anaesthesia. During periods of critical illness associated with haemodynamic instability, we also advise cessation of vagus nerve stimulation and early consultation with neurology services.     

The peri-operative management of atrial fibrillation

Atrial fibrillation is a common arrhythmia frequently seen in surgical patients. The onset of new atrial fibrillation during the peri-operative period is less common. There are many possible precipitating factors, although volatile agents themselves may have an antifibrillatory action. The management of atrial fibrillation includes removal of any precipitating factors and treatment of the arrhythmia itself. Immediate management of acute-onset atrial fibrillation is usually direct current cardioversion. Alternatively, anti-arrhythmic drugs can be used to achieve cardioversion. In patients with rapid, chronic atrial fibrillation or those refractory to cardioversion, priority is given to control of the ventricular rate. Thrombo-embolism is a significant risk if atrial fibrillation is paroxysmal or persists for more than 48 h.     

Exertion-induced rhabdomyolysis in a patient on statin therapy

Sir, We describe a patient on long-term statin treatment who developedacute renal failure (ARF) from rhabdomyolysis following severeunaccustomed exertion. Reviewing the available literature, wedid not find reports of exertion-induced rhabdomyolysis andARF requiring dialysis while on statins. A 57-year-old male, with hypertension and hyperlipidaemia (on     

Improved postoperative outcomes associated with preoperative statin therapy

Statin therapy is well established for prevention of cardiovascular disease. Statins may also reduce postoperative mortality and morbidity via a pleiotropic (non-lipid-lowering) effect. The authors conducted a meta-analysis to determine the influence of statin treatment on adverse postoperative outcomes in patients undergoing cardiac, vascular, or noncardiovascular surgery. Two independent authors abstracted data from 12 retrospective and 3 prospective trials (n = 223,010 patients). A meta-analysis was performed to evaluate the overall effect of preoperative statin therapy on postoperative outcomes. Preoperative statin therapy was associated with 38% and 59% reduction in the risk of mortality after cardiac (1.9% vs. 3.1%; P = 0.0001) and vascular (1.7% vs. 6.1%; P = 0.0001) surgery, respectively. When including noncardiac surgery, a 44% reduction in mortality (2.2% vs. 3.2%; P = 0.0001) was observed. Preoperative statin therapy may reduce postoperative mortality in patients undergoing surgical procedures. However, the statin associated effects on postoperative cardiovascular morbidity are too variable to draw any conclusion.     

The peri-operative implications of herbal medicines

An increasing number of patients are taking herbal medicines such as echinacea, garlic, ginkgo biloba, ginseng, St John's Wort, valerian, ephedra, kava, grapefruit juice and ginger. Although these herbal medications are considered 'natural' products that may have some benefits, adverse effects such as increased bleeding tendencies and drug interactions are associated with their use. Surgeons and anaesthetists may be unaware of their patients' use of these medications because it is common for patients not to disclose their use of this form of medication, and both surgeons and anaesthetists often fail to enquire about their use. Anaesthetists and surgeons must be familiar with the effects of herbal medicines and should specifically enquire about the use of herbal medicines during pre-operative assessment. Currently available data suggest that all herbal medicines should be ceased 2 weeks before surgery.     

Role of statin therapy in the coronary bypass patient

Statins have been proven to prevent or delay ischemic events in patients at risk for atherosclerotic coronary disease. Increasing evidence suggests that statin therapy is also beneficial to patients undergoing coronary revascularization. In this review statin therapy will be shown to improve vein graft patency, minimize recurrent ischemic events, and decrease the need for repeat revascularization procedures in patients who have undergone coronary artery bypass grafting.