Blocking complement to reduce perioperative risk
To investigate whether inhibiting the pro-inflammatory effects of cytokines might decrease the risk of postoperative events, Verrier et al looked at the effect of a single dose of pexelizumab (a C5 complement inhibitor) on the rates of death or myocardial infarction (MI) 30 days after surgery. In those who had coronary artery bypass graft (CABG) surgery only (2732 patients), no significant difference was found in the rate of events in those receiving pexelizumab (9.8%) versus those receiving placebo (11.8%). However, in the larger population of those who received CABG and artificial valves (3099 patients), 11.5% of those receiving the drug versus 14% of those receiving placebo died or experienced MI (p = 0.03). This effect persisted through to day 180 of follow up. The authors propose that the reduction in events may be mediated by an amelioration of ischaemia–reperfusion injury induced inflammation via terminal complement inhibition.
Verrier ED, Shernan SK, Taylor KM, Van de Werf F, Newman MF, Chen JC et al. Terminal complement blockade with pexelizumab during coronary artery bypass graft surgery requiring cardiopulmonary bypass. JAMA 2004;291:2319–27. [PubMed]
Statins reduce perioperative risk in non-cardiac surgery
Approximately one million of non-cardiac operations in the USA each year are complicated by a perioperative cardiovascular event. In light of the known effects of statins on plaque stabilisation and endothelial function, this study set out to examine retrospectively the relation between statin use and postoperative mortality in non-cardiac surgery. In the 780 591 patients studied, treatment with lipid lowering agents from at least two days before surgery was associated with a lower crude in-hospital mortality (2.13% v 3.05%, p < 0.001). This relation also held true when patients were stratified according to their other risk factors for perioperative cardiac events. However, the authors acknowledge that the length of preoperative statin treatment needed to establish this advantage was not elaborated by their study.
Lindenauer PK, Pekow P, Wang K, Gutierrez B, Benjamin EM. Lipid-lowering therapy and in-hospital mortality following major noncardiac surgery. JAMA 2002;291:2092–9.
Clopidogrel is cost effective in PVD and stroke
Based on the lifetime treatment of a 63 year old patient facing event probabilities derived from the CAPRIE (clopidogrel versus aspirin in patients at risk of ischemic events) trial as the base case, cost effectiveness of aspirin versus clopidogrel in peripheral vascular disease (PVD), stroke, and ischaemic heart disease were calculated. Outcome measures included costs, life expectancy in quality adjusted life-years (QALYs), incremental cost effectiveness ratios, and events averted. In patients with peripheral arterial disease, clopidogrel increased life expectancy by 0.55 QALYs at an incremental cost effectiveness ratio of $25 100 per QALY, as compared with aspirin. In post-stroke patients, clopidogrel increased life expectancy by 0.17 QALYs at a cost of $31 200 per QALY. Aspirin was both less expensive and more effective than clopidogrel in post-myocardial infarction patients. In probabilistic sensitivity analyses, the evaluation for patients with peripheral vascular disease was robust. The study is limited by being a retrospective analysis of costs.
Schleinitz MD, Weiss JP, Owens DK. Clopidogrel versus aspirin for secondary prophylaxis of vascular events: a cost-effectiveness analysis. Am J Med 2004;116:797–806. [PubMed]
Early statin treatment for ACS
A total of 19 537 patients with an acute coronary syndrome (ACS) were enrolled from April 1999 to September 2002. Statin use before and after presentation with ACS was associated with the composite end point including death, in-hospital MI, and stroke. Patients who were already taking statins when they presented to the hospital were less likely to have ST segment elevation (odds ratio (OR) 0.79, 95% confidence interval (CI) 0.71 to 0.88) or MI (OR 0.78, 95% CI 0.70 to 0.86). Patients who continued to take statins in the hospital were less likely to experience complications or die than patients who never received statins (OR 0.66, 95% CI 0.56 to 0.77). Patients not previously taking statins who began statin treatment in the hospital were less likely to die than patients who never received statin treatment (OR 0.38, 95% CI 0.30 to 0.48). However, adjustment for the hospital of admission attenuated the association between initiation of statin treatment and the composite end point (OR 0.84, 95% CI 0.65 to 1.10). These data support the hypothesis that statin treatment can modulate early pathophysiologic processes in patients with ACS. A randomised trial of statin treatment in acute MI is warranted.
Spencer FA, Allegrone J, Goldberg RJ, Gore JM, Fox KAA, Granger CB, Mehta RH, Brieger D, the GRACE Investigators. Association of statin therapy with outcomes of acute coronary syndromes: the GRACE study. Ann Intern Med 2004;140:857–66. [PubMed]