Chlorhexidine compared with povidone-iodine solution for vascular catheter site care: a meta-analysis

Perspective: This analysis of the TARGET trial suggests a “class effect” for GP IIb/IIIa inhibitors at least in stable patients, and, given the known difference in cost between the 2 GP IIb/IIIa inhibitors evaluated, it has important economic implications. It is important to note that the long-term mortality rate in ACS patients was low. Although there were no significant differences in 6-month survival rates between the 2 treatment arms, some studies have shown that the negative relationship between peri-procedural MI and long-term survival becomes more pronounced beyond 6-month follow-up. It is hoped that clinical follow-up of patients enrolled in the TARGET trial will continue over the years. MM

answered by the CREDO trial. If we find that 12 months (or longer) of clopidogrel is better than the current standard of 4 weeks of therapy post stenting, the next logical question is whether the therapy is cost-effective beyond the first few post-procedure months as compared to other treatments in cardiology and medicine in general. DM

Impact of Clinical Syndrome Acuity on the Differential Response to 2 Glycoprotein IIb/IIIa Inhibitors in Patients Undergoing Coronary Stenting. The TARGET Trial Stone GW, Moliterno DJ, Bertrand M, et al. Circulation 2002;105: 2347–54.

Chlorhexidine Compared With Povidone-Iodine Solution for Vascular Catheter Site Care: A MetaAnalysis

Study Question: To determine whether the acuity of clinical coronary syndrome influences the response to different glycoprotein IIb/IIIa (GPIIb/IIIa) receptor inhibitors in patients undergoing stent implantation. Methods: The study population included 4809 patients undergoing planned coronary stenting who were randomized to receive abciximab or tirofibin. Patients were divided into two groups: the first group included 3025 patients with acute coronary syndromes (ACS group) and the second group included 1784 patients without acute coronary syndromes (non-ACS Group). The primary end point was a composite including death, myocardial infarction or urgent target vessel revascularization at 30-day follow-up. Secondary clinical end points included total mortality, myocardial infarction or any target vessel revascularization at 6 months. Results: ACS patients had significantly higher rates of the combined end point at 30 days and 6 months than nonACS. In patients with ACS, treatment with abciximab resulted in lower rates of myocardial infarction at 30 days (5.8% vs. 8.5%; p⫽0.004) and at 6 months (7.2% vs. 9.8%; p⫽0.013) and in a lower rate of the combined end point at 6 months (15.5% vs. 18%, p⫽0.056) while there were no significant differences in 6-month mortality rates (1.39% for both abciximab and tirofiban). In the non ACS group, there was a trend toward a lower incidence of the combined end point at 6 months in patients treated with tirofibin when compared with patients treated with abciximab (10.3% vs. 13.4%; p⫽0.056). No differences in mortality rates were observed in this group (0.69% vs. 0.57%). There were no significant differences in the incidence of major bleeding, or the need for blood product transfusions. The incidence of thrombocytopenia and minor bleeding was significantly higher in the abciximab group when compared with the tirofiban group. Conclusions: In patients with ACS undergoing stent implantation, abciximab use as compared to tirofiban use results in a lower incidence of peri-procedural myocardial infarction but not in a survival benefit. In non-ACS patients, tirofiban’s effect on long-term outcomes is similar to the effect of abciximab, but with fewer minor bleeding and hematologic complications.

Chaiyakunapruk N, Veenstra DL, Lipsky BA, Saint S. Ann Intern Med 2002;136:792– 801. Study Question: Randomized controlled clinical trials have compared chlorhexidine gluconate with povidone-iodine solution in preventing central venous or arterial catheter– related blood stream infection, but none of these studies was individually powered to assess comparative efficacy. The objective of this study was to aggregate all randomized clinical trial results to assess the comparative efficacy chlorhexidine gluconate vs. povidone-iodine solution. Methods: Data from 8 studies involving a total of 4143 catheters were pooled, and a formal meta-analysis was performed. The primary end point was catheter-related blood stream infection defined as isolation of the same organism from a peripheral blood culture and a semiquantitative culture of a catheter segment. The secondary end point was catheter colonization defined as significant growth of a microorganism from a catheter segment by quantitative or semi-quantitative culture techniques. Results: Analysis of data from 4143 procedures revealed a significant reduction in the incidence of catheter-related bloodstream infection with chlorhexidine when compared with povidone-iodine solution. (Risk ratio 0.49, 95% CI 0.28 – 0.88). The risk ratio for catheter colonization in the chlorhexidine gluconate group when compared with the povidone-iodine group was also 0.49 (95% CI 0.31– 0.71). The overall risk reduction was 7.1% for catheter colonization and 1.1% for catheter related bloodstream infection respectively. Conclusions: Pooled analysis of randomized clinical trials suggests that skin disinfection with chlorhexidine gluconate is superior to skin disinfection with povidone-iodine in preventing catheter related bloodstream infections. Perspective: This study is a good example of how metaanalysis can help in answering questions that were not answered directly by clinical trials because of inadequate sample size. Although vascular access site infections follow-

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ing diagnostic cardiac catheterization or percutaneous coronary interventions are rare, the recent introduction of vascular closure devices has been associated with an increase in their occurrence. Based on these results, perhaps strong consideration should be given to local disinfection with chlorhexidine when the use of a vascular closure device is planned. MM

lipid lowering therapy in patients with coronary artery disease. MM

Influenza Vaccine Pilot Study in Acute Coronary Syndromes and Planned Percutaneous Coronary Interventions. The FLU Vaccination Acute Coronary Syndromes (FLUVACS) Study

Fluvastatin for Prevention of Cardiac Events Following Successful First Percutaneous Coronary Intervention. A Randomized Controlled Clinical Trial

Gurfinkel EP, de la Fuente RL, Mendiz O, Mautner B. Circulation 2002;105:2143–7. Study Question: Prior studies have suggested a relationship between viral infections and both myocardial infarction and major adverse cardiovascular events following percutaneous coronary intervention. (PCI) The objective of this study was to evaluate the effects of influenza vaccination in patients with coronary artery disease in a single blind randomized clinical trial. Methods: Patients presenting with acute ST segment elevation myocardial infarction (MI) or non–ST-segment elevation MI (n⫽204) and patients undergoing planned PCI with stenting (n⫽101) were randomly allocated to either vaccine therapy (a single unique intra muscular vaccination containing 0.5 mm of A/Moscow/10/99 like virus, A/New Caledonia/20/99 (H1N1)-like virus and AB/Sichuan/379/ 99-like virus (151 patients) or to a control group (150 patients). The primary end point was cardiovascular death at 6-month follow-up. The secondary end points was a composite of major adverse cardiac events including death, non-fatal MI or severe recurrent ischemia at 6-month follow-up. Results: The long-term mortality rate was significantly lower in the vaccine group when compared with the control group (2% vs. 8%, relative risk 0.25; 95% CI 0.07 to 0.86; p⫽0.01). A subset analysis in the group of patients with MI revealed a significant reduction in mortality in the vaccine group when compared with the control group (2% vs. 8%, relative risk 0.25, 95% CI 0.05–1.15, p⫽0.05), and a significant reduction in the incidence of the combined end point (10% vs. 24%, relative risk 0.42, 95% CI 0.21– 0.83, p⫽0.008). A non-significant trend toward a reduction in the incidence of both end points was observed in the group of patients undergoing planned PCI. Conclusion: Influenza vaccination may reduce the risk of death and major adverse cardiac events in patients with acute myocardial infarction and in patients undergoing planned PCI. Perspective: The results of this study are provocative but the sample size was quite small. A larger study is needed to confirm these findings. It remains to be determined whether the observed reduction in mortality and major cardiac events was due to prevention of influenza infection or to an effect on potential events linking viral infections and atherosclerosis. MM

Serruys PWJC, de Feyter P, Macaya C, et al., for the Lescol Intervention Prevention Study (LIPPS) Investigators. JAMA 2002; 287:3215–22 Study Question: Does lipid lowering with Fluvastatin following successful completion of first percutaneous coronary intervention (PCI) reduce major adverse cardiac events? Methods: Patients undergoing their first PCI (ⱖ1 lesions) in native coronary arteries, and with cholesterol level between 135 mg/dL and 270 mg/dL were randomized at hospital discharge to receive fluvastatin 80 mg/d (n⫽844) or matching placebo (n⫽833) for 3 to 4 years. The primary end point was a major adverse cardiac event (MACE) composite including death, non-fatal myocardial infarction (MI) and stroke. Results: Baseline clinical characteristics were similar between the two groups, except for a higher frequency of diabetes mellitus in the fluvastatin group (14.2% vs. 9.8%, p⬍0.05). The median LDL-C cholesterol level was 132 mg/dL, while the median cholesterol level was 200 mg/dL. At a median follow-up time of 3.9 years, the incidence of the combined end point was significantly lower in the fluvastatin group when compared with the placebo group (21.4% vs. 26.7%, p⫽0.0063). The rates of secondary end points were 4.3% vs. 5.9% for all-cause death (p⫽0.65), 1.5% vs. 2.9 for cardiac death (p⫽0.06), 2.7% vs. 3.0% for non-cardiac death, 5.0% vs. 7.2% for cardiac death or MI (p⫽0.05) and 7.7% vs. 10.1% for all-cause death or MI (p⫽0.07) in the fluvastatin and placebo groups, respectively. The effect of fluvastatin in reducing MACE was independent of gender and of baseline total cholesterol and of LDL-C cholesterol levels. Subset analysis revealed a significant reduction in the risk of MACE with fluvastatin in patients with diabetes mellitus (RR 0.53, 95% C.I. 0.29 – 0.97; p⫽0.04) and in patients with multivessel disease (RR 0.66, 95% C.I. 0.48 – 0.91; p⫽0.01). Conclusion: When compared with placebo, long-term therapy with fluvastatin in patients undergoing their first PCI results in a significant reduction in major adverse cardiac events. Perspective: Although the results are not surprising, the value of this study is in confirming the importance of combining mechanical therapy (i.e., PCI) with aggressive

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