Integrating cost-effectiveness evidence into clincal practice guidelines in Australia for acute myocardial infarction

 A teaching hospital is working with the Victorian State Government and universities, integrating cost-effectiveness evidence into clinical practice guidelines (CPGs), protocols and pathways for respiratory and cardiology interventions. Acute myocardial infarction (AMI) findings are reported. Results will stimulate cost-effective practice and inform medical associations, federal and state governments and international organisations developing CPGs. Published CPGs by the American College of Cardiology/American Heart Foundation for AMI in 1999 are reviewed by a large interdis- ciplinary hospital-based committee given cost-effectiveness evidence. Levels of evi- dence criteria rating on methodological rigor for effectiveness and costs are applied. National Health and Medical Research Council (NHMRC) grades of recommendation criteria for combinations of relative effectiveness versus relative costs and cut-off points are used. Extrapolating results between countries was addressed by applying the OECD's health purchasing power parity series. Recommendations for revisions to United States guidelines and for local application are formulated. United States Guide- lines require updating: Regarding angioplasty, percutaneous transluminal coronary angioplasty (PTCA) is cost-effective for men aged 60 years relative to recombinant tissue plasminogen activator (tPA),with additional cost per life year saved of 274 ecu. PTCA with discharge after 3 days is cost-effective in low-risk AMI. Regarding GP llb/Illa drugs, Abciximab during intervention incurred equal mean hospital costs for placebabciximab bolus, and abciximab bolus+ infusion with incremental 6-month cost for the latter treatment costing US$ 293 per patient. Agent recouped almost all initial therapy costs with significant benefits. Incre- mental cost of abciximab per event prevent- ed is US$ 3,258.Tirofiban was compared to placebo after high-risk angioplasty for AMI or unstable angina.Tirofiban decreased the rate of hospital deaths, myocardial infarc- tion, revascularisation at 2 days by 36% relative to placebo (8% vs. 12%) without increased cost. Clinical benefits were similar at 30 days.Tirofiban+heparin+aspirin was compared to heparin+aspirin.Tirofiban arm resulted in net savings of 33,418 ecu per 100 patients for the first 7 days of treatment. Regarding thrombolytics,tPA is more cost- effective than streptokinase. Incremental costs for each life saved when streptokinase is substituted by recombinant tissue plasmi- nogen are 31%,45%, 97% higher in Germa- ny, Italy and the United States than in the United Kingdom. Regarding anticoagulants, enoxaparin is a promising alternative to unfractionated heparin for hospitalised patients with non-Q-wave myocardiai infarc- tion or unstable angina, saving C$ 1,485 per patient over 12 months with 10% reduction in 1 year risk of death, myocardial infarction or recurrent angina. Regarding anti- arrhymics, the cost-effectiveness of no amiodarone, amiodarone for patients with depressed heart rate variability (DHRV),and amiodarone for patients with DHRV plus positive programmed ventricular stimula- tion (PPVS) for high-risk post-AMI was investigated. Amiodarone for DHRV+PPVS patients was dominated by a blend of the two alternatives. Compared to no amioda- rone, the incremental cost-effectiveness of amiodarone for DHRV patients was US$ 39,422 per quality adjusted life year gained. Amiodarone for DHRV is the most appropriate. Other CPG updates concern serum markers, for example, cardiac troponin I assay (c-Tnl), cost advantages of ad hoc angioplasty and secondary prevention through antioxidants and pravastatin. Australian costs are reported later in the paper.

Modulating the interaction of CXCR4 and CXCL12 by low-molecular-weight heparin inhibits hepatic metastasis of colon cancer

Liver metastasis is the major obstacle for prolonging the survival of colon cancer patients. Low-molecular-weight heparin (LMWH), a common drug for venous thromboembolism, has displayed beneficial effects in improving the survival of cancer patients, though the mechanism remains unclear. This study aimed to investigate the effects of LMWH on hepatic metastasis of colon cancer and its underlying molecular mechanism by targeting the interaction of the chemokine receptor CXCR4 and its ligand CXCL12 (formerly known as stromal cell-derived factor 1α, SDF-1α), as the CXCR4-CXCL12 axis has been shown to regulate the interaction of cancer cells and stroma. Experimental results revealed that LMWH (Enoxaparin, 3500-5500 Da) inhibited the CXCL12-stimulated proliferation, adhesion and colony formation of human colon cancer HCT-116 cells that highly expressed CXCR4. Interestingly, LMWH or an anti-CXCR4 blocking antibody diminished the migrating and invading abilities of HCT116 cells stimulated by the recombinant CXCL12 protein or liver homogenates which contained endogenous CXCL12 protein. Although LMWH did not significantly inhibit the growth of subcutaneous colon tumors, it significantly suppressed the formation of hepatic metastasis established by intrasplenic injection of colon cancer cells in nude Balb/c mice and also downregulated the expression of CXCL12 in hepatic sinusoidal endothelial cells. The results suggest that LMWH inhibits the formation of hepatic metastasis of colon cancer by disrupting the interaction of CXCR4 and CXCL12, supporting that perioperative administration of LMWH may help to prevent the seeding and subsequent growth of hepatic metastases of colon cancer cells.

Modification of the National Inpatient Medication Chart improves venous thromboembolism prophylaxis rates in high-risk medical patients

Background : Venous thromboembolism (VTE) is a significant contributor to morbidity and mortality in Australia. While there is well-established evidence for the use of VTE prophylaxis in hospital inpatients, adherence to such guidelines is poor. Aim : The aim of the present study is to assess the impact of education and system change on improving rates of VTE prophylaxis in hospital inpatients. Methods : We performed four consecutive audits of inpatient medical records of a regional hospital service over 2 years. The audits aimed to test the impact of serial interventions at increasing the appropriate use of VTE prophylaxis (based on risk assessment). The interventions were (i) staff education and (ii) a process change that mandated a prophylaxis decision by modifying the National Inpatient Medication Chart with ‘VTE avoidance’ preprinted in the first medication box. Results : Our results from the baseline study showed that of the 236 medical inpatients reviewed, 80% were at high risk of VTE. Of this high-risk cohort, 34.9% (confidence interval (CI) 28–42%) had appropriate prophylaxis decisions. Post the education intervention, 43.2% (CI 37–49%) of the high-risk cohort received appropriate VTE prophylaxis, an improvement of 8.3% (CI −1% to 18%) from baseline. With the subsequent introduction of a process change, 82.1% (CI 66–92%) of the high-risk cohort received appropriate prophylaxis, an improvement of 47.2% and 38.8% (CI 24–54%) when compared with baseline and education respectively. Retention rates at 11 months postsystem change were 73% (CI 55–86%). Conclusions : This study therefore concluded that while education has an impact on rates of appropriate VTE prophylaxis, it is system change that has the most marked and sustained effect.