1. Andrew Gilbert Quality Use of Medicines and Pharmacy Research Centre Sansom Institute University of South Australia Effectiveness of collaborative medicine reviews in reducing hospitalisations for heart failure patients in the ambulatory setting: Results of a cohort study.

2. Disclosure The research to prepare this paper was conducted under a Contract Research Grant between the University of South Australia and the Australian Government’s Department of Veterans’ Affairs (DVA) to deliver the Veterans’ Medicines Advice and Therapeutics Education Services (Veterans’ MATES). DVA provides the Veterans’ MATES project team at the University of South Australia with identified PBS/RPBS and Medicare data on all Australia veterans and war widows/widowers. The Veterans’ MATES project team undertook all study design, data analysis and interpretation and writing of this paper. Elizabeth Roughead, John Barratt, Emmae Ramsay, Nicole Pratt, Phil Ryan and Andrew Gilbert all declare that they no have competing interest. Robert Peck and Graeme Killer are employees of the Department of Veterans’ Affairs, the funder of the research.

3. Introduction The Department of Veterans' Affairs (DVA), operates a national program: Veterans’ MATES. We use DVA’s database, covering 300,000 veterans, to provide –patient-specific-prescriber-feedback, –therapeutic updates and –Medicines and health care information for veterans to assist veterans and their health practitioners improve health outcomes. Over 12000 veterans are being treated for heart failure.

4. Background Medicines play a significant role in the management of heart failure 1. 44% of patients with heart failure will be re- hospitalised within six months of discharge 1. Home Medicines Reviews are effective in preventing and resolving medication-related problems 2. Some systematic reviews indicate limited effects of pharmacist-led medicines reviews on patient outcomes, such as reduction in hospitalisations 3. 1. National Heart Foundation of Australia and the Cardiac Society of Australia and New Zealand. Guidelines on the contemporary management of the patient with chronic heart failure in Australia. Sydney: Cardiac Society of Australia and New Zealand, 2002. 2. Gilbert AL, Roughead EE, Beilby J, Mott K, Barratt JD. Collaborative medication management services: improving patient care. Med J Aust 2002;177(4):189-92. 3. Holland R, Desborough J, Goodyer L, Hall S, Wright D, Loke YK. Does pharmacist-led medication review help to reduce hospital admissions and deaths in older people? A systematic review and meta-analysis. Br J Clin Pharmacol 2008;65(3):303-16..

5. Randomised controlled trials however demonstrate that the effectiveness of medicines reviews in influencing health outcomes appears to depend on the type of review and disease characteristics 3,4 Australia has funded a collaborative Home Medicines Review services since 2001. We aimed to determine if the results from randomised controlled trials for the heart failure population translated into practice as it is currently funded in Australia. 3. Koshman SL, Charrois TL, Simpson SH, McAlister FA, Tsuyuki RT. Pharmacist care of patients with heart failure: a systematic review of randomized trials. Arch Intern Med 2008;168(7):687-94. 4. Holland R, Brooksby I, Lenaghan E, Ashton K, Hay L, Smith R, et al. Effectiveness of visits from community pharmacists for patients with heart failure: HeartMed randomised controlled trial. BMJ 2007;334(7603):1098.

6. Objective To determine the impact of general medical practitioner & pharmacist collaborative Home Medicines Review (HMR) 5 on time to hospitalisation for heart failure in the population with heart failure 5. Medicare Australia. Home Medicines Review. Canberra: Australian Government, 2009.

7. Method Design: Retrospective cohort study using administrative claims data. Cox proportional hazards models were used to compare time to next hospitalisation for heart failure between the HMR exposed and unexposed groups. Setting: The ambulatory veteran and war widow population, Australia Time period 1 Jan 2004 until 1 July 2006 Participants: Veterans >65 years receiving beta-blockers subsidised for heart failure Exposure: General medical practitioner and pharmacist collaborative HMR

8. Method; continued Exposed group: Veterans who; had received a home medicines review, had all health services fully subsidized by DVA, had been dispensed a beta-blocker subsidized for heart failure* in the six months prior to the home medicines review, were aged 65 years or over at the time of the review. Unexposed group: Veterans who; had all health services fully subsidized by DVA, had been dispensed a beta-blocker subsidized for heart failure, were aged 65 years and over, but had not had a home medicines review. Exclusions: Veterans resident in aged-care facilities Main outcome measure: Time to next hospitalisation for heart failure *bisoprolol, carvedilol or metoprolol succinate

9. Method; continued Eligibility for the unexposed group was determined each month. These veterans were randomly allocated to an index month to match the time of a HMR in the exposed group. (20 to 1) Subjects were followed up until time to first hospitalization for heart failure post the index month for the unexposed group or post the home medicines review in the exposed group.

10. Results There were 273 veterans exposed to a home medicines review and 5444 unexposed patients.

11. Demographics of study participants Exposed N=273 Unexposed N=5444 p-value Male gender70% male74% male0.11 Age81.6 years (SD 4.8) 0.87 Number of co-morbidities7.6 (SD 2.2)6.7 (SD 2.4)<0.0001 Number of prescriptions in year prior95 (69-123)76 (54-104)<0.0001 Number of changes in medicines over 6 month period in year prior 3 (2-6)3 (1-5)<0.0001 Number of prescribers5 (3-6)4 (3-6)0.002 Number of pharmacies2 (1-3) 0.43 Number of occupational therapy visits0 (0-0) 0.16 Number of speech therapy visits0 (0-0) 0.4 Previously targeted by Veterans’ MATES7%6%0.47 Socio-economic index of disadvantage Lowest disadvantage Med/low disadvantage Med/high disadvantage Highest disadvantage 31% 25% 24% 20% 25% 0.01 Prior hospitalisations 0 1 2 >2 27% 23% 22% 28% 34% 23% 17% 25% 0.03 Region Remote Outer regional Inner regional Major city 0% 12% 29% 59% 1% 9% 31% 59% 0.86

12. Parameter Para- meter Estimate Standard Error Chi- SquareP value Hazard Ratio* 95% Hazard Ratio Confidence Limits Unadjusted: exposed to home medicines review -0.470.187.00350.0080.630.440.89 Adjusted: exposed to home medicines review -0.610.1811.960.00050.540.380.77 Cox proportional hazards model results for time to hospitalisation for heart failure *adjusted for age, gender, co-morbidity, socioeconomic index of disadvantage, season, and region of residence as well as the number of prescriptions, prescribers, pharmacies, changes in medications, hospitalizations, occupational therapy visits and speech therapy visits.

13. Results Unadjusted results: HMR group; 37% reduction in likelihood of hospitalisation for heart failure at any time (HR 0.63; 95%CI 0.44-0.89). Adjusted results: HMR group; 46% reduction in the likelihood of hospitalisation for heart failure at any time (HR, 0.54 95% CI, 0.38- 0.77).

14. Did home medicines review have an impact?

15. Increased time to next hospitalisation for HF patients who received an HMR The effect is clinically significant For the 5 th percentile of the population, this delay in time to hospitalisation equated to over 200 days (~7 months). 5.5% of the exposed group compared to 12% of the unexposed group were hospitalised for HF within 365 days.

16. Study limitations Only 5% of veterans with heart failure have received a HMR, despite all veterans in this treatment population being eligible for the service. The focus of this study on veterans. However veterans are treated in the same way as non-veteran patients in both the primary and tertiary care sectors. receive the same health services, and they are delivered by the same practitioners, as those visited by non-veterans. have slightly more general practice visits (rate ratio 1.17; p < 0.05) and hospitalisations (rate ratio 1.21; p < 0.05) per year than other Australians aged 40 years and over. Receive similar numbers of prescription per general practitioner visit as the Australian population; however, because of the higher rate of GP visits, veterans receive slightly more prescriptions annually than other Australians (rate ratio 1.13; p < 0.05).

17. Conclusion Outcomes from randomised controlled trials of the effectiveness of collaborative medication reviews in the heart failure population can be translated into practice. The effect is clinically significant with a delay in time to hospitalisation of over 200 days for some patients. The results are consistent with findings that medication-related problems are contributors to admissions for heart failure. With hospitalisations in Australia for heart failure estimated to cost $140 million per annum these delays to next hospitalisation will contribute to significant cost savings to the health system.

18. Authors and affiliations Authors: Andrew L Gilbert, PhD 1, Elizabeth E Roughead, PhD 1, John D Barratt, B. Pharm. Grad Dip C 1, Emmae Ramsey, B. App Sc; Grad Dip 2, Nicole Pratt, BSc (hons) 2, Phillip Ryan, MBBS 2, Robert Peck, B. Pharm 3 and Graeme Killer, MBBS 3. Affiliations 1.Sansom Institute, University of South Australia, Adelaide, South Australia, Australia, 5000; 2.Data Management & Analysis Centre, Adelaide University, Adelaide, South Australia, Australia, 5000 and 3.Department of Veterans' Affairs, Australian Government, Canberra, Australian Capital Territory, Australia, 2600.