Matire Harwood

Effect of fixed dose combination treatment on adherence and risk factor control among patients at high risk of cardiovascular disease: randomised controlled trial in primary care

Objective To evaluate whether provision of fixed dose combination treatment improves adherence and risk factor control compared with usual care of patients at high risk of cardiovascular disease in primary care. Design Open label randomised control trial: IMPACT (IMProving Adherence using Combination Therapy). Setting 54 general practices in the Auckland and Waikato regions of New Zealand, July 2010 to August 2013. Participants 513 adults (including 257 indigenous Māori) at high risk of cardiovascular disease (established cardiovascular disease or five year risk ≥15%) who were recommended for treatment with antiplatelet, statin, and two or more blood pressure lowering drugs. 497 (97%) completed 12 months’ follow-up. Interventions Participants were randomised to continued usual care or to fixed dose combination treatment (with two versions available: aspirin 75 mg, simvastatin 40 mg, and lisinopril 10 mg with either atenolol 50 mg or hydrochlorothiazide 12.5 mg). All drugs in both treatment arms were prescribed by their usual general practitioners and dispensed by local community pharmacists. Main outcome measures Primary outcomes were self reported adherence to recommended drugs (antiplatelet, statin, and two or more blood pressure lowering agents) and mean change in blood pressure and low density lipoprotein cholesterol at 12 months. Results Adherence to all four recommended drugs was greater among fixed dose combination than usual care participants at 12 months (81% v 46%; relative risk 1.75, 95% confidence interval 1.52 to 2.03, P<0.001; number needed to treat 2.9, 95% confidence interval 2.3 to 3.7). Adherence for each drug type at 12 months was high in both groups but especially in the fixed dose combination group: for antiplatelet treatment it was 93% fixed dose combination v 83% usual care (P<0.001), for statin 94% v 89% (P=0.06), for combination blood pressure lowering 89% v 59% (P<0.001), and for any blood pressure lowering 96% v 91% (P=0.02). Self reported adherence was highly concordant with dispensing data (dispensing of all four recommended drugs 79% fixed dose combination v 47% usual care, relative risk 1.67, 95% confidence interval 1.44 to 1.93, P<0.001). There was no statistically significant improvement in risk factor control between the fixed dose combination and usual care groups over 12 months: the difference in systolic blood pressure was −2.2 mm Hg (−4.5 v −2.3, 95% confidence interval −5.6 to 1.2, P=0.21), in diastolic blood pressure −1.2 mm Hg (−2.1 v −0.9, −3.2 to 0.8, P=0.22) and in low density lipoprotein cholesterol −0.05 mmol/L (−0.20 v −0.15, −0.17 to 0.08, P=0.46). The number of participants with cardiovascular events or serious adverse events was similar in both treatment groups (fixed dose combination 16 v usual care 18 (P=0.73), 99 v 93 (P=0.56), respectively). Fixed dose combination treatment was discontinued in 94 participants (37%). The most commonly reported reason for discontinuation was a side effect (54/75, 72%). Overall, 89% (227/256) of fixed dose combination participants’ general practitioners completed a post-trial survey, and the fixed dose combination strategy was rated as satisfactory or very satisfactory for starting treatment (206/227, 91%), blood pressure control (180/220, 82%), cholesterol control (170/218, 78%), tolerability (181/223, 81%), and prescribing according to local guidelines (185/219, 84%). When participants were asked at 12 months how easy they found taking their prescribed drugs, most responded very easy or easy (224/246, 91% fixed dose combination v 212/246, 86% usual care, P=0.09). At 12 months the change in other lipid fractions, difference in EuroQol-5D, and difference in barriers to adherence did not differ significantly between the treatment groups. Conclusions Among this well treated primary care population, fixed dose combination treatment improved adherence to the combination of all recommended drugs but improvements in clinical risk factors were small and did not reach statistical significance. Acceptability was high for both general practitioners and patients, although the discontinuation rate was high. Trial registration Australian New Zealand Clinical Trial Registry ACTRN12606000067572.

Risk of mortality associated with formoterol: a systematic review and meta-analysis

There is concern long-acting β-agonist (LABA) drugs may increase the risk of asthma mortality. We undertook a systematic review which included the AstraZeneca Formoterol Clinical Trial Safety Database and Novartis Food and Drug Aministration Formoterol Briefing Document. Randomised controlled clinical trials of duration ≥4 weeks that compared formoterol with a non-LABA comparator treatment in asthma were included in a meta-analysis of the risk of all-cause mortality and asthma death. Simple contingency tables, Petos one-step method and a Bayesian analysis were used. There were 42 deaths (nine from asthma) recorded in 62 studies with 49,327 subjects. The simple contingency table odds ratio for risk of all-cause mortality with formoterol was 1.1 (95% CI 0.6–2.2) and for asthma death was 2.7 (95% CI 0.5–26.7). Analyses by the other methods using both “as randomised” and “as exposed” classifications of treatment gave similar risk estimates with wide confidence and credible intervals. We conclude that there was insufficient power to determine whether formoterol increases the risk of mortality. However, the point estimates of a 2.0- to 3.2-fold increased risk of asthma death are not reassuring and add weight to evidence that LABA use in certain circumstances may increase the risk of asthma mortality.

Cohort Profile: The PREDICT Cardiovascular Disease Cohort in New Zealand Primary Care (PREDICT-CVD 19)

Cohort Profile: The PREDICT Cardiovascular Disease Cohort in New Zealand Primary Care (PREDICT-CVD 19) Sue Wells,* Tania Riddell, Andrew Kerr, Romana Pylypchuk, Carol Chelimo, Roger Marshall, Daniel J. Exeter, Suneela Mehta, Jeff Harrison, Cam Kyle, Corina Grey, Patricia Metcalf, Jim Warren, Tim Kenealy, Paul L. Drury, Matire Harwood, Dale Bramley, Geeta Gala and Rod Jackson School of Population Health, University of Auckland, Auckland, New Zealand, Middlemore Hospital, Cardiology Department, Auckland, New Zealand, School of Pharmacy, University of Auckland, Auckland, New Zealand, Endocrinology Services, Auckland District Health Board, Auckland, New Zealand, Computer Sciences, University of Auckland, School of Medicine, University of Auckland, Auckland, New Zealand, Waitemata District Health Board, Auckland, New Zealand and Northern Regional Alliance, Auckland, New Zealand

Access and Society as Determinants of Ischaemic Heart Disease in Indigenous Populations

BACKGROUND Ischaemic Heart Disease (IHD) is a leading cause of death in New Zealand and the burden falls disproportionately on Māori, the indigenous population of Aotearoa New Zealand. METHODS Data for Māori:non-Māori disparities in risk factors, hospitalisation, procedure receipt and mortality for IHD are analysed. Age-adjusted rates of IHD mortality (2000-2004) and publicly funded hospitalisations and procedures (2003-2005) for Māori and non-Māori are reported and compared. RESULTS Significant inequalities between Māori and non-Māori in IHD risk factors, hospitalisations, mortality and the receipt of related procedures exist. IHD hospitalisation rates for Māori are 1.4 times that of non-Māori, however mortality rates are more than twice that of non-Māori. In recent years Māori revascularisation rates have increased (as have non-Māori rates) but are still considerably less than might be expected given the much higher mortality rates. CONCLUSION Despite high need, Māori receive relatively low access to appropriate care for IHD. The role of society, policy, and the clinician are three key factors to be considered in reducing inequalities for IHD between Māori and non-Māori.

Rehabilitation and indigenous peoples: the Māori experience

Indigenous peoples often have the worst health status in comparison to non-indigenous people in their own nations; urgent action to address the health inequities for indigenous people is required. The role of rehabilitation in addressing health and disability inequities is particularly important due to the health need of indigenous peoples; the unequal distribution of health determinants; and disparities in access to, quality of care through and outcomes following rehabilitation. This article will present a perspective for Māori, the indigenous peoples of New Zealand, on a framework for improving rehabilitation services for Māori and ultimately their health and wellbeing.

Combination budesonide/formoterol inhaler as maintenance and reliever therapy in Māori with asthma

There are significant health disparities between Māori and non‐Māori with asthma, a pattern seen between other ethnic populations. This study investigates outcomes for Māori in a randomized controlled trial (RCT) of combination budesonide/formoterol inhaler therapy in asthma.

Cardiovascular disease medication health literacy among Indigenous peoples: design and protocol of an intervention trial in Indigenous primary care services

BackgroundCardiovascular diseases (CVD) are leading causes of mortality and morbidity among Indigenous people in New Zealand, Australia and Canada and are a major driver of the inequities in life expectancy between Indigenous and non-Indigenous people in these countries. Evidence-based pharmaceutical management of CVD can significantly reduce mortality and morbidity for persons diagnosed with CVD or for those at intermediate or high risk of CVD. Health literacy has been identified as a major barrier in the communication and implementation of appropriate pharmaceutical management plans for CVD. Addressing health literacy is particularly relevant in Indigenous populations where there are unique health and adult literacy challenges.Methods/designThis study will examine the effect of a customized, structured CVD medication programme, delivered by health professionals, on the health literacy of Indigenous people with, or at risk, of CVD. Primary outcomes are patient’s knowledge about CVD medications; secondary outcomes examine changes in health literacy skills and practices. The study will employ a multi-site pre-post design with multiple measurement points to assess intervention efficacy. Participants will be recruited from four Indigenous primary care services in Australia, Canada and New Zealand. Three educational sessions will be delivered over four weeks. A tablet application will support the education sessions and produce a customized pill card for each participant. Participants will be provided with written information about CVD medications. Medication knowledge scores, and specific health literacy skills and practices will be assessed before and after the three sessions. Statistical analyses will identify significant changes in outcomes over each session, and from the pre-session one to post-session three time points.DiscussionThis study will make an important contribution to understanding the effect of a structured primary care-based intervention on CVD health literacy in Indigenous populations. The study also illustrates the incorporation of Indigenous health research principles and processes in clinical trials and provides insights that may be useful in other contexts.Trial registrationAustralian and New Zealand Clinical Trials Register (ACTRN12612001309875; date of registration 18/12/2012).

Polypill-based therapy likely to reduce ethnic inequities in use of cardiovascular preventive medications: Findings from a pragmatic randomised controlled trial

Objective The purpose of this study was to investigate the consistency of the proportional effect of fixed-dose combination therapy (the ‘polypill’) on the use of recommended cardiovascular preventative medications among indigenous Māori and non-indigenous adults in New Zealand. Methods We randomised Māori and non-Māori primary care patients at high risk of cardiovascular disease (either because of a prior event or with an estimated 5-year risk of a first event of at least 15%) to a polypill (containing aspirin, statin and two antihypertensives) or usual care for a minimum of 12 months. All patients had indications for all polypill components according to their general practitioner, and all medications (including the polypill) were prescribed by the patient’s general practitioner and dispensed at community pharmacies. The main outcome for this study was the use of all recommended medications (antiplatelet, statin and two antihypertensives) at 12 months. Heterogeneity in the effect of polypill-based care compared with usual care on this outcome by ethnicity was assessed by logistic regression. Results Baseline use of recommended medications was 36% (93/257) among Māori and 51% (130/156) among non-Māori participants. Polypill-based care was associated with an increase in the use of recommended medications among Māori (relative risk [RR]: 1.87; 95% confidence interval [CI]: 1.50–2.34) and non-Māori (RR: 1.66; 95% CI: 1.37–2.00) when compared with usual care at 12 months, and there was no statistically significant heterogeneity in this outcome by ethnicity (p = 0.92). Conclusion Polypill-based care is likely to reduce absolute inequities between Māori and non-Māori in the use of recommended cardiovascular preventative medications given baseline absolute differences and the consistency of the proportional effect of this intervention by ethnicity in this pragmatic trial in primary care.

Recruiting equal numbers of indigenous and non-indigenous participants to a ‘polypill’ randomized trial

IntroductionMāori are disproportionately affected by cardiovascular disease (CVD), which is the main reason for the eight year difference in life expectancy between Māori and non-Māori. The primary care-based IMPACT (IMProving Adherence using Combination Therapy) trial evaluates whether fixed dose combination therapy (a “polypill”) improves adherence to guideline-based therapy compared with current care among people at high risk of CVD. Interventions shown in trials to be effective do not necessarily reduce ethnic disparities, and may in fact widen them. Indigenous populations with poorer health outcomes are often under-represented in trials so the effect of interventions cannot be assessed for them, specifically. Therefore, the IMPACT trial aimed to recruit as many Māori as non-Māori to assess the consistency of the effect of the polypill. This paper describes the methods and results of the recruitment strategy used to achieve this.MethodsExperienced Māori researchers were involved in trial governance throughout trial development and conduct. The trial Steering Committee included leading Māori researchers and was committed to equal recruitment of Māori and non-Māori. Additional funding and Māori research nurses were sought to allow home-based assessment, establishment of the relationship between research nurse and participant, more family involvement prior to enrollment, continuity of the research nurse-participant relationship, and acknowledgement of other Māori culturally important procedures, interactions, language and manners. Primary care practices with high enrollment of Māori were targeted, with over-sampling of potentially eligible Māori patients, lower thresholds for screening of Māori and 6 months continued Māori recruitment after non-Māori recruitment had finished.ResultsA total of 257 Māori and 256 non-Māori participants were randomized. Four Māori and eight non-Māori participants were randomized per research nurse per month. Potentially eligible Māori were more likely than non-Māori to proceed to subsequent stages of recruitment. Differences between randomized Māori and non-Māori were evident (e.g. Maori were less likely to have established coronary artery disease).ConclusionsRecruitment of equal numbers of indigenous and non-indigenous participants is possible if it is prioritised, adequately resourced and self-determination is supported.Trial registrationThe trial is registered with the Australian New Zealand Clinical Trial Registry ACTRN12606000067572

Ethnic Differences in Coronary Revascularisation following an Acute Coronary Syndrome in New Zealand: A National Data-linkage Study (ANZACS-QI 12)

BACKGROUND The aim of this study was to describe ethnic differences in angiography and revascularisation rates following an acute coronary syndrome (ACS) in New Zealand. METHODS National hospitalisation and mortality data were anonymously linked to determine receipt of angiography and revascularisation for 30-84 year-olds hospitalised with ACS between 2007 and 2012. Multilevel Cox regression, accounting for individual factors and admitting hospital, was used to estimate adjusted procedural rates within 30 days of admission. RESULTS Of the 50,324 ACS patients included, 10% were Māori, 4% Pacific, 3% Indian and 83% New Zealand European or Other ethnicities (NZEO). A larger proportion of Māori (48%) than NZEO (36%), Pacific (19%) and Indian (14%) patients were admitted to hospitals without catheterisation facilities. More Māori and Pacific (22-24%) than NZEO and Indian patients (12-13%) had severe comorbidities. Māori and Pacific were less likely than NZEO patients to receive angiography (adjusted HRs 0.94 [0.91-0.98] and 0.93 [0.87-0.98] respectively) and revascularisation (adjusted HRs 0.79 [0.75-0.83] and 0.77 [0.71-0.83]), even after adjusting for important demographic and clinical factors. CONCLUSIONS A higher comorbidity burden in Māori and Pacific patients and reduced access to catheterisation facilities for non-urban Māori contributed to lower procedure rates after ACS admission. Ethnic differences remained after adjustment for these factors and require further investigation.