Cost-effectiveness of low-dose colchicine in patients with chronic coronary disease in the netherlands.

AIMS: Recent trials have shown that low-dose colchicine (0.5 mg once daily) reduces major cardiovascular events in patients with acute and chronic coronary syndromes. We aimed to estimate the cost-effectiveness of low-dose colchicine therapy in patients with chronic coronary disease when added to standard background therapy. METHODS AND RESULTS: This Markov cohort cost-effectiveness model used estimates of therapy effectiveness, transition probabilities, costs and quality of life obtained from the Low-dose Colchicine 2 (LoDoCo2) trial, as well as meta-analyses and public sources. In this trial, Low-dose colchicine was added to standard of care and compared to placebo. The main outcomes were cardiovascular events including myocardial infarction, stroke and coronary revascularisation, quality-adjusted life-year (QALY), the cost per QALY gained (incremental cost-effectiveness ratio), and net monetary benefit. In the model, low-dose colchicine therapy yielded 0.04 additional QALYs compared with standard of care at an incremental cost of €455 from a societal perspective and €729 from a healthcare perspective, resulting in a cost per QALY gained of €12,176/QALY from a societal perspective and €19,499/QALY from a healthcare perspective. Net monetary benefit was €1,414 from a societal perspective and €1,140 from a healthcare perspective. Low-dose colchicine has a 96% and 94% chance of being cost effective, from respectively a societal and healthcare perspective when using a willingness to pay of €50,000/QALY. Net monetary benefit would decrease below zero when annual low-dose colchicine costs would exceed an annual cost of €221 per patient. CONCLUSION: Adding low-dose colchicine to standard of care in patients with chronic coronary disease is cost-effective according to commonly accepted thresholds in Europe and Australia and compares favourably in cost-effectiveness to other drugs used in chronic coronary disease.

Performance of cardiovascular risk prediction equations in Indigenous Australians.

OBJECTIVE: To assess the performance of cardiovascular disease (CVD) risk equations in Indigenous Australians. METHODS: We conducted an individual participant meta-analysis using longitudinal data of 3618 Indigenous Australians (55% women) aged 30-74 years without CVD from population-based cohorts of the Cardiovascular Risk in IndigenouS People(CRISP) consortium. Predicted risk was calculated using: 1991 and 2008 Framingham Heart Study (FHS), the Pooled Cohorts (PC), GloboRisk and the Central Australian Rural Practitioners Association (CARPA) modification of the FHS equation. Calibration, discrimination and diagnostic accuracy were evaluated. Risks were calculated with and without the use of clinical criteria to identify high-risk individuals. RESULTS: When applied without clinical criteria, all equations, except the CARPA-adjusted FHS, underestimated CVD risk (range of percentage difference between observed and predicted CVD risks: -55% to -14%), with underestimation greater in women (-63% to -13%) than men (-47% to -18%) and in younger age groups. Discrimination ranged from 0.66 to 0.72. The CARPA-adjusted FHS equation showed good calibration but overestimated risk in younger people, those without diabetes and those not at high clinical risk. When clinical criteria were used with risk equations, the CARPA-adjusted FHS algorithm scored 64% of those who had CVD events as high risk; corresponding figures for the 1991-FHS were 58% and were 87% for the PC equation for non-Hispanic whites. However, specificity fell. CONCLUSION: The CARPA-adjusted FHS CVD risk equation and clinical criteria performed the best, achieving higher combined sensitivity and specificity than other equations. However, future research should investigate whether modifications to this algorithm combination might lead to improved risk prediction.

Colchicine: an affordable anti-inflammatory agent for atherosclerosis.

PURPOSE OF REVIEW: Inflammation has been shown to be central to the development and progression of atherosclerosis. Despite detailed understanding of its central role and the cellular dynamics, which contribute to atherosclerotic inflammation, there has been slow progress in finding suitable agents to treat it. The recent CANTOS trial showed that the interleukin-1ß inhibitor canakinumab can improve outcomes after acute coronary syndromes. Being a monoclonal antibody, it is expensive and inconvenient to administer for long-term treatment. This review summarizes recent work in finding effective, affordable alternatives to canakinumab. RECENT FINDINGS: Statin drugs have anti-inflammatory properties but separating their LDL lowering effect from their anti-inflammatory effect has been difficult. Drugs acting on targets outside of the interleukin-1ß (IL-1ß) pathway have been tested without finding a suitable candidate. Following the proof of principle provided by the success of canakinumab, other candidates targeting the IL-1ß pathway are undergoing detailed evaluation. The most likely candidates are low-dose methotrexate and low-dose colchicine. The potential mechanisms and ongoing clinical trials are described. SUMMARY: Targeting the IL-1ß pathway has already been successful with canakinumab but its expense and inconvenience of administration may limit its widespread uptake for controlling inflammation in atherosclerosis. Low-dose methotrexate and low-dose colchicine are affordable and more accessible alternatives, currently undergoing detailed evaluation for safety and efficacy in large randomized controlled trials.

Transfers to metropolitan hospitals and coronary angiography for rural Aboriginal and non-Aboriginal patients with acute ischaemic heart disease in Western Australia.

BACKGROUND: Aboriginal people have a disproportionately higher incidence rate of ischaemic heart disease (IHD) than non-Aboriginal people. The findings on Aboriginal disparity in receiving coronary artery procedures are inconclusive. We describe the profile and transfers of IHD patients admitted to rural hospitals as emergency admissions and investigate determinants of transfers and coronary angiography. METHODS: Person-linked hospital and mortality records were used to identify 28-day survivors of IHD events commencing at rural hospitals in Western Australia. Outcome measures were receipt of coronary angiography, transfer to a metropolitan hospital, and coronary angiography if transferred to a metropolitan hospital. RESULTS: Compared to non-Aboriginal patients, Aboriginal patients with IHD were more likely to be younger, have more co-morbidities, reside remotely, but less likely to have private insurance. After adjusting for demographic characteristics, Aboriginal people with MI were less likely to be transferred to a metropolitan hospital, and if transferred were less likely to receive coronary angiography. These disparities were not significant after adjusting for comorbidities and private insurance. In the full multivariate model age, comorbidities and private insurance were adversely associated with transfer to a metropolitan hospital and coronary angiography. CONCLUSION: Disparity in receiving coronary angiography following emergency admission for IHD to rural hospitals is mediated through the lower likelihood of being transferred to metropolitan hospitals where this procedure is performed. The likelihood of a transfer is increased if the patient has private insurance, however, rural Aboriginal people have a lower rate of private insurance than their non-Aboriginal counterparts. Health practitioners and policy makers can continue to claim that they treat Aboriginal and non-Aboriginal people alike based upon clinical indications, as private insurance is acting as a filter to reduce rural residents accessing interventional cardiology. If health practitioners and policy makers are truly committed to reducing health disparities, they must reflect upon the broader systems in which disparity is perpetuated and work towards a systems improvement.

Complex impact of remoteness on the incidence of myocardial infarction in Aboriginal and non-Aboriginal people in Western Australia.

OBJECTIVE: To determine the impact of remoteness on Aboriginal and non-Aboriginal myocardial infarction incidence rates in men and women of different ages. DESIGN: Descriptive study. SETTING: Western Australia. PARTICIPANTS: Incident cases of myocardial infarction in Western Australia from 2000-2004 identified from person-linked files of hospital and mortality records. Analysis was undertaken for Aboriginal and non-Aboriginal populations, separately and combined, by broad age group, sex and remoteness. MAIN OUTCOME MEASURE: Incidence of myocardial infarction. RESULTS: In the combined analysis, age-standardised incidence was significantly higher for men in very remote areas (rate ratio 1.31: 95% confidence interval (CI), 1.19-1.45) and in women in both regional (rate ratio 1.12: 95% CI, 1.01-1.20) and very remote (rate ratio 2.05: 95% CI, 1.75-2.41) areas. Aboriginal rates were substantially higher than non-Aboriginal rates in all substrata. Compared with metropolitan people, regional Aboriginal men and very remote non-Aboriginal men aged 25-54 years had significantly higher incidence rates. For the remaining rural strata, there was either no geographical disadvantage or inconclusive findings. CONCLUSIONS: Non-metropolitan disadvantage in myocardial infarction rates is confirmed in regional areas and women in very remote areas. This disadvantage is partly explained by the high rates in Aboriginal people. Non-metropolitan dwellers are not uniformly disadvantaged, reflecting the interplay of the many factors contributing to the complex relationship between myocardial infarction incidence and sex, age, Aboriginality and residence. Aboriginal Western Australians in all regions and young non-Aboriginal men living in very remote areas need to be targeted to reduce disparities in myocardial infarction.

Variable effects of prevalence correction of population denominators on differentials in myocardial infarction incidence: a record linkage study in Aboriginal and non-Aboriginal Western Australians.

OBJECTIVES: To investigate the impact of prevalence correction of population denominators on myocardial infarction (MI) incidence rates, rate ratios, and rate differences in Aboriginal vs. non-Aboriginal Western Australians aged 25-74 years during the study period 2000-2004. STUDY DESIGN AND SETTING: Person-based linked hospital and mortality data sets were used to estimate the number of prevalent and first-ever MI cases each year from 2000 to 2004 using a 15-year look-back period. Age-specific and -standardized MI incidence rates were calculated using both prevalence-corrected and -uncorrected population denominators, by sex and Aboriginality. RESULTS: The impact of prevalence correction on rates increased with age, was higher for men than women, and substantially greater for Aboriginal than non-Aboriginal people. Despite the systematic underestimation of incidence, prevalence correction had little impact on the Aboriginal to non-Aboriginal age-standardized rate ratios (6% and 4% underestimate in men and women, respectively), although the impact on rate differences was more marked (12% and 6%, respectively). The percentage underestimate of differentials was greater at older ages. CONCLUSION: Prevalence correction of denominators, while more accurate, is difficult to apply and may add modestly to the quantification of relative disparities in MI incidence between populations. Absolute incidence disparities using uncorrected denominators may have an error >10%.

A comparison of coronary heart disease event rates among urban Australian Aboriginal people and a matched non-Aboriginal population.

BACKGROUND: Age-specific death from cardiovascular disease among Australian Aboriginals is estimated to be four to seven times that of general population, and the major cause of premature death. There is little reliable information on the incidence of coronary heart disease (CHD). This study compares CHD event rates in urban-dwelling Aboriginal people and the general population. METHODS: The Perth Aboriginal Atherosclerosis Risk Study (PAARS) cohort was assessed at baseline (1998/1999) and 913 participants followed-up to 2006. A comparison group of age-matched, sex-matched and postcode-matched non-Aboriginals (n=3582) were selected from the Perth, Western Australia, Electoral Roll. Electronic record linkage captured prior CHD and first CHD events in both groups. The rates of first CHD events (hospital admission or CHD death) per 1000 person years (PY) and incidence rate ratios (IRR) were calculated. RESULTS: The event rate for the PAARS population was 14.9 per 1000 PY (95% CI 12.3 to 18.2) versus 2.4 (1.9 to 3.1) for the general population. The IRR was 6.1 (4.5 to 8.4). For Aboriginal men the rate was 15.0 (11.2 to 20.0) versus 3.8 (2.5 to 5.0) per 1000 PY, with age-specific rates being two to five times that of non-Aboriginals. Incidence for Aboriginal women was 15.0 (11.5 to 19.5) versus 1.4 (0.9 to 2.1) with age-specific rates being 8-25 times that of non-Aboriginals. CONCLUSIONS: Age and sex-specific CHD event rates in urban Aboriginals far exceeded that of a matched general population. Events occurred at a much younger age among the Aboriginal participants and were equally excessive among men and women.

Incidence of and case fatality following acute myocardial infarction in Aboriginal and non-Aboriginal Western Australians (2000-2004): a linked data study.

BACKGROUND: Despite Coronary Heart Disease exacting a heavy toll among Aboriginal Australians, accurate estimates of its epidemiology are limited. This study compared the incidence of acute myocardial infarction (AMI) and 28-day case fatality (CF) among Aboriginal and non-Aboriginal Western Australians aged 25-74 years from 2000-2004. METHODS: Incident (AMI hospital admission-free for 15 years) AMI events and 28-day CF were estimated using person-based linked hospital and mortality data. Age-standardised incidence rates and case fatality percentages were calculated by Aboriginality and sex. RESULTS: Of 740 Aboriginal and 6933 non-Aboriginal incident events, 208 and 2352 died within 28 days, respectively. The Aboriginal age-specific incidence rates were 27 (males) and 35 (females) times higher than non-Aboriginal rates in the 25-29 year age group, decreasing to 2-3 at 70-74 years. The male:female age-standardised incidence rate ratio was 2.2 in Aboriginal people 25-54 years compared with 4.5 in non-Aboriginal people. Aboriginal age-standardised CF percentages were 1.4 (males) and 1.1 (females) times higher at age 25-54 years and 1.5 times higher at age 55-74 years. CONCLUSION: These data suggest higher CF and, more importantly, AMI incidence contribute to the excess ischaemic heart disease mortality in Aboriginal Western Australians. The poorer cardiovascular health in Aboriginal women, particularly in younger age groups, should be investigated.

The impact of nurses on patient morbidity and mortality - the need for a policy change in response to the nursing shortage.

CONTEXT: Workforce projections indicate that by 2012 there will be a shortfall of 61,000 registered nurses in Australia. There is a growing body of evidence that links registered nurse staffing to better patient outcomes. PURPOSE: This article provides a comprehensive review of the research linking nurse staffing to patient outcomes at a time of growing shortages, highlighting that a policy response based on substituting registered nurses with lower skilled workers may have adverse effects on patient outcomes. METHOD: An electronic search of articles published in English using the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Journals @ OVID and Medline was undertaken. FINDINGS: Robust evidence exists nationally and internationally that links nurse staffing to patient outcomes. Recent meta-analyses have found that there was a 3-12% reduction in adverse outcomes and a 16% reduction in the risk of mortality in surgical patients with higher registered nurse staffing. Evidence confirms that improvements in nurse staffing is a cost-effective investment for the health system but this is not fully appreciated by health policy advisors. CONCLUSIONS: An appropriate policy response demands that the evidence that patient safety is linked to nurse staffing be recognised. Policy makers must ensure there are sufficient registered nurses to guarantee patient safety.

Interleukin-18 levels are not associated with subclinical carotid atherosclerosis in a community population. The Perth Carotid Ultrasound Disease Assessment Study (CUDAS).

Interleukin (IL)-18 is a novel proinflammatory cytokine that plays a central role in innate and acquired immunity, making it a likely inflammatory candidate in atherosclerosis. We investigated whether circulating IL-18 levels were associated with subclinical atherosclerosis in a community population. Carotid intimal medial thickness (IMT) and carotid plaques were assessed in a cross-sectional study of 1111 randomly selected community subjects, aged 27-77 years. Baseline levels of IL-18, IL-6, high sensitive CRP (hsCRP), fibrinogen and white cell counts were measured along with conventional cardiovascular risk factors. Men had higher mean IL-18 levels than women (P<0.0001). Spearman rank correlations (r(s)) showed that IL-18 was weakly correlated with all inflammatory markers in the whole population (r(s) between 0.11 and 0.23, all P<0.001). IL-18 was also correlated with conventional risk factors including waist-hip ratio, BMI, blood pressure, triglycerides, HDL (inversely) and pack-years smoking (r(s) between 0.18 and 0.39, all P<0.001) but not with LDL-cholesterol. Independent predictors of IL-18 concentrations were waist-hip ratio, HDL, IL-6, hsCRP and hypertension. There was a positive univariate association of IL-18 levels with carotid IMT (P<0.001) and plaque prevalence (P<0.001) but no residual association after adjustment for conventional risk factors (both P>0.05). In a cross-sectional community population, IL-18 levels were related to traditional risk factors and inflammatory markers but were not independently associated with subclinical carotid atherosclerosis.

Apolipoprotein E gene polymorphisms are associated with carotid plaque formation but not with intima-media wall thickening: results from the Perth Carotid Ultrasound Disease Assessment Study (CUDAS).

BACKGROUND AND PURPOSE: Several studies have investigated the role of apolipoprotein E (apoE) polymorphisms on carotid intima-media thickness (IMT) with conflicting results. The objective of this study was to use a large, community-based population to investigate associations between apoE gene polymorphisms and cardiovascular disease-associated phenotypes: IMT, carotid artery plaque, and low- (LDL-C) and high-density lipoprotein cholesterol (HDL-C). METHODS: ApoE genotypes were determined in 1109 randomly selected community subjects with an equal man-to-woman ratio and equal numbers in each age decile who were 27 to 77 years of age and had bilateral carotid B-mode ultrasound and cardiovascular risk factor measurements. RESULTS: Multivariate analyses, stratified by sex, demonstrated an association between apoE genotypes and LDL-C levels in men (P=0.03) and women (P<0.001). A significant linear trend in increasing LDL-C (beta=0.33 per unit change in genotype; SE=0.07; P<0.001) levels with increasing number of epsilon4 alleles across the epsilon3/epsilon3, epsilon3/epsilon4, or epsilon4/epsilon4 genotypes was observed in women but not in men. The associations were independent of age, diastolic blood pressure, and history of diabetes mellitus. Multivariate analyses found a log-additive trend in risk of developing carotid plaque with increasing numbers of epsilon4 alleles across the epsilon3/epsilon3, epsilon3/epsilon4, and epsilon4/epsilon4 genotypes (odds ratio [OR], 1.72 per unit change in genotype; 95% CI, 1.05 to 2.80; P=0.03) in men. There was no association between plaque frequency and the epsilon4 allele in women. However, the epsilon2/epsilon3 genotype was shown to be associated with a lower OR (OR, 0.40; 95% CI, 0.17 to 0.91; P=0.03) for carotid plaques relative to the epsilon3/epsilon3 genotype in women. The associations were independent of age and standard vascular risk factors. There were no significant independent associations between apoE genotypes and IMT in either men or women. CONCLUSIONS: Our data suggest that polymorphisms in the apoE gene are significantly associated with LDL-C levels and increased risk of carotid plaque formation in men but not IMT in either men or women.