Reduction in Natural Death and Renal Failure From a Systematic Screening and Treatment Program in an Australian Aboriginal Community

BACKGROUND: Australian Aborigines in remote areas are experiencing an epidemic of renal and cardiovascular disease. In November 1995, we introduced a renal and cardiovascular treatment program into the Tiwi community, which has a three- to fivefold increase in death rates and a recent annual incidence of treated end-stage renal disease (ESRD) of 2760 per million. Our previous study described an estimated 50% reduction in renal failure and all-cause natural deaths in the treatment group through December 31, 1998. We now describe a reduction in these events through mid 2000. METHODS: People eligible for treatment were those with confirmed hypertension, diabetics with microalbuminuria or overt albuminuria, and people with overt albuminuria, regardless of blood pressure and diabetes. Treatment centered around the use of perindopril (Coversyl, Servier), with additional agents as needed to reach defined blood pressure goals, attempts at control of glucose and lipid levels, and health education. Two hundred and sixty-seven people, or 30% of the adult population, have been enrolled, with mean follow up of 3.39 years. Rates of terminal endpoints were compared on an intention-to-treat basis with those of 327 historical controls matched for baseline disease severity, who were followed for a mean of 3.18 years in the pre-treatment program era, against a background of no treatment or inconsistent changing treatment. RESULTS: Terminal events occurred in 38 controls and 23 people in the treatment group. The estimated rate of natural deaths in the treatment group was 50% that of the controls, (P=0.012); the rate of renal deaths was 47% (P=0.038) and the rate of non-renal deaths was 54% that of controls (P=0.085). Survival benefit in the treatment group was observed at all levels of overt albuminuria, in non-diabetics and diabetics, in normotensive as well as hypertensive people, and in people who had been taking angiotensin converting enzyme-inhibitors (ACEi) in the pre-program era, as well as those who had not. Benefit was absent among the low death rates of people without overt albuminuria, and questionable among people with glomerular filtration rates (GFRs

Peripheral arterial disease: A high risk – but neglected – disease population

Peripheral arterial disease (PAD) is a common, progressive manifestation of atherothrombotic vascular disease, which should be managed no different to cardiac disease. Indeed, there is growing evidence that PAD patients are a high risk group, although still relatively under-detected and under treated. This is despite the fact that PAD patients are an increased mortality rate comparable to those with pre-existing or established cardiovascular disease [myocardial infarction, stroke]. With a holistic approach to atherothrombotic vascular disease, our management of PAD can only get better

Indications for and Utilization of ACE Inhibitors in Older Individuals with Diabetes

Angiotensin-converting enzyme inhibitors (ACE) and angiotensin receptor blockers (ARB) improve cardiovascular outcomes in high-risk individuals with diabetes. Despite the marked benefit, it is unknown what percentage of patients with diabetes would benefit from and what percentage actually receive this preventive therapy. OBJECTIVES : To examine the proportion of older diabetic patients with indications for ACE or ARB (ACE/ARB). To generate national estimates of ACE/ARB use. DESIGN AND PARTICIPANTS : Survey of 742 individuals≥55 years (representing 8.02 million U.S. adults) self-reporting diabetes in the 1999 to 2002 National Health and Nutrition Examination Survey. MEASUREMENTS : Prevalence of guideline indications (albuminuria, cardiovascular disease, hypertension) and other cardiac risk factors (hyperlipidemia, smoking) with potential benefit from ACE/ARB. Prevalence of ACE/ARB use overall and by clinical indication. RESULTS : Ninety-two percent had guideline indications for ACE/ARB. Including additional cardiac risk factors, the entire (100%) U.S. noninstitutionalized older population with diabetes had indications for ACE/ARB. Overall, 43% of the population received ACE/ARB. Hypertension was associated with higher rates of ACE/ARB use, while albuminuria and cardiovascular disease were not. As the number of indications increased, rates of use increased, however, the maximum prevalence of use was only 53% in individuals with 4 or more indications for ACE/ARB. CONCLUSIONS : ACE/ARB is indicated in virtually all older individuals with diabetes; yet, national rates of use are disturbingly low and key risk factors (albuminuria and cardiovascular disease) are being missed. To improve quality of diabetes care nationally, use of ACE/ARB therapy by ALL older diabetics may be a desirable addition to diabetes performance measurement sets.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74734/1/j.1525-1497.2006.00351.x.pd

Individualised therapy of angiotensin converting enzyme (ACE) inhibitors in stable coronary artery disease: overview of the primary results of the PERindopril GENEtic association (PERGENE) study

In patients with stable coronary artery disease (CAD) without overt heart failure, ACE inhibitors are among the most commonly used drugs as these agents have been proven effective in reducing the risk of cardiovascular events. Considerable individual variations in the blood pressure response to ACE inhibitors are observed and as such heterogeneity in clinical treatment effect would be likely as well. Assessing the consistency of treatment benefit is essential for the rational and cost-effective prescription of ACE inhibitors. Information on heterogeneities in treatment effect between subgroups of patients could be used to develop an evidence-based guidance for the installation of ACE-inhibitor therapy. Obviously, therapy should only be applied in those patients who most likely will benefit. Attempts to develop such treatment guidance by using clinical characteristics have been unsuccessful. No heterogeneity in risk reduction by ACE inhibitors has been observed in relation to relevant clinical characteristics. A new approach to such ‘guided-therapy’ could be to integrate more patient-specific characteristics such as the patients’ genetic information. If proven feasible, pharmacogenetic profiling could optimise patients’ benefit of treatment and reduce unnecessary treatment of patients. Cardiovascular pharmacogenetic research of ACE inhibitors in coronary artery disease patients is in a formative stage and studies are limited. The PERGENE study is a large pharmacogenetic substudy of the EUROPA trial, aimed to assess the achievability of pharmacogenetic profiling. We provide an overview of the main results of the PERGENE study in terms of the genetic determinants of treatment benefit and blood pressure response. The main results of the PERGENE study show a pharmacogenetic profile related to the treatment benefit of perindopril identifying responders and non-responders to treatment

Preferential benefits of nifedipine GITS in systolic hypertension and in combination with RAS blockade: further analysis of the ‘ACTION' database in patients with angina

A retrospective analysis of the database from A Coronary Disease Trial Investigating Outcome with Nifedipine (ACTION) evaluated the effectiveness of nifedipine gastrointestinal therapeutic system (GITS) (i) in combination with renin angiotensin system (RAS) blockers and (ii) in patients with isolated systolic hypertension (ISH). Analysed on an intention-to-treat basis, treatment groups were compared by the log-rank test without adjustment for covariates and hazard ratios with 95% CIs were obtained using Cox proportional hazards models. Of 7665 randomized patients, 1732 patients were receiving RAS blockade at baseline, the addition of nifedipine GITS significantly reduced any cardiovascular (CV) event (−20% P<0.05), the composite of death, any CV event and revascularization (−16% P<0.05) and coronary angiography (−22% P<0.01). These benefits were achieved with relatively small differences in systolic (3.2 mm Hg) and diastolic blood pressure (BP) (2.3 mm Hg). In 2303 patients (30.0%) who had ISH at baseline (1145 nifedipine GITS and 1158 placebo), nifedipine significantly reduced the primary efficacy end point (−18% P<0.03), any CV event (−22% P<0.01) and new heart failure (−40% P<0.01). The benefits were associated with between-group differences in achieved BP of 4.7 and 3.3 mm Hg for systolic and diastolic BP, respectively. In summary, the lowest CV event rates were seen in those receiving (i) the combination of RAS blockade and nifedipine GITS and (ii) in those specifically treated for ISH

Testing for heterogeneity among the components of a binary composite outcome in a clinical trial

<p>Abstract</p> <p>Background</p> <p>Investigators designing clinical trials often use composite outcomes to overcome many statistical issues. Trialists want to maximize power to show a statistically significant treatment effect and avoid inflation of Type I error rate due to evaluation of multiple individual clinical outcomes. However, if the treatment effect is not similar among the components of this composite outcome, we are left not knowing how to interpret the treatment effect on the composite itself. Given significant heterogeneity among these components, a composite outcome may be judged as being invalid or un-interpretable for estimation of the treatment effect. This paper compares the power of different tests to detect heterogeneity of treatment effect across components of a composite binary outcome.</p> <p>Methods</p> <p>Simulations were done comparing four different models commonly used to analyze correlated binary data. These models included: logistic regression for ignoring correlation, logistic regression weighted by the intra cluster correlation coefficient, population average logistic regression using generalized estimating equations (GEE), and random effects logistic regression.</p> <p>Results</p> <p>We found that the population average model based on generalized estimating equations (GEE) had the greatest power across most scenarios. Adequate power to detect possible composite heterogeneity or variation between treatment effects of individual components of a composite outcome was seen when the power for detecting the main study treatment effect for the composite outcome was also reasonably high.</p> <p>Conclusions</p> <p>It is recommended that authors report tests of composite heterogeneity for composite outcomes and that this accompany the publication of the statistically significant results of the main effect on the composite along with individual components of composite outcomes.</p

A randomized trial to assess the impact of opinion leader endorsed evidence summaries on the use of secondary prevention strategies in patients with coronary artery disease: the ESP-CAD trial protocol [NCT00175240]

BACKGROUND: Although numerous therapies have been shown to be beneficial in the prevention of myocardial infarction and/or death in patients with coronary disease, these therapies are under-used and this gap contributes to sub-optimal patient outcomes. To increase the uptake of proven efficacious therapies in patients with coronary disease, we designed a multifaceted quality improvement intervention employing patient-specific reminders delivered at the point-of-care, with one-page treatment guidelines endorsed by local opinion leaders ("Local Opinion Leader Statement"). This trial is designed to evaluate the impact of these Local Opinion Leader Statements on the practices of primary care physicians caring for patients with coronary disease. In order to isolate the effects of the messenger (the local opinion leader) from the message, we will also test an identical quality improvement intervention that is not signed by a local opinion leader ("Unsigned Evidence Statement") in this trial. METHODS: Randomized trial testing three different interventions in patients with coronary disease: (1) usual care versus (2) Local Opinion Leader Statement versus (3) Unsigned Evidence Statement. Patients diagnosed with coronary artery disease after cardiac catheterization (but without acute coronary syndromes) will be randomly allocated to one of the three interventions by cluster randomization (at the level of their primary care physician), if they are not on optimal statin therapy at baseline. The primary outcome is the proportion of patients demonstrating improvement in their statin management in the first six months post-catheterization. Secondary outcomes include examinations of the use of ACE inhibitors, anti-platelet agents, beta-blockers, non-statin lipid lowering drugs, and provision of smoking cessation advice in the first six months post-catheterization in the three treatment arms. Although randomization will be clustered at the level of the primary care physician, the design effect is anticipated to be negligible and the unit of analysis will be the patient. DISCUSSION: If either the Local Opinion Leader Statement or the Unsigned Evidence Statement improves secondary prevention in patients with coronary disease, they can be easily modified and applied in other communities and for other target conditions