Showing papers by "Anushka Patel published in 2009"

Intensive glucose control and macrovascular outcomes in type 2 diabetes

Abstract: Improved glucose control in type 2 diabetes is known to reduce the risk of microvascular events. There is, however, continuing uncertainty about its impact on macrovascular disease. The aim of these analyses was to generate more precise estimates of the effects of more-intensive, compared with less-intensive, glucose control on the risk of major cardiovascular events amongst patients with type 2 diabetes. A prospectively planned group-level meta-analysis in which characteristics of trials to be included, outcomes of interest, analyses and subgroup definitions were all pre-specified. A total of 27,049 participants and 2,370 major vascular events contributed to the meta-analyses. Allocation to more-intensive, compared with less-intensive, glucose control reduced the risk of major cardiovascular events by 9% (HR 0.91, 95% CI 0.84–0.99), primarily because of a 15% reduced risk of myocardial infarction (HR 0.85, 95% CI 0.76–0.94). Mortality was not decreased, with non-significant HRs of 1.04 for all-cause mortality (95% CI 0.90–1.20) and 1.10 for cardiovascular death (95% CI 0.84–1.42). Intensively treated participants had significantly more major hypoglycaemic events (HR 2.48, 95% CI 1.91–3.21). Exploratory subgroup analyses suggested the possibility of a differential effect for major cardiovascular events in participants with and without macrovascular disease (HR 1.00, 95% CI 0.89–1.13, vs HR 0.84, 95% CI 0.74–0.94, respectively; interaction p = 0.04). Targeting more-intensive glucose lowering modestly reduced major macrovascular events and increased major hypoglycaemia over 4.4 years in persons with type 2 diabetes. The analyses suggest that glucose-lowering regimens should be tailored to the individual.

Albuminuria and Kidney Function Independently Predict Cardiovascular and Renal Outcomes in Diabetes

Abstract: There are limited data regarding whether albuminuria and reduced estimated GFR (eGFR) are separate and independent risk factors for cardiovascular and renal events among individuals with type 2 diabetes. The Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) study examined the effects of routine BP lowering on adverse outcomes in type 2 diabetes. We investigated the effects of urinary albumin-to-creatinine ratio (UACR) and eGFR on the risk for cardiovascular and renal events in 10,640 patients with available data. During an average 4.3-yr follow-up, 938 (8.8%) patients experienced a cardiovascular event and 107 (1.0%) experienced a renal event. The multivariable-adjusted hazard ratio for cardiovascular events was 2.48 (95% confidence interval 1.74 to 3.52) for every 10-fold increase in baseline UACR and 2.20 (95% confidence interval 1.09 to 4.43) for every halving of baseline eGFR, after adjustment for regression dilution. There was no evidence of interaction between the effects of higher UACR and lower eGFR. Patients with both UACR >300 mg/g and eGFR <60 ml/min per 1.73 m(2) at baseline had a 3.2-fold higher risk for cardiovascular events and a 22.2-fold higher risk for renal events, compared with patients with neither of these risk factors. In conclusion, high albuminuria and low eGFR are independent risk factors for cardiovascular and renal events among patients with type 2 diabetes.

Combined Effects of Routine Blood Pressure Lowering and Intensive Glucose Control on Macrovascular and Microvascular Outcomes in Patients With Type 2 Diabetes New results from the ADVANCE trial

Abstract: OBJECTIVE To assess the magnitude and independence of the effects of routine blood pressure lowering and intensive glucose control on clinical outcomes in patients with long-standing type 2 diabetes. RESEARCH DESIGN AND METHODS This was a multicenter, factorial randomized trial of perindopril-indapamide versus placebo (double-blind comparison) and intensive glucose control with a gliclazide MR–based regimen (target A1C ≤6.5%) versus standard glucose control (open comparison) in 11,140 participants with type 2 diabetes who participated in the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial. Annual event rates and risks of major macrovascular and microvascular events considered jointly and separately, renal events, and death during an average 4.3 years of follow-up were assessed, using Cox proportional hazards models. RESULTS There was no interaction between the effects of routine blood pressure lowering and intensive glucose control for any of the prespecified clinical outcomes (all P > 0.1): the separate effects of the two interventions for the renal outcomes and death appeared to be additive on the log scale. Compared with neither intervention, combination treatment reduced the risk of new or worsening nephropathy by 33% (95% CI 12–50%, P = 0.005), new onset of macroalbuminuria by 54% (35–68%, P < 0.0001), and new onset of microalbuminuria by 26% (17–34%). Combination treatment was associated with an 18% reduction in the risk of all-cause death (1–32%, P = 0.04). CONCLUSIONS The effects of routine blood pressure lowering and intensive glucose control were independent of one another. When combined, they produced additional reductions in clinically relevant outcomes.

Lowering Blood Pressure Reduces Renal Events in Type 2 Diabetes

Abstract: BP is an important determinant of kidney disease among patients with diabetes. The recommended thresholds to initiate treatment to lower BP are 130/80 and 125/75 mmHg for people with diabetes and nephropathy, respectively. We sought to determine the effects of lowering BP below these currently recommended thresholds on renal outcomes among 11,140 patients who had type 2 diabetes and participated in the Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) study. Patients were randomly assigned to fixed combination perindopril-indapamide or placebo, regardless of their BP at entry. During a mean follow-up of 4.3 yr, active treatment reduced the risk for renal events by 21% (P < 0.0001), which was driven by reduced risks for developing microalbuminuria and macroalbuminuria (both P < 0.003). Effects of active treatment were consistent across subgroups defined by baseline systolic or diastolic BP. Lower systolic BP levels during follow-up, even to <110 mmHg, was associated with progressively lower rates of renal events. In conclusion, BP-lowering treatment with perindopril-indapamide administered routinely to individuals with type 2 diabetes provides important renoprotection, even among those with initial BP <120/70 mmHg. We could not identify a BP threshold below which renal benefit is lost.

Risks of cardiovascular events and effects of routine blood pressure lowering among patients with type 2 diabetes and atrial fibrillation: results of the ADVANCE study.

Abstract: AIMS: The aim of this study was to investigate serious clinical outcomes associated with atrial fibrillation (AF) and the effects of routine blood pressure lowering on such outcomes in the presence or absence of AF, among individuals with type 2 diabetes. METHODS AND RESULTS: About 11 140 patients with type 2 diabetes (7.6% of whom had AF at baseline) were randomized to a fixed combination of perindopril and indapamide or placebo in the Action in Diabetes and Vascular Disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) study. We compared total mortality and cardiovascular disease outcomes and effects of randomized treatment for 4.3 years on such outcomes between patients with and without AF at baseline. After multiple adjustments, AF was associated with a 61% (95% confidence interval 31-96, P < 0.0001) greater risk of all-cause mortality and comparable higher risks of cardiovascular death, stroke, and heart failure (all P < 0.001). Routine treatment with a fixed combination of perindopril and indapamide produced similar relative, but greater absolute, risk reductions for all-cause and cardiovascular mortalities in patients with AF, compared with those without AF. The number of patients needed to be treated with perindopril-indapamide for 5 years to prevent one cardiovascular death was 42 for patients with AF and 120 for patients without AF at baseline. CONCLUSION: Atrial fibrillation is relatively common in type 2 diabetes and is associated with substantially increased risks of death and cardiovascular events in patients with type 2 diabetes. This arrhythmia identifies individuals who are likely to obtain greater absolute benefits from blood pressure-lowering treatment. Atrial fibrillation in diabetic patients should be regarded as a marker of particularly adverse outcome and prompt aggressive management of all risk factors.

Cognitive function and risks of cardiovascular disease and hypoglycaemia in patients with type 2 diabetes: the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial

Abstract: Aims/hypothesis The relationship between cognitive function, cardiovascular disease and premature death is not well established in patients with type 2 diabetes. We assessed the effects of cognitive function in 11,140 patients with type 2 diabetes who participated in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. Furthermore, we tested whether level of cognitive function altered the beneficial effects of the BP-lowering and glycaemic-control regimens in the trial.

Effects of blood pressure lowering and intensive glucose control on the incidence and progression of retinopathy in patients with type 2 diabetes mellitus: a randomised controlled trial

Abstract: The aim of the present study was to investigate the effect of blood pressure lowering and intensive glucose control on the incidence and progression of retinopathy in type 2 diabetic patients. The Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) Retinal Measurements study, a substudy of ADVANCE, is a randomised (using a central, computer-based procedure) controlled 2 × 2 factorial trial comprising a double-blind comparison of blood pressure lowering with perindopril–indapamide vs placebo, and an open comparison of standard vs intensive glucose control targeting a HbA1c of ≤ 6.5% in 1,602 diabetic patients from ADVANCE centres with access to retinal cameras conducted from 2001 to 2008. At baseline and the final visit, seven-field stereoscopic retinal photographs were taken and graded by blinded readers (gradeable baseline and final photographs from 1,241 patients). Progression of ≥2 steps in the Early Treatment of Diabetic Retinopathy Study classification (using the eye with worst grading) was the primary outcome. Retinopathy progressed in 59 (4.8%) patients and developed in 128 (10.3%) patients over 4.1 years. Fewer patients on blood pressure-lowering treatment (n = 623) experienced incidence or progression of retinopathy compared with patients on placebo (n = 618), but the difference was not significant (OR 0.78; 95% CI 0.57–1.06; p = 0.12). Blood pressure-lowering treatment reduced the occurrence of macular oedema (OR 0.50; 95% CI 0.29–0.88; p = 0.016) and arteriovenous nicking compared with placebo (OR 0.60; 95% CI 0.38–0.94; p = 0.025). Compared with standard glucose control (n = 611), intensive glucose control (n = 630) did not reduce (p = 0.27) the incidence and progression of retinopathy (OR 0.84; 95% CI 0.61–1.15). Lower, borderline significant risks of microaneurysms, hard exudates and macular oedema were observed with intensive glucose control, adjusted for baseline retinal haemorrhages. These effects of the two treatments were independent and additive. Adverse events in the ADVANCE study are reported elsewhere. Blood pressure lowering or intensive glucose control did not significantly reduce the incidence and progression of retinopathy, although consistent trends towards a benefit were observed, with significant reductions in some lesions observed with both interventions. ClinicalTrials.gov ID no. NCT00145925. Grants from Servier and the National Health and Medical Research Council of Australia

Systematic review: Sodium bicarbonate treatment regimens for the prevention of contrast-induced nephropathy

Abstract: In this review of 23 trials on whether sodium bicarbonate reduced risk for contrast-induced nephropathy (CIN) more than saline, the pooled relative risk for CIN was 0.62 (95% CI, 0.45 to 0.86). How...

Gaps in cardiovascular disease risk management in Australian general practice.

Abstract: Objective: To evaluate the management of cardiovascular disease (CVD) risk in Australian general practice.

An Electronic Clinical Decision Support Tool to Assist Primary Care Providers in Cardiovascular Disease Risk Management: Development and Mixed Methods Evaluation

Abstract: Background: Challenges remain in translating the well-established evidence for management of cardiovascular disease (CVD) risk into clinical practice. Although electronic clinical decision support (CDS) systems are known to improve practitioner performance, their development in Australian primary health care settings is limited. Objective: Study aims were to (1) develop a valid CDS tool that assists Australian general practitioners (GPs) in global CVD risk management, and (2) preliminarily evaluate its acceptability to GPs as a point-of-care resource for both general and underserved populations. Methods: CVD risk estimation (based on Framingham algorithms) and risk-based management advice (using recommendations from six Australian guidelines) were programmed into a software package. Tool validation: Data from 137 patients attending a physician’s clinic were analyzed to compare the tool’s risk scores with those obtained from an independently programmed algorithm in a separate statistics package. The tool’s management advice was compared with a physician’s recommendations based on a manual review of the guidelines. Field test: The tool was then tested with 21 GPs from eight general practices and three Aboriginal Medical Services. Customized CDS-based recommendations were generated for 200 routinely attending patients (33% Aboriginal) using information extracted from the health record by a research assistant. GPs reviewed these recommendations during each consultation. Changes in CVD risk factor measurement and management were recorded. In-depth interviews with GPs were conducted. Results: Validation testing: The tool’s risk assessment algorithm correlated very highly with the independently programmed version in the separate statistics package (intraclass correlation coefficient 0.999). For management advice, there were only two cases of disagreement between the tool and the physician. Field test: GPs found 77% (153/200) of patient outputs easy to understand and agreed with screening and prescribing recommendations in 72% and 64% of outputs, respectively; 26% of patients had their CVD risk factor history updated; 73% had at least one CVD risk factor measured or tests ordered. For people assessed at high CVD risk (n = 82), 10% and 9%, respectively, had lipid-lowering and BP-lowering medications commenced or dose adjustments made, while 7% newly commenced anti-platelet medicines. Three key qualitative findings emerged: (1) GPs found the tool enabled a systematic approach to care; (2) the tool greatly influenced CVD risk communication; (3) successful implementation into routine care would require integration with practice software, minimal data entry, regular revision with updated guidelines, and a self-auditing feature. There were no substantive differences in study findings for Aboriginal Medical Services GPs, and the tool was generally considered appropriate for use with Aboriginal patients. Conclusions: A fully-integrated, self-populating and potentially Internet-based CDS tool could contribute to improved global CVD risk management in Australian primary health care. The findings from this study will inform a large-scale trial intervention. [J Med Internet Res 2009;11(4):e51]

Cardiovascular disease risk management for Aboriginal and Torres Strait Islander peoples in primary health care settings: findings from the Kanyini Audit

Abstract: Objective: To describe cardiovascular disease (CVD) risk management in Indigenous primary health care. Design, setting and participants: Review of 1165 randomly selected case records of Indigenous Australian adults, aged ≥ 18 years, regularly attending eight health services in diverse settings in New South Wales, Queensland and Central Australia, October 2007 - May 2008. Main outcome measure: Adherence to CVD risk screening and management guidelines, especially with respect to overall or absolute CVD risk. Results: More than half the people in the sample (53%) were not adequately screened for CVD risk according to national recommendations. Underscreening was significantly associated with younger age, less frequent attendance, and lower uptake of the Medicare Health Assessment. Of the sample, 9% had established CVD, and 29% of those aged ≥ 30 years were classified as high risk according to the 2004 National Heart Foundation of Australia (NHFA) adjusted Framingham equation. Of those with CVD, 40% (95% CI, 30%-50%) were not prescribed a combination of blood pressure (BP) medicines, statins and antiplatelet agents, and 56% (95% CI, 49%-62%) of high-risk individuals without CVD were not prescribed BP medicines and statins. For high-risk individuals not prescribed BP medicines or statins, 74% (95% CI, 64%-84%) and 30% (95% CI, 23%-39%) respectively, did not meet 2004 NHFA criteria for prescribing of these medications, and of those already prescribed BP medicines or statins, 41% (95% CI, 36%-47%) and 59% (95% CI, 52%-66%) did not meet respective guideline targets. Conclusions: These management gaps are similar to those found in non-Indigenous health care settings, suggesting deficiencies across the health system. Prescribing guidelines which exclude many high-risk individuals contribute to suboptimal management. Guideline reform and improved health service capacity could substantially improve Indigenous vascular health.

Smoking, diabetes and cardiovascular diseases in men in the Asia Pacific region.

Abstract: Background: To assess whether there is a statistical interaction between smoking and diabetes that is related to the risk of cardiovascular disease (CVD) in men in the Asia Pacific region. Methods: An individual participant data meta-analysis was conducted on 34 cohort studies, involving 16 492 participants with diabetes (47.4% smokers) and 188 897 without (47.6% smokers). Hazard ratios (HR) and 95% confidence intervals (CI) were calculated for smoking (stratified by study and adjusted for age) for those with and without diabetes. Results: In men with diabetes, the HR (95% CI) comparing current smokers with non-smokers was 1.42 (1.10–1.83) for coronary heart disease, 1.10 (0.88–1.37) for total stroke and 1.15 (0.98–1.35) for total CVD. The corresponding figures for men without diabetes were 1.47 (1.33–1.61), 1.27 (1.16–1.39) and 1.35 (1.27–1.44), respectively. There was no evidence of a statistical interaction between diabetes and current smoking, the number of cigarettes smoked per day or quitting smoking. Smoking cessation was associated with a 19% reduction in CVD risk, irrespective of diabetes status. Conclusions: The effects of cigarette smoking and smoking cessation are broadly similar in men with and without diabetes. In Asia, where there are high rates of smoking and a rapidly increasing prevalence of diabetes, strategies that encourage smokers to quit are likely to have huge benefits in terms of reducing the burden of CVD in men with diabetes.

Recalibration of a Framingham risk equation for a rural population in India

Abstract: Background: Coronary heart disease (CHD) risk estimation tools are a simple means of identifying those at high risk in a community and hence a potentially cost-effective strategy for CHD prevention in resource-poor countries. Since India has few local data upon which to develop such a tool de novo, in this study a Framingham risk equation has been recalibrated to estimate CHD risks in a population from rural India and the sensitivity of the method to information resources examined. Recent surveys of this population have found high levels of cardiovascular risk factors, particularly metabolic risk factors and a high proportion of mortality due to cardiovascular diseases. Methods: The proportion of a rural Indian population at high risk of CHD using three risk estimation equations was estimated. The first a published version of the Framingham risk equation, the second a recalibrated equation using local mortality surveillance data and local risk factor data, and the third a recalibrated equation using national mortality data and local risk factor data. Results: The mean 10-year probability of CHD for adults >30 years was 10.4% (9.6% to 11.1%) for men and 5.3% (4.9% to 5.7%) for women using the Framingham equation; 10.7% (9.9% to 11.5%) for men and 4.2% (3.9% to 4.5%) for women using the local recalibration; and 18.9% (17.7% to 20.1%) for men and 8.2% (7.6% to 8.8%) for women using the national recalibration. Conclusion: These findings indicate that in India, equations recalibrated to summary national data are unlikely to be relevant to all regions of India and demonstrate the importance of local data collection to enable development of relevant CHD risk tools.

Trials of cardiovascular risk factor management in type 2 diabetes.

Abstract: PURPOSE OF REVIEW: To provide an overview of recent clinical trial findings relevant to cardiovascular risk management in patients with diabetes RECENT FINDINGS: Recent trial evidence has demonstrated benefits of routine blood pressure (BP) lowering, regardless of initial BP levels, in people with type 2 diabetes In addition, new data indicate that any BP-lowering strategy in diabetic patients needs to be continued to realise sustained benefits The effects of blood glucose lowering have been addressed in a number of recently concluded clinical trials; together, these have failed to provide clear evidence of cardioprotection with intensive glucose control over a 4-5-year period Long-term data, however, suggest that such benefits may only appear later A recent meta-analysis of statin trials has confirmed the benefits of these agents in patients with diabetes Two new trials of aspirin for 'primary prevention' of cardiovascular events in diabetic patients have failed to show benefit; however, both were underpowered SUMMARY: Recent clinical trial data have cemented the crucial role of BP-lowering and statin treatment for the prevention of cardiovascular events in patients with diabetes, but the uncertainty about intensive glucose control for these outcomes remains New evidence relating to other lipid-modifying agents and routine antiplatelet therapy in diabetes is anticipated over the next few years

Cardiovascular risk in Type 2 diabetes – reflecting on the ADVANCE study

Abstract: The world is facing an unprecedented increase in type 2 diabetes. Most disability and premature mortality experienced by patients with diabetes is related to vascular disease and, in particular, macrovascular disease (such as coronary heart disease and stroke) and microvascular disease (such as retinopathy, nephropathy and neuropathy). Indeed, around 1.9 million cardiovascular deaths worldwide are attributable to high blood glucose levels and diabetes, as well as to their associated dangerous companions of high blood pressure and abnormal lipid levels. The global economic costs of diabetes, including foregone economic growth and increasing healthcare expenditure, are substantial and are anticipated to grow. Therefore, strategies to reduce disease burden have continued to focus on reducing cardiovascular risk. Recently, a number of large-scale clinical trials have evaluated approaches for managing cardiovascular risk in patients with type 2 diabetes. Among them the Action in Diabetes and Vascular Disease: PreterAx and DiamicroN MR Controlled Evaluation (ADVANCE) trial has reported the effects of blood pressure lowering and intensive glucose control on major vascular events in patients with established type 2 diabetes. In this article we summarise the findings of the ADVANCE trial and discuss its relevance to the management of cardiovascular risk in patients with type 2 diabetes worldwide.

Cardiovascular risk: who should we treat, and how much should we stratify?

Abstract: Over the past decade, there has been a fundamental shift in the clinical paradigm for cardiovascular disease prevention, away from an approach based on defining and managing single risk factor abnormalities, and towards basing the need for and intensity of risk factor management on an evaluation of an individual’s future risk of experiencing a cardiovascular event. This “absolute risk” approach is rooted in an understanding of the nature of the association between key modifiable risk factors, such as blood pressure and cholesterol, and the occurrence of vascular events. In a range of diverse populations, these associations have been shown to be continuous, such that no obvious threshold value can be identified that clearly defines abnormal levels of blood pressure or cholesterol.1–4 Furthermore, these associations have been shown to be log-linear, suggesting that the relative benefits from a given reduction in blood pressure or cholesterol is likely to be similar, regardless of the initial level of that risk factor.1–4 This in turn provides a basis for expecting the absolute benefits of treatment to be greatest among those at highest initial risk of a cardiovascular event, rather than necessarily in those with the highest initial level of a particular risk factor. So, for example, one might expect that a 60-year-old smoking male with diabetes and a systolic blood pressure of 135 mm Hg will benefit more, in absolute terms, from being administered a blood-pressure-lowering drug than a 50-year-old non-smoking, non-diabetic woman with a systolic blood pressure of 160 mm Hg. These epidemiological principles have been supported by …

Routine blood pressure lowering and intensive glucose control in patients with Type 2 diabetes: the ADVANCE trial

Abstract: The Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial investigated the effects of routine blood pressure lowering and intensive blood glucose control on major vascular events in people with Type 2 diabetes. In this factorial randomized study, 11,140 individuals with Type 2 diabetes were randomly assigned to a fixed combination of perindopril and indapamide or matching placebo, and to intensive glucose control with the use of modified-release gliclazide plus other drugs required to achieve a hemoglobin A1c of 6.5% of less, or standard guideline-based glucose control. The primary outcomes were composites of major macrovascular and major microvascular events (major vascular events), analyzed jointly and separately. Active treatment in the blood pressure-lowering arm reduced blood pressure by 5.6/2.2 mmHg compared with placebo, and the relative risks of major vascular events, all deaths and cardiovascular deaths by 9% (p = 0.043), 14% (p = 0.025) and 18% (p = 0.027), respectively. These effects appeared independent of the initial blood pressure level or the use of concomitant treatments. Intensive glucose control lowered glycated hemoglobin levels to a mean of 6.5% and reduced the relative risk of major vascular events by 10% (p = 0.01), primarily through a 21% (p = 0.006) reduction in nephropathy. Intensive glucose control was not associated with a significant reduction in macrovascular events; however, unlike reports from the recently reported Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, there was no evidence of any increase in all-cause mortality or cardiovascular death with more intensive glucose control. This trial has provided important new evidence with direct implications for clinical management of blood pressure and blood glucose in patients with Type 2 diabetes.

Management of cardiovascular risk factors in Australian General Practice of those at highest risk

Abstract: Aims: To evaluate the management of cardiovascular risk in patients with high risk conditions in Australian General Practice Methods: National cross-sectional survey of 99 Australian General Practitioners participating in the Bettering the Evaluation and Care of Health (BEACH) program. Information was collected on the presence of cardiovascular risk factors, prescribed treatment and achievement of target levels. Results: Information was obtained for 2,618 adult patients of whom 702 had at least one high risk condition (coronary heart disease [CHD], cerebrovascular disease, peripheral vascular disease, diabetes or chronic renal failure). In this high risk group, blood pressure (BP) and diabetes screening were well assessed across all the disease groups (92 to 98%). Full lipid sub-fractions within the last 12 months were only available for approximately half (47 to 61%). The treatment gap (either indicated for prescribed treatment and not receiving it or receiving prescribed therapy but not reaching target) for lipids was between 29 and 57% and for BP was between 32 and 47%. Patients with diabetes had the lowest treatment gap for lipids with CHD having the lowest treatment gap for BP. Conclusion: Management of cardiovascular risk in those at highest risk of a future event remains substantially suboptimal. Development of novel strategies to help bridge evidence-practice gaps is necessary.

ADVANCE: Blood Pressure Lowering in Diabetes

Abstract: To the Editor: We were surprised at a notable omission in the recently published ‘‘ASH Position Paper: Treatment of Hypertension in Patients With Diabetes—An Update,’’ by Bakris and Sowers for the American Society of Hypertension Writing Group. This update purports to focus on ‘‘clinical outcomes literature published within the last 3 years,’’ yet it fails to mention the largest-ever trial conducted on blood pressure lowering in patients with type 2 diabetes, the results of which were published in The Lancet in September 2007. The Action in Diabetes and Vascular Disease (ADVANCE) trial, which involved 11,140 patients from 20 countries, evaluated the effects on vascular events of, first, routine blood pressure lowering using a fixed-dose combination of an angiotensinconverting enzyme (ACE) inhibitor and a diuretic and, second, intensive blood glucose control. While the results of the glucose-lowering intervention were referenced in the update by Bakris and Sowers, there was no mention of the more relevant findings from the blood pressure intervention. In this part of the study, patients were randomized in a double-blind fashion to a fixed-dose combination of perindopril and indapamide or placebo. Participants were included regardless of initial blood pressure level, and randomized therapy was provided in addition to other blood pressure lowering and cardiovascular preventative treatments that patients were typically receiving, including ACE inhibitors. The mean blood pressure of participants at baseline was 145 ⁄81 mm Hg, and the ACE inhibitor ⁄diuretic combination reduced blood pressure by an average of 5.6 ⁄2.2 mm Hg compared with placebo. At the end of an average follow-up period of 4.3 years, active treatment reduced combined macrovascular and microvascular complications by 9% and also resulted in significant reductions in allcause mortality (14%), cardiovascular death (18%), total coronary events (14%), and total renal events (21%). The relative effects of treatment did not appear to vary according to initial blood pressure value or the use of concomitant therapies, including ACE inhibitors or angiotensin receptor blockers. Overall, adherence to randomized treatment was high, and there were no significant differences in glycemic status or the use of glucoselowering therapies between the randomized groups at the end of follow-up. We believe that the results of the ADVANCE trial have important and direct implications for the management of blood pressure in patients with diabetes. The findings point to a particular strategy and therapeutic regimen that improved blood pressure levels, produced reductions in important clinical outcomes, and was well tolerated with few adverse effects. Given the persistent difficulties in achieving blood pressure targets in patients with diabetes, alluded to by Bakris and Sowers, it might have been useful to refer to these findings and to this strategy for reducing cardiovascular mortality and morbidity in patients with type 2 diabetes.—Anushka Patel, MD, PhD; John Chalmers, MD, PhD; Stephen MacMahon, DSc, PhD; Bruce Neal, MD, PhD, The George Institute for International Health, University of Sydney, PO Box M201, Missenden Road, NSW 2050, Australia E-mail: apatel@george.org.au