Importance of Blood Pressure Lowering in Type 2 Diabetes: Focus on ADVANCE

Abstract

Routine blood pressure lowering with the fixed combination of perindopril and indapamide in 11,140 patients with type 2 diabetes was very well tolerated and produced substantial benefits in reducing all-cause and cardiovascular mortality, the primary combined outcome of macro- or microvascular events, total coronary events, and total renal events, as reported previously. We present here a wealth of evidence, most of it previously published either in journal articles or in recent abstract form, that the relative risk reductions conferred by the combination of perindopril and indapamide are broadly consistent across subgroups defined by a wide range of baseline characteristics, including blood pressure at entry, age from below 65 to above 75 years, total cardiovascular risk defined according to the European guidelines, stage of chronic disease, and cognitive function. Furthermore, we report that the absolute risk reductions are significantly greater in those with increased cardiovascular risk, with more advanced nephropathy and in older subjects. We confirm that the effects of blood pressure lowering with perindopril-indapamide and of intensive glucose control with the gliclazide modified release (MR)-based regimen are independent and produce substantial additional benefits when combined. We also discuss these results in the context of other major trials and demonstrate how they extend the evidence on the benefits of blood pressure lowering in patients with diabetes. Finally, we present evidence that the results of The Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE trial) are broadly generalizable to patients with type 2 diabetes in community practice, and that if the joint benefits from routine blood pressure lowering with perindopril-indapamide and more intensive control with the gliclazide-MR-based regimen were applied worldwide, close to 2 million lives would be saved over the next 5 years.

Do Cardiac Biomarkers NT-proBNP and hsTnT Predict Microvascular Events in Patients With Type 2 Diabetes? Results From the ADVANCE Trial

“…As such, our findings should be considered hypothesis generating. Our results relating to clinical risk predictors are, however, consistent with other data from an ethnically distinct cohort (7), and the baseline characteristics of the ADVANCE cohort are very comparable with those in several observational studies at the community level (33). Although the large study population and case-cohort design ensure considerable statistical power and allow reliable correction for many potential confounding factors, other possible confounders may be present, leading to an overestimate of risk associations.…”

Impact of age, age at diagnosis and duration of diabetes on the risk of macrovascular and microvascular complications and death in type 2 diabetes

“…The limitations include the post hoc nature of the analysis and the highly selected study population, which was enriched with patients with complications or at high risk of cardiovascular disease and excluded patients on long-term insulin therapy. However, given the similarities between our cohort and other community-based observational cohorts of people with type 2 diabetes, we still believe our findings are somewhat generalisable [22]. Another limitation was our dependence on physician or patient report of age at first diabetes diagnosis (from which diabetes duration was determined).…”

Circulating Inflammatory Markers and the Risk of Vascular Complications and Mortality in People With Type 2 Diabetes and Cardiovascular Disease or Risk Factors: The ADVANCE Study

“…While our findings cannot be generalized to persons with T2DM who have neither CVD nor risk factors, the baseline characteristics of the ADVANCE Study cohort are comparable to several other observational studies at the community level (32), and hence it seems reasonable to conclude that its results are broadly generalizable, particularly for relative risks. Nevertheless, the selection criteria in the ADVANCE Study may have affected the IDI and NRI, which will not be constant across all subgroups; for example, each may differ between nonsmokers in the ADVANCE Study (who, by the selection criteria, had to have another risk factor if they were free of CVD) and nonsmokers in general diabetes populations aged $55 years.…”