The world health organization—International society of hypertension blood pressure lowering treatment trialists’ collaboration: Prospective collaborative overviews of major randomized trials of blood pressure-lowering treatments

Clear evidence shows that decreasing blood pressure reduces risks for major cardiovascular events in patients with hypertension. However, there is considerable uncertainty about the separate effects of the various classes of blood pressure-lowering agents and the effects of blood pressure lowering in patients at high risk, particularly in the absence of hypertension. Several new randomized controlled trials have been started in the past few years in an effort to address these questions. However, individually, these studies are unlikely to resolve all current uncertainties. For this reason, systematic overviews and meta-analyses of the major ongoing trials are planned. The overviews will be conducted as a collaboration among the principal investigators of the participating trials and will involve about 270,000 patients and 1.1 million patientyears of follow-up. The combined trial results should provide good statistical power to detect even modest differences in the effects of various treatments on major cardiovascular outcomes.     

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

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.

Methods

Cognitive function was assessed using the Mini Mental State Examination at baseline, and defined by scores 28-30 (‘normal’, n?=?8,689), 24-27 (‘mild dysfunction’, n?=?2,231) and <24 (‘severe dysfunction’, n?=?212). Risks of major cardiovascular events, death and hypoglycaemia and interactions with treatment were assessed using Cox proportional hazards analysis.

Results

Relative to normal function, both mild and severe cognitive dysfunction significantly increased the multiple-adjusted risks of major cardiovascular events (HR 1.27, 95% CI 1.11–1.46 and 1.42, 95% CI 1.01–1.99; both p?<?0.05), cardiovascular death (1.41, 95% CI 1.16–1.71 and 1.56, 95% CI 0.99–2.46; both p?≤?0.05) and all-cause death (1.33, 95% CI 1.16–1.54 and 1.50, 95% CI 1.06–2.12; both p?<?0.03). Severe, but not mild, cognitive dysfunction increased the risk of severe hypoglycaemia (HR 2.10, 95% CI 1.14–3.87; p?=?0.018). There was no evidence of heterogeneity of treatment effects on cardiovascular outcomes in subgroups defined by cognitive function at baseline.

Conclusions/interpretation

Cognitive dysfunction is an independent predictor of clinical outcomes in patients with type 2 diabetes, but does not modify the effects of BP lowering or glucose control on the risks of major cardiovascular events.

Trial registration:

ClinicalTrials.gov NCT00145925

Funding:

Supported by grants from Servier and from the National Health and Medical Research Council of Australia.