Hypertension Control in Adults with Diabetes Mellitus and Recurrent Cardiovascular Events: Global Results from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin

Systolic blood pressure (SBP) treatment targets for adults with diabetes mellitus remain unclear. SBP levels among 12 275 adults with diabetes mellitus, prior cardiovascular disease, and treated hypertension were evaluated in the TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin) randomized trial of sitagliptin versus placebo. The association between baseline SBP and recurrent cardiovascular disease was evaluated using multivariable Cox proportional hazards modeling with restricted cubic splines, adjusting for clinical characteristics. Kaplan-Meier curves by baseline SBP were created to assess time to cardiovascular disease and 2 potential hypotension-related adverse events: worsening kidney function and fractures. The association between time-updated SBP and outcomes was examined using multivariable Cox proportional hazards models. Overall, 42.2% of adults with diabetes mellitus, cardiovascular disease, and hypertension had an SBP ≥140 mm Hg. The association between SBP and cardiovascular disease risk was U shaped, with a nadir ≈130 mm Hg. When the analysis was restricted to those with baseline SBP of 110 to 150 mm Hg, the adjusted association between SBP and cardiovascular disease risk was flat (hazard ratio per 10-mm Hg increase, 0.96; 95% confidence interval, 0.91-1.02). There was no association between SBP and risk of fracture. Above 150 mm Hg, higher SBP was associated with increasing risk of worsening kidney function (hazard ratio per 10-mm Hg increase, 1.10; 95% confidence interval, 1.02-1.18). Many patients with diabetes mellitus have uncontrolled hypertension. The U-shaped association between SBP and cardiovascular disease events was largely driven by those with very high or low SBP, with no difference in cardiovascular disease risk between 110 and 150 mm Hg. Lower SBP was not associated with higher risks of fractures or worsening kidney function

Causes of death in a contemporary cohort of patients with type 2 diabetes and atherosclerotic cardiovascular disease: Insights from the TECOS trial

Objective: We evaluated the specific causes of death and their associated risk factors in a contemporary cohort of patients with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD). Research Design and Methods: We used data from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) study (n = 14,671), a cardiovascular (CV) safety trial adding sitagliptin versus placebo to usual care in patients with type 2 diabetes and ASCVD (median follow-up 3 years). An independent committee blinded to treatment assignment adjudicated each cause of death. Cox proportional hazards models were used to identify risk factors associated with each outcome. Results: A total of 1,084 deaths were adjudicated as the following: 530 CV (1.2/100 patientyears [PY], 49% of deaths), 338 non-CV (0.77/100 PY, 31% of deaths), and 216 unknown (0.49/100 PY, 20% of deaths). Themost common CV death was sudden death (n = 145, 27% of CV death) followed by acute myocardial infarction (MI)/stroke (n = 113 [MI n = 48, stroke n = 65], 21% of CV death) and heart failure (HF) (n = 63, 12% of CV death). Themost common non-CV deathwas malignancy (n = 154, 46% of non-CV death). The risk of specific CV death subcategories was lower among patients with no baseline history of HF, including sudden death (hazard ratio [HR] 0.4; P = 0.0036), MI/stroke death (HR 0.47; P = 0.049), and HF death (HR 0.29; P = 0.0057). Conclusions: In this analysis of a contemporary cohort of patients with diabetes and ASCVD, sudden death was the most common subcategory of CV death. HF prevention may represent an avenue to reduce the risk of specific CV death subcategories

Statistical considerations in the intent-to-treat principle.

ABSTRACT: This paper describes some of the statistical considerations in the intent-to-treat design and analysis of clinical trials. The pivotal property of a clinical trial is the assignment of treatments to patients at random. Randomization alone, however, is not sufficient to provide an unbiased comparison of therapies. An additional requirement is that the set of patients contributing to an analysis provides an unbiased assessment of treatment effects, or that any missing data are ignorable. A sufficient condition to provide an unbiased comparison is to obtain complete data on all randomized subjects. This can be achieved by an intent-to-treat design wherein all patients are followed until death or the end of the trial, or until the outcome event is reached in a time-to-event trial, irrespective of whether the patient is still receiving or complying with the assigned treatment. The properties of this strategy are contrasted with those of an efficacy subset analysis in which patients and observable patient data are excluded from the analysis on the basis of information obtained postrandomization. I describe the potential bias that can be introduced by such postrandomization exclusions and the pursuant effects on typ