Safety and Efficacy of Low Blood Pressures Among Patients With Diabetes: Subgroup Analyses From the ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial)

Study Questions:

Do blood pressure (BP) levels at which cardiovascular (CV) protection is achieved differ between diabetic and nondiabetic patients during treatments based on blockade of the renin-angiotensin system?

Methods:

A total of 25,584 patients (9,603 diabetic), older than 55 years, at high CV risk were randomized to ramipril, telmisartan, or both and observed for 4.6 years. The investigators pooled the treatment arms to examine the relationships between BP and the primary composite outcome (CV death, nonfatal myocardial infarction or stroke, or hospitalized heart failure) and its components. The relation between baseline systolic BP, divided into quartiles and risk of the primary and other outcomes, was explored using Cox regression, as well as the relation between outcome and the magnitude of systolic BP changes during follow-up, divided into tertiles, for each systolic BP entry quartile.

Results:

The primary outcome occurred in 1,938 (20.2%) diabetic patients and in 2,276 (14.2%) nondiabetic patients. Compared with nondiabetic patients, diabetic patients had a significantly higher risk for the primary endpoint (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.38-1.57) and CV death (HR, 1.56; 95% CI, 1.42-1.71); myocardial infarction (HR, 1.30 (95% CI, 1.17-1.46); stroke (HR, 1.39; 95% CI, 1.23-1.56); and congestive heart failure hospitalization (HR, 2.06; 95% CI, 1.82-2.32). The CV risk was significantly higher in diabetic than in nondiabetic patients regardless of the systolic BP changes during treatment. In both diabetic and nondiabetic patients, progressively greater systolic BP reductions were accompanied by reduced risk for the primary outcome only if baseline systolic BP levels ranged from 143 mm Hg to 155 mm Hg; except for stroke, there was no benefit in fatal or nonfatal CV outcomes by reducing systolic BP below 130 mm Hg.

Conclusions:

The authors concluded that the relationship between BP and overall CV risk had a similar pattern in diabetic and nondiabetic patients.

Perspective:

This post-hoc analysis of the large ONTARGET database shows that the relationship between BP and overall CV risk had a similar pattern in diabetic and nondiabetic patients over a wide range of baseline and in-treatment BP values. The role of diabetes was to shift the relationship of events with BP upward compared with that in the nondiabetic group. Pending additional data from prospective studies, diabetic patients with hypertension should be treated to a target BP <130/80 mm Hg, based on Joint National Committee 7 and American Diabetes Association recommendations.

Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Novel Agents, Hypertension

Keywords: Risk, Myocardial Infarction, Follow-Up Studies, Benzimidazoles, Cardiovascular Diseases, Renin-Angiotensin System, Hypotension, Hypertension, Diabetes Mellitus, Benzoates, United States


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