In patients with type 2 diabetes (T2D), more intense antihypertensive treatment with perindopril-indapamide may reduce all-cause mortality and major vascular events, irrespective of baseline blood pressure (BP) or 10-year risk for atherosclerotic cardiovascular disease (ASCVD), according to study results published in Hypertension.

Previous studies, including SPRINT (Systolic Blood Pressure Intervention Trial) and HOPE-3 (Heart Outcomes Prevention Evaluation-3), provided data supporting more intense BP control to lower the risk for cardiovascular events and death, but both studies focused mainly on patients without T2D.

The goal of this study was to assess the benefits and risks of intensified BP control in patients with T2D according to their baseline BP or cardiovascular risk. The researchers used data from the ADVANCE trial (Action in Diabetes and Vascular Disease: Preterax and Diamciron Modified Release Controlled Evaluation), in which participants at moderate to high risk were randomly assigned to intensive BP therapy with a combination of perindopril and indapamide or placebo.

Participants were classified according to their baseline systolic BP: <140 mm Hg or ≥140 mm Hg. The 10-year risk for ASCVD was estimated using risk equations described by the American College of Cardiology/American Heart Association guidelines and analyzed in 2 groups (ASCVD risk <20% or ≥20%).

Of 10,948 participants, 2333 had ASCVD risk <20%, including 1509 with systolic BP <140 mm Hg and 824 with systolic BP ≥140 mm Hg. Of 8615 participants with ASCVD risk ≥20%, 3133 patients had systolic BP <140 mm Hg and 5482 had systolic BP ≥140 mm Hg.

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During a mean follow-up of approximately 4 years, the researchers identified 837 deaths and 966 major vascular events. Compared with placebo, the combination of perindopril-indapamide was associated with a 9% lower risk for major vascular events (hazard ratio [HR], 0.91; 95% CI, 0.83-0.997) and 14% lower risk for all-cause mortality (HR, 0.86; 95% CI, 0.75-0.99). The effect was not dependent on baseline systolic BP, diastolic BP, or 10-year ASCVD risk.

The investigators noted that they found no statistical evidence that cough or hypotension/dizziness was more likely to lead to permanent discontinuation of the drug treatment in patients with baseline systolic BP <140 mm Hg vs ≥140 mm Hg compared with placebo.

According to the researchers, one of the study limitations was the small number of individuals with a 10-year ASCVD risk <10%; for that reason, they chose a cutoff of 20% to power the analysis. Furthermore, the study used a specific antihypertensive regimen and the effects of other drug treatments are unknown.

“[I]n the current study, ADVANCE participants with [T2D] benefited from more intensive BP treatment regardless of baseline BP and of 10-year estimated ASCVD risk,” concluded the investigators.

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Reference

Rahman F, McEvoy JW, Ohkuma T, et al. Effects of blood pressure lowering on clinical outcomes according to baseline blood pressure and cardiovascular risk in patients with type 2 diabetes mellitus [published online April 24, 2019]. Hypertension. doi:10.1161/hypertensionAHA.118.12414