What is the truth about renin angiotensin blockers for diabetic patients?

Abstract

Many type 2 diabetic patients have concomitant hypertension. These patients require treatment to maintain their blood pressure (BP) within acceptable ranges to decrease the risk of cardiovascular disease or diabetic nephropathy. Lowering BP can decrease the risk or slow the progression of diabetic nephropathy, and thus it is important to evaluate diabetic patients with albuminuria and perform proper staging of diabetic nephropathy. In the Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) study in 2009 [1], of 11,140 patients with type 2 diabetes, those who achieved lower BP presented fewer renal events. The BP target for hypertensive patients with diabetes is\130/80 mmHg in Japan. The Guidelines of the Japan Diabetes Society and the Japan Hypertension Society recommend angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) as the first choice of antihypertensive treatment for diabetic patients [2, 3]. As recommended, we usually prescribe a renin angiotensin system (RAS) blocker to diabetic patients with hypertension. However, the treatment goal of BP for patients with diabetes and hypertension is\140/90 mmHg based on the recommendations from the American Diabetes Association [4]. The evidence supporting this goal was obtained from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. In that trial, no benefit was found regarding cardiovascular outcomes when comparing aggressive BP treatment goals (\120 mmHg) with moderate treatment goals (\140 mmHg) in patients with type 2 diabetes [5]. The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) also assessed the BP levels at which cardiovascular protection is achieved with treatment by ACE inhibitors, ARB, or both for diabetic and nondiabetic patients [6]. In that subgroup analysis, a progressive reduction in the incidence of stroke was observed when systolic BP reached 115 mmHg, but a J-curve relationship was observed for cardiovascular death and myocardial infarction. In 2015, Edmin and colleagues reported a systematic review and meta-analysis on the association between BP-lowering treatment and vascular outcomes (including macrovascular and microvascular outcomes) in type 2 diabetes [7]. They reported that each 10 mmHg decrease in systolic BP was significantly associated with improved mortality, cardiovascular disease, coronary heart disease, stroke, retinopathy, and albuminuria. They also evaluated outcomes stratified by achieved systolic BP. The outcomes of stroke and albuminuria were also significantly reduced in the stratum with BP lower than 130 mmHg. In a recent meta-analysis published in the BMJ, Bangalore and colleagues evaluated the outcomes of diabetic patients treated with RAS blockers compared with other antihypertensive agents [8]. They evaluated 19 randomized controlled trials that enrolled 25,414 diabetic patients and were followed up for a mean of 3.8 years. The trials included in that meta-analyses were published between 1998 and 2012, and most of the trials began before 2000. In 2003, the Seventh Report of the Joint National & Atsuko Abiko aabiko@asahikawa-med.ac.jp