Furthermore a recently published network meta analysis inclu

Furthermore, a recently published network meta-analysis including 30 trials in patients with hypertension and diabetes demonstrated that ARBs have efficacy similar to that of ACEIs for all-cause and cardiovascular mortality (HR 0.95, 95% CI 0.73 to 1.30 and HR 1.23, 95% CI 0.64 to 2.78, respectively) (21).
Strategies to Improve Cardiovascular and Renal Outcomes in Patients with Diabetes Who Are Taking ARBs
Sodium-Glucose Cotransporter Type 2 Inhibitors in Association With ARBs in Patients With Diabetes ACEIs and ARBs have demonstrated cardio- and nephroprotective properties in patients with diabetes, and no other single drug group has been able to show any benefit on hard outcomes in patients with diabetes. Recently introduced selective sodium-glucose cotransporter type 2 (SGLT-2) inhibitors constitute a major breakthrough in the management of patients with diabetes, showing high efficacy for the prevention of cardiovascular and renal outcomes in this population (27). The Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients trial enrolled adult patients who had type 2 diabetes, had an estimated GFR ≥30 mL/min/1.73 m2 and had established cardiovascular disease (28). A total of 80% of patients were already taking an ACEI or an ARB. They were randomized to receive empagliflozin (10 mg or 25 mg) or matching placebo. The primary cardiovascular outcome, a composite of cardiovascular death, nonfatal myocardial infarction or stroke occurred in 10.5% of patients in the empagliflozin group and in 12.1% in the placebo group (HR 0.86, 95% CI 0.74 to 0.99). The incidence of hospitalization for Antagonist G australia failure was significantly lower in the empagliflozin arm compared with the placebo arm. A secondary analysis assessed the renal outcomes of the same trial (29). Empagliflozin was associated with significant risk reduction compared with placebo for the outcomes of incident or worsening nephropathy, progression to macroalbuminuria, doubling of serum creatinine with an estimated GFR ≤45 mL/min/1.73 m2, initiation of renal replacement therapy, or the composite outcomes of incident or worsening nephropathy and cardiovascular death or the doubling of serum creatinine with an estimated GFR ≤45 mL/min/1.73 m2, initiation of renal replacement therapy and death from renal disease. The Canagliflozin Cardiovascular Assessment Study program included 2 sister trials in individuals with diabetes and an estimated GFR >30 mL/min/1.73 m2(30). Patients 30 years of age or older who had histories of symptomatic cardiovascular disease or patients 50 years of age or older who had 2 additional cardiovascular risk factors were randomized to receive canagliflozin (100 or 300 mg) or matching placebo. A total of 80% of patients were receiving a renin angiotensin inhibitor at baseline. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction or nonfatal stroke. A total of 26.9 participants had an event per 1000 patients-years in the canagliflozin group vs. 31.5 in the placebo group (HR 0.86, 95% CI 0.75 to 0.97). Regression of albuminuria occurred more commonly in patients assigned to canagliflozin. A composite renal outcome of sustained 40% decline in GFR, need for renal replacement therapy or death from renal cause was observed less commonly in the canagliflozin group (HR 0.60, 95% 0.47 to 0.77) (30). The renoprotective effects of canagliflozin seem to be independent of its glycemic effects (31).
Conclusions
Author Disclosures
Introduction The functional role of the renin-angiotensin system (RAS) has historically been implicated in cardiovascular and fluid homeostasis. The precursor molecule angiotensinogen is cleaved by renin into angiotensin I, which is then converted into angiotensin II (ANG2) by angiotensin-converting enzyme (ACE) (Wright and Harding, 2011). The primary actions of ANG2 are mediated by angiotensin II receptors type 1 (AGTR1) and 2 (AGTR2) (Wright and Harding, 2011).