Table 2.

Major randomized controlled trials evaluating the effect of dual RAAS-blockade on renal outcomes and the associated risk of hyperkalemia.

Study	Patient characteristics	N	Intervention	Follow- up	Effect on renal outcomes		Associated hyperkalemia risk
					DScr	ESRD	Definition	Incidence in dual RAAS group	Incidence in mono- therapy	Comparison	Ref
ONTARGET	Established CV disease or high risk DM	26620	Ramipril (10 mg/d) vs telmisartan (80 mg/d) vs their combination	4.6 yrs	↑	↑	sK ≥5.5 mEq/L	1.29 events per 100 patient-years	0.74 events per 100 patient-years	P<0.001 vs monotherapy	13
ALTITUDE	Type 2 DM, CKD, CV disease or both	8651	Aliskiren (300 mg/d) vs placebo on top of background therapy with ACEI or ARB	2.7 yrs	No difference	No difference	sK ≥6.0 mEq/L	11.2%	7.2%	P<0.001 vs monotherapy	9
VA-NEPHRON-D	Type DM with overt nephropathy	1448	Lisinopril (10–40 mg/d) vs placebo on top of background therapy with losartan (100 mg/d)	2.2 yrs	No difference	No difference	sK ≥6.0 mmol/L	6.3 events per 100 patient-years	2.6 events per 100 patient-years	HR:2.80; 95% CI: 1.80–4.30, P<0.001 vs monotherapy	8

Abbreviations: DM= diabetes mellitus; CV= cardiovascular; CKD= chronic kidney disease; ACEI= angiotensin-converting-enzyme-inhibitor; ARB= angiotensin-receptor-blocker; DSCr= doubling of serum creatinine; ESRD= end-stage-renal-disease; ONTARGET= Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial; ALTITUDE= Aliskiren Trial in Type 2 Diabetes Using Cardiorenal Endpoints; VA-NEPHRON-D= Veteran’s Administration Nephron-Diabetes Trial;