02365nas a2200205   4500000000100000008004100001100001100042700001200053700001600065700001300081700001300094700001500107700001300122700001100135700001900146245014400165250001500309520178900324020004602113       2012                            d1 aGao P.1 aMann J.1 aGerstein H.1 aBoehm M.1 aRyden L.1 aSleight P.1 aYusuf S.1 aTeo K.1 aAnderson Craig00aDual inhibition of the renin-angiotensin system in high-risk diabetes and risk for stroke and other outcomes: results of the ONTARGET trial  a2012/12/203 a<p>
BACKGROUND:: A recent study suggested that addition of a direct renin inhibitor to either an angiotension-converting enzyme (ACE) inhibitor (ACEi) or an angiotensin receptor blocker (ARB) may increase stroke risk in people with diabetes and renal disease. METHODS:: We examined the effects of addition of an ACE inhibitor (ramipril) to an ARB (telmisartan) for a mean follow-up of 56 months in people with diabetes [n = 9628, mean age 66 years, baseline blood pressure 144/82 mmHg, BMI 29 kg/m, estimated glomerular filtration rate (eGFR) 73 ml/min, and urine albumin 11 mg/mmol] who participated in the ONTARGET trial, divided by those with (n = 3163) and without (n = 6465) nephropathy. We compared participants on monotherapy with either ramipril or telmisartan with those on dual therapy. RESULTS:: SBP decreased more with dual over monotherapy (-7.1 vs. -5.3 mmHg, P &lt; 0.0001) and the same number of strokes occurred (1.19 vs. 1.22 per 100 patient-years; hazard ratio 0.99, 95% confidence interval 0.82-1.20). Stroke rate was higher in participants with than those without diabetic nephropathy (1.5 vs. 1.0 per 100 patient-years), but effects of dual-therapy vs. monotherapy were not different in either subgroup (1.59 vs. 1.55 and 1.01 vs. 1.08 per 100 patient-years; P value for interaction = 0.60). Other cardiovascular and kidney outcomes (dialysis or doubling of serum creatinine) did not differ between dual-therapy and monotherapy in subgroups, but adverse events, namely acute dialysis, hyperkalemia and hypotension, tended to be more frequent with dual therapy, CONCLUSION:: A combination of ACEi and ARB does not increase strokes or alter other major cardiovascular or renal events in patients with diabetes, irrespective of the presence of nephropathy.
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