Varying patterns of the antihypertensive and antialbuminuric response to higher doses of renin-angiotensin-aldosterone system blockade in albuminuric hypertensive type 2 diabetes mellitus patients

Objective: In patients with type 2 diabetes mellitus (T2DM), blocking of the renin-angiotensin-aldosterone system (RAAS) has demonstrated efficacy in lowering blood pressure (BP) and urinary albumin excretion rate (UAER). Nonetheless, not all patients successfully respond to RAAS blockade with a reduction in BP and UAER. Methods: This secondary analysis of a double-blind study of 391 patients with T2DM assessed the importance of using higher doses of the RAAS blocker valsartan to improve the BP and UAER response in patients initially identified as prompt or delayed responders. All patients received a starting dose of valsartan 160mg for a 4-week run-in period to classify them as either prompt responders (SBP<130mmHg or reduction in SBP≥10mmHg, 53%) or delayed responders (47%). All patients were then subsequently randomized to one of three valsartan doses: 160, 320, or 640 mg/day for 26 weeks. Results: Higher doses of valsartan (640 mg) demonstrated additional reductions in SBP among the prompt responders and led to greater SBP reductions from baseline (19.8mmHg) compared with valsartan 160 (14.4mmHg, P<0.05) and 320mg (16.5 mmHg). Among delayed responders, SBP reductions from baseline to end of study were similar (11-14mmHg, P≥0.05) across all valsartan doses. For UAER, higher valsartan doses produced further reductions by week 30, regardless of initial response. Conclusion Higher doses of valsartan did not appear to recruit delayed responders, but enhanced the prompt responder effects in patients with T2DM. Not all patients successfully respond in concordance to RAAS blockade with both reductions in BP and UAER. Reduction in BP dominates the antialbuminuric effect in both valsartan prompt responders and delayed responders independent of dose.