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There was, however, a positive signal for stroke. The annual rate for stroke was 0.32% and 0.53% in the lower and higher BP groups, respectively (P<.01). Stroke is the most BP-sensitive target organ damage associated with hypertension. Thus, the negative outcome of ACCORD lies with the lack of a beneficial effect of lowering BP on the ischemic heart disease events included in the composite end point. An important aspect of understanding this result is to scrutinize the means by which BP was lowered between the two groups. In the ��intensive treatment arm,�� investigators were advised to begin a regimen of an ACE inhibitor or angiotensin receptor blocker (ARB) plus a thiazide-type diuretic, chlorthalidone. Such prescriptive advice was not given in the less intensively treated group. This resulted <a href="http://www.selleckchem.com/products/Paclitaxel(Taxol).html">buy Paclitaxel in the intensively treated group receiving roughly twice as much diuretic as the less-intensively treated group. Again, one might reason that the lower BP levels did not result in improvement. On the other hand, one might equally reason that the diuretics reduced the benefit of lowering BP as previously seen in ALLHAT and ACCOMPLISH. In the Intensive treatment group, diuretics were used 83% and 89% at 12 months and at the last visit, respectively, while in the standard care group, the usage was 52% and 56%. Thus, at 12 months, diuretic use was 33% higher in the intensive arm. This diuretic usage could account for the greater incidence of hypokalemia seen in the intensive treatment group (P=.01).4�C6 Analysis of data Sitaxentan from the Systolic Hypertension in the Elderly Program (SHEP) trial,7 suggests that this degree of hypokalemia would essentially eliminate the projected benefit on ischemic heart disease events from the BP reduction achieved in the ACCORD trial. ACCORD illustrates the difficulty in using composite end points. For example, patients with stroke benefitted from the BP reduction while those with ischemic cardiovascular events did not. It is likely Panobinostat that the decrease in BP had a beneficial effect on stroke, while the potential benefit on ischemic events was offset perhaps by adverse effects of drug therapy. Stroke is generally improved by treatment with diuretics, while ischemic heart disease outcomes are not. Sudden death has been a concern with diuretic therapy.8 We believe that all possibilities for the results seen in these large clinical trials should be considered, even the ever-elusive ��J�� curve. We do believe, however, that it is paramount that when a more successful lowering of BP does not result in the expected beneficial result, it should be considered that the regimen used to lower BP may have had a negative effect. At starting levels of BP near normal, the benefits of lowering are reduced compared with higher levels so that the adverse effects of antihypertensive drugs become more apparent. It is not clear why a difference in treatment strategies was permitted in ACCORD.