It seems that there could be a dissociation between results of RCTs showing the efficacy of ACE inhibitors or ARBs with the effectiveness observed in clinical practice. failure, CKD, established CV disease, and progression of coronary atherosclerosis failed to show differences when added on top of an ACE inhibitor or an ARB.4?6 This drug, aliskiren, was never given the opportunity to show its capacities in a head to head comparison with either an ACE inhibitor or an ARB, and was used as monotherapy or in combination preferentially with a diuretic or a calcium antagonist for the treatment of arterial hypertension. Only two studies were designed to investigate the capacity of aliskiren alone; in the first, the ATMOSPHERE study, it is compared with an XL184 free base (Cabozantinib) ACE inhibitor or with the combination of the two in chronic heart failure with low ejection portion,7 and, the second, the APOLLO trial, was designed to investigate the capacity of aliskiren to reduce CV disease in elderly hypertensives with systolic blood pressure (SBP) between 130 and 159 mmHg through the administration of the drug alone or in combination using a stratified 2 2 factorial trial and added on top of other medications (48.2% were taking an ACE inhibitor or an ARB). Regrettably, the second study was prematurely halted at the request of the sponsor. Now the results of the tolerability and efficacy of aliskiren alone or in combination with hydrochlorothiazide or amlodipine and its antihypertensive efficacy in elderly hypertensives (72.1 5.2 years) during the XL184 free base (Cabozantinib) short duration of the study (0.6 year of follow-up) are presented.8 The study confirmed the good antihypertensive efficacy of aliskiren that induced sizeable reductions in BP, with potential for substantial CV reduction, that were safely achieved in the elderly with highCnormal or stage 1 Rabbit polyclonal to ECHDC1 hypertension. The final data of this study would have been of great interest for several reasons, among which the most relevant would have been to know: first, whether SBP 160 mmHg can be safely treated in the elderly, including those with XL184 free base (Cabozantinib) established CV disease; secondly, whether SBP levels between 130 and 139 mmHg can be treated; and, thirdly, and related to the previous two, whether the reduction of SBP below 130 mmHgwhich the European Society of Hypertension (ESH)/European Society of Cardiology (ESC) hypertension Guidelines do not recommend because of absence of evidence and a potential riskis safe.9 In this sense, in patients with SBP below 140 mmHg and with established CV disease, the adminstration of antihypertensive drugs for reasons other than lowering BP has been shown to have a positive effect.10 We will not know the anwers to any of these three questions because the study was stopped, and this probably occurred because of the previous failures of aliskiren and the risk of failing again in an area of interest but accompanied by a potentially high margin of risk if the BP was lowered too much. The ALTITUDE study5 also contributed to the acknowledgement by Guidelines that dual blockade of the RAS cannot be used in clinical practice. A second study now published contains data from your Reduction of Atherothrombosis for Continued Health (REACH) registry that show that the use of an ACE inhibitor or an ARB was not associated with better outcomes in stable CAD.11 These data do not replicate previous findings in randomized clinical trials. Results also obtained from the REACH registry in patients with CAD risk factors only, known prior XL184 free base (Cabozantinib) MI, or known CAD XL184 free base (Cabozantinib) without MI show similar results for the use of beta-blockers that were not accompanied by a lower.