reviewer COMMENTARY
nature publishing group
See Brief communication page 954
Jean E. Sealey1 and John H. Laragh2
A
review of clinical trials of aliskiren published by Stanton et al.1 in this issue reveals that almost half of all hypertensive patients given the direct renin inhibitor, aliskiren, or an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB) fail to have their systolic BP (SBP) reduced by at least 10 mm Hg or their SBP controlled to <140 mm Hg (see their Figures 1 and 2). We previously explored the reasons for these poor responses.2 Stanton et al.1 now accept our view that patients with low baseline plasma renin activity (PRA) have no renin to block and are more likely to respond to natriuretic than to antirenin system drug types.3 Thus, we can use the information provided by an ambulatory PRA test to determine whether each patient is more likely to respond to a natriuretic drug or instead to an antirenin system drug. But, although we now agree that low-renin patients are poor responders to antirenin system drugs, Stanton et al.1 dispute our suggestion that BP can actually rise when on-treatment PRA increases instead of falls while taking aliskiren, or when PRA increases to more than tenfold baseline while taking an ACEI or ARB.2,4 However, they do not dispute that ACEIs, ARBs, and aliskiren all induce reactive increases in renin secretion. Nor do they dispute that clinical doses of antirenin system drugs can only block renin system activity by about 90%. Taken together, this means that renin–angiotensin system blockers are limited in their ability to block the effects of renin so that significant amounts of plasma renin–angiotensin remain unblocked when on-treatment PRA levels are high. Thus, there are at least two quite different reasons for an antirenin system drug to fail to correct a patient’s high BP that require two different drug type treatment strategies: (i) When PRA is low and there is no renin to block. (ii) When the on-treatment PRA rises so high that one antirenin system drug type is unable to block the renin system sufficiently to correct the hypertension. The low-renin patient requires the 1Department of Medicine, Weill Cornell Medical College, New York, New York,
s ubstitution or strengthening of a natriuretic drug for BP control. In contrast, a natriuretic drug may even be contraindicated in the patient with high on-treatment PRA levels because it further increases the amount of renin that must be blocked. An ambulatory PRA test while taking the drugs can readily discriminate between these two types of uncontrolled hypertensive patients. Based on these lines of reasoning, we developed an ontreatment PRA test-guided algorithm3 for controlling the BP of unsuccessfully treated hypertensive patients. This algorithm was successfully tested in a randomized clinical trial reported by Egan et al.5 Thus, an understanding of the relationships among PRA levels, sodium-volume status, and BP has both theoretical and practical clinical relevance for the treatment of all hypertensive patients irrespective of whether they are already taking antihypertensive medications.5 Acknowledgments: This work was supported by May and Samuel Rudin Family Foundation, Lawrence M. Gelb Foundation, Trust of Frederick Schwartz, Starr Foundation, and Wallace Foundation. Disclosure: J.E.S. is a Consultant for Diasorin Inc., Stillwater, MN. J.H.L is a consultant, Diasorin Inc., Stillwater, MN and holds a Licensed Patent #09/657,027 “Method for Evaluating and Treating Hypertension” to Diasorin Inc., Stillwater, MN. 1. Stanton AV, Dicker P, O’Brien ET. Aliskiren monotherapy results in the greatest and the least blood pressure lowering in patients with high- and low-baseline PRA levels, respectively. Am J Hypertens 2009; 22:954–957. 2. Sealey JE, Laragh JH. Aliskiren fails to lower blood pressure in patients who have either low PRA levels or whose PRA falls insufficiently or reactively rises. Am J Hypertens 2009; 22:112–121. 3. Laragh J. Laragh’s lessons in pathophysiology and clinical pearls for treating hypertension: lesson XVI: how to choose the correct drug treatment for each hypertensive patient using a plasma renin-based method with volume-vasoconstriction analysis. Am J Hypertens 2001; 14:491–503. 4. Sealey JE, Laragh JH. Aliskiren, the first renin inhibitor for treating hypertension: reactive renin secretion may limit its effectiveness. Am J Hypertens 2007; 20:587–597. 5. Egan B, Basile J, Rehman S, Davis P, Grob C, Riehle J, Walters CA, Lackland DT, Merali C, Sealey JE, Laragh JH. Plasma renin test-guided drug treatment algorithm for correcting patients with treated but uncontrolled hypertension: a randomized controlled trial. Am J Hypertens 2009; 22:792–801.
USA; 2Cardiovascular Center, Department of Cardiothoracic Surgery, New York–Presbyterian Hospital, Weill Cornell Medical College, New York, New York, USA. Correspondence: Jean E. Sealey (
[email protected]) doi:10.1038/ajh.2009.123 © 2009 American Journal of Hypertension, Ltd.
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september 2009 | VOLUME 22 NUMBER 9 | 950 | AMERICAN JOURNAL OF HYPERTENSION
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Using Plasma Renin (PRA) Testing to Design Follow-Up Drug Treatment Strategies in Hypertensive Patients Already Taking Antirenin System Drugs
