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Effectiveness of first renin inhibitor drug for treating hypertension is limited

Hypertension is a serious condition affecting millions. Currently there are seven classes of drugs used to reduce blood pressure. Aliskiren (Tekturna®, Rasilez®) is the first of a new class of orally active antihypertensive drugs that works by inhibiting renin. A review of six large-scale clinical trials of aliskiren is being published in the May issue of the American Journal of Hypertension. The authors report that, because of reactive renin secretion, this drug has not been any more effective than those already widely available to control hypertension.

Renin inhibitors, for which aliskiren is a prototype, become the fourth class of drugs to lower blood pressure by blocking the renin-angiotensin system. Previously existing classes are beta blockers, converting enzyme inhibitors (CEIs) and angiotensin receptor blockers (ARBs). Many drugs in these classes have lost patent protection and are available as generics.

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In analyzing clinical trials involving over 5000 hypertensive patients, aliskiren was not more effective as an antihypertensive agent than CEIs, ARBs or diuretics and it has a limited antihypertensive dose response curve. Although aliskiren lowered blood pressure to a greater extent when combined with a CEI or an ARB or a diuretic, blood pressure control was achieved by less than 50% of patients. Because aliskiren stimulates kidney renin secretion to a greater degree than do CEIs or ARBs, its antihypertensive capabilities can be counteracted by large reactive increases in renin secretion; this is particularly likely at higher dosage.

Writing in the article, Jean E. Sealey D.Sc. states, "Aliskiren’s pervasive stimulation of varying degrees of renin secretion could especially be a problem for those hypertensive patients who have hyper reactive renin systems such as patients with renovascular, advanced or malignant hypertension, all of whom were excluded from the trials. Their reactive renin responses might be so great as to induce a rise in blood pressure. Until the possibility of aliskiren inducing increases in blood pressure is eliminated it seems safer, and simple and wiser to stick to the less expensive, equally effective and widely available generic drugs for treating hypertensive disorders."

The article is "Aliskiren, The First Renin Inhibitor for Treating Hypertension: Reactive Renin Secretion May Limit Its Effectiveness" by Jean E. Sealey DSc and John H. Laragh MD. It appears in the May 2007 issue of the American Journal of Hypertension, Volume 20/Issue 5, published by Elsevier.