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Devising new drugs for the treatment of hypertension--"novel drugs targeting hypertension: renin inhibitors and beyond".

Beginning with this issue and continuing in the following two, a series of nine review articles dealing with real or possible novel drugs for the treatment of hypertension will appear in the Journal of Cardiovascular Pharmacology. Appropriately, the series is subtitled ‘‘Renin Inhibitors and Beyond,’’ because just in March 2007, the U.S. Food and Drug Administration approved the use of a new drug, aliskiren (Tekturna) to treat hypertension. Aliskiren, the first representative of a new class of orally active, nonpeptide inhibitors of renin, was developed by Novartis in conjunction with the biopharmaceutical company Speedel. The class of renin inhibitors is an important addition to the arsenal of antihypertensive drugs, which now numbers over 75. In keeping with the JNC 7 guidelines, aliskiren would seem a likely add-on drug to a thiazide diuretic for the 20% or so hypertensive patients who have high plasma renin levels. Given the worsening blood pressure control with time in some patients prescribed an ACE inhibitor or ARB, presumably because of the ‘‘renin escape’’ phenomenon, aliskiren may also be initially prescribed in combination with those other drug classes that target the renin angiotensin system. Prudent use of aliskiren as a monotherapy awaits the outcome of clinical studies designed to assess what effect this drug has on target organ damage and cardiovascular events associated with hypertension. The need for new drugs targeting hypertension is discussed in the lead-off article to this series, by Leibovitz and Schiffrin. Not only are high blood pressure and its associated adverse cardiovascular events the leading cause of death in the world, but the death rate from hypertension is on the rise. According to 2004 statistics, the American Heart Association reports that nearly one in three adults in the United States has high blood pressure, with about 65% of those being treated failing to reach target blood pressure levels. Furthermore, the prevalence of hypertension globally and in the United States is increasing at an alarming rate, driven in part by increasing obesity and longer life expectancy. Numerous clinical studies have established by now that even moderate decreases in blood pressure have profound effects in cardiovascular risk reduction. Consequently, hypertension treatment to date has focused on lowering blood pressure in patients by drug treatment (invariably with more than one drug) and lifestyle modification. In this context, renin inhibitors represent a traditional approach to hypertension, and if history is any precedent, they are unlikely to be the last word, even assuming that they exhibit a ‘‘beyond blood pressure’’ benefit for target organ damage, as is suspected for other renin angiotensin system inhibitors. Drug compliance, normal aging of blood vessels, and cardiovascular escape mechanisms are among a number of factors that will likely conspire to thwart ideal blood pressure control. Indeed, as discussed by Danser in the next issue, renin inhibitors themselves may have untoward effects. An alternative therapeutic strategy for treating hypertension that could be described as ‘‘propalliative’’ would be to not only block vasoconstriction, but simultaneously to activate endogenous vasodilatory and/or cardioprotective systems. Some support for the utility of this type of approach is found in the observation that ACE inhibitors are at least as good as,