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Aliskiren is the first orally active
inhibitor of renin to be approved for clinical
use as an antihypertensive agent. The
development program has established that at the
licensed doses of 150 mg and 300 mg, there are
dose-related falls in blood pressure comparable
to those seen with other major classes of
antihypertensive drugs and that these falls are
associated with a placebo level of side effects.
Aliskiren was found to be effective either as
monotherapy or in combination with drugs from
the other major classes. As expected, there was
a greater benefit from adding aliskiren to
natriuretic drugs than to other blockers of the
renin system. However, there was also some
consistent benefit from dual renin blockade.
Aliskiren is likely to be of most value in
patients uncontrolled by, or intolerant of,
other classes. Rational understanding of the
renin system will maximize its value, for
instance, by encouraging greater use of
natriuretic agents in patients with resistant
hypertension to render their hypertension renin
dependent. Whether there are cardiovascular
benefits other than blood pressure control in
blocking the renin system remains to be
demonstrated. It is hoped that long-term outcome
studies with aliskiren will finally allow this
question to be answered.
Circulation. 2008;118:773-784
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