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2014 ; 13
(ä): 1111-9
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Renin inhibitors in diabetes and hypertension: an update
#MMPMID26417326
Sen S
; Ufuktepe B
; Özünal ZG
; Üresin Y
EXCLI J
2014[]; 13
(ä): 1111-9
PMID26417326
show ga
The coexistence of hypertension and diabetes increases the incidence of
cardiovascular events and long-term morbidity and mortality. Blood pressure
should be controlled with the most appropriate drugs as well as tight blood
glucose control in patients with diabetes and hypertension. RAAS (Renin
Angiotensin Aldosterone System) blockers have an important role in the treatment
of these patients, in this sense, ACEi and ARB remained the major treatment
option in hypertension guidelines. The most recent RAAS blocker to be approved by
the FDA was aliskiren in 2007, a renin inhibitor. Studies showed that aliskiren
is as effective as other antihypertensive drugs and has a safety profile similar
to placebo. The potent renin inhibitor aliskiren directly inhibits the RAAS
system at its rate limiting step and differently from other RAAS blockers; it
decreases plasma renin activity (PRA). Although the relationship of increased PRA
levels and cardiovascular risk has been shown, it is unclear if the PRA decrease
provided by aliskiren has an impact on clinical outcomes and cardiovascular
endpoints. On the other hand, large trials like ASPIRE, AVANT-GARDE, ALTITUDE,
ASTRONAUT, which investigated the combination of aliskiren with other RAAS
blockers, failed to show the expected outcomes or resulted with an increased
incidence of adverse effects, which raised more questions. As a result of the
ALTITUDE trial, combination of aliskiren with an ACEi or ARB is not recommended
in patients with hypertension and diabetes, or at least moderate renal
dysfunction. Trials designed to prove aliskiren's efficacy in new indications
like diabetes, may face similar problems related to dual RAAS blockade because in
the majority of cases, the optimal treatment is achieved with an ACEi or ARB. In
this conjuncture, the increase in adverse events seen with aliskiren might be
related to dual RAAS blockade rather than aliskiren directly. For instance, it is
unclear whether the adverse event incidence would be the same, less, or higher if
ALTITUDE was designed to investigate ACEi and ARB combination without aliskiren.
In fact, every new molecular entity and mechanism of action faces the same
barriers. For the time being, differentiating points like PRA lowering effects as
an add-on therapy to calcium channel blockers or hydrochlorothiazide, and the
populations that might have additional benefit, should be carefully investigated.