April 15, 2008

April 15, 2008 (Chicago, IL) - The new direct renin inhibitor aliskiren (Tekturna, Novartis), in combination with losartan (Cozaar, Merck) is no more effective than either drug alone for reducing left ventricular mass in patients with hypertension, according to the results of the Aliskiren Left Ventricular Assessment of Hypertrophy (ALLAY) trial, presented by Dr Scott Solomon (Brigham and Women's Hospital, Boston, MA) during a late-breaking abstract session at the recent American College of Cardiology 57th Annual Scientific Session.

"This was a trial designed to ask whether we would get more bang from adding aliskiren to losartan that was independent of blood-pressure lowering, because the two drugs inhibit the renin-angiotensin system in two different places," he told heartwire . "But we did not see incremental benefit to the combination, which suggests that the benefit in terms of end-organ damage is primarily mediated through BP lowering."

Encouragingly, there was no increase in adverse events with the combination group--in particular, hypotension, hyperkalemia, and renal dysfunction--he noted, and use of concomitant medications was considerably lower in the combination arm. "This is the first solid data that aliskiren not only can lower BP but can affect this very important and predictive measure of cardiac end-organ damage--LV hypertrophy [LVH], and it can do it to the same as the gold standard, losartan. We definitely didn't know that before, and it adds to our body of knowledge about aliskiren," he commented.

LV mass second only to age as predictor of CV events

Solomon explained how LVH is present in approximately 30% of patients with hypertension and is associated with an increased risk of cardiovascular morbidity and mortality. In fact, LVH is second only to age in predictive power for cardiovascular events, he noted.

Regression of LVH is associated with lower overall cardiovascular risk, independent of BP lowering, he added. He explained to heartwire that losartan was chosen as the comparator in ALLAY because "in the LIFE trial it was shown to be the gold standard in terms of LV-mass regression and it also had a beneficial effect on hard end points, such as cardiovascular death, MI, and stroke."

In ALLAY, 460 overweight hypertensive patients with evidence of LVH were randomized to one of three treatment arms and titrated up to doses of aliskiren 300 mg per day (n=154); losartan 100 mg per day (n=152); or aliskiren 300 mg plus losartan 100 mg (n=154). All patients were treated to blood-pressure targets, and therapy continued for 36 weeks.

The primary end point was reduction in LV mass, as measured by cardiac MRI. Secondary objectives included safety and tolerability of the treatments.

The primary end point was comparable across the three treatment arms: aliskiren alone reduced LV-mass index by -4.9 g/m2, compared with -4.8g/m2 with losartan alone and –5.8 g/m2 with the combination. Although the reduction in LV mass was numerically greater in the combination arm, it was not significantly greater than with losartan alone. There were no differences in adverse events across the three treatment groups and a very low level of adverse events overall, Solomon noted.

Blood-pressure lowering was also similar across the three groups, with a lowering of just a few mm Hg in all three arms, primarily because the trial was a treatment-to-target study. Solomon told heartwire that the patients in the study actually had much lower blood pressures at baseline than they had intended. "Had we started with a more hypertensive population, allowed for greater blood-pressure lowering, or treated for longer, we might have seen a greater LV-mass reduction with the combination. We can't be sure." This, he says, remains to be determined in future studies.

ALLAY results give comfort

In the meantime, Solomon says: "We now know that aliskiren is as effective as an angiotensin receptor blocker [ARB], which is arguably more effective than other ways to lower BP or reduce LV mass. Aliskiren can be used as an alternative antihypertensive drug and as a potential additive drug, but probably not as a first-line agent.

"We are learning about aliskiren, and we are trying to learn beyond BP lowering," he added. "These results give us comfort that we now have solid end-organ-protection data with aliskiren, and we don't have that for every drug we use to treat hypertension. It presents an alternative to ARB therapy--that's the key thing with hypertension, it always has to be tailored."

He noted also that a large outcomes trial with the drug has just begun. Named ALTITUDE, this will recruit around 8000 patients with diabetic kidney disease who will receive aliskiren on top of standard therapy, he explained.

Solomon has received research support from Novartis.

The complete contents of Heartwire , a professional news service of WebMD, can be found at www.theheart.org, a Web site for cardiovascular healthcare professionals.



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