Aliskirenと左室肥大

The direct renin inhibitor aliskiren is as effective as losartan in reducing left ventricular hypertrophy in overweight patients with hypertension, according to a late-breaking clinical trial presented at the meeting of the American College of Cardiology.

The ALLAY (The ALiskiren Left Ventricular Assessment of HypertrophY) Trial, conducted at 77 centers in eight countries, examined whether aliskiren, alone or in combination with losartan, was at least as effective as losartan in reducing hypertrophy in this patient population.

After screening 1,086 patients, 460 patients with a body mass index greater than 25 kg/m² were randomized to one of three treatment arms: aliskiren 300 mg daily (154 patients), losartan 100 mg daily (152 patients), or aliskiren 300 mg daily plus losartan 100 mg daily (154 patients), with all patients treated to blood pressure targets. Treatment with the study drug was continued for 36 weeks.

Researchers compared changes in left ventricular mass index as assessed by cardiovascular magnetic resonance imaging between baseline and 36 weeks. The researchers also looked at changes in left ventricular volumes, 24-hour ambulatory blood pressure and electrocardiographic voltage during the same 36-week period.

Aliskiren was as effective as losartan in reducing left ventricular mass, which improved significantly in all treatment groups after nine months of therapy. The degree of left ventricular mass reduction was numerically greater in the combination arm, but it failed to reach statistical significance.

Aliskiren, either alone or in combination with losartan, was very well tolerated with no differences in adverse events between groups and a very low level of adverse events. There were no increases in hyperkalemia, hypotension or renal dysfunction in patients receiving aliskiren either alone or in combination.

"Aliskiren inhibits the renin-angiotensin-aldosterone axis at the beginning of the cascade. It is likely that patients would derive many of the same benefits from inhibiting the renin angiotensin system at this step as they do with inhibition at more proximal steps in the system," said Scott Solomon, MD, of Brigham and Women's Hospital and Harvard Medical School, and lead author of the study.

"Moreover, inhibiting the renin-angiotensin-aldosterone (RAAS) system with ACE inhibitors or angiotensin receptor blockers results in reflexive rises in plasma renin activity. This provides a rationale for combining a renin inhibitor with another inhibitor of the renin-angiotensin-aldosterone system, as aliskiren has been shown to reduce plasma renin activity either alone or when combined with other RAAS-blocking drugs. Because treatment of hypertension can be difficult, physicians and patients will benefit from additional agents that can not only lower blood pressure, but can affect the end-organ damage that hypertension causes."

"These data suggest that aliskiren, which is the first orally active direct renin inhibitor and is currently approved for treatment of hypertension, is as effective as an angiotensin receptor blocker for reducing left ventricular mass. Along with other recently reported studies with aliskiren showing incremental benefits in reducing abnormal protein excretion in the urine (proteinuria) in diabetic patients and improvements of indicators of heart function in heart failure patients, these data suggest that aliskiren is efficacious for end-organ protection, beyond just blood pressure reduction."

The patients in this study had relatively well-controlled hypertension and thus the overall degree of blood pressure lowering observed was moderate.

"It is conceivable that treating patients with higher blood pressures or for a longer period of time would have resulted in greater left ventricular mass reduction with the combination of aliskiren plus an angiotensin receptor blocker, but this remains to be determined in future studies," he concluded.