Annals of Long Term Care

Aliskiren Monotherapy Superior to Ramipril Monotherapy at 12 Weeks, Aliskiren-Based Therapy Noninferior to Ramipril-Based Therapy at 36 Weeks in Elderly Patients with Systolic Hypertension

New Orleans—In elderly patients with systolic hypertension, aliskiren monotherapy was noninferior to ramipril monotherapy at week 12, week 22, and week 36, and achieved a greater reduction in systolic blood pressure. Aliskiren was more successful than ramipril in achieving target blood pressure control, and a smaller percentage of patients treated with aliskiren-based therapy required add-on therapy with hydrochlorothiazide (HCTZ) and amlodipine. Both drugs were safe and well tolerated, with the exception of cough, which occurred in 30% of the ramipril-treated group but only 4% of the aliskiren-treated group.

Treatment for isolated systolic hypertension relies on blockade of the renin-angiotensin-aldosterone system (RAAS) with angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARBs), and, most recently, the first direct renin inhibitor, aliskiren. Although ACE inhibitors and ARBs are considered first-line treatment, more than two-thirds of patients require two or more drugs to achieve target blood pressure, explained Daniel Duprez, MD, of the University of Minnesota, Minneapolis. Dr. Duprez reported results of the AGELESS study, which was designed to compare the effects of aliskiren with those of ramipril on lowering systolic blood pressure in a group of elderly patients with systolic hypertension. The study was sponsored by Novartis Pharmaceutical Corp.

AGELESS was a 36-week, double-blind, parallel-group, active-controlled trial with 457 patients randomized to aliskiren and 444 to ramipril. At baseline, mean age of both groups was 72 years. Mean sitting systolic blood pressure (msSBP) was >140 mmHg and < 180 mmHg. About 50% of participants were female. Patients age 75 years or older comprised about one-third of the study population.

After a 4-week washout period, treatment was initiated with aliskiren 150 mg/day versus ramipril 5 mg/day. At 4 weeks, if msSBP was >140 mmHg, doses of both drugs were doubled. HCTZ 12.5 mg/day was added if msSBP was not controlled at 12 weeks, and the dose of HCTZ was doubled if needed at 16 weeks. If msSBP remained >140 mmHg at 22 weeks, amlodipine 5 mg/day was added; at 28 weeks, if msSBP remained >140 mmHg, the dose of amlodipine was doubled.

Aliskiren monotherapy was deemed noninferior to ramipril monotherapy for the primary end point (ie, change from baseline msSBP at week 12). In fact, at week 12, aliskiren achieved a reduction of -13.96 mmHg versus a reduction of -11.64 mmHg for ramipril. Aliskiren was superior to ramipril in lowering msSBP at week 12 and also at week 22, when HCTZ was added, Dr. Duprez said. At week 36, aliskiren achieved a mean reduction of –19.97 mmHg in msSBP versus a reduction of -18.05 mmHg for ramipril-based therapy. Aliskiren was noninferior to ramipril but not superior, Dr. Duprez added.

At week 12, 46.3% of the aliskiren group versus 39.3% of the ramipril group achieved blood pressure control (P = .03 for aliskiren vs ramipril). At week 22, blood pressure control was achieved in 69% versus 57.7%, respectively (P = .0005). At week 36, more patients treated with aliskiren-based therapy remained at goal.

Patients treated with ramipril required more add-on therapy, including HCTZ and amlodipine, than those treated with aliskiren, Dr. Duprez noted.

During the discussion following his presentation, Dr. Duprez was asked why maximal doses of aliskiren were allowed in the trial but only usual care doses of ramipril. He said the dose of ramipril 5 mg to 10 mg/day was based on the dose used in the HOPE trial.