Is combination hypertension therapy effective and safe in the elderly?

This study examined the effect of aliskiren alone and with other antihypertensive drugs on blood pressure lowering and cardiovascular diseases prevention in elderly patients with mild hypertension.

Hypertension (high blood pressure) is a major risk factor in the development of cardiovascular diseases (such as heart attacks and strokes).Different anti-hypertensive drugs work in diverse methods in order to reduce blood pressure. Commonly used anti-hypertensive drug classes include beta-blockers, calcium channel blockers (such as amlodipine; Norvasc), diuretics (such as thiazides) and inhibitors of the renin angiotensin system (RAS; an important system responsible for elevating blood pressure in the body).  Aliskiren (Tekturna) is a new RAS-directed anti-hypertensive drug, referred to as a direct rennin inhibitor.

Achieving target levels of blood pressure recommended by guidelines frequently requires combinations of various drugs with different mechanisms of action. However, use of multiple blood pressure lowering medications may be associated with drug interactions, intolerance, poor adherence and increased costs, particularly in the elderly. Therefore, outcome data showing that use of multiple drugs reduces cardiovascular diseases and is safe, is needed to justify additional therapy in the elderly with systolic blood pressure (pressure when the heart is contracting) between 130 and 159 mm Hg (stage 1 hypertension).

This study enrolled 1,759 participants, with an average age of 72.1 and systolic blood pressure between 130 mm Hg and 159 mm Hg. Participants were randomized to aliskiren (300 mg) or placebo (a substance that has no therapeutic effect) and also to an additional blood pressure lowering drug, amlodipine (5 mg) or hydrochlorothiazide (Microzide; 25 mg) or placebo.

Before being randomly assigned the average systolic blood pressure was 146.1 mm Hg and the average diastolic blood pressure (pressure when the heart is relaxing or filling) was 82.6 mm Hg. After an average follow up of 0.6 years data was analyzed.

Researchers concluded that aliskiren, when taken alone or when combined with another antihypertensive drug (amlodipine or hydrochlorothiazide), reduces blood pressure compared with placebo. Aliskiren alone reduced systolic blood pressure by 3.5 mmHg and diastolic blood pressure by 1.7 mm Hg compared with placebo. The reduction in blood pressure in the combination therapy was 10.3 mmHg for systolic blood pressure and 5.0 mm Hg for diastolic blood pressure compared with double placebo.

Furthermore there were trends towards fewer clinical outcomes (cardiovascular death, non-fatal heart attacks, non-fatal stroke or significant heart failure) with the aliskeren alone and combination therapies (those who were treated with the combined therapy had a 75% reduced morbidity risk compared with placebo) compared to placebo.

Finally none of the randomized treatment groups exhibited any excess adverse outcomes compared with placebo.

This study concluded that administration of aliskiren and hydrochlorothiazide or amlodipine is associated with a significant systolic blood pressure reduction and appears to be safe. There are also trends towards fewer cardiovascular events when therapies are combined. 

Due to the small sample size and short follow up duration further trials should be performed to confirm the effect of the therapy on cardiovascular diseaseDue to the small sample size and short follow up duration further trials should be performed to confirm the effect of the therapy on cardiovascular diseases.s.