Hypertension Therapy Should Be Guided by Underlying Disease

April 06, 2011

April 6, 2011 (New Orleans, Louisiana) — Treating elderly hypertensive patients with a combination of an angiotensin receptor blocker (ARB) and a calcium antagonist seems to be as similarly effective as using a high (double) dose of an ARB alone, a new study reported today at the American College of Cardiology 2011 Scientific Sessions shows.

Calcium-channel blockers (CCBs) have generally been recommended as first-line treatment for hypertension in elderly patients, explained Dr Hisao Ogawa (Kumamotom University, Japan), who presented the results of the OSCAR study during a late-breaking clinical-trial session here today. But ARBs have also been shown to be of benefit in this population--for example, in the SCOPE study. And in the CASE-J trial, another Japanese study conducted in elderly patients, a CCB and an ARB were equally effective in preventing cardiovascular morbidity and morbidity.

"To my knowledge, this is the first large-scale study in the world to compare these two therapeutic strategies," Ogawa said.

Although the two approaches showed equivalence in the overall study population, when subgroups were examined, those with preexisting cardiovascular disease fared better on the combination of ARB plus CCB than on the high-dose ARB, indicating that doctors should consider patients' underlying disease before deciding which type of antihypertensive therapy to opt for, Ogawa noted.

Panel member Dr Sara J Sirna (Temple University Medical Center, Philadelphia, PA) said the OSCAR results are "extremely relevant with our aging population, where in the US alone 11 000 baby boomers are turning 65 every day."

ARBs Used Often in Japan Because of High Rate of ACE-Inhibitor Cough

Ogawa told heartwire that although ACE inhibitors may be preferentially recommended over ARBs in many countries, in Japan there is a high incidence of cough associated with ACE inhibitors, so ARBs are widely used there and have a similar recommendation to ACE inhibitors in the Japanese hypertension guidelines, he said.

In OSCAR, Ogawa and his team enrolled 1164 high-risk elderly Japanese hypertension patients--aged 65 to 84 years with an average age of 74--at 134 centers throughout Japan. To be included, patients must have been unable to manage their high blood pressure (systolic BP >140 mm Hg, diastolic BP >90 mm Hg through standard-dose (20 mg per day) monotherapy with the ARB olmesartan (Benicar, Daiichi Sankyo) and had to have at least one of the following risk factors: cerebrovascular disease, cardiac disease, vascular disease, or type 2 diabetes mellitus.

Patients were randomized to either high-dose olmesartan (40 mg per day; n=578) or a standard dose of a CCB (either amlodipine or azelnidipine [Calblock, Daiichi Sankyo]) combined with 20-mg/day olmesartan (n=586). Addition of other antihypertensive drugs, with the exception of ARBs, ACE inhibitors, and CCBs, was allowed if BP remained uncontrolled.

The primary end point was a composite of cardiovascular events--including cerebrovascular disease, coronary artery disease (CAD), heart failure, other atherosclerotic disease, diabetic complications, and the deterioration of renal function--and all-cause death.

Although blood pressure was adequately controlled in both groups, the combination therapy reduced BP to a significantly greater degree than the high-dose ARB (systolic BP 2.4 mm Hg lower [p=0.0315] and diastolic BP 1.7 mm Hg lower [p=0.0240]). But there was no significant difference overall between the two treatment arms in terms of the primary end point--48 events occurred in the combination group compared with 58 in the high-dose-ARB group (hazard ratio 1.21; p=0.1717).

More Data Needed on High-Dose ARBs in Hypertensive Diabetics

But with regard to subgroups, those with preexisting cardiovascular disease appeared to benefit more from the combination treatment--those in the high-dose-ARB arm had significantly more CV events and death than those in the combination arm (HR=1.63; p=0.02610).

"The OSCAR study provides the first evidence showing that a standard dose of ARB plus CCB combination is superior to high-dose ARB in reducing adverse events in elderly hypertensive patients with cardiovascular disease," Ogawa commented.

Conversely, those with diabetes seemed to fare better on the high-dose ARB than on the combination, although this difference was not significant (seven events vs 14; p=0.1445). This suggests that the high-dose ARB better prevented adverse events in diabetics, "in spite of its weaker antihypertensive effect," Ogawa noted.

But Dr Toyoaki Murohara (Nagoya University Graduate School of Medicine, Japan), who was not involved in the OSCAR study, told heartwire he does not believe the findings support the conclusion to use high-dose ARBs in diabetics. "The number of patients is still low, so it was underpowered, and we definitely need a new study to examine whether ARB [dose] doubling or ARB plus CCB is good for diabetic hypertensive patients."

Ogawa has received research support over the past five years from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Eisai, Kowa, Kyowa Hakko Kirin, Merck Sharp Dohme, Novartis, Pfizer, Sanofi-Aventis, Schering-Plough, and Takeda.