Treating elderly hypertensive patients with a combination of an angiotensin II receptor blocker (ARB) and a calcium channel blocker (CCB) leads to similar rates of cardiovascular events and death compared to therapy with a high-dose ARB alone, according to research presented at the American College of Cardiology's 60th Annual Scientific Session. The findings add to a growing body of knowledge on the best hypertension treatment for elderly patients.

Although CCBs have generally been recommended as the first-line treatment, ARBs have also been shown to exert beneficial effects on this patient population, especially in the SCOPE trial. The CASE-J trial - a Japanese study conducted in elderly patients - showed that a CCB and an ARB were equally effective in preventing cardiovascular morbidity and mortality.

"The CASE-J trial supported the idea that ARBs and CCBs are both beneficial as first-line agents for the treatment of hypertension in elderly patients," said Hisao Ogawa, M.D., Ph.D., lead study author and professor in the Department of Cardiovascular Medicine at Kumamoto University in Japan. "However, our research team did not know of any studies comparing the efficacy of high-dose ARB monotherapy with standard-dose combination therapy in terms of preventing cardiovascular morbidity and mortality in elderly patients. Thus, the OSCAR study may have a significant impact on determining the best antihypertensive therapeutic strategy for these patients."

For the study, Ogawa's research team enrolled 1,164 high-risk elderly hypertension patients at 134 centers throughout Japan from June 2005 to May 2007. To meet the inclusion criteria, patients must have been unable to manage their high blood pressure through standard-dose monotherapy with the ARB olmesartan (Benicar®, manufactured by Daiichi Sankyo) and had to have at least one of the cardiovascular diseases or type 2 diabetes. Patients were randomized to receive either: 1) high-dose olmesartan at 40 mg per day (n = 578) or 2) a CCB combined with olmesartan at 20 mg per day (n = 586).

The study's primary endpoint was a composite of cardiovascular events - including cerebrovascular disease, coronary artery disease, heart failure, other atherosclerotic disease, diabetic complications, and the deterioration of renal function - and all-cause death.

At a follow-up point of 36 months, the researchers found that blood pressure was adequately controlled by both treatment groups, although the combination therapy reduced blood pressure to significantly lower levels than monotherapy (mean SBP and DBP were lower by 2.4 mmHg [p = 0.0315] and 1.7 mmHg [p =0.0240], respectively). However, no significant difference was seen between the two cohorts in the number of primary endpoints, with 58 events occurring in the monotherapy group and 48 occurring in the combination group (Hazard ratio [HR] 1.31; 95 percent confidence interval [CI] 0.89 - 1.92, p = 0.1717).

The team did find a statistically significant difference, however, when conducting a subgroup analysis only on patients with pre-existing cardiovascular disease. In the subgroup analysis, study subjects randomized to the combination therapy group had significantly fewer occurrences of cardiovascular events and death than those in the monotherapy group, at 34 and 51, respectively (HR = 1.63; 95 percent CI, 1.06 - 2.52; p = 0.02610).

Conversely, another subgroup analysis including patients with only diabetes showed a higher incidence of the primary endpoint in the combination therapy group, at 14 events compared to seven events in the monotherapy group, although this difference was not statistically significant (HR = 0.52; 95 percent CI 0.21 - 1.28; p = 0.1445).

According to Ogawa, the data show that cardiologists should consider the type of risk factors that patients may have - such as cardiovascular disease or type 2 diabetes - before prescribing high-dose ARBs.

"The OSCAR study provides the first evidence showing that a standard dose of ARB plus CCB combination is superior to high-dose ARB treatment in reducing adverse events in elderly hypertensive patients with cardiovascular disease," Ogawa said. "However, high-dose ARB better prevented adverse events in diabetic patients in spite of its weaker antihypertensive effect."

The researchers received grant support for the OSCAR study from the Japan Heart Foundation. Ogawa has received grant support over the past five years from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Eisai, Kowa, Kyowa Hakko Kirin, MSD, Novartis, Pfizer, Sanofi-Aventis, Schering-Plough, and Takeda.