2011 ACC: OSCAR Study Shows Combo Therapy Better Than Monotherapy for Hypertensives

Combination calcium channel blocker and angiotensin II receptor blocker proves most effective in a study of elderly patients with hypertension.

NEW ORLEANS — April 5, 2011 – The combination of a calcium channel blocker and high-dose angiotensin II receptor blocker beat out high-dose monotherapy for reducing adverse events in a study of Japanese elderly hypertensives, reported Hisao Ogawa, MD, PhD, who presented results of the OSCAR study today in a late-breaking news conference at the American College of Cardiology’s (ACC) 60th Annual Scientific Session and ACC.i2 Summit.

“In OSCAR, blood pressure was significantly lower in the angiotensin II receptor blocker (ARB) plus calcium channel blocker (CCB) group and at the high dose in a subgroup of patients with cerebrovascular disease,” said Ogawa, a professor in the department of cardiovascular medicine at Kumamoto University in Japan. “This is the first study to show this finding in an elderly high-risk population and also determined that there are subgroups that have extra benefit.”

Ogawa said the data show that cardiologists should consider the type of risk factors that patients have and before prescribing.

The study, “Effect of High Dose Angiotensin II Receptor Blocker (ARB) Monotherapy Versus Combination Therapy of ARB with Calcium Channel Blocker on Cardiovascular Events in Japanese Elderly High-Risk Hypertensive Patients: (OSCAR) Randomized Trial” included 1,164 high-risk elderly subjects who were enrolled from 134 centers throughout Japan from June 2005 to May 2007.

The study researchers noted that ARBs are increasingly used in antihypertensive treatment and have been shown to be beneficial in this population, but Ogawa said that “the CASE-J trial, which was conducted in an elderly population, showed that CCB and ARB were equally effective in preventing CVD morbidity and mortality… and as first-line treatment.”

Ogawa also noted that “few studies have been performed in Japan to assess the difference between high-dose ARB monotherapy and combination therapy of ARB with calcium channel blockers in prevention of cardiovascular diseases for patients whose blood pressure is not well controlled by ARB monotherapy.”

The OSCAR study is a multicenter, active-controlled, two-arm parallel group comparison, prospective study, with 578 patients assigned to a high-dose ARB group and 586 assigned to ARB plus CCB. Baseline characteristics included, sex, age, BMI, blood pressure, and smoking status.

The study showed that ARBs are effective in the treatment of hypertension and also stroke, diabetic nephropathy, and heart failure, while high-dose ARBs are more effective than low-dose ARBs in the prevention of cardiovascular disease for diabetic nephropathy or heart failure. Ogawa said “it remains to be determined which therapeutic strategy is more effective than high doses of ARB or ARB plus CCB.”

To answer this question, the researchers compared high-dose ARB or ARB plus CCB in the prevention of cardiovascular disease in an elderly Japanese population. TO be eligible for inclusion, patients had to have unmanageable blood pressure despite standard monotherapy with ARBs and a history of at least one cardiovascular diseases or type 2 diabetes. Patients were randomized to receive either a high dose of olmesartan (40 mg per day a CCB) or olmesartan (20 mg /day), plus a calcium channel blocker.

The study’s primary endpoint was a composite of CVD events -- fatal and non-fatal CVD and non-cardiac death. Secondary endpoints were cerebrovascular disease, coronary artery disease, heart failure, other atherosclerotic disease, diabetic complications, and renal dysfunction.

At 36-month follow up, blood pressure was adequately controlled in both treatment groups, although the combination therapy resulted in a significantly lower blood pressure than monotherapy (mean SBP were lower by 2.4mmHg [p=0.0315] and 1.7mmHg [p=0.240, respectively). However, no significant difference was seen between the two cohorts in the number of primary endpoint, with 51 events occurring in the monotherapy group and 34 occurring in the combination therapy group.

For the primary composite endpoint in subgroup of patients with CVD diabetes, there was a statistically associated (HR 1.63 95% CI, 106-2.52). For CVD with only diabetes, there was a statistical finding of HR 0.52 (95% CI 0.0021-1.28). “The diabetes subgroup had a higher incidence of the primary endpoint and the than the combo group but it was not signifantant,” Ogawa reported.

The researchers received a grant support from the Japan Heart Foundation. Ogawa has received grant support over the past five years from Astellas, AstraZeneca, Bayer, Boehinger Ingelheim, Daiichi-Sanky, Eisai, Kowa, Kyowa Hakka Kirin, MSD, Novartis, Pfizer, Sanof-Aventis, Schering-Plough and Takeda.