NEW ORLEANS – Prevention of major cardiovascular events was similar in a comparison of valsartan and amlodipine in patients with hypertension and diabetes or glucose intolerance, according to a Japanese study presented April 5 at the annual meeting of the American College of Cardiology.

The Novel Antihypertensive Goal of Hypertension With Diabetes – Hypertensive Events and ARB Treatment (NAGOYA-HEART) Study is the first randomized trial to compare the effects of an angiotensin II receptor blocker (ARB) with a calcium channel blocker (CCB) on cardiovascular outcomes in this patient population. No significant differences were found between the two classes, reported Dr. Toyoaki Murohara of Nagoya (Japan) University.

"Our study showed no difference in the efficacies between the ARB and the CCB in terms of prevention of major cardiovascular events, [however] the ARB was superior to the CCB in preventing heart failure, especially in diabetic patients," Dr. Murohara said.

All-cause mortality also was similar. Hospital admission for heart failure was the only outcome measure in which there was a statistically significant difference between the two agents.

In previous nonrandomized analyses comparing ARBs with CCBs, results have been conflicting and, therefore, the preferred first-line class of agents is not well established, Dr. Murohara said. Guidelines mainly recommend ARBs and ACE inhibitors for first-line treatment and reserve CCBs as alternatives or second-line agents, he added.

The NAGOYA-HEART Study is an investigator-initiated trial applying a prospective, randomized open-label, blinded-endpoint (PROBE) method in which allocated treatment was open label but outcomes were adjudicated in a blinded manner as for drug assignment.

The Japanese research team enrolled 1,150 hypertensive patients with either type 2 diabetes (82%) or impaired glucose tolerance (18%) at 46 facilities across the country between 2004 and 2010. Mean glycosylated hemoglobin was 7.0% on the valsartan arm and 6.9% on the amlodipine arm and fasting plasma glucose levels were 8.2 mmol/L and 7.9 mmol/L, respectively. Mean blood pressure was 144/82 mm Hg in each arm.

Patients were randomized to receive either valsartan or amlodipine as their first-line antihypertensive agent. After a run-in phase, patients received valsartan 80 mg/day, titrating to 160 mg/day after 1 week of treatment, or amlodipine 5 mg/day, titrating to 10 mg/day. Both arms could receive other antihypertensives as needed, excluding ACE inhibitors, other ARBs, or CCBs.

The treatment goal was to reduce blood pressure to below 130/80 mm Hg. The primary outcome was a composite of cardiovascular events (acute myocardial infarction, stroke, coronary revascularization, admission due to heart failure, and sudden cardiac death); all-cause mortality was a secondary outcome.

The efficacy and safety analyses included 575 in both the valsartan and amlodipine arms. Patients were followed a median of 3.2 years.

Blood pressure lowering and glucose control were similar between the treatment arms. Blood pressure levels achieved were 131/73 mm Hg with valsartan and 132/74 mm Hg with amlodipine. Final hemoglobin A1C was 6.7% in each arm, Dr. Murohara reported.

There was no difference between the agents in the primary composite cardiovascular outcome. At 3.2 years, cardiovascular events were observed in 54 (9.4%) patients in the valsartan group and 56 (9.7%) in the amlodipine group. "The time-to-event curves showed no difference between the two groups," he said.

Among the components of the composite, only heart failure was affected by treatment, noted in 3 (0.5%) patients on valsartan, compared with 15 (2.6%) on amlodipine, a significant difference. Valsartan use was associated with an 80% relative risk reduction in heart failure admissions.

Safety outcomes were similar, with at least one adverse event reported by 106 patients in the valsartan arm and 112 in the amlodipine arm.

"Our results highlight the safety and efficacy of an ARB, especially in preventing heart failure," he noted, "and support the current recommendations for diabetic hypertensive patients."

Session panelist Dr. Sara Sirna of Temple University, Philadelphia, commented that the NAGOYA-HEART Study is "an excellent study on two drugs we commonly use for patients with diabetes and hypertension, which we see every day in our practices."

She questioned whether there may be a subgroup that would fare better with one versus the other agent. "The ejection fraction was about 40%, mildly reduced, yet those patients seemed to do better on valsartan," she observed.

Dr. Murohara responded that the study did not recruit patients with overt heart failure, but he noted that since the renin-angiotensin system is activated in the setting of heart failure, it makes sense that new-onset heart failure may be prevented better with the ARB.

The study was funded and supported by Nagoya University. Dr. Murohara reported receiving lecturer’s fees from Daiichi-Sankyo, Novartis, Pfizer, and Takeda. Dr. Sirna reported no relevant disclosures.

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