ACCOMPLISH: Systolic Blood Pressure With 24-Hour Monitoring No Different in Treatment Arms

May 11, 2009

May 11, 2009 (San Francisco, California) – An analysis of the Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial has shown that systolic blood pressure assessed by 24-hour ambulatory blood-pressure monitoring did not differ between the two study arms at two years.

Presenting the results of the study during the late-breaking clinical-trials session here at the American Society of Hypertension 2009 Scientific Meeting, lead investigator Dr Kenneth Jamerson (University of Michigan, Ann Arbor) said the results support their earlier conclusions that the observed difference in morbidity and mortality was driven by a more effective combination therapy with the ACE inhibitor benazepril plus the calcium-channel blocker amlodipine and not by differences in blood pressure.

"These types of data have the potential to change paradigms for treating blood pressure from being more diuretic-based combination therapy to using more amlodipine/benazepril-combination regimens," Jamerson said during a press conference. "It has huge implications for the millions of patients who are taking these medications for blood-pressure control."

Initial Criticisms of ACCOMPLISH

ACCOMPLISH compared the effects of two forms of antihypertensive combination therapies--benazepril and amlodipine vs benazepril and hydrochlorothiazide (HCTZ)--on major fatal and nonfatal cardiovascular events in 11 506 men and women aged 55 years or older who had systolic blood pressure >160 mm Hg. All patients were currently on antihypertensive therapy and had evidence of cardiovascular or renal disease or target-organ damage.

First presented at the American College of Cardiology 2008 Scientific Sessions in Chicago, IL and reported by heartwire at that time, the results showed that the single-tablet benazepril/amlodipine combination reduced the risk of morbidity and mortality by 20% compared with conventional diuretic-based therapy.

Despite the impressive results, some reserved full judgment on the trial until more data were available regarding the 24-hour ambulatory blood-pressure monitoring. Of concern, particularly, was the diuretic used in ACCOMPLISH. Some argued that HCTZ was a weaker diuretic than chlorthalidone and that the dose used was too low. For that reason, ambulatory blood-pressure monitoring was essential to determine whether the reduction in morbidity and mortality was the result of differences in blood pressure between the two arms or the result of something inherent to therapy.

In total, 573 subjects underwent 24-hour ambulatory blood-pressure monitoring at two years. Overall, mean systolic blood pressure was 1.6 mm Hg lower with benazepril and HCTZ compared with amlodipine and benazepril, but this difference was not statistically significant. Additional analyses of 24-hour mean blood pressure, daytime and nighttime pressures, and surges in blood pressure showed the combinations to be equivalent.

"There are lots of healthcare providers and experts who think that just getting the blood pressure down is the most important thing to do," said Jamerson. "That's what is so unique and important about this message. This is the first trial to show that it really does matter what agent you use. Certain combinations give you an advantage over others, and in this particular case the combination of a calcium-channel blocker with a drug that blocks the renin-angiotensin system reduces stroke, heart attack, and cardiovascular death compared with what we're telling our society to use--that is, a diuretic-based therapy."

Speaking with the media, press-conference moderator Dr George Bakris (University of Chicago Medical Center, IL), who was also an ACCOMPLISH investigator, said there are data showing that benazepril and amlodipine individually increase nitric-oxide (NO) production and that synergistically they increase NO production even further, which can increase coronary perfusion. Other studies with diuretics have not shown the same effects on the vessel, despite lowering blood pressure.

"There is a background that would support the differences [with the drugs]," said Bakris.

"A lot of people said you picked the wrong diuretic, but what we showed is that we didn't," Jamerson added to heartwire . "We really do clarify that this isn't because hydrochlorothiazide is a bad drug, which is what the argument was before. Hydrochlorothiazide is really quite good at lowering blood pressure." He added that some patients treated with HCTZ had ambulatory systolic blood pressures as low as 120 mm Hg.

Experts are eagerly awaiting the publication of the eighth edition of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 8), which is expected sometime this year. Current recommendations suggest the use of a diuretic as add-on therapy, and while ACCOMPLISH directly challenges those recommendations, most are unsure of what to expect in the upcoming publication.

Novartis sponsored the ACCOMPLISH study. Jamerson reports receiving consulting fees from Novartis, Merck, and Daiichi Sankyo; lecture fees from Novartis, Abbott, Bristol-Myers Squibb, GlaxoSmithKline, and Merck; and research support from Novartis and King Pharmaceuticals.