New data from the Avoiding Cardiovascular Events in Combination
Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH)
trial were presented today at the American College of Cardiology
2008 Scientific Sessions [1]. They showed that a single-tablet dual-
mechanism therapy initiated in high-risk hypertensive patients
significantly reduced the risk of morbidity and mortality by 20%
compared with conventional therapy.

ACCOMPLISH, a major morbidity and mortality trial, compared the
effects of two forms of antihypertensive combination therapies on
major fatal and nonfatal cardiovascular events. It was stopped early
because treatment with antihypertensive combination therapy--the ACE
inhibitor benazepril plus the calcium-channel blocker amlodipine--
was more effective than treatment with the ACE inhibitor plus
diuretic.

Lead investigator Dr Kenneth Jamerson (University of Michigan, Ann
Arbor), who presented the results of the study during the late-
breaking clinical-trials session, said he was "absolutely thrilled"
to present the findings of a study designed to challenge current
guidelines in defining the optimal strategy for blood-pressure
control and preventing cardiovascular events in high-risk patients.

"If you use the combination of a calcium-channel blocker with an ACE
inhibitor, you get exquisite blood-pressure control," said Jamerson,
who added that similar control was observed with the ACE inhibitor
and diuretic. Despite the similar blood pressure, the combination
with the calcium-channel blocker and ACE inhibitor reduced
cardiovascular morbidity and mortality 20%.

During a press conference announcing the results, Jamerson told the
media that the findings are "paradigm-shifting" and the data are a
clear win with a clear message. He said the ACCOMPLISH findings
challenge the guidelines, especially in terms of starting with a one-
drug strategy and the use of diuretics in combination with ACE
inhibitors.

Clear data, clear win, and a clear message

Current recommendations for the treatment of stage 1 hypertension
include the use of thiazide-type diuretics for most patients, with
additional consideration given to ACE inhibitors, angiotensin-
receptor blockers (ARBs), beta blockers, and calcium-channel
blockers. In patients with stage 2 hypertension--those with blood
pressure >160/>100 mm Hg--two-drug combination therapy, usually with
a diuretic and ACE inhibitor, is recommended.

ACCOMPLISH compared the effects of two forms of antihypertensive
combination therapies on major fatal and nonfatal cardiovascular
events. In total, 11 400 men and women aged 55 years or older who
had systolic blood pressure >160 mm Hg or were currently on
antihypertensive therapy and who had evidence of cardiovascular or
renal disease or target-organ damage were included in the trial.
Patients enrolled in the trial were obese, with 60% having diabetes
mellitus, and nearly all had been treated previously for
hypertension.

More than 70% had been treated with two or more hypertensive agents,
but, as was previously reported by heartwire at the American Society
of Hypertension 2007 Scientific Sessions, just 37.5% of patients had
their blood pressure controlled to <140/90 mm Hg at baseline, the
currently recommended target of the Joint National Committee on
Prevention, Detection, Evaluation, and Treatment of High Blood
Pressure. As part of the study protocol, all patients stopped their
medication and, without a washout period, were randomized to
combination treatment with benazepril plus hydrochlorothiazide or
amlodipine plus benazepril.

At 36 months, blood-pressure levels were significantly improved,
with more than 75% of patients in both treatment arms having blood-
pressure levels <140/90 mm Hg. Investigators report that combination
treatment with benazepril plus amlodipine reduced cardiovascular
morbidity and mortality, defined as cardiovascular death,
fatal/nonfatal MI, fatal/nonfatal stroke, hospitalization for
unstable angina, and coronary revascularization, by 20%, compared
with those treated with benazepril plus a diuretic.

Speaking with the media, Jamerson noted that the average patient in
the study was 68 years old, and the oldest patient was 98 years old.
Although hypotension might be a concern and can result in falls and
fractures in elderly patients or in the frail, this was not borne
out in the ACCOMPLISH study.

Dr Michael Weber (SUNY Downstate Medical Center, Brooklyn, NY), who
was on the executive committee of the ACCOMPLISH trial, agreed with
Jamerson, telling heartwire that the findings will change the
guidelines.

"Right now, there is a recommendation that when you're putting
together combination treatment for hypertension you need to normally
include a diuretic as one of the two agents," said Weber. "I'm sure
that recommendation will change. It might not change to the point of
stating that a calcium-channel blocker like amlodipine be the
preferred partner, but it will take away the recommendation for
diuretics, and adding the calcium-channel blocker will invariably be
a part of that."

Dr Salim Yusuf (McMaster University, Hamilton, ON) said the
study "looks good" but held back full praise until the complete
findings are published. He agreed, though, that, based on the
presented data, the ACCOMPLISH study will challenge current
guidelines.

Jamerson KA, on behalf of the ACCOMPLISH investigators. Avoiding
cardiovascular events in combination therapy in patients living with
systolic hypertension. American College of Cardiology Scientific
Sessions; March 31, 2008; Chicago, IL.