ACC: Pushing Blood
Pressure Too Low May be Harmful
By Todd Neale, Staff Writer, MedPage TodayPublished: March 14, 2010
ATLANTA -- Lower is not necessarily
better for blood pressure control in patients with diabetes and coronary
artery disease, a secondary analysis of a randomized trial showed.
There was no difference in a composite endpoint of death, myocardial
infarction, or stroke between patients with an average systolic pressure
130-140 mm Hg and those with a lower average pressure, according to
Rhonda Cooper-DeHoff, PharmD, of the University of Florida in
As expected, patients who had uncontrolled systolic blood pressure
(140 mm Hg and higher) had significantly increased cardiovascular risk,
she reported at the American College of Cardiology meeting here.
Patients who were most tightly controlled, however, had an increased
risk of all-cause mortality compared with those in the middle range,
during both the trial and an extended follow-up of about five years.
"We probably can rethink lower goals in this particular population
... and put our efforts toward lifestyle modifications and other things
where we can achieve benefit," Cooper-DeHoff said.
Past ACC president Douglas Weaver, MD, of the Henry Ford Health
System in Detroit, who moderated a press briefing at which the results
were discussed, found a mixed message in the results.
"So I guess the takeaway is that getting good blood pressure control
is good. Getting perfect blood pressure control may not be so good," he
Although guidelines recommend keeping systolic pressure below 130 mm
Hg in diabetic patients (with no lower boundary), evidence to support
that guidance is lacking, Cooper-DeHoff said.
To explore the issue, she and colleagues performed a pre-specified
secondary analysis of diabetic patients in the INVEST trial, which
compared two blood pressure-lowering strategies in 22,576 patients with
coronary artery disease and hypertension.
One approach led with the calcium channel blocker verapamil, followed
by the ACE inhibitor trandolapril and hydrochlorothiazide as needed.
The other led with the beta-blocker atenolol, followed by
hydrochlorothiazide and trandolapril as needed.
There were no differences between the strategies in blood pressure
control or on the primary endpoint of cardiovascular events.
In this secondary analysis, 6,400 patients with diabetes were grouped
in thirds, according to the mean on-treatment systolic blood pressure
control achieved during the trial:
- Uncontrolled (140 mm Hg
- Usual control (at least 130 mm Hg but less than 140
- Tight control (less than 130 mm Hg).
As expected, the uncontrolled group had a significantly higher rate
of death, MI, or stroke (19.8%, P
But the tight and usual groups had a similar rate on the primary
outcome (12.7% and 12.6%, respectively), and on most of the secondary
However, during the trial, the tight control group had a slightly
higher rate of all-cause mortality than the usual control group (11%
versus 10.2%, P
The elevated risk persisted in an extended follow-up lasting about
five years in the U.S. cohort of 5,077 patients.
After controlling for baseline characteristics, there was a 15%
higher risk of all-cause death in the tightly controlled group (HR 1.15,
95% CI 1.01 to 1.32, P
To further evaluate mortality, the researchers broke the tightly
controlled group into two groups. In this group of patients with
systolic blood pressure below 130 mm Hg, mortality risk was increased
only when pressure dropped below 115 mm Hg.
Cooper-DeHoff acknowledged that the study was limited in that it was a
secondary analysis of a randomized trial, and thus, represented
In addition, she said, the blood pressure levels during the extended
follow-up were unknown.
Finally, she said, the findings might not be generalizable outside
the specific population of diabetics with coronary artery disease.
Michael Crawford, MD, of the University of California San Francisco,
who served as a moderator of the session at which the results were
presented, also noted that patients in the uncontrolled group required a
greater number of medications than the other two groups -- and got
worse control as a result.
"This suggests that this is a unique group of patients with very
difficult-to-control blood pressure, and so these data may not be
applicable to someone who comes in on no drugs or on one drug and has a
blood pressure of 145," he said. "So this may not be broadly
The trial and analysis were funded by Abbott
Laboratories.Cooper-DeHoff reported receiving a research grant
from the National Heart, Lung, and Blood Institute.Her co-authors
reported relationships with AstraZeneca, AtCor Medical, Daiichi Sankyo,
Eli Lilly, Pfizer, sanofi-aventis, Schering-Plough, Juvenile Diabetes
Research Foundation, GlaxoSmithKline, Forest Laboratories, CVRx, Merck,
Novartis, Boehringer-Ingelheim, Takeda, Abbott Laboratories, Walgreen's,
Bristol Myers-Squibb/Sanofi, Gilead, the National Heart, Lung, and
Blood Institute, Baxter, Bioheart Inc., Novartis/Cleveland Clinic,
NicOx, Angioblast, NIH, Medtelligence, and SLACK Inc.Weaver
reported receiving consulting fees from Phrixis Pharmaceuticals,
receiving research grants from Johnson & Johnson, Schering-Plough,
and GlaxoSmithKline, and serving on data safety boards for trials
sponsored by Boston Scientific, The Medicines Co., Johnson &
Johnson, Bayer, Boehringer Ingelheim, and Direct Flow Medical.Crawford
reported no conflicts of interest. Primary source:
American College of Cardiology
Cooper-DeHoff R, et al "Rethinking lower BP goals for diabetics
with documented coronary artery disease -- findings fom the
International Verapamil SR -- Trandolapril Study (INVEST)" ACC 2010;