Therapeutics
Randomised controlled trial
10.1136/ebm1099
1
Department of Cardiology,
University of Louisville Medical
Center, Louisville, Kentucky, USA
2
Pritzker School of Medicine,
University of Chicago, Chicago,
Illinois, USA
Correspondence to:
George Bakris
Pritzker School of Medicine,
University of Chicago, 5841 S.
Maryland Avenue, MC 1027,
Chicago, IL 60637, USA;
gbakris@gmail.com
142 Evidence-Based Medicine October 2010 | volume 15 | number 5 |
Intensive lowering of systolic blood pressure to a target of
less than 120 mm Hg has no effect on the rate of fatal and
non-fatal major cardiovascular events in high-risk patients
with type 2 diabetes
Atul Chugh,1 George Bakris2
Commentary on: Cushman WC, Evans GW, Byington RP, et al.; ACCORD Study Group. Effects of
intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med 2010;362:1575–85.
Context
The Seventh Report of the Joint National Committee on
Prevention, Detection, Evaluation and Treatment of High
Blood Pressure recommends a blood pressure (BP) treat-
ment goal of <130/80 mm Hg for patients with diabetes and
hypertension.1 This goal was derived from observational
data.2 3 The BP arm of the Action to Control Cardiovascular
Risk in Diabetes (ACCORD) trial prospectively addressed
whether this lower BP further reduced cardiovascular
events in high-risk patients with type 2 diabetes.
Methods
ACCORD was a prospective, open-label, randomised trial
that enrolled 10 251 patients at high-cardiovascular risk
and type 2 diabetes. Of these, 4733 patients were ran-
domised to either intensive (goal systolic BP (SBP) <120
mm Hg) or standard (goal SBP <140 mm Hg) control in
a two-by-two factorial design. High risk was defined as
a presence of clinical cardiovascular disease (CVD) or
a high likelihood of CVD based upon established car-
diovascular risk factors. Patients with baseline SBPs of
130–180 mm Hg taking three or less antihypertensive
agents and a 24 h protein exertion rate of <1.0 g were
included. Exclusion criteria included patients with body
mass index >45 and/or a serum creatinine level >1.5
mg/dl. Antihypertensive regimens included a drug class
demonstrating cardiovascular benefit in diabetics. In the
intensive group, a combination of a diuretic and either an
angiotensin-converting enzyme inhibitor or a β-blocker
was recommended as initial therapy. The primary end
point was the composite of non-fatal myocardial infarc-
tion, non-fatal stoke or cardiovascular death. Mean fol-
low-up time was 4.7 years.
Findings
The average SBP was 119.3 mm Hg (95% CI 118.9 to 119.7)
in the intensive-therapy group and 133.5 mm Hg (95%
CI 133.1 to 133.8) in the standard-therapy group while
mean diastolic BP (DBP) in the intensive-therapy group
was 64.4 mm Hg (95% CI 64.1 to 64.7) and 70.5 mm Hg in
the standard-therapy group (95% CI 70.2 to 70.8). The pri-
mary composite outcome rate was 1.87% per year in the
intensive-therapy group as compared with 2.09% per year
in the standard-therapy group (HR with intensive therapy
0.88; 95% CI 0.73 to 1.06; p=0.20). Similarly, no differ-
ence in all-cause or cardiovascular mortality was noted
between groups. (All-cause mortality: 1.28% per year in
the intensive-therapy group and 1.19% in the standard-
therapy group (HR with intensive therapy 1.07; 95% CI
0.85 to 1.35; p=0.55); CV death rate: 0.52% per year in the
intensive-therapy group vs 0.49% per year (HR 1.06; 95%
CI 0.74 to 1.52; p=0.74)). In the intensive-therapy group,
a statistically lower rate of total stroke (0.32% per year vs
0.53% per year; HR 0.59; 95% CI 0.39 to 0.89; p=0.01) and
non-fatal stroke (0.30% per year vs 0.47% per year; HR
0.63; 95% CI 0.41 to 0.96; p=0.03) were shown. Higher
rates of serious adverse events and hypokalaemia were
attributed to the intensive-therapy arm.
Commentary
This study fails to support the contention that a lower
SBP is associated with a lower cardiovascular event rate.
Moreover, the intensive-therapy group had almost three
times more adverse events. A benefit was seen on stroke
rate and this bears further examination. Similar results
were garnered from retrospective analyses of large out-
come trials.4 5 Taken together, these studies suggest that a

lower BP is not always better. A factor contributing to this
lack of benefit may be related to a DBP that is too low rela-
tive to the SBP, as this has been independently associated
with higher cardiovascular events. A DBP <70 mm Hg was
the nadir established where risk starts to increase; a BP
cut-off significantly higher than the mean DBP achieved
in the intensive-therapy arm of this trial.6 Thus, this may
also be a contributing factor and is being evaluated.
ACCORD will play an important role in changing BP goals
in future guidelines for patients with diabetes.
Competing interests GB is a consultant for NIH/NIDDK,
GSK, Merck, Novartis, Boehringer-Ingelheim, Takeda,
Abbott, Walgreen’s, BMS/Sanofi, Gilead, Forest, CVRx,
Fibrogen, Spherix, Johnson & Johnson, Daiichi-Sankyo.
GB has also received investigator initiated grants from
GSK Forest Labs.
References
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of the Joint National Committee on Prevention, Detection,
Evidence-Based Medicine October 2010 | volume 15 | number 5 |
Therapeutics
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