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Clinical question
Are newer antihypertensive medications better at preventing cardiovascular
events than older agents in high-risk patients?
Bottom line
In this study, patients with hypertension and at least 3 additional cardiac
risk factors have slightly fewer deaths from all causes, slightly fewer
strokes, and were slightly less likely to develop diabetes if they were
treated with amlodipine plus perindopril than if they were treated with
atenolol and bendroflumethiazide. One would need to treat between 60 and
1000 high-risk patients for a median of 5.5 years with amlodipine instead of
atenolol to prevent one additional death.
Reference
Dahlof B, Sever PS, Poulter NR, et al, for the ASCOT Investigators.
Prevention of cardiovascular events with an antihypertensive regimen of
amlodipine adding perindopril as required versus atenolol adding
bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes
Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised
controlled trial. Lancet 2005;366:895-906.
Study design: Randomized controlled trial (nonblinded)
Setting: Outpatient (any)
Synopsis
The management of hypertension is getting confusing. The Seventh Joint
National Commission recommends that most patients with hypertension be
managed with a thiazide diuretic. Additionally, the Antihypertensive and
Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)*
demonstrated conclusively that patients with hypertension are better off
when treated with diuretics: patients taking amlodipine did not fare as
well. However, a recent systematic review** also showed that atenolol was no
more effective than placebo in preventing cardiovascular complications. In
the ASCOT study, more than 19,000 patients between the ages of 40 years and
79 years with untreated or inadequately treated hypertension and at least 3
additional cardiac risk factors were randomly assigned (concealed
allocation) to open-label amlodipine (Norvasc) or atenolol. Depending on
response, the patients were also placed on perindopril (Aceon) or
bendroflumethiazide (Corzide). The goal was for blood pressure to be lower
than 140/90 (130/80 for patients with diabetes). In reality, the study arms
should be considered as combination therapy since in each group,
approximately half needed 2 drugs by the second year of the study. The main
outcome, assessed via intention to treat, was the combined end point of
nonfatal myocardial infarction and fatal coronary artery disease. All study
outcomes were evaluated by personnel blinded to allocation. After a median
follow-up of 5.5 years, an independent safety monitoring committee halted
the trial early because of a small increased mortality in the atenolol-based
treatment group (7.7% for amlodipine versus 8.5% for atenolol; number needed
to treat = 115; 95% CI, 61-1012). Among the secondary end points, patients
in the amlodipine group had fewer strokes (3% vs 4%) and were less likely to
develop diabetes (6% vs 8%). There was also a reduction in procedures in the
amlodipine group, although this was a post hoc analysis that is probably
best used merely to generate additional hypotheses for additional study. Why
is it that patients taking amlodipine in the ALLHATwere worse off, but in
this study they fared better? Both studies included patients at high risk of
cardiovascular disease (ALLHAT patients had 1 cardiac risk factor beyond age
and hypertension compared with 3 additional risk factors in ASCOT); ALLHAT,
with more than 30,000 patients, was funded by the National Institutes of
Health and Pfizer with medications provided by other manufacturers; and
ASCOT included patients from the United Kingdom and Scandinavia, while
ALLHAT was conducted in North American centers. But I'm not sure any of
these explain the differences. Perhaps a better explanation is that since
atenolol appears to be no better than placebo in lowering blood pressure or
in improving outcomes, ASCOT compares, in essence, 2 active drugs against 1.
* ALLHAT Officers and Coordinators. Major outcomes in high-risk hypertensive
patients randomized to angiotensin-converting enzyme inhibitor or calcium
channel blocker vs. diuretic. The Antihypertensive and Lipid-Lowering
Treatment to prevent Heart Attack Trial (ALLHAT). JAMA 2002;288:2981-97. **
Carlberg B, Samuelsson O, Lindholm LH. Atenolol in hypertension: Is it a
wise choice? Lancet 2004; 364:1684-89.
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