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Editorials

Information from drug companies and opinion leaders

BMJ 2003; 326 doi: https://doi.org/10.1136/bmj.326.7400.1156 (Published 29 May 2003) Cite this as: BMJ 2003;326:1156

Rapid Response:

Regarding ALLHAT, heart failure, and race

Dear editors:

I agree with the authors that reports from so-called opinion leaders
are overused by the pharmaceutical industry, whereas more relevant and
quality evidence is rarely, if ever, discussed. However, I take issue with
the seeming dismissal of some of the criticism levelled at ALLHAT as being
biased and thus less than credible.

First, I disagree that the absence of washout was not significant.
Davis et al (BMJ 2002;325:1156) reported a very high prevalence(22.1%) of
left ventricular (LV) systolic dysfunction in a community cohort of high
cardiovascular risk patients, half of whom were asymptomatic. Men were
more likely to have systolic dysfunction. By design, ALLHAT participants
were at high-risk for cardiovascular events, and the prevalence of
systolic dysfunction in ALLHAT was undoubtably important. Abrupt
withdrawal of stable diuretic therapy certainly had the potential to
unmask asymptomatic LV systolic dysfunction in some of these patients. The
early difference in heart failure incidence between the lisinopril and
chlorthalidone groups is entirely consistent with this possibility.
Furthermore, the heart failure curves started merging towards the end of
the trial, suggesting that perhaps longer follow-up would have shown at
least equivalence, if not superiority, of lisinopril in heart failure
prevention.

Second, the authors suggest that the heart failure end-point was
"totally validated". In ALLHAT, the heart failure diagnosis was left up to
the local investigator. A single sample of 39 heart failure
hospitalizations was reviewed by an ALLHAT subcommittee, who only agreed
with 85% of heart failure diagnoses. In contrast, blinded endpoint
committees found no difference in heart failure incidence in STOP-
Hypertension 2 (Hansson et al, Lancet 1999;354:1751) or in ANBP2 (Wing et
al, NEJM 2003; 348:583). In the latter study, men in particular appeared
to benefit more from ACE inhibitors than diuretics, perhaps a reflection
of the findings by Davis et al.

Third, the authors suggest that in ALLHAT "results did not change
according to race". In the ALLHAT report (JAMA 2002; 288:2981), there do
appear to be race-based differences between the lisinopril and
chlorthalidone group with respect to the risks of stroke, and possibly
combined coronary heart disease, combined cardiovascular disease, and
indeed heart failure. Unfortunately, the statistical significance of these
apparent interactions is not provided.

While the tone of the entire ALLHAT debate has been somewhat
strident, the arguments for and against the study results should not be
dismissed lightly, for we may neglect to pursue potentially important
racial and gender differences.

Respectfully,

George A. Heckman MD FRCPC
Heart and Stroke Fellow
Geriatrics and Internal Medicine
McMaster University

Competing interests:  
As a geriatric medicine resident, I received funding from Astra Zeneca to attend the 1999 AHA meeting in Atlanta.

Competing interests: No competing interests

30 May 2003
George A Heckman
Clinical Scholar
McMaster University, Box 2000 Station A, Hamilton, ON, CAN L8N 3Z5