ALLHAT overhyped – as I said originally


Category : Medical Rants

Scientists should avoid political agendas. I fear that the principal investigators of the ALLHAT study wanted to advance an agenda with their initial press conferences about the results. Apparently I am not alone. Two ALLHAT Investigators Say Results Misinterpreted and Misused

“Diuretics probably are not the preferred antihypertensive therapy in most North American patients,” said Dr. Houston, who, along with Dr. Weber, was one of the many investigators in the NHLBI-sponsored Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. The study compared cardiovascular outcomes among 42,418 patients age 55 and older who had at least one heart disease risk factor.
In an undated statement given to reporters Wednesday, NHLBI director Claude Lenfant acknowledged the on-going controversy. The NHLBI “recognizes that ALLHAT’s data can be variously interpreted, and the Institute is looking into other conclusions,” he said in the statement, adding that the NHLBI-sponsored hypertension treatment guidelines are in the midst of revision.

Drs. Houston and Weber charge that the ALLHAT study results will be used as the rationale in those guidelines for putting an even greater emphasis on using diuretics as a first-line treatment. The guidelines, formulated by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, will be issued at the American Society for Hypertension meeting in May.

Even though a majority of physicians don’t follow the JNC guidelines, the group’s backing will add to the perception that diuretics are best, said Dr. Houston.

Dr. Houston said that ALLHAT’s design was flawed, leading to muddied results, particularly for African Americans. Overall, he said, when the study is adjusted to reflect the underdosing in people randomized to the ACE inhibitor lisinopril, all the drugs studied show an equal reduction in heart attack, with perhaps a slight edge for lisinopril.

He argued against emphasizing diuretics as a first-line therapy, claiming that the drugs might be nephrotoxic, and cause more diabetes. Plus, said Dr. Houston, there’s a huge body of evidence that contradicts the ALLHAT findings.

Dr. Weber agreed that chlorthalidone was no more effective in reducing myocardial infarction, and he said it had not done a better job at reducing mortality.

“Diuretics are a necessary treatment in many patients,” said Dr. Weber, who told Reuters Health that 70% of his patients are on a diuretic, but as part of a multidrug regimen. “They should not be the foundation for antihypertensive therapy,” he said.

It is nice to see that reason is starting to prevail here.

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Comments (3)

I’m pleased that someone has the guts to bring some common sense into this debate. The NYT and other media outlets spun the results simplistically as a triumph of science over corporate greed with their “cheaper is better” mantra. Consequently it’s been virtually impossible to challenge the results without being labeled as a drug company shill. The fact is the study design stacked the deck heavilly against lisinopril not only by inappropriate initial monotherapy in African Americans, but also due to irrational chioces of step 2 and 3 drugs (clonidine, hydralazine and reserpine). This is contrary to what was already known about the optimal use of ACE inhibitors, and certainly not the way the drugs are used in the community. Assuming that the investigators knew this, I too wonder if they had an agenda.

Well I found the original ALLHAT results inherently plausible partly because the lower stroke rate fit in with discussions in earlier articles such as:

Antihypertensive drug therapies and the risk of ischemic stroke.
Arch Intern Med. 2001 Jan 8;161(1):37-43.
PMID: 11146696 [PubMed – indexed for MEDLINE] by Klungel OH, Heckbert SR, Longstreth WT Jr, Furberg CD, Kaplan RC, Smith NL, Lemaitre RN, Leufkens HG, de Boer A, Psaty BM.

which I found quite persuasive when published. I see the bounceback not as common sense reasserting itself but as denial and pharma bouncing back. Thiazide diuretics are best first choice for hypertension for most IMO.

Lest Anne suspect that my sentiments are influenced by Pharma, perhaps I should provide my conflict of interest disclosure.

1) A have no financial interest or other ties to the pharmaceutical industry.
2) I dislike the politicization of issues of science.

I think Anne has given some credence to the point I made in the third sentence of my original post.

Robert W. Donnell