Bethesda, MD - Hoping to speed up the flow of information from hypertension-therapy guidelines to clinical practice, investigators from an influential trial teaming with the National Heart, Lung, and Blood Institute (NHLBI) have launched a sweeping physician- and public-education program designed to bring contemporary practice more in line with the evidence base, according to an NHLBI announcement. But some experts believe the program, like the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) itself, is deeply flawed.

About 150 physicians have been trained to update primary-care and other doctors in communities across most of the US on the tenets of hypertension therapy based on the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC-7) and contributions from the NHLBI-sponsored ALLHAT study. Among the major apparent gaps between the guidelines and much of clinical practice, according to the agency's press release, is underuse of diuretics for initial drug management.

The educational initiative's primary talking points, leading ALLHAT investigator Dr Barry R Davis (University of Texas Health Science Center at Houston) told heartwire, include 140/90 mm Hg as the blood-pressure goal for drug therapy and the value of a thiazide-type diuretic for initial therapy, "whether it be the first drug or in combination with other drugs." The teachers will lead community physicians in "small, interactive educational sessions," using literature and other materials designed specially for the program, which is being implemented in collaboration with the National High Blood Pressure Education Program (NHBPEP), the NHLBI statement said.

In addition to lifestyle changes, diuretics should be the drug of choice for first-line blood-pressure treatment.

Initially launched in 1994, the seminal but sometimes controversial ALLHAT trial randomized >40 000 hypertensive patients to initial therapy based on a drug from one of four classes then in use: the alpha blocker doxazosin, the ACE inhibitor lisinopril, amlodipine as a calcium-channel blocker, and the thiazide diuretic chlorthalidone. After the doxazosin arm was terminated due to poor results compared with the diuretic, the three other agents emerged as essentially equivalent at improving major clinical outcomes. Chlorthalidone seemed to work the best on some secondary end points, leading ALLHAT authors to recommend diuretics as integral to first-tier drug management. The trial, its treatment implications, and reaction in the cardiology community have been extensively covered by heartwire.

"Based on the results, the ALLHAT investigators recommend that in addition to lifestyle changes, diuretics should be the drug of choice for first-line blood pressure treatment," Dr William C Cushman (Veterans Affairs Medical Center, Memphis, TN), another of the trial's top-level investigators, is quoted as saying in the NHLBI press release. He goes on to promote the major JNC-7 message that "most patients require more than one drug," one of them a diuretic. Drugs in that class, according to Cushman in a reiteration of observations from the original ALLHAT report, have the further advantage of being "much less expensive than the other two drug classes."

In an interview with heartwire,Dr Joseph L Izzo (State University of New York at Buffalo) recognized the potential advantage of low cost in a drug regimen but said, "ALLHAT, in my view, is a highly flawed study." Rather than compare drug classes, according to Izzo, the trial should have asked whether it's better to lower systolic pressure to less than 140 mm Hg or even lower, such as 120 mm Hg. Also, he said, the trial was overweighted with higher-risk patients who are "the least responsive to ACE inhibitors," such as African Americans, diabetics, and the elderly. He also said blood pressures were measured at peak rather than the more appropriate trough drug effect, important because the ACE-inhibitor doses were small and didn't last 24 hours, while amlodipine and chlorthalidone are longer acting.

The use of diuretics has not been going up as much as they were hoping, and use of the more expensive trade-name medications, which are being so heavily advertised and marketed, continue to rise.

Dr Norman Kaplan (University of Texas Southwestern Medical Center, Dallas) supported the ALLHAT team's efforts to promote diuretics for hypertension. "I've seen the figures. The use of diuretics has not been going up as much as they were hoping, and use of the more expensive trade-name medications, which are being so heavily advertised and marketed, continue to rise," he said to heartwire. "I guess it's all part of the feeling that we need to keep after physicians to do the right thing."

While acknowledging his own participation in speakers' bureaus of many drug companies, Kaplan commented that marketing dollars seldom go to promoting diuretics, "and I think that there is a little bit of scare-mongering going on that diuretics are bad for you, and you can't use them, and you have to use 'our' angiotensin receptor blocker, ACE inhibitor, or calcium-channel blocker, or whatever."

He added, "My attitude is that a low-dose diuretic is valuable for virtually everyone." Referring to cautions from some observers that diuretics shouldn't be given to patients with gout and may promote diabetes, Kaplan said, "At the doses we generally recommend, there really shouldn't be any of the metabolic problems."