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WEST PALM BEACH, Fla., Sep 16, 2005 (United Press International via COMTEX) -- European researchers have kicked over the neat bottle that contained U.S. government guidelines for the treatment of high blood pressure.
The inexpensive drugs suggested by the most recent National Institutes of Health task force appear to be inferior to more modern drugs, said researchers reporting the final results of a massive study that compared "old" and "new" strategies of treating high blood pressure, a disease that affects 60 million people in the United States.
In the Anglo-Scandinavian Cardiac Outcomes Trial Blood Pressure Lowering Arm -- also known as the ASCOT-BPLA trial -- the more modern strategy was so effective the trial was halted prematurely -- because of a higher mortality among those getting the older drugs.
ASCOT researchers said that patients receiving the angiotensin-converting enzyme, or ACE inhibitor perindopril (ACEON) and the calcium channel blocker amlodipine (NORVASC) had reduced the risk of death, stroke or other cardiovascular events when compared with patients on older drugs -- diuretics and beta blockers.
"The combination of the contemporary blood pressure lowering drugs, amlodipine and perindopri, plus effective lowering of cholesterol, abolished more than half the risk of strokes and heart attacks -- the most important causes of death in millions of men and women with high blood pressure," said Dr. Bjorn Dahlof, professor of medicine at Sahlgrenska University Hospital in Goteborg, Sweden.
Dahlof presented the final results of the largest European trial at the annual meeting of the European Society of Cardiology Congress 2005 last week. The results were published simultaneously online in The Lancet, the prestigious British medical journal.
The ASCOT results flew in the face of the controversial recommendations of the Seventh Joint National Committee on Prevention, Detection and Treatment of High Blood Pressure, a U.S. government-sponsored task force. Based on results of clinical trials such as the Anti-hypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), sponsored by the National Heart, Lung and Blood Institute, the JNC-7 recommendations suggested patients with high blood pressure be started on drugs such as diuretics and beta blockers. The older drugs also are far less expensive than the more recent medications -- a fact many observers saw as a way to decrease financial pressure on major government health agencies.
The ASCOT results knock JNC-7 guidelines into a cocked hat.
ASCOT, which involved more than 19,000 participants, was prematurely halted by the Data Monitoring and Safety Board, a factor that prevented the results from reaching statistical significance for non-fatal or fatal heart attacks, or for fatal heart disease.
"That should not detract from the value of the findings," however, Dahlof said.
Other researchers concurred.
"There is little question that if the trial was allowed to continue for just a bit further it would have reached statistical significance," said Dr. Richard Devereux, professor of medicine at Weill Medical College at Cornell University in Ithaca, N.Y. "The fact that it was stopped early should not be viewed as a criticism of this trial."
ASCOT researchers also reported:
-- Among those on the modern regimen, 327 patients experienced fatal and non-fatal strokes, compared with 422 patients on the traditional treatment.
-- Among those on the modern regimen, 738 people died, compared to 820 patients on the traditional treatment, a relative risk reduction of 11 percent in favor of the newer drugs.
-- Among those on the modern regimen, 1,362 patients experienced cardiovascular events, compared with 1,602 patients on the traditional treatment, a 16-percent relative-risk reduction.
-- Among those on the modern regimen, 567 developed diabetes during the course of the trial, compared with 799 on the traditional treatment, translating into a 30-percent relative-risk reduction.
"One of the hallmarks of drugs that combat the angiotensin system, such as ACE-inhibitors and angiotensin receptor blockers," Devereux said, "is the reduction in the risk of developing new onset diabetes."
He said Losartan Intervention For Endpoint, or LIFE, reduction in hypertension -- according to a study in Australia and New Zealand that used angiotensin-blocking drugs -- development of new onset diabetes was reduced.
ASCOT patients were assigned to receive either amlodipine, followed, if needed, by perindopril -- the so-called modern strategy, or the traditional therapy of the beta-blocker atenolol followed by the diuretic bendroflumethiazide, if necessary.
Dahlof said about 10 percent to 15 percent of the patients were able to maintain lowered blood pressure on monotherapy. The others required combination treatment to keep blood pressure under control.
Dr. Salim Yusuf, professor of medicine and director of cardiology at McMaster University in Hamilton, Ontario, said despite the failure to reach statistical significance, as well as questions about whether the results were due to greater drug pressure lowering seen among the patients on the modern regimen, "it should not take away from the good results we have seen. There is a real benefit to the treatment with the newer drugs, but the size of the benefit may not be as big as seen. Some part of the difference is due to the difference in blood pressure but the rest is due to other factors."
Along with the advantages of lower rates of death, stroke and heart attack, the newer regimens also were helpful in other issues, said Dr. Franz Messerli, director of hypertension and cardiology at St. Luke's Roosevelt Hospital in New York City.
"In ASCOT, those getting the amlodipine-based therapy had far fewer episodes of erectile dysfunction and peripheral coldness -- numbness in the fingers -- than those taking beta blockers," he said. "Quality of life is important."
The assault on JNC-7 recommendations will appear in other ongoing trials, Devereux said, including the ambitious, 13,000 person study called Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension, or ACCOMPLISH.
In both ASCOT and ALLHAT, patients with high blood pressure were begun on monotherapy, then placed on a second medication. In the new trial, expected to conclude in 2008, patients were started on fixed doses of combination medicines -- either the ACE-inhibitor benazepril combined with amlodipine (Lotrel) or benazepril with the diuretic hyrdrochlorothiazide.
Devereux said the trial essentially would answer the question of whether the calcium channel-blocker is better than the diuretic in controlling morbidity and mortality of patients.
"It's clear that the use of multiple medications or combination therapy is a superior strategy for controlling blood pressure," said Dr. Kenneth Jamerson, professor of internal medicine at the University of Michigan Medical Center in Ann Arbor.
"ACCOMPLISH is a critically important trial because it will answer the next big question: Which antihypertensive combination best protects patients from cardiovascular disease and death?" Jamerson asked.
In addition to lowering blood pressure, previous ASCOT findings indicated the addition of the cholesterol-lowering drug atorvastatin reduced still further the remaining risk, irrespective of the patient's original cholesterol level. In fact, ASCOT patients only had average or below-average levels of cholesterol at the outset of the study. The striking effect of cholesterol-lowering in the patients also resulted in an early termination in favor of cholesterol-lowering.
"High blood pressure is a major public health problem," Dahlof said. "Despite the availability of effective blood pressure lowering drugs, many people who are being treated still suffer strokes, heart attacks and other related diseases, such as diabetes. Now, the evidence from ASCOT offers us a simple and effective combination of treatments which both control the blood pressure and lower cholesterol to more effectively reduce this risk. This is very important news for patients and their physicians."
Dahlof and other researchers suggested, based on the new studies, that international recommendations for managing high blood pressure may need to be reviewed.
Edward Susman covers medical research for UPI. E-mail: email@example.com
Copyright 2005 by United Press International.