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Two Drugs Better Than One for High Blood Pressure
Date:3/31/2008

Pairing ACE inhibitor with calcium channel blocker beat pairing it with diuretic; Celebrex study finds dose related to heart risk

MONDAY, March 31 (HealthDay News) -- A large trial shows that combining an ACE inhibitor with a calcium channel blocker in individuals with high blood pressure who are at high risk for cardiovascular complications resulted in a 20 percent reduction in the risks of death, heart attack, stroke and other cardiovascular troubles.

The ACE inhibitor and calcium channel blocker were combined in a single pill. Patients receiving this treatment were compared to patients who received an ACE inhibitor combined with a diuretic.

The authors of the study, which was halted early because the results were so strong, presented the interim results during a news conference Monday at the American College of Cardiology annual meeting, in Chicago. Their hope is that the findings will change current practice guidelines.

"This strategy challenges our current guidelines in two important ways. First, the idea that monotherapy [starting out on a single pill] should be the rule of stay is now challenged and, second, guidelines have recommended that we use a diuretic, and we show that an ACE inhibitor and calcium channel blocker are superior," said study author Dr. Kenneth Jamerson, a professor of internal medicine at the University of Michigan Medical School.

The trial randomized more than 10,000 individuals, two-thirds of whom came into the study with inadequately controlled blood pressure. The use of the combination tablet as the first line of treatment more than doubled the number of patients who managed to get their hypertension under control, the study authors said in a statement. Novartis, which is one of the companies offering the two-drug combination tablet, funded the study.

A second study presented at the news conference refines the safety profile for Celebrex, the only cox-2 painkiller still sold in the United States and the most widely prescribed in its class around the world. The drug carries a black-box warning about an increase in cardiovascular risks for users.

The authors reviewed existing data from several trials and combined them in one comprehensive analysis, finding a clear relationship between dose and cardiovascular risk.

Individuals taking 400 milligrams of Celebrex twice a day had a threefold increase in cardiovascular risk. Those taking 200 milligrams twice a day had double the risk.

In addition, patients who had a low risk when they started taking the painkiller continued to show a low risk of having a Celebrex-induced cardiovascular problem later, while those starting out at high risk were more likely to suffer cardiovascular consequences while taking Celebrex, especially at the higher doses. The analysis was published simultaneously Monday in the online edition of Circulation.

"Perhaps this will give us a little bit of comfort when we prescribe Celebrex to patients who are at very, very low cardiovascular risk, but it will perhaps make us considerably more cautious when prescribing to those at high risk," said study author Dr. Scott Solomon, director of noninvasive cardiology at Brigham and Women's Hospital in Boston. "The doses we were able to test were considerably higher than typical arthritis patients are taking."

A third study from the news conference brought more good news for Crestor (rosuvastatin). In a study funded by drug maker AstraZeneca, treatment with this statin for two years lowered average LDL ("bad") cholesterol levels and increased HDL ("good") cholesterol levels, resulting in regression of coronary atherosclerosis. Earlier Monday, AstraZeneca announced that it had halted another trial of Crestor because of "unequivocal" evidence that it was better than a placebo.

"Ninety-seven percent of participants were either stable or had regression," said Dr. Christie M. Ballantyne, of the section of atherosclerosis and vascular medicine in the department of medicine at Baylor College of Medicine and the Methodist DeBakey Heart & Vascular Center. Ballantyne added that the trial lends credence to the strategy of lowering LDL levels.

More information

Visit the American Heart Association for more on high blood pressure.



SOURCES: March 31, 2008, teleconference with Kenneth Jamerson, M.D., professor, internal medicine, University of Michigan Medical School, Ann Arbor; Scott D. Solomon, M.D., director, noninvasive cardiology, Brigham and Women's Hospital, Boston; Christie M. Ballantyne, M.D., section of atherosclerosis and vascular medicine, department of medicine, Baylor College of Medicine, and the Methodist DeBakey Heart & Vascular Center; March 31, 2008, presentations, American College of Cardiology annual meeting, Chicago


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