New Drug Combo Fights High Blood Pressure

FRIDAY July 20, 2007 -- Combining two drugs that act in different ways to block activity of a molecule called angiotensin II brings about a steeper reduction in high blood pressure than using either drug alone, a new study finds.

However, taking the two drugs Diovan and Tekturna, "might not be the first choice for newly diagnosed patients," in part because it is very expensive, said lead researcher Dr. Suzanne Oparil, director of the vascular biology and hypertensive program at the University of Birmingham in Alabama. "But, for patients with certain conditions, such as an enlarged heart, kidney disease or diabetes, there may be an advantage to really blocking angiotensin, because we think that angiotensin is toxic for the kidney," Oparil said.

Her team published its findings in the July 21 issue of The Lancet. The study was funded by Novartis Pharmaceuticals, which makes both Diovan and Tekturna.

Combined therapy using diuretics -- drugs that are available in inexpensive generic form -- has been found to produce satisfactory blood pressure control in most people. But newer drugs that target angiotensin are not yet available as generics, making them much more expensive.

Angiotensin II is a blood molecule that raises blood pressure by narrowing vessels. The two drugs used in the study were valsartan (Diovan), which blocks the cell receptors on which angiotensin acts, and aliskiren (Tekturna), which blocks the molecular pathway for production of angiotensin II.

The trial included almost 1,800 people with high blood pressure. A quarter of them got daily doses of Diovan, a quarter took Tekturna daily, a quarter got both drugs and the final quarter were given a placebo, an inactive substance.

The treatment was given for a four-week period, followed by another four weeks in which drug dosages were doubled.

Blood pressure was reduced by an average of 12.2 points in those getting the higher doses of combined therapy, compared to a 9-point reduction for those getting Tekturna alone, a 9.7-point reduction for those getting Diovan alone, and 4.1 points for those taking placebo.

"These findings provide a clear rationale for further studies to investigate the potential effects of long-term treatment with the combination of aliskiren and valsartan, and combinations of aliskiren and other angiotensin receptor blockers, on possible benefits beyond treating hypertension," the journal report said.

A number of such studies using a variety of medications are under way, Oparil said.

However, an accompanying editorial raised serious doubts about the safety of the two-drug combination used in the study. The editorial noted that there was a sharp spike in blood potassium levels among some patients getting the combined therapy. This type of spike can cause "potentially life-threatening side effects" such as paralysis and cardiac arrest, the article's authors wrote.

"If this is given to patients, serum potassium levels should be monitored from the start," added Dr. Jan Staessen, professor of medicine at the University of Leuven, Belgium, co-author of the editorial. "This is a major limitation on its use."

Because of the need to monitor potassium levels, use of the two-drug therapy should be limited to "patients who already have complications and require special therapy but not in the majority of patients," Staessen said.

Oparil described that criticism as "inflammatory and unfair."

"They just wanted to paint the drugs in an unfavorable light," she said.

Data in the published report showed that the incidence of high blood potassium levels was as common in participants getting the placebo as those receiving the two-drug combination, Oparil said. And of 18 participants who had potassium readings higher than the danger level, "12 were normal on retest," she said.

Posted: July 2007


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