Hypertension Combo Works, With Risks

Wall Street Journal - July 20, 2007

Novartis’s Hypertension Combo Works, With Risks

When you sell as many blood pressure drugs as Novartis, it’s natural to get creative, mixing and matching medicines to create new combinations.

But while combinations may lower blood pressure more effectively than a single drug, they may also heighten risk, as a [1] study published in this week’s Lancet shows.

The company’s blood pressure drugs already include single agents Tekturna and Diovan, as well as combination pills Exforge and Lotrel. (For an analysis of the sales of all these drugs, see [2] this Health Blog post.)

The new study enrolled 1797 patients and compared a combination of Tekturna and Diovan against each drug individually and against placebo. Diastolic blood pressure (the second number in a blood pressure reading) went down an average of 12.2 millimeters of mercury for patients who received the combination, compared with 9.7 mm Hg for Diovan, 9.0 mm Hg for Tekturna and 4.1 mm Hg for placebo. The study was funded by Novartis, which also paid medical writers to edit the manuscript.

The authors note that the percentage of patients with a high level of potassium in the blood was higher for patients who received the combination — 4%, compared with 3% for placebo and 2% for each of the single drugs. But they point out that the increase was not associated with serious medical problems and tended to return to normal by the study’s eight-week endpoint.

“Physicians have managed these mild increases in potassium very successfully for over 20 years,” the study’s [3] lead author, Suzanne Oparil of the University of Alabama Birmingham, said in a [4] statement issued by Novartis.

But a [5] commentary accompanying the study strikes a more cautious note about the heightened potassium levels, which, the authors note, can be associated with severe complications including paralysis and cardiac arrest. (One of the commentary’s authors, Willem H Birkenhäger of Erasmus University Rotterdam, claims no conflicts of interest; the other, Jan A Staessen of University of Leuven, reports funding from AstraZeneca and Pfizer, among other companies.)

The commentary argues that there may be a small group of patients suited to the Tekturna-Diovan combination. “However,” they conclude, “because of the potential life-threatening side-effects, which require biochemical monitoring, this concept of treatment is unlikely to make it to general practice or even to primary prevention in specialist care.”