One important reason for using combination therapy rather than increasing the dose of monotherapy is to reduce the risk of uncontrolled hypotension and other dose-related adverse events, explained Michael Weir, MD, professor of medicine and head, division of nephrology, University of Maryland School of Medicine, Baltimore, Maryland.

In addition to its cardiovascular benefits, achieving lowered blood pressure faster can help ensure patient compliance with the antihypertensive regimen, Dr. Weir noted.

Daily valsartan monotherapy doses in the 9 studies were 80 mg, 160 mg, or 320 mg; in the combination arms, valsartan/hydrochlorithiazide doses were 80/12.5 mg, 160/12.5 mg, 320/12.5 mg, 160/25 mg, or 320/25 mg.

Patients were all 50 to 55 years of age, and two thirds had stage II hypertension, while one third had stage I hypertension.

The meta-analysis was designed to determine which dose achieved the best time to target blood pressure of (< 140/90 mm Hg); those who used the combination therapy, or those who had their doses of valsartan increased.

Results of the analysis show that patients who received the higher doses of valsartan monotherapy reached target blood pressure levels faster than those receiving lower valsartan doses. For example, patients on 160 mg/day reached the target levels within 2 weeks, while it took 8 weeks for patients receiving 80 mg/day to reach target levels.

Similarly, patients receiving the combination therapy at doses of 160/12.5 mg/day reached the target level within 2 weeks, while those receiving 80/12.5 mg/day did so within 8 weeks.

The median time to achieve the target goal was 2 weeks for patients treated with 160/12.5 mg/day, 320/12.5, or 320/25 mg/day. By comparison, it took a mean of 6 weeks for patients treated with valsartan alone to achieve their target goal.

Patients receiving either of the valsartan/diuretic combination therapies reached their goal within a mean of 4 weeks, while those receiving any dose of valsartan monotherapy needed at least 8 weeks.

The most common adverse events were fatigue, dizziness, and headache, which occurred in all 3 treatment groups, including those in the placebo arm, and which were more prevalent as the drug doses were increased. Each of these events was more common in the combination therapy arms.

This was an exploratory trial, Dr. Weir commented, so the results should be interpreted with caution. He added that the time points for measuring blood pressure were highly variable, 6 times over 8 weeks in 1 trial, and only over 4 weeks in another. Therefore, it is not possible to say precisely to the day when a particular patient achieved his or her blood pressure target goal, he said.

Nonetheless, the findings indicate that combination therapy is preferable to monotherapy when blood pressure needs to be lowered as quickly as possible, in a controlled and predictable manner, he concluded.


[Presentation title: Time to Achieving Blood Pressure Goal With Incremental Doses of Valsartan and Valsartan/Hydrochlorothiazide Based on a Pooled Analysis of Randomized, Placebo-Controlled Trials. Abstract P3995]

Copyright © 2009 P\S\L Consulting Group Inc. All rights reserved. Republication or redistribution of P\S\L content is expressly prohibited without the prior written consent of P\S\L. P\S\L shall not be liable for any errors, omissions or delays in this content or any other content on its sites, newsletters or other publications, nor for any decisions or actions taken in reliance on such content.