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Second fixed-dose triple antihypertensive under review in US
  May 12, 2010
New York, NY - Phase 3 data on an investigational triple-antihypertensive drug combination, given as a single pill, were reported at the American Society of Hypertension (ASH) 2010 Scientific Meeting last week. The new product, which is being developed by Daiichi Sankyo, is currently under review by the FDA and, if approved, would become only the second triple-antihypertensive combination available in the US.
President of the European Society of Hypertension, Dr Krzysztof Narkiewicz (Medical University of Gdansk, Poland) told heartwire that in the reappraisal of the European guidelines on hypertension, published last November [1], "We estimated that between 15% and 20% of hypertensive patients do require three or more drugs. So I think it is an important message for our patients that multiple drugs could be taken in one pill, which might improve compliance."
However, Narkiewicz and other experts at the meeting cautioned that triple combinations are very powerful antihypertensive agents and that they should be reserved for use only in those who are proving most difficult to treat.
Dr John Flack (Wayne State University, Detroit. MI) told heartwire: "There is absolutely no indication right now for a triple combination for initial antihypertensive therapy in anyone. You wouldn't initiate therapy with more than two drugs." Flack, who outlined an update to the International Society of Hypertension in Blacks (ISHIB) management guidelines at the ASH meeting, added that where triple drug combinations really come into their own "is where a patient is already on multiple drugs, and they are taking single pills, and it makes sense to combine them into one tablet."
An ASH position paper discussing the relative advantages and disadvantages of single pill combinations of two antihypertensive agents, of which there are many, has recently been published [2], as reported by heartwire.
Phase 3 pivotal data on investigational triple combination
The investigational triple product combines Daiichi Sankyo's angiotensin-receptor blocker, olmesartan, the calcium-channel blocker amlodipine, and the diuretic hydrochlorothiazide (HCTZ). In the new study, TRINITY, reported in a poster at the ASH meeting last week, 2492 patients with moderate to severe hypertension (>140/100 mm Hg; mean BP 168/101 mm Hg) from more than 300 centers were randomized to the triple combination product (olmesartan 40 mg, amlodipine 10 mg, and HCTZ 25 mg) or one of three dual therapies using the same medications.
Those who received the triple combination had greater reductions in both systolic and diastolic blood pressure over the 12 weeks of the study compared with the three dual therapies (p<0.0001 for all), reported Dr Suzanne Oparil (University of Birmingham, Alabama).
And a greater proportion of those receiving the triple therapy reached their goal BP (<140/90 mm Hg or <130/80 mm Hg for those with diabetes, chronic renal disease, or cardiovascular disease)-64.3% vs 34.9% to 46.6% of those taking the dual therapies (p<0.0001 for all). The findings were consistent across prespecified age, gender, and racial subgroups and were the same regardless of hypertension severity, Oparil noted.
The study shows that treating patients with a triple combination, "each component of which has a different mechanism of action, is more effective at lowering BP than the dual combination of any two individual components and was well tolerated among the patients studied," she said.
If approved, the olmesartan/amlodipine/HCTZ triple combination would be the second on the US market following the approval of Exforge HCT (Novartis)-a three-drug combo of amlodipine/valsartan/HCTZ-which was approved by the FDA last year.
Related Links:
Fixed-dose combinations: The way to go in hypertension? [Hypertension > Hypertension; May 11, 2010]
High adherence to antihypertensive therapy lowers cardiovascular risk [Hypertension > Hypertension; Oct 09, 2009]
Some surprises in update to European hypertension guidelines? [Hypertension > Hypertension; Jun 15, 2009]
Combination diuretic, ARB, and CCB approved for treatment of hypertension [Hypertension > Hypertension; May 01, 2009]
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