New combination therapy offers promising approach for hypertension management
American Society of Hypertension 2011 Annual Scientific Meeting
NEW YORK — Among patients with stage II systolic hypertension, azilsartan medoxomil, a newly approved angiotensin II receptor antagonist, plus chlorthalidone led to greater reductions in systolic BP compared with olmesartan plus hydrochlorothiazide, according to findings presented here at the American Society of Hypertension 2011 Annual Scientific Meeting and Exposition.
According to study investigator William C. Cushman, MD, of the University of Tennessee College of Medicine in Memphis, this was the first large, forced titration study of an angiotensin II receptor blocker fixed-dose combination.
“This [study] gives the maximum comparison in terms of the effectiveness of these products … and demonstrates superior efficacy of the [azilsartan medoxomil-chlorthalidone] fixed-dose combinations compared with [olmesartan-hydrochlorothiazide],” Cushman said in a press conference.
In the phase 3, multicenter, double blind, randomized study, the effects of two doses of azilsartan medoxomil (AZL-M; Edarbi, Takeda Pharmaceuticals) plus chlorthalidone (CLD) were compared with olmesartan (OLM) plus hydrochlorothiazide (HCTZ). The study design called for force titrating to maximum doses for all three arms during a 12-week interval: 20 mg AZL-M/12.5 mg CLD to 40 mg AZL-M/25 mg CLD (n=355); 40 mg AZL-M/12.5 mg CLD to 80 mg AZL-M/25 mg (n=352); and 20 mg OLM/12.5 mg HCTZ to 40 mg OLM/25 mg HCTZ (n=364). Only patients aged at least 18 years and with post-washout clinic systolic BP of between 160 mm Hg and 190 mm Hg were included.
At 12 weeks, the study’s primary endpoint of change in clinic systolic BP favored both the 40/25-mg (–42.5 mm Hg) and 80/25-mg AZL-M arms (–44 mm Hg) vs. the OLM arm (–37.1 mm Hg; P<.001 for both comparisons). Similarly, change in 24-hour mean systolic BP also favored the 40/25-mg (–33.9 mm Hg) and 80/25-mg AZL-M arms (–36.3 mm Hg) compared with the OLM arm (–27.5 mm Hg; P<.001 for both).
Overall, adverse events appeared more frequently in the 40/25-mg (71.3%) and 80/25-mg (70.7%) AZL-M groups vs. the OLM group (60.2%). However, serious adverse events were least common in the 40/25-mg group (0.3%), followed by OLM (2.2%) and ALZ 80/25 mg (2.8%).
The study was sponsored by Takeda. – by Brian Ellis
Disclosure: In the past 12 months, Dr. Cushman reports receiving grant/research support from Merck, GlaxoSmithKline and Novartis and has consulted for Takeda, Novartis and Noven.
For more information:
Cushman W. LB-OR-03. Presented at: American Society of Hypertension 2011 Annual Scientific Meeting and Exposition; May 21-24, 2011; New York.
This certainly is an impressive study. AZL-M as mono-therapy seems to be an absolutely superb angiotensin II receptor blocker. It has been shown to lower BP more efficaciously than 40 mg of OLM, which is a very good angiotensin II receptor blocker as we know. However, why AZL-M is so much better than the others is not entirely clear.
It is important to consider, though, that there was no placebo in this study. There would certainly be a placebo reduction [in systolic BP] of about 10 mm HG. Therefore what you would then see when you then look at 24-hour BP is much more realistic, but still extremely good.
Another point is that we have shown that CLD is absolutely more powerful than HCTZ. It has been established in quite a few studies, though never in a combination, so we cannot say this is a good way of comparing the two. But it is my suspicion that the good anti-hypertensive effects of AZL-M and CLD are obviously synergistic and will beat the competition.
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High prevalence of masked hypertension confirmed among blacks
American Society of Hypertension 2011 Annual Scientific Meeting
NEW YORK — New research presented here has confirmed previous data that indicated a high prevalence of masked hypertension among blacks and further reinforces the importance of ambulatory BP monitoring to help identify patients with high BP who do not present as such at doctors’ office visits.
The preliminary study included 38 black patients (mean age, 51 years; 86.8% women) from the Philadelphia region who were sedentary, nondiabetic, nonsmoking, not on antihypertensive medication and did not have CVD. Office BP measurements were taken during three visits on an average of three readings per visit, whereas ambulatory BP monitoring was performed on a typical day of the patient and was set to go off at 30-minute intervals during the day (6 a.m. to 10 p.m.) and 60-minute intervals during the night (10 p.m. to 6 a.m.).
According to study data, the BP measurements at the office were 124.4 mm Hg/79.1 mm Hg for the first visit, 126.4 mm Hg/80.1 mm Hg for the second visit 1 week later and 128.7 mm Hg/79.7 mm Hg for the third, whereas the mean ambulatory BP monitoring for 24 hours was 126.7 mm Hg/78.5 mm Hg (daytime, 128.4 mm Hg/80.2 mm Hg; nighttime, 116.8 mm Hg/68.6 mm Hg). The prevalence of masked hypertension decreased with each visit, from 59% on the first visit to 40% on the second visit and 38% on the third visit. Additionally, as an average for all three BP office measurements, roughly 45% of the population consistently had masked hypertension.
“The take-home message is office BP may not be sufficient, especially in this cohort,” study researcher Praveen Veerabhadrappa, MD, MS, research fellow, International Society of Hypertension Doctoral Candidate, Hypertension Molecular & Applied Physiology Lab, said in a press conference. “Close to 45% had masked hypertension, and they were not even aware they had hypertension. They may require some kind of intervention, whether it be nonpharmacological or pharmacological.” – by Brian Ellis
If you look at end-organ damage for African Americans compared with whites for the same level of office BP, African Americans have significantly higher rates of stroke, kidney disease and HF. This is probably the reason (for reasons that we don’t quite understand yet) that African Americans have higher BP outside the office than inside the office. The implication then is we can’t be complacent with a normal BP for an African American in the office. We are going to have to do more ambulatory BP monitoring and home monitoring.