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Azilsartan medoxomil is a relatively new angiotensin receptor blocker and a study was recently published in Hypertension which compared the combination of two different doses of this drug with chlorthalidone against olmesartan in combination with hydrochlorothiazide for the treatment of stage II hypertension. Both combinations were effective at treating hypertension although the reduction in systolic blood pressures was significantly higher in both azilsartan medoxomil/chlorthalidone arms. There was very little difference between the higher and lower doses of azilsartan medoxomil in terms of effectiveness but there was a higher incidence of adverse effects (mostly dizziness/hypotension or an elevated creatinine) in the high dose group.
This begs the question whether the increased effectiveness of the new combination was due to the effect of the azilsartan medoxomil or the chlorthalidone. Chlorthalidone and hydrochlorothiazide have never been directly compared in a randomized trial and this study is unlikely to ever be done because it simply is not cost effective. However, there is a growing consensus that chlorthalidone is the more effective drug for the treatment of hypertension and prevention of secondary events. Add this to the fact that the majority of patients are on suboptimal doses of hydrochlorothiazide and there is an argument that we should be starting patients primarily on chlorthalidone (if not switching existing patients). To give the authors of this paper their due, they did not gloss over this fact and included a paragraph in both the introduction and discussion about the relative effectiveness of chlorthalidone vs. hydrochlorothiazide and suggested that this could have contributed to the increased effectiveness of their combination drug.
I believe that we should always try to give patients as few tablets as possible and as a result, there is a certain logic to combinations of ARB/ACEi + thiazide diuretics. This is the first ACE/ARB that has been combined with chlorthalidone in a single pill and it may be an attractive option for that reason. See this review about the relative benefits of chlorthalidone vs. hydrochlorothiazide (although these authors did not think that the evidence was sufficient to argue convincingly for one over the other), and this previous post by Lisa about the relative efffectiveness of the two drugs.
It’s a pity that this study was not done as a direct comparison of two ARBs in combination with chlorthalidone as it would have been easier to judge the relative merits of the drugs without this significant confounding factor.

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