Triple Antihypertensive Therapy with Amlodipine, Valsartan, and Hydrochlorothiaz

1. TeCalhoun DA, Lacourciere Y, Chiang YT, Glazer RD, ,  Triple antihypertensive therapy with amlodipine, valsartan, and hydrochlorothiazide: a randomized clinical trial.,  Hypertension,  54 (1) 32-9. View in PubMed xt Here

The study described in this article reports treatment for 8 weeks with daily doses of the three drugs A/V/T at 10/320/25 mg, or different combinations or two drugs (V/T at 320/25 mg, A/V at 10/320 mg or A/T at 10/25 mg). Patients were titrated up to target doses by 3 weeks. Of 4,285 patients, 2,271 were treated and 2,060 completed the study. The results indicate that triple therapy was superior to all of the dual therapies with more patients achieving overall blood pressure (BP) values less than 140/90 mmHg. Triple therapy was well tolerated regardless of age, sex, race, ethnicity, or baseline BP values. 

Clinical Implication/Application

The authors point out that, in spite of the vast array of medications available, only about one-third of hypertensive patients consistently achieve adequate BP control. Thus, most patients require treatment with two or even three agents to achieve target values. The rationale for the use of combinations of drugs is discussed, and the case is made that combining a calcium channel blocker, an angiotensin II receptor blocker, and a thiazide diuretic could prove superior to any dual-drug combination. An important point is that, when used in combination, one agent may attenuate adverse effects of another. The implications of a generally available triple-drug combination pill relative to ease of use are also discussed as a potential advantage.

The study was well designed, and appropriate precautions were taken to avoid adverse effects. The results provide impressive evidence for the overall superiority of the triple-drug treatment by week 5 of treatment, which continued for the duration of the study. Triple therapy lowered mean systolic BP by 40 mmHg and diastolic PB by 25 mmHg, decreases that achieved the target values and that were statistically greater than the responses achieved with any of the dual treatments regardless of age, sex, race, and ethnicity.

Because achieving target BP can be extremely challenging in certain patient populations, these results provide encouraging evidence that the triple therapy can work on difficult patients with resistant hypertension and still have a very high safety profile. However, it would be prudent, and the authors acknowledge, that the triple-drug in a single pill option should be reserved for those resistant patients who do not achieve target values with single or dual-drug combinations.