January 14th, 2011

Combination Therapy Beats Single Therapy As Initial Antihypertensive Therapy

In the ACCELERATE (Aliskiren and the calcium channel blocker amlopdipine combination as an initial treatment strategy for hypertension control) trial, more than 1200 patients with early essential hypertension were randomized to either aliskiren, amlodipine, or the combination of the two drugs for 4 months. The results, which have been published online in the Lancet, showed that blood pressure reduction was greater by 6.5 mm Hg in the combination group than in the monotherapy groups (p<0.0001). After 4 months, when all patients were switched to combination therapy, the difference between the groups had narrowed to 1.4 mm Hg (p=0.059). The investigators concluded that their results suggest that “a move towards routine initial reduction of blood pressure with combination therapy can now be advocated.”

In an accompanying comment,  Ivana Lazich and George Bakris write that “a change in guidelines is clearly necessary after the ACCELERATE report” and the previously reported ACCOMPLISH study. They recommend that “initial combination therapy should be advocated for all those already implementing lifestyle changes who are still above 150/90 mm Hg, as most people in ACCELERATE were.”

6 Responses to “Combination Therapy Beats Single Therapy As Initial Antihypertensive Therapy”

  1. Robin Motz, M.D., Ph.D. says:

    But, if I am not mistaken, only diuretic Rx of hypertension has conclusively been shown to reduce the risk of CVA’s. So for any other initial therapy, the endpoint should be reduction in strokes, heart failure/heart attacks, or renal failure. The degree to which we can lower the blood pressure should be secondary to the benefit to the patient in reduced morbidity.

  2. Stephen Austin, MD says:

    A logical combination would be Aliskiren and a thiazide diuretic, but , unfortunately, thiazides are generic and inexpensive, i.e., less money to be made!

    Competing interests pertaining specifically to this post, comment, or both:

  3. I believe that there is substantial evidence that initial therapy with mechanistically appropriate antihypertensive agents is the way to go for most hypertensives (and certainly any that have a SBP >160. Diuretics have been the most used agent on these combinations and have proven stroke-prevention efficacy.

    However, diuretics are probably not the “only” agent known to prevent stroke. The ACCOMPLISH Trial (N Engl J Med 2008;359:2417-28.) compared a hydrochlorothiazide/benazapril combination to an amlodipine/benazapril combination in 11,506 hypertension patients. Although excellent and nearly identical SBP control was achieved, the combination with amlodipine was associated with a highly significant 21% lower hazard of the composite of death, non-fatal MI or non-fatal stroke (p<0.002) than the hydrochlorthiazide combination. The hazard of fatal and non-fatal stroke was 16% lower (p=0.16).

    In the ALLHAT trial (JAMA 2002;288(23):2981-2997), amlodipine based therapy was associated with similar (actually slightly lower) rates of stroke as chlorthalidone-based therapy. As in ALLHAT, BP control was similar with both agents. Thiazide diuretics are excellent agents for stroke prevention, but they are not the only agents. Thankfully, both are now generic.

    Competing interests pertaining specifically to this post, comment, or both:
    Dr. Massie served on the ACCOMPLISH Trial Steering Committee, for which he received modest consulting fees) and on the writing committee for the ALLHAT trial.

  4. What I like about this discussion is the focus on outcomes – knowing which strategy reduces bp more effectively does not tell you which one most effectively reduces risk. That is what is most important.

    • Saurav Chatterjee, MD says:

      actually there has been quite a few recent publications reviving the interest in the J shaped curve of mortality benefit with HTN control-eg Bangalore et al,EHJ….and if indeed the J shaped curve of mortality benefit with HTN control is a reality,we need to focus on meds and dosages that not only reduce BP but maintain it within a window for having a conclusive mortality/beneficial endpoint advantage………..anyone aware of any such studies?

      Competing interests pertaining specifically to this post, comment, or both:

  5. Lorenzo Marchini, MD says:

    The most obvious limitation of the ACCELERATE trial is that it’s focused on BP reduction, and not on risk reduction, which would’ve required a much more extended duration of the study.
    A prolonged observation would’ve also provided information about the possible adverse events linked with the combination therapy.
    Only after years of post-marketing observations and trials a doubt has arisen about a feeble but possible link between ARBs and cancer. This needs further investigation, but should strenghten an attitude of caution when adopting a new first line aggressive combination strategy, especially when involving a relatively new drug such as Aliskiren.

    Competing interests pertaining specifically to this post, comment, or both: