Rationale for triple fixed-dose combination therapy with an angiotensin II receptor blocker, a calcium channel blocker, and a thiazide diuretic

Vascular Health and Risk Management, 06/12/2012

The availability of these fixed–dose combinations should lead to improvement in blood pressure control and aid compliance with long–term therapy, optimizing the management of this chronic condition.

  • Hypertension is a growing global health problem, and is predicted to affect 1.56 billion people by 2025.
  • Treatment remains suboptimal, with control of blood pressure achieved in only 20%–35% of patients, and the majority requiring two or more antihypertensive drugs to achieve recommended blood pressure goals.
  • To improve blood pressure control, the European hypertension guidelines recommend that angiotensin II receptor blockers (ARBs) or angiotensin–converting enzyme inhibitors (ACEIs) are combined with calcium channel blockers (CCBs) and/or thiazide diuretics.
  • The rationale for this strategy is based, in part, on their different effects on the renin–angiotensin system, which improves antihypertensive efficacy.
  • Data from a large number of trials support the efficacy of ACEIs or ARBs in combination with CCBs and/or hydrochlorothiazide (HCTZ).
  • Combining two different classes of antihypertensive drugs has an additive effect on lowering of blood pressure, and does not increase adverse events, with the ARBs showing a tolerability advantage over the ACEIs.
  • Among the different ARBs, olmesartan medoxomil is available as a dual fixed–dose combination with either amlodipine or HCTZ, and the increased blood pressure–lowering efficacy of these two combinations is proven.
  • Triple therapy is required in 15%–20% of treated uncontrolled hypertensive patients, with a renin–angiotensin system blocker, CCB, and thiazide diuretic considered to be a rational combination according to the European guidelines.
  • Olmesartan, amlodipine, and HCTZ are available as a triple fixed–dose combination, and significant blood pressure reductions have been observed with this regimen compared with the possible dual combinations.

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