Current Status of Dual Renin Angiotensin Aldosterone System Blockade for the Treatment of Cardiovascular Diseases

Clinical and experimental studies have shown that the initial suppression of angiotensin II after the administration of angiotensin-converting enzyme (ACE) inhibitors is later reversed and returns almost to pretreatment levels. This raised the hypothesis of the “escape phenomenon,” which was strengthened by the discovery that angiotensin II can also be generated through non-ACEs. Therefore, the addition of angiotensin receptor blockers to ACE inhibitors would produce additional benefits by blocking all angiotensin II at the angiotensin II receptor type 1 level and in addition allowing angiotensin II to stimulate the unoccupied angiotensin II receptor type 2, causing additional vasodilation and antiremodeling effects. However, analysis of various studies including hypertension, heart failure, and renal disease has demonstrated that the gain is modest when combining ACE inhibitors, angiotensin receptor blockers, or the renin blocker aliskiren. In conclusion, on the basis of the results of this analysis, dual blockade of the renin-angiotensin-aldosterone system should not be used for the treatment of hypertension, heart failure, and renal disease, with perhaps the exception of diabetic nephropathy with albuminuria, until additional information is provided from ongoing studies.