DO NOT COMBINE ACE INHIBITORS, ARBS AND ALISKIREN

November 19, 2012

A study published in the Nov. 3, 2012, New England Journal of Medicine (NEJM) showed that aliskiren-containing medications (TEKTURNA, TEKTURNA HCT, AMTURNIDE or TEKAMLO), used to treat high blood pressure, are dangerous in patients with type 2 diabetes when prescribed in combination with one of two other classes of blood pressure drugs: angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs).  

Clinical research further suggests that patients should not take ACE inhibitors, ARBs or aliskiren-containing drugs together in any combination (see the tables below for a list of these drugs), except after careful evaluation and discussion with a physician of the risks of such therapy. If you are on an ACE inhibitor, ARB or aliskiren-containing drug for high blood pressure, congestive heart failure or chronic kidney disease, and your blood pressure, heart or kidney function are not responding adequately, ask your doctor about ways to safely increase the dose of that medication instead of adding one of the other two drug classes to your regimen.

The Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE) set out to assess more than 8,000 patients with type 2 diabetes to examine whether adding aliskiren to ACE inhibitor or ARB therapy reduced death and complications of heart and kidney disease more than using either ACE inhibitors or ARBs alone.  

The trial was stopped early, however, when it became clear that adding aliskiren to ACE inhibitor or ARB therapy harmed patients, causing higher rates of worsening kidney disease, low blood pressure and high potassium levels — potentially life-threatening adverse effects — without adding any clinical benefit over either drug class alone.

The Food and Drug Administration (FDA) responded in April 2012, alerting the public of these results and warning against the use of aliskiren with either ACE inhibitor or ARB therapy in patients with type 2 diabetes or chronic kidney disease.

The ALTITUDE findings concerning aliskiren are identical to those seen when ACE inhibitors and ARBs are given in combination with one another. ACE inhibitor and ARB therapies are clearly beneficial and life-saving — when used alone — for patients with high blood pressure, congestive heart failure and chronic kidney disease. However, combining the two drugs causes an increase in the same side effects seen in ALTITUDE (worsening of kidney disease, low blood pressure and high potassium levels) without providing any added benefit over therapy with either drug class alone.

Table 1. Aliskiren-containing Drugs Available in the U.S.*  

*A fifth drug, VALTURNA (a combination of aliskiren and valsartan, an ARB) was withdrawn from the market in July 2012 in response to the ALTITUDE findings.

Table 2. ACE Inhibitors Available in the U.S. (several ACE inhibitors are also marketed in combination with other medications)

Table 3. ARBs Available in the U.S. (several ARBs are also marketed in combination with other medications)