Two FDA Officials Quarrel Over Safety Of Angiotensin Receptor Blockers 1

Two FDA officials are quarreling in public about their different views about the safety of angiotensin-receptor blockers (ARBs), according to a story by Thomas Burton in Friday’s Wall Street Journal.

One official, Thomas Marciniak, contends that ARBs may increase the risk of cancer. Marciniak has been a vocal critic of FDA’s efforts to assess drug  safety. In the past he has raised questions about other major drugs, including prasugrel, rosiglitazone, and rivaroxaban. But Marciniak’s boss, Ellis Unger, who is the acting director of the office of new drugs, told the WSJ  that Marciniak’s concerns are a “diversion.”

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European Medicines Agency Starts Review of Combined Use Of Drugs That Block The Renin-Angiotensin System 1

The European Medicines Agency said last week that it was initiating a review of the combined use of agents that block the renin-angiotensin system (RAS). The three classes of RAS-blocking drugs (ACE inhibitors, ARBs, and direct renin inhibitors) are used to treat hypertension and congestive heart failure.

The EMA said that the review was being performed to address concerns that combined RAS-blocking drugs could increase the risk for hyperkalemia, hypotension, and kidney failure when compared with a single agent.  A recent meta-analysis of 33 clinical studies published in the British Medical Journal concluded that ”although dual blockade of the renin-angiotensin system may have seemingly beneficial effects on certain surrogate endpoints, it failed to reduce mortality and was associated with an excessive risk of adverse events… The risk to benefit ratio argues against the use of dual therapy.”

Franz Messerli, senior author of the BMJ meta-analysis, applauded the EMA action and said that “as usual the FDA is dragging its feet.”

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Study Warns Against Dual Blockade of Renin-Angiotensin System In Heart Failure And Hypertension 1

The enormous success of ACE inhibitors in hypertension and heart failure spurred hope that adding a second drug to block the renin-angiotensin system would yield improved outcomes. Although definitive evidence supporting dual blockade of the renin-angiotensin system has never been found, more than 200,000 patients in the US currently receive  this therapy. Now a large new meta-analysis suggests that dual blockade results in no improvement in mortality but is associated with an increase in important adverse events.

In a paper published online in BMJ, Harikrishna Makani and colleagues at Columbia University and New York University performed a meta-analysis of more than 68,000 patients who were enrolled in clinical trials comparing dual blockade of the renin-angiotensin system with monotherapy. They found no significant difference between the groups for all cause mortality or cardiovascular mortality, although dual blockade was associated with a signifcant 18% reduction in hospital admission for heart failure:

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Acute Kidney Injury Associated With Dual Antihypertensive Therapy And NSAIDs Reply

Adding a non-steroidal anti-inflammatory drug (NSAID) to dual antihypertensive therapy (a diuretic plus either an ACE inhibitor or an angiotensin receptor blocker) is associated with an increase in risk for kidney injury, according to a large new retrospective study published in BMJ.

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