Ketorolac Should Be Avoided in Heart Failure Patients
Ketorolac and other NSAIDs should not be used in patients with heart failure, as they significantly increase the risk of heart failure exacerbation, hospitalization, worsening renal function, and fluid retention. 1
Guideline Recommendations
Multiple major cardiology societies provide consistent Class III recommendations (meaning "not recommended/may cause harm") against NSAID use in heart failure:
The 2016 European Society of Cardiology (ESC) guidelines explicitly state that NSAIDs and COX-2 inhibitors are not recommended in patients with heart failure because they increase the risk of heart failure worsening and hospitalization. 1
The 2012 ESC guidelines similarly recommend that NSAIDs and COX-2 inhibitors should be avoided if possible, as they may cause sodium and water retention, worsening renal function, and worsening heart failure (Class III, Level B evidence). 1
The 2009 ACC/AHA guidelines state that drugs known to adversely affect clinical status in heart failure patients should be avoided or withdrawn whenever possible, specifically listing NSAIDs. 1
Even the older 1995 ACC/AHA guidelines warned that hyperkalemia and sodium retention are particularly common when NSAIDs are used in patients with severe heart failure, recommending they be avoided. 1
Specific Risks of Ketorolac in Heart Failure
The FDA drug label for ketorolac provides additional warnings particularly relevant to heart failure patients:
Ketorolac should be used "only very cautiously in patients with cardiac decompensation, hypertension or similar conditions" due to documented fluid retention, edema, retention of NaCl, oliguria, and elevations of serum urea nitrogen and creatinine. 2
Ketorolac can lead to onset of new hypertension or worsening of preexisting hypertension, and patients taking thiazides or loop diuretics (standard heart failure therapy) may have impaired response to these therapies when taking NSAIDs. 2
The drug is contraindicated in patients with serum creatinine concentrations indicating advanced renal impairment, and patients with underlying renal insufficiency are at increased risk of developing acute renal decompensation or failure. 2
Pathophysiological Mechanisms
The mechanisms by which ketorolac worsens heart failure are well-established:
Inhibition of prostaglandin synthesis adversely affects cardiovascular homeostasis in patients with a propensity to develop heart failure. 3
NSAIDs attenuate the effect of diuretics, leading to fluid retention and edema. 4
Acute renal failure has been reported after ketorolac treatment, particularly in postoperative patients with third-spacing of fluid and renal hypoperfusion. 5
Hyperkalemia is a documented complication, especially problematic in heart failure patients already on ACE inhibitors, ARBs, and mineralocorticoid receptor antagonists. 6
Alternative Pain Management Strategies
When heart failure patients require analgesia, safer alternatives exist:
Paracetamol (acetaminophen) appears to be safe in heart failure patients and should be the first-line analgesic. 4
For gout pain specifically, colchicine is recommended instead of NSAIDs. 4
Non-pharmacologic therapy should be maximized for chronic non-cancer pain. 4
If pain persists despite acetaminophen and non-pharmacologic approaches, opioids may be considered at the lowest effective dose for the shortest duration. 4
In patients with severely impaired renal function, opioids with a safer metabolic profile (methadone, buprenorphine, or fentanyl) are preferred. 4
Critical Clinical Caveats
The risk of adverse events with ketorolac increases with high doses, prolonged therapy (>5 days), and in vulnerable patients such as the elderly—populations that overlap significantly with heart failure patients. 7
Postoperative ketorolac therapy should be avoided in patients who have conditions that predispose to NSAID nephrotoxicity. 5
Patients must be educated to avoid over-the-counter NSAIDs not prescribed by a physician. 1, 4
If NSAIDs must be used despite these warnings (which should be extremely rare), watch closely for signs of worsening heart failure including increased dyspnea, edema, weight gain, and deteriorating renal function. 4