Congestive heart failure NSAIDs

These findings from special renal studies and the clinical trial data indicate that inhibition of Cox-2 does not eliminate the renal effects of NSAIDs because Cox-2-derived prostanoids are involved in normal renal function. However, the kidney contains considerably more Cox-1 than Cox-2, and the localization of the two isoforms is different It is not yet known whether the Cox-2 inhibitors will be safer in subgroups of patients prone to develop acute renal failure with NSAIDs, such as those patients with severe volume depletion, congestive heart failure, or hepatic cirrhosis with ascites (Bosch-Marce et al., 1999). Also, it is not known whether rare events, such as interstitial nephritis or papillary necrosis, will occur with long-term use of Cox-2 inhibitors, although studies in animals suggest that such events may be related to Cox-1 inhibition, since only Cox-1 is found in the papilla. Therefore, Cox-2 inhibitors may not produce these serious adverse effects (Khan etal., 1998). 

NSAIDs should be avoided in patients with chronic renal insufficiency due to the risk of inducing further kidney damage. In patients at risk, acute renal feilure can occur after a single dose of drug. Risk fectors include dehydration, hypertension, congestive heart failure, concomitant use of angiotensin-converting enzyme inhibitors, and advanced age. 

Feenstra J, Grobbee DE, Mosterd A, Strieker BH. Adverse cardiovascular effects of NSAIDs in patients with congestive heart failure. Dmg Safety 1S>97 17 166-180. 

Much less is known about the risk of congestive heart failure with NSAIDs. The rate of hospitalization for congestive heart failure in more than 10 000 patients over 55 years of age during exposure to both diuretics and NSAIDs was compared with the rate in those exposed to diuretics alone (31). At mean follow up of 4.7 years, there was an increased risk of hospitalization when diuretics and NSAIDs were used concomitantly (RR = 1.8 95% Cl = 1.4, 2.4). 

In 600 elderly patients with documented congestive cardiac failure there was a possible or probable link between NSAIDs and heart failure in 27 cases (32). In some, the mechanism was apparently a reduction in the effect of furosemide. In others the NSAID may have caused an imbalance in circulatory homeostasis. Preexisting renal impairment was not observed in any of the 27 cases. This study suggests that in elderly people congestive heart failure may be a complication of NSAIDs. 

The actual risk of NSAID-associated acute renal dysfunction also continues to be the subject of controversy. There is adequate evidence that underlying renal insufficiency, congestive heart failure, or hepatic cirrhosis are conditions that carry a high risk of NSAID-related renal functional impairment. It is still not known whether old age is a risk factor, whether the risk of renal impairment varies with different NSAIDs, or whether renal function continues to deteriorate, stabilize, or even improve in affected patients with continued use of NSAIDs. Three cases of renal insufficiency caused by topical NSAIDs have been described (SEDA-18,100). 

Heerdink ER, Leufkens HG, Herings RM, Ottervanger JP, Strieker BH, Bakker A. NSAIDs associated with increased risk of congestive heart failure in elderly patients taking diuretics. Arch Intern Med 1998 158(10) 1108-12. 

Page J, Henry D. Consumption of NSAIDs and the development of congestive heart failure in elderly patients an underrecognized public health problem. Arch Intern Med 2000 160(6) 777-84. 

The NSAID-induced abnormahties of renal function, in descending order of chnical frequency, are (i) fluid and electrolyte disturbances (ii) destabilizahon of con-troUed hypertension (hi) decompensated congestive heart failure (iv) acute deterioration of renal function (v) nephrotic syndrome with interstitial nephritis and (Vi) chronic renal failure/papillary necrosis [1, 3-5]. 

Abbreviations NSAID = nonsteroidal anti-inflammatory drugs, PG = prostaglandin, RBF = renal blood flow, GFR = glomerular filtration rate,HTN = hypertension, DM = diabetes mellitus, = potassium, RAA = renin-angiotensin- aldosterone, CHF = congestive heart failure, AGE = angiotensin-converting enzyme, SLF = systemic lupus erythematosis. 

Persons at greatest risk for NSAID hemodynamic nephropathy generally have pre-existing renal insufficiency, medical problems associated with high plasma renin activity (hepatic disease with ascites, decompensated congestive heart failure, or intravascular volume depletion), or systemic lupus erythematosus. Additional risk factors include atherosclerotic cardiovascular disease and diuretic therapy. The elderly are also at higher risk due to interaction of prevalent medical problems, multiple drug therapies, and reduced renal hemodynamics. Advanced age, however, has not been shown to be an independent risk factor for toxicity in limited trials in otherwise healthy elderly subjects. Combined NSAID and ACEl or ARB therapy is also a concern and should be avoided. 

McGettigan, P., Han, P., Jones, L., Whitaker, D., Henry, D. (2008 Jun). Selective COX-2 inhibitors, NSAIDs and congestive heart failure Differences between new and recurrent cases. British Journal of Clinical Pharmacology, d5(6), 927—934. 

NSAIDs can cause renal impairment, particularly in patients in whom prostaglandins are playing an important role in maintaining renal function. Such patients include those taking diuretics, the elderly and those with concurrent conditions such as congestive heart failure and ascites. Hence the combination of diuretics and NSAIDs may increase the nephrotoxicity ofNSAIDs.30. - ... 

There is evidence that most NSAIDs can increase blood pressure in patients taking antihypertensives, including diuretics, although some studies have not found the increase to be clinically relevant. The concurrent use of NSAIDs with thiazide diuretics may exacerbate congestive heart failure and increase the risk of hospitalisation. 

The functional variety of acute renal failure tends to appear in patients with pre-existing renal disease and factors predisposing to impaired renal perfusion, such as diminished effective intravascular volume from diuretic use or congestive heart failure (reviewed in ref. 138). In the few cases where renal biopsy was performed, histology was compatible with acute tubular necrosis ° ° . The hypothesis proposed is that the nature of the primary insult is haemodynamic, and that inhibition of PG synthesis would worsen pre-existing circulatory compromise. In summary, this category would encompass cases of NSAID use resulting in acute tubular necrosis or poor renal perfusion with ARF. 

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