Acute Congestive Heart Failure Induced by Rofecoxib
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J Am Board Fam Pract: first published as 10.3122/jabfm.17.2.131 on 13 April 2004. Downloaded from Acute Congestive Heart Failure Induced by Rofecoxib Robert J. Campbell, MD, and Kevin B. Sneed, PharmD Nonsteroidal anti-inflammatory drugs (NSAIDs) COX-1 in the stomach is believed to have protec- are routinely prescribed for the treatment of vari- tive properties of the gastric mucosa.12,13 COX-2 is ous conditions requiring analgesia and anti-inflam- expressed in response to inflammatory stimuli, and matory activity. People also have access to NSAIDs is affected by cytokines and other inflammatory over-the-counter for relief of mild aches, pains, and mediators. Most NSAIDs inhibit both isoforms to headaches. NSAIDs have the potential to produce varying degrees, relative to the activity of the indi- several adverse effects in patients. They are known vidual chemical properties of the NSAID. In recent to have the potential to produce gastrointestinal years, COX-2 specific inhibitors have become toxicities leading to dyspepsia or even ulceration. available [celecoxib, rofecoxib, valdecoxib (in order Gastrointestinal symptoms are the most common of US market release)]. It had been hypothesized adverse effects associated with NSAID use.1 Plate- that by targeting the COX-2 enzyme specifically, let aggregation is known to be inhibited by only the inflammatory prostaglandins would be in- NSAIDs because of their ability to inhibit the ac- hibited while sparing the activity of COX-1. This tion of thromboxane A, a potent platelet aggrega- would allow the medication to produce anti- tor.2–4 This could lead to hemorrhaging in patients inflammatory and analgesia activities without po- with vascular injuries or congenital hematologic tentially decreasing the protective effects of the conditions. Some patients may display allergic re- COX-1 enzyme. It was also hypothesized that it actions to NSAIDs, possibly as severe as anaphy- may offer an improved renal safety profile in pa- laxis. Further, NSAID-induced nephropathy may tients at risk for NSAID-induced renal toxicity.14 also occur in patients.5–7 These complications may Some studies have now suggested that renal injury include renal injuries such as acute tubular necrosis may result secondary to COX-2 inhibitors.15 Thus, and chronic interstitial nephritis. They may pro- the clinical development of COX-2 inhibitors the- duce hemodynamic effects by promoting the reten- oretically improved the overall safety profile for http://www.jabfm.org/ tion of salt and water within patients.8–10 This may patients while producing the clinical benefits of result from their activity on renal prostaglandins, inflammation management in affected patients. leading to edema and reduction in the effectiveness We report the case of a patient that presented of antihypertensive regimens.8,10,11 Despite these with acute congestive heart failure (CHF) symp- possible adverse effects, NSAIDs remain a first-line toms associated with COX-2 inhibitor use. We also therapeutic alternative for patients suffering painful offer possible explanations for the CHF onset sec- on 27 September 2021 by guest. Protected copyright. ailments. ondary to COX-2 inhibitor use and management NSAIDs act by inhibiting synthesis of prosta- techniques and pharmacologic considerations for glandins from arachidonic acid via cyclooxygenase this situation from a primary care standpoint. COX-1 and COX-2, the 2 isoforms of cyclooxy- genase. COX-1 is constitutively found in normal cells and tissues throughout the body, with a dom- Case Reports inant expression in the stomach. The expression of A 42-year-old woman sought treatment from an orthopedist that she had been referred to for bilat- eral knee arthritis. Her medical history included Submitted, revised, 2 September 2003. severe sleep apnea, reasonably controlled hyperten- From the Department of Family Medicine, University of sion, asthma, allergic rhinitis, gastroesophageal South Florida College of Medicine, Tampa (RC, KS), and Florida A&M University College of Pharmacy, Tallahassee reflux disease, urinary incontinence, thalassemia (KS). Address correspondence to Kevin B. Sneed, PharmD, minor, and depression. Long-term medications in- University of South Florida, Department of Family Medi- cine, 12901 Bruce B. Downs Blvd., MDC 13, Tampa, FL cluded loratadine, omeprazole, oxybutynin, sertra- 33612 (e-mail: [email protected]). line, an estradiol/norethindrone oral contraceptive, Congestive Heart Failure and Rofecoxib 131 J Am Board Fam Pract: first published as 10.3122/jabfm.17.2.131 on 13 April 2004. Downloaded from atenolol, albuterol, and alprazolam. She used nasal L), glucose of 111 mg/dL (reference range, 65–109 continuous positive airway pressure device at night. mg/dL), serum urea nitrogen of 16 mg/dL (refer- For treatment of her knee osteoarthritis, she had ence range, 7–25 mg/dL), and creatinine of 0.5 been on 25 mg/day rofecoxib for several weeks mg/dL (reference range, 0.5–1.2 mg/dL). Hemo- when she had last seen her orthopedist 1 week globin was slightly low at 11.5 g/dL (reference before. At that visit, the orthopedist increased her range, 11.7–15.5 g/dL), with a mean corpuscular rofecoxib to 50 mg/day. volume of 64.1 fL (reference range, 80–100 fL), Seven days later, she presented to the clinic with mean corpuscular hemoglobin of 20.6 pg (reference the chief complaint of “I’m short of breath.” She range, 27–33 pg), mean corpuscular hemoglobin described a 1-day history of coughing up foamy concentration of 32.2 g/dL (reference range, 32–36 blood-tinged sputum, swelling of her lower ex- g/dL), and red cell distribution width was 16.3% tremities, dyspnea on exertion, 3-pillow orthopnea, (reference range, 9%–15%). Her platelet count, and a “rattling in the chest” with coughing. She differential, and thyroid-stimulating hormone level denied any fever, sore throat, myalgias, chest pain, were normal. An echocardiogram was performed or syncope. Her height was 5Ј 5Љ; weight, 290 lbs; the next day. It was somewhat suboptimal because BMI, 48; temperature, 98.0°F; pulse, 69 beats/min; of the patient’s body habitus. The left atrium was blood pressure, 162/96 mm Hg; respirations, 20 mildly dilated at 4.6 cm. The left ventricle was beats/min; oxygen saturation on room air, 94%. normal in its systolic and diastolic dimensions and Physical examination showed an obese woman in wall thickness. The ejection fraction was estimated mild respiratory distress, probable jugular veinous to be 63%. The aortic and mitral valves appeared distention (limited assessment because of obesity), normal, and the right atrium and right ventricle bilateral crackles on lung auscultation with good air appeared normal. There was no pericardial effusion movement, distant heart sounds with normal S1 or thickening. and S2, and 2ϩ pitting edema to mid-shin level of On the follow-up visit 2 days later, the patient both lower extremities. reported heavy diuresis with resolution of her dys- An electrocardiogram showed a normal sinus pnea. There was a weight loss of more than 5 rhythm with no abnormalities. It was believed that pounds. Her crackles resolved as well as her jugular the patient was suffering from acute congestive venous distension. The patient’s furosemide was heart failure secondary to rofecoxib. The differen- discontinued, and she returned to her normal state tial diagnoses included acute myocardial infarction, of health. This case was reported to the Food and http://www.jabfm.org/ pulmonary embolism, and acute valvular abnormal- Drug Administration as an adverse event. ity. It was also believed that the congestive heart failure was fairly mild and could be addressed in an outpatient setting with close monitoring. The pa- Discussion tient was counseled to stop all NSAIDs. She was to NSAIDs have been widely prescribed for chronic begin the workup for this condition, and she was pain and represent first-line pharmacotherapy for on 27 September 2021 by guest. Protected copyright. started on 20 mg/day furosemide. She was sched- many inflammatory conditions. Because of un- uled for laboratory work, a chest radiograph, and differentiated inhibition of the cyclooxygenase an echocardiogram. She was instructed that if her enzyme by NSAIDs, various adverse effects may symptoms worsened, she was to call immediately or occur. Because of their pronounced effect on renal call 911. Close follow-up was scheduled for 2 days. perfusion and renal prostaglandins, elevations in A chest radiograph (posterior/anterior and lat- blood pressure and incidence of edema are possible eral) showed the heart to be at the upper limits of in patients on NSAID therapy.8 COX-2 inhibitors normal in size and had prominent vasculature sug- were initially believed to have renal-sparing effects, gestive of early congestive heart failure. Laboratory thus creating a safer renal profile than traditional data revealed essentially normal serum chemistry, NSAIDs.10 We report the case of a patient that with sodium of 140 mEq/L (reference range, 135– suffered acute congestive heart failure secondary to 146 mEq/L), potassium of 4.6 mEq/L (reference taking the COX-2 inhibitor rofecoxib. This case range, 3.5–5.3 mEq/L), chloride of 105 mEq/L was impressive in that the patient was not suffering (reference range, 98–110 mEq/L), total carbon di- symptoms of congestive heart failure before initia- oxide of 24 mEq/L (reference range, 21–23 mEq/ tion of the rofecoxib and experienced quick reso- 132 JABFP March–April 2004 Vol. 17 No. 2 J Am Board Fam Pract: first published as 10.3122/jabfm.17.2.131 on 13 April 2004. Downloaded from lution of the heart failure symptoms after its dis- reports and studies have shown the ability of continuation. Explanations for this occurrence are NSAIDs to negatively affect blood pressure.16,22,23 offered in this discussion.