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Anti-Inflammatory Agents for Malignant Pericardial Effusion
Quick Takes
- In patients with malignant pericardial effusion undergoing pericardiocentesis, adhesions and constrictive pericarditis were frequently seen (71% and 36.5%, respectively) on immediate follow-up echocardiography.
- The use of colchicine was associated with less all-cause mortality and reduced need for subsequent interventions.
- In contrast, administration of NSAIDs or steroids did not show a beneficial effect, and in fact, steroids were associated with higher risk of mortality or need for follow-up intervention.
Study Questions:
In active cancer patients with malignant pericardial effusion requiring drainage, what is the effect of colchicine and other anti-inflammatory agents on long-term outcomes after pericardiocentesis?
Methods:
Consecutive cancer patients who underwent echocardiography-assisted pericardiocentesis between May 2007 and December 2018, were identified retrospectively via database search. Patients with active cancer and malignant pericardial effusion were included. Clinical, laboratory, and outcome data were obtained as well as echocardiographic data at baseline and follow-up. Adjunctive anti-inflammatory agents included colchicine 0.6 mg twice daily for 2 months, steroids, and nonsteroidal anti-inflammatory drugs (NSAIDs). The primary outcome was a composite of all-cause mortality and recurrent pericardial effusion requiring repeat pericardiocentesis or surgical pericardial window. End-of-study date was defined either as 24 months after pericardiocentesis or December 2019.
Results:
Of 488 active cancer patients who underwent pericardiocentesis, 445 (91.2%) were found to have malignant pericardial effusion. Sixty-nine of these patients were ultimately excluded due to lack of follow-up echocardiography. The median age was 57 years (48-66 years), 55.7% were male, 63.4% had lung cancer, and 11% breast cancer. About 65% of patients were receiving concurrent chemotherapy, while 27% had received radiation to the mediastinum within the previous year. Tamponade was present in 384 (86.3%) patients based on clinical criteria, and 386 (86.7%) by echocardiographic criteria. Pericardiocentesis was successful for 97% of patients. There was one procedure-related death. The median duration for indwelling catheter was 4 days. Follow-up echocardiography after removal of the drainage catheter revealed pericardial adhesions in 71%. Constrictive pericarditis, based on widely accepted echocardiographic criteria, was present in 36.5% of patients.
Colchicine, steroids, and NSAIDs were given to 91 (24%), 52 (14%), and 90 (24%) of patients, respectively. Colchicine was used for a mean period of 63 days after pericardiocentesis. While there were no significant differences in baseline patient characteristics in the colchicine versus noncolchicine groups, the former had higher rates of pericardial adhesions (83% vs. 66%, p = 0.003) and constriction (57% vs. 29%, p < 0.001) prior to treatment.
The primary composite outcome occurred less frequently in the colchicine than the noncolchicine group (hazard ratio [HR], 0.76; 95% confidene interval [CI], 0.59-0.98). Propensity score matching was performed to minimize the effect of treatment group assignment bias. Adjusted HRs for both the composite primary outcome and all-cause mortality were statistically significant (0.55, 95% CI, 0.37-0.82; p = 0.003 and 0.50, 95% CI, 0.33-0.75; p = 0.001, respectively). In contrast, steroid administration was associated with a higher rate of composite events (HR, 1.37; 95% CI, 1.01-1.86; p = 0.04).
Conclusions:
In patients with malignant pericardial effusion who underwent pericardiocentesis, the use of colchicine was associated with less all-cause mortality and reduced need for subsequent interventions, despite the fact that the drug was given more frequently to patients with adhesions and constriction after initial catheter drainage. In contrast, administration of NSAIDs or steroids did not show a beneficial effect, and in fact, steroids were associated with higher risk of mortality or need for follow-up intervention.
Perspective:
This was the first large study to evaluate the long-term effects of anti-inflammatory agents in patients with malignant pericardial effusion undergoing pericardiocentesis. Overall procedural failure and complication rates were low in this study. While the malignancy is believed to be the underlying cause for the pericardial effusion, the authors postulate that the subsequent adhesions and elevated serum inflammatory markers reflect more of an inflammatory reaction to the pericardiocentesis procedure itself. Colchicine’s exact anti-inflammatory mechanism is unknown, but its microtubule assembly inhibition and subsequent decrease in proinflammatory white blood cell function appears to be decreasing the incidence of this “post-pericardiocentesis syndrome.”
Limitations of the study include its single-center, observational, and retrospective design. This was not a randomized trial with significant risk of treatment group assignment bias, although propensity score matching attempted to minimize its effect. The total dose and duration of all anti-inflammatory agents was not standardized and up to each physician’s discretion. As a result, the NSAID and steroid group may not have received optimal doses or duration due to concerns over side effects, while colchicine was considered a safer and more tolerable medication. Nonetheless, this study shows promising results for colchicine with the need for further prospective, randomized trials of specific doses, duration, and types of anti-inflammatories.
Clinical Topics: Cardiac Surgery, Cardio-Oncology, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Pericardial Disease, Prevention, Cardiac Surgery and Arrhythmias, Interventions and Imaging, Echocardiography/Ultrasound
Keywords: Anti-Inflammatory Agents, Anti-Inflammatory Agents, Non-Steroidal, Cardiac Tamponade, Cardiotoxicity, Catheters, Indwelling, Colchicine, Constriction, Echocardiography, Heart Neoplasms, Leukocytes, Lung Neoplasms, Pericardial Effusion, Pericardiocentesis, Pericarditis, Pericarditis, Constrictive, Secondary Prevention, Steroids
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