Do NSAIDs alone (I.e. not in combination with colchicine) reduce the recurrence of pericarditis?

Comment by InpharmD Researcher

Guidelines recommend colchicine in combination with non-steroidal anti-inflammatory drugs (NSAIDs) as first-line therapy to reduce pericarditis recurrence, improve therapy response, and increase remission rates. One meta-analysis evaluating colchicine plus NSAIDs versus aspirin or ibuprofen found less treatment failure and lower rates of recurrence in the treatment arm utilizing colchicine, with similar tolerability between groups. Thus, although aspirin or NSAIDs remain a crucial component of therapy for recurrent pericarditis, there is a lack of robust evidence to support NSAID drug therapy without adjunct colchicine. Please refer to Table 1 for a summary of studies evaluating the efficacy of NSAIDs alone versus in combination with colchicine for reducing pericarditis recurrence.
Background

The 2015 European Society of Cardiology (ESC) guidelines for the management of pericardial diseases include recommendations for recurrent pericarditis. In general, colchicine is recommended as a first-line agent to be added to conventional anti-inflammatory therapies in order to improve therapy responses; newer therapeutic options include alternative immunosuppressive therapies, intravenous immunoglobulins (IVIG), and interleukin-1 (IL-1) antagonists. Aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) remain the mainstay of therapy, but recommendations on its use without colchicine to reduce the recurrence of pericarditis are not provided. [1]

A 2020 review on the management of acute and recurrent pericarditis by the Journal of the American College of Cardiology primarily recommends colchicine for reduction in recurrences; corticosteroids at low doses, IL-1 blockade with anakinra, and additional immunosuppressive drugs may alternatively be used depending on disease refractory to colchicine. Management with NSAIDs is not discussed within the review. [2]

A 2023 systematic review and meta-analysis evaluated pharmacological therapies on recurrences or treatment failure in patients with episodes of acute idiopathic pericarditis (AIP). Seven randomized controlled trials (RCTs) were included, of which six compared outcomes with colchicine plus NSAIDs versus active controls comprised of aspirin, ibuprofen, or indomethacin. Overall, the rate of recurrence was significantly lower in the treatment arms utilizing colchicine (odds ratio [OR] 0.37; 95% confidence interval [CI] 0.27 to 0.51), as well as treatment failure after 72 hours (OR 0.29; 95% CI 0.21 to 0.41). Similarly, remission rate at 1 week, time to first recurrence, and hospitalization rate all significantly favored colchicine. Incidence of adverse events was reportedly similar between groups (OR 1.16; 95% CI 0.72 to 1.86). The authors conclude that colchicine in addition to NSAIDs is efficacious for the prevention of AIP recurrences, and although clinical experience exists for NSAIDs, no robust evidence is available for NSAIDs in the treatment of AIP. [3]

References:

[1] Adler Y, Charron P, Imazio M, et al. 2015 ESC Guidelines for the diagnosis and management of pericardial diseases: The Task Force for the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (ESC)Endorsed by: The European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2015;36(42):2921-2964. doi:10.1093/eurheartj/ehv318
[2] Chiabrando JG, Bonaventura A, Vecchié A, et al. Management of Acute and Recurrent Pericarditis: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020;75(1):76-92. doi:10.1016/j.jacc.2019.11.021
[3] Melendo-Viu M, Marchán-Lopez Á, Guarch CJ, et al. A systematic review and meta-analysis of randomized controlled trials evaluating pharmacologic therapies for acute and recurrent pericarditis. Trends Cardiovasc Med. 2023;33(5):319-326. doi:10.1016/j.tcm.2022.02.001
Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

Do NSAIDs alone (I.e. not in combination with colchicine) reduce the recurrence of pericarditis?

Level of evidence

B - One high-quality study or multiple studies with limitations  Read more→


Please see Table 1 for your response.

Studies evaluating the efficacy of NSAIDs in reducing pericarditis recurrence
Citation/ Study design Objective Patients Intervention Outcomes/Conclusions

Musick et al. 2023 

Retrospective, observational cohort study

 To compare the efficacy of colchicine monotherapy to NSAID monotherapy or combination therapy
for the prevention of recurrent pericarditis in patients with HFrEF and/or CAD

Adults with acute pericarditis and HFrEF and/or CAD

N= 77

Colchicine monotherapy (n= 43)

NSAID monotherapy (n= 7)

Combination therapy (n= 27)

  

Chart reviews were conducted to compile data on discharge regimen, length of hospital stay, timing of follow-up appointments relative to hospital discharge, occurrence and timing of recurrent pericarditis, subsequent hospitalizations, and discontinuation rates of pericarditis therapies.

There was no significant difference in the occurrence of pericarditis recurrence or documentation of incessant symptoms between patients treated with colchicine monotherapy (16.3%), NSAID monotherapy (28.6%), and combination therapy (18.5%; p= 0.740).

Conclusion: In this study, no difference in the primary outcome was observed between groups. However, a prospective, randomized trial is needed to further elucidate the efficacy of colchicine monotherapy for the treatment of acute pericarditis in patients with HFrEF and/or CAD.

Sambola et al., 2019

Randomized multicenter open-label study

 To assess the real efficacy of colchicine in patients with AIP who did not receive corticosteroids

Patients with AIP

N= 110

Colchicine (n= 59)

Conventional (n= 51)

All patients received aspirin at initial doses of 1 g q6 or q8h, ibuprofen 600 mg q8h, or indomethacin 50 mg q8h for 2 to 10 days (with tapering over 3 to 4 weeks). Patients in the colchicine group received colchicine in addition to the conventional treatments, starting at diagnosis of AIP, at a dose of 1 mg/12 hours in patients >70 kg or 0.5 mg/12 hours in patients <70 kg for 3 months. Treatment commenced within the first week of symptom onset.  No corticosteroids were administered.

No differences were found in the rate of recurrent pericarditis between patients treated with colchicine and conventional therapy (10.9% vs. 13.5%; p= 0.34). Similarly, the time to first recurrence did not differ between the two treatment groups (9.6 ± 9.0 months vs. 8.3 ± 10.5 months; p= 0.80).

Conclusion: Among patients with a first episode of AIP who had not received corticosteroids, the addition of colchicine to conventional anti-inflammatory treatment does not seem to reduce the recurrence rate.

Imazio et al., 2014 

Multicenter, double-blind, placebo-controlled, randomized trial (CORP-2)

 To assess the efficacy and safety of colchicine to treat
patients with multiple recurrences of pericarditis.

N= 240

Colchicine (n= 120)

Conventional/Placebo (n= 120)

Adults with ≥2 recurrences of pericarditis 

Patients were randomized 1:1 to either the colchicine group or the conventional/placebo group. All patients received conventional treatment for recurrent pericarditis, including aspirin (800 mg), ibuprofen (600 mg), or indometacin (50 mg) orally q8h for 7–10 days with tapering over 3–4 weeks. Corticosteroid treatment (prednisone 0.2–0.5 mg/kg/day for 4 weeks, then tapered) was given to patients already taking corticosteroids or with contraindications to NSAIDs. Colchicine was administered at a dose of 0.5 to 1.0 mg daily for 3 months (based on weight).

All patients also received a proton pump inhibitor for gastroduodenal prophylaxis. Placebo was used as the comparator. Colchicine was administered at 0.5 or 1.0 mg daily for 6 months without a loading dose.

In the colchicine group, 26 patients (21.6%) experienced recurrent pericarditis compared to 5 patients (42.5%) in the conventional/placebo group (RR 0.49; 95% CI 0.24 to 0.65; p=0.0009; NNT 5).

Adverse effects and discontinuation of the study drug occurred in similar proportions in both groups. The most common adverse events were gastrointestinal intolerance (9 patients in each group) and hepatotoxicity (3 patients in the colchicine group vs. 1 in the conventional/placebo group). No serious adverse events were reported.

Conclusion: Colchicine added to conventional anti-inflammatory treatment significantly reduced the rate of subsequent recurrences of pericarditis in patients with multiple recurrences. Taken together with results from other randomized controlled trials, these findings suggest that colchicine should be probably regarded as a first-line treatment for either acute or recurrent pericarditis in the absence of contraindications or specific indications.

Imazio et al., 2013

Randomized, double-blind, placebo-controlled, multicenter trial (ICAP)

 To evaluate the efficacy and safety of colchicine to treat a first attack of acute pericarditis and to prevent recurrences

N= 240

Colchicine (n= 120)

Conventional/Placebo (n= 120)

Adults with first episode of acute pericarditis

Patients were randomized 1:1 to either the colchicine group or the conventional/placebo group. All patients received conventional treatment for recurrent pericarditis, including aspirin (800 mg) or ibuprofen (600 mg) orally q8h for 7–10 days with tapering over 3–4 weeks. Corticosteroid treatment (prednisone 0.2–0.5 mg/kg/day for 2 weeks, then tapered) was given to patients already taking corticosteroids or with contraindications to NSAIDs. Colchicine was given at a dose of 0.5 to 1.0 mg daily for 3 months (based on weight).

All patients also received a proton pump inhibitor for gastroduodenal prophylaxis. Placebo was used as the comparator. Colchicine was administered at 0.5 or 1.0 mg daily for 3 months without a loading dose.

Incessant or recurrent pericarditis occurred in 20 patients (16.7%) in the colchicine group and 45 patients (37.5%) in the conventional/placebo group (RR 0.56; 95% CI 0.30 to 0.72; NNT 4; p<0.001).

Colchicine reduced the rate of symptom persistence at 72 hours (19.2% vs. 40.0%; p= 0.001), the number of recurrences per patient (0.21 vs. 0.52; p= 0.001), and the hospitalization rate (5.0% vs. 14.2%; p= 0.02). Additionally, colchicine improved the remission rate at 1 week (85.0% vs. 58.3%; p<0.001).

Overall adverse effects and rates of study-drug discontinuation were similar in the two study groups, with no serious adverse events observed.

Conclusions In patients with acute pericarditis, colchicine, when added to conventional antiinflammatory therapy, significantly reduced the rate of incessant or recurrent pericarditis.

Imazio et al., 2011

Prospective, randomized, double-blind, placebo-controlled multicenter trial (CORP)

 To evaluate the efficacy and safety of colchicine for the secondary prevention of recurrent pericarditis.

N= 120

 

Colchicine (n= 60)

Conventional/Placebo (n= 60)

Adults with first episode of acute pericarditis

Patients were randomized 1:1 to either the conventional/placebo group or the colchicine group. All patients received conventional treatment, including aspirin (800 to 1000 mg) or ibuprofen (600 mg) orally every 8 hours for 7 to 10 days, with gradual tapering over 3 to 4 weeks. Patients in the colchicine group received an initial dose of 1.0 to 2.0 mg, followed by a maintenance dosage of 0.5 to 1.0 mg/day for 6 months. 

Corticosteroid treatment (prednisone 0.2–0.5 mg/kg/day for 4 weeks, then tapered) was provided to patients already taking corticosteroids or with contraindications to NSAIDs.

At 18 months, the recurrence rate was 24% in the colchicine group and 55% in the conventional/placebo group (ARR 0.31; 95% CI 0.13 to 0.46; RR 0.56; 95% CI 0.27 to 0.73; NNT 3).

Colchicine reduced symptom persistence at 72 hours (ARR 0.30; CI 0.13 to 0.45; RR 0.56 95% CI 0.27 to 0.74), decreased mean number of recurrences, increased remission rate at 1 week, and prolonged time to subsequent recurrence. Rates of side effects and drug withdrawal were similar between study groups.

Conclusion: Colchicine is safe and effective for secondary prevention of recurrent pericarditis.

Abbreviations: AIP= acute idiopathic pericarditis; ARR= absolute risk reduction; CAD= coronary artery disease; CI= confidence interval; HFrEF= heart failure with reduced ejection fraction; NSAIDs: non-steroidal anti-inflammatory drugs; RR= relative risk; NNT= number needed to treat
References:

[1] Musick K, Knoell C, Clarke MM. Comparison of Colchicine Monotherapy Versus Nonsteroidal Anti-Inflammatory Drugs Monotherapy or Combination Therapy for the Prevention of Recurrent Pericarditis in Patients With Heart Failure With Reduced Ejection Fraction and/or Coronary Artery Disease. J Pharm Pract. Published online September 1, 2023. doi:10.1177/08971900231196081
[2] Sambola A, Roca Luque I, Mercé J, et al. Colchicine Administered in the First Episode of Acute Idiopathic Pericarditis: A Randomized Multicenter Open-label Study. Rev Esp Cardiol (Engl Ed). 2019;72(9):709-716. doi:10.1016/j.rec.2018.11.016
[3] Imazio M, Belli R, Brucato A, et al. Efficacy and safety of colchicine for treatment of multiple recurrences of pericarditis (CORP-2): a multicentre, double-blind, placebo-controlled, randomised trial. Lancet. 2014;383(9936):2232-2237. doi:10.1016/S0140-6736(13)62709-9
[4] Imazio M, Brucato A, Cemin R, et al. A randomized trial of colchicine for acute pericarditis. N Engl J Med. 2013;369(16):1522-1528. doi:10.1056/NEJMoa1208536
[5] Imazio M, Brucato A, Cemin R, et al. Colchicine for recurrent pericarditis (CORP): a randomized trial. Ann Intern Med. 2011;155(7):409-414. doi:10.7326/0003-4819-155-7-201110040-00359