Community-acquired pneumonia (CAP) is the most common infectious disease leading to hospitalization. Recent studies documented a frequent association between CAP and the occurrence of acute cardiac complications such as heart failure, atrial fibrillation and myocardial infarction. At this regard, we recently showed that CAP is often complicated by elevation of cardiac troponin, a marker of myocardial injury, that can be isolated or associated to myocardial infarction. The importance of these cardiac complications is supported by their prognostic role, as they are associated with an increased short- and long-term mortality.
Glucocorticoids inhibit the expression and action of many cytokines involved in the inflammatory response associated with pneumonia. Recent studies also suggest an anti-platelet effect in this setting. Thus, glucocorticoids could have a potential protective role in preventing myocardial injury and cardiovascular complications in CAP patients.
Primary aim of our study will be to evaluate the effect of systemic glucocorticoids on myocardial injury in a cohort of patients hospitalized for CAP. Secondary aims will be to test their effect on markers of platelet activation and on cardiovascular events during hospitalization, at 30 day from hospital admission and during 2 years¿ follow-up.
To explore this issue, 100 eligible patients will be randomized to a treatment with methylprednisolone 20 mg twice daily ev or placebo for a week from hospital admission.
As troponin elevation is an independent predictor of mortality, a reduction in myocardial injury in patients treated with methylprednisolone will open new perspectives to lower mortality and cardiovascular events.
CAP, especially in elderly patients with comorbidities, is associated to enhanced risk of cardiovascular disease, the leading cause of death worldwide.
Our hypothesis is that a treatment with systemic corticosteroids could reduce myocardial injury, as expressed by enhanced levels of hs-cTnT, during the acute phase of pneumonia. Myocardial injury has been associated to increased intra-hospital cardiovascular events and short- and long-term mortality (1, 2). Thus, a treatment capable of reducing myocardial injury during CAP will open new perspectives in the therapeutic approach of pneumonia to counteract the enhanced cardiovascular risk.
In clinical practice, use of glucocorticoids for patients with CAP remains controversial, with some studies showing a benefit in clinical outcomes and other studies showing no effect. A recent meta-analysis of trials in pneumonia (3), reported significant heterogeneity in terms of both patient characteristics and type of glucocorticoids used and found an uncertain effect on mortality.
The novelty of this proposal is in its primary end-point, i.e. myocardial damage, as expressed as increased levels of hs-cTnT during the hospitalization phase. To this purpose, hs-cTnT will be serum hs-cTnT will be repeated every 12 hours up to 72 hours and every 24 hours thereafter until discharge. Preliminary retrospective data suggest a possible reduction of myocardial injury in CAP patients treated with corticosteroids.
Another important novelty concerns the type of glucocorticoid, as prednisolone and its derivative methylprednisolone could have an exquisite anti-platelet effect, not shared by other glucocorticoids (4)
The possible impact on clinical practice is meaningful because pneumonia is one of the most important cause of death in elderly patients in our country; moreover, the costs of the proposed treatment is very low because it consists in an inexpensive and well-known drug, the treatment will last no more than 7 days (only during the intra-hospital stay).
Possible side effects of such short-term treatments can be considered negligible as shown by different RCTs (5).
In conclusion, we will test the hypothesis that a short-term in-hospital treatment with glucocorticoids could be beneficial in reducing the increased risk of myocardial injury and possibly cardiovascular events in patients hospitalized CAP. These results might have important clinical relevance as myocardial injury an in-hospital cardiovascular events are associated with poor outcomes in short- and long-term follow-up.
References
1. Vestjens SM, Spoorenberg SM, Rijkers GT, Grutters JC, Ten Berg JM, Noordzij PG, Van de Garde EM, Bos WJ, Ovidius Study G. High-sensitivity cardiac troponin T predicts mortality after hospitalization for community-acquired pneumonia. Respirology 2017.
2. Cangemi R, Calvieri C, Falcone M, Bucci T, Bertazzoni G, Scarpellini MG, Barilla F, Taliani G, Violi F, Group SS. Relation of Cardiac Complications in the Early Phase of Community-Acquired Pneumonia to Long-Term Mortality and Cardiovascular Events. Am J Cardiol 2015; 116: 647-651.
3. Chen Y, Li K, Pu H, Wu T. Corticosteroids for pneumonia. The Cochrane database of systematic reviews 2011: CD007720.
4. Liverani E, Banerjee S, Roberts W, Naseem KM, Perretti M. Prednisolone exerts exquisite inhibitory properties on platelet functions. Biochemical pharmacology 2012; 83: 1364-1373.
5. Wan YD, Sun TW, Liu ZQ, Zhang SG, Wang LX, Kan QC. Efficacy and Safety of Corticosteroids for Community-Acquired Pneumonia: A Systematic Review and Meta-Analysis. Chest 2016; 149: 209-219.