ticagrelor and Pneumonia

In the PLATelet inhibition and patient Outcomes (PLATO) study of patients with acute coronary syndromes, ticagrelor reduced mortality compared to clopidogrel but the mechanisms for this mortality reduction remain uncertain. We analysed adverse events (AEs) consistent with either pulmonary infection or sepsis, and subsequent mortality, in 18,421 PLATO patients treated with ticagrelor or clopidogrel. AEs occurring within 7 days of last dose of study medication were defined as "on-treatment". Serial measurements of blood leukocyte counts, C-reactive protein and interleukin-6 were performed. Fewer on-treatment pulmonary AEs occurred in the ticagrelor compared to the clopidogrel group (275 vs. 331 respectively; p = 0.019), with fewer deaths following these AEs (33 vs. 71; p < 0.001), particularly in those who remained on study medication three days after AE onset (10 vs. 43; p < 0.001). There were fewer deaths attributed to sepsis in the ticagrelor group (7 vs. 23; p = 0.003). Leukocyte counts were lower in the clopidogrel group during treatment (p < 0.0001 at 1, 3 and 6 months) but not at 1 month post-discontinuation. C-reactive protein increased more at discharge in the ticagrelor group (28.0 ± 38.0 vs. 26.1 ± 36.6 mg/l; p < 0.001) and interleukin-6 remained higher during the first month of treatment with ticagrelor. We conclude that the mortality risk following pulmonary AEs and sepsis in acute coronary syndrome patients appears to be lower during ticagrelor compared to clopidogrel therapy. Further work should assess whether ticagrelor and clopidogrel have differential effects on immune signalling.

Topics: Adenosine; Aged; Clopidogrel; Coronary Artery Disease; Female; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Pneumonia; Sepsis; Ticagrelor; Ticlopidine; Treatment Outcome

Previous studies have shown that ticagrelor reduced risk of pneumonia in patients with acute coronary syndrome (ACS) compared to clopidogrel, however, its effect in patients with non-ACS cardiovascular diseases remains uncertain. The aim was to investigate the effect of ticagrelor on pneumonia and pneumonia-specific death compared to clopidogrel in non-ACS patients in Hong Kong. This was a population-based cohort study. We included consecutive patients using ticagrelor or clopidogrel admitted for non-ACS conditions in Hong Kong public hospitals from March 2012 to September 2019. Patients using both drugs were excluded. The outcomes of interest were incident pneumonia, all-cause death, and pneumonia-specific death. Multivariable survival analysis models were used to estimate the effects [hazard ratio (HR) and 95% confidence interval (CI)]. Propensity score matching, adjustment and weighting were performed as sensitivity analyses. In total, 90,154 patients were included (mean age 70.66 years, males 61.7%). The majority of them (97.2%) used clopidogrel. Ticagrelor was associated with a lower risk of incident pneumonia [0.59 (0.46-0.75)], all-cause death [0.83 (0.73-0.93)] and pneumonia-specific death [0.49 (0.36-0.67)]. Sensitivity analyses yielded similar results. Ticagrelor was associated with lower risk of all-cause death, pneumonia-specific death, and incident pneumonia in patients with non-ACS cardiovascular conditions, consistent with previous evidence in patients with ACS. This additional effect of anti-pneumonia should be considered when choosing a proper P2Y12 inhibitor for patients with high risk of pneumonia.

Topics: Aged; Cardiovascular Diseases; Cause of Death; Clopidogrel; Cohort Studies; Female; Hong Kong; Hospitals, Public; Humans; Male; Platelet Aggregation Inhibitors; Pneumonia; Propensity Score; Retrospective Studies; Ticagrelor

Topics: Acute Coronary Syndrome; Clopidogrel; Cohort Studies; Humans; Platelet Aggregation Inhibitors; Pneumonia; Ticagrelor; Treatment Outcome

A 55-year-old man presented with acute ST-elevation myocardial infarction. He received rescue angioplasty with one drug eluting stent. He developed marked breathlessness and haemoptysis two days later. Investigations led to the diagnosis of pulmonary haemorrhage, possibly from pneumonitis caused by ticagrelor. He was successfully managed with high-dose steroids and ticagrelor was replaced with clopidogrel. On stopping the steroids a month later, mild haemoptysis recurred and this was managed conservatively. Pneumonitis and pulmonary haemorrhage is rarely reported with acute myocardial infarction, but poses serious challenge to the patient and the clinician. Diagnosis may be delayed as breathlessness can occur due to myriad causes after myocardial infarction. Interrupting dual anti-platelet therapy after angioplasty could lead to devastating stent thrombosis.

Topics: Adenosine; Angioplasty; Hemoptysis; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Pneumonia; Purinergic P2Y Receptor Antagonists; Radiography, Thoracic; Thrombosis; Ticagrelor

We report a case of significant pulmonary hemorrhage developing shortly after commencing ticagrelor and aspirin therapy and requiring coronary artery bypass grafting to safely cease the antiplatelet therapy. Lung biopsy findings were consistent with drug-induced lung injury. Clinicians should be aware of this significant adverse event with this drug class.

Topics: Acute Coronary Syndrome; Adenosine; Aspirin; Biopsy; Coronary Artery Bypass; Diagnosis, Differential; Hemoptysis; Humans; Lung; Male; Middle Aged; Platelet Aggregation Inhibitors; Pneumonia; Purinergic P2Y Receptor Antagonists; Ticagrelor; Tomography, X-Ray Computed