The primary complications of chronic aspirin use span several organ systems, with bleeding being the most clinically significant and well-documented adverse effect.
Gastrointestinal Bleeding
This is the most common serious complication.
Low-dose aspirin (100 mg/day) is associated with a 50-58% relative increase in major GI bleeding.
The incidence ranges from 0.48 to 3.64 cases per 1,000 person-years.
Mechanisms include direct mucosal injury and inhibition of COX-1-mediated prostaglandin synthesis, which impairs the protective gastric mucosal barrier.
Risk is amplified by concomitant use of NSAIDs, clopidogrel, or SSRIs, while proton pump inhibitors reduce upper GI bleeding risk.
Aspirin increases intracranial bleeding risk by approximately 31-34%.
This includes hemorrhagic stroke, subarachnoid hemorrhage, and subdural hemorrhage.
While the relative risk of bleeding does not appear to differ by age, the absolute incidence of bleeding increases substantially with age, particularly in adults > 60 years.
This is a key reason the USPSTF recommends against initiating aspirin for primary CVD prevention in adults >60 years.
Gastritis and dyspepsia are the most common reasons for aspirin discontinuation.
Chronic aspirin use can cause erosive gastritis, peptic ulcer disease, and esophagitis through direct topical injury and systemic prostaglandin inhibition.
The nephrotoxic potential of chronic aspirin is debated but clinically relevant in certain populations:
A Swedish case-control study found regular aspirin use was associated with a 2.5-fold increased risk of chronic renal failure, with a dose-dependent relationship.
In elderly patients, even low-dose aspirin (100 mg/day) can transiently reduce creatinine clearance, with persistent decline in ~48% of patients three weeks after cessation.
In patients with pre-existing renal disease, SLE, or cirrhosis, aspirin can precipitate reversible acute renal failure through prostaglandin-mediated reductions in renal blood flow.
Chronic low-dose aspirin was associated with faster kidney function decline.
Tinnitus and sensorineural hearing loss are dose-dependent effects, typically associated with higher or anti-inflammatory doses.
These are generally reversible upon discontinuation.
Tinnitus may occur at serum salicylate concentrations of 19.6 to >67 mg/dL and is often the first symptom of salicylate toxicity.
Notably, frequent low-dose aspirin use does not appear to elevate tinnitus risk, whereas moderate-dose use may increase risk in younger individuals.
Aspirin-Exacerbated Respiratory Disease (AERD)is an acquired inflammatory syndrome characterized by the triad of asthma, chronic rhinosinusitis with nasal polyps, and hypersensitivity to COX-1 inhibitors.
AERD affects up to 15% of patients with nasal polyps and/or asthma.
Reactions occur within 30-180 minutes of NSAID ingestion and include rhinorrhea, bronchospasm, and laryngospasm.
Aspirin can trigger urticaria/angioedema (particularly in patients with chronic urticaria, with a 21-30% prevalence of flares and rarely anaphylactoid reactions.
Aspirin use in children and adolescents with viral illness (particularly influenza or varicella) is associated with Reye syndrome an acute hepatic encephalopathy.
This led to the recommendation to avoid aspirin in pediatric populations for antipyretic use.