Giuseppe Roberto1, Monica Simonetti2, Carlo Piccinni3, Pier Lora Aprile4, Iacopo Cricelli2, Andrea Fanelli5, Claudio Cricelli2, Francesco Lapi2. 1. Epidemiology Unit, Regional Agency for Healthcare Services of Tuscany, Florence, Italy. 2. Health Search, Italian College of General Practitioners and Primary Care, Florence, Italy. 3. Department of Medical and Surgical Sciences - Pharmacology Unit, University of Bologna, Bologna, Italy. 4. Italian College of General Practitioners and Primary Care, Florence, Italy. 5. Department of Anesthesia and Postoperative Intensive Care Unit, "Istituti ortopedici Rizzoli", Bologna, Italy.
Abstract
STUDY OBJECTIVE: To determine whether acetaminophen or an acetaminophen-codeine combination is associated with an increased risk of acute cerebrovascular and cardiovascular events (ACCEs) in patients with osteoarthritis. DESIGN: Nested case-control study. DATA SOURCE: Health Search IMS Health Longitudinal Patient Database. PATIENTS: A total of 36,754 adults with a diagnosis of osteoarthritis and an incident (first-time) prescription of nonsteroidal antiinflammatory drugs (NSAIDs) between January 2002 and June 2012 were identified; of these patients, cases were defined as those who had a diagnosis of an ACCE during the follow-up period (index date was the date of ACCE diagnosis; 2182 cases). For each case, up to five controls were randomly selected who were matched based on age, sex, month and year of cohort entry, and duration of follow-up (10,301 controls). Matched controls were assigned the same index date as their respective cases. MEASUREMENTS AND MAIN RESULTS: For each case and matched controls, all prescriptions of acetaminophen-containing medicines filled during follow-up were identified. The risk of ACCEs was investigated with respect to the recency of use of acetaminophen and/or an acetaminophen-codeine combination. Patients were classified as current (0-90 days preceding index date), recent (91-180 days), or past (181-365 days) acetaminophen users, or nonusers (longer than 365 days), with nonusers representing the reference category. Conditional logistic regression was estimated to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Of the 36,754 patients with osteoarthritis and newly prescribed NSAIDs, the incidence rate of ACCEs was 117.6 per 10,000 person-years. No significant association between exposure to acetaminophen-containing medications and ACCEs was observed in current (OR 1.22, 95% CI 0.96-1.55), recent (OR 1.12, 95% CI 0.80-1.55), or past users (OR 1.13, 95% CI 0.86-1.48). A secondary analysis evaluating exposure to acetaminophen monotherapy or acetaminophen-codeine combination therapy showed similar results for current users. CONCLUSION: Our findings indicate that no association can be made between the use of acetaminophen and/or an acetaminophen-codeine combination and the occurrence of ACCEs. This information contributes to support clinicians in the choice of acetaminophen therapy for osteoarthritis-related pain, especially in those patients presenting with cerebrovascular and cardiovascular morbidities or related risk factors.
STUDY OBJECTIVE: To determine whether acetaminophen or an acetaminophen-codeine combination is associated with an increased risk of acute cerebrovascular and cardiovascular events (ACCEs) in patients with osteoarthritis. DESIGN: Nested case-control study. DATA SOURCE: Health Search IMS Health Longitudinal Patient Database. PATIENTS: A total of 36,754 adults with a diagnosis of osteoarthritis and an incident (first-time) prescription of nonsteroidal antiinflammatory drugs (NSAIDs) between January 2002 and June 2012 were identified; of these patients, cases were defined as those who had a diagnosis of an ACCE during the follow-up period (index date was the date of ACCE diagnosis; 2182 cases). For each case, up to five controls were randomly selected who were matched based on age, sex, month and year of cohort entry, and duration of follow-up (10,301 controls). Matched controls were assigned the same index date as their respective cases. MEASUREMENTS AND MAIN RESULTS: For each case and matched controls, all prescriptions of acetaminophen-containing medicines filled during follow-up were identified. The risk of ACCEs was investigated with respect to the recency of use of acetaminophen and/or an acetaminophen-codeine combination. Patients were classified as current (0-90 days preceding index date), recent (91-180 days), or past (181-365 days) acetaminophen users, or nonusers (longer than 365 days), with nonusers representing the reference category. Conditional logistic regression was estimated to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Of the 36,754 patients with osteoarthritis and newly prescribed NSAIDs, the incidence rate of ACCEs was 117.6 per 10,000 person-years. No significant association between exposure to acetaminophen-containing medications and ACCEs was observed in current (OR 1.22, 95% CI 0.96-1.55), recent (OR 1.12, 95% CI 0.80-1.55), or past users (OR 1.13, 95% CI 0.86-1.48). A secondary analysis evaluating exposure to acetaminophen monotherapy or acetaminophen-codeine combination therapy showed similar results for current users. CONCLUSION: Our findings indicate that no association can be made between the use of acetaminophen and/or an acetaminophen-codeine combination and the occurrence of ACCEs. This information contributes to support clinicians in the choice of acetaminophen therapy for osteoarthritis-related pain, especially in those patients presenting with cerebrovascular and cardiovascular morbidities or related risk factors.
Authors: Yazed AlRuthia; Sultan Alghadeer; Bander Balkhi; Haya M Almalag; Hana Alsobayel; Faris Alodaibi; Fakhr Alayoubi; Amal S Alkhamali; Samar Alshuwairikh; Futoun N Alqahtani; Hisham Alsanawi Journal: Saudi Pharm J Date: 2019-06-10 Impact factor: 4.330