Maintenance use of non-steroidal anti-inflammatory drugs and risk of gastrointestinal cancer in a nationwide population-based cohort study in Sweden

ObjectivesAspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) are potential candidates for chemoprevention of gastrointestinal cancer. We aimed to assess the association between contemporary NSAID use (≥180 days) and gastrointestinal cancer.DesignNationwide Swedish population-based cohort study (2005–2012).SettingSwedenParticipantsAll adults exposed to maintenance NSAIDs use (aspirin, n=783 870; unselective NSAIDs, n=566 209, selective cyclo-oxygenase (COX)-2 inhibitors, n=17 948) compared with the Swedish background population of the same age, sex and calendar period.Outcome measuresThe risk of different gastrointestinal cancer types expressed as standardised incidence ratios (SIR) and 95% CIs, taking into account concurrent proton pump inhibitors (PPIs) and statins usage.ResultsThe SIR for gastrointestinal cancer for aspirin use was 1.02 (95% CI 1.00 to 1.04), with clearly reduced risk for long-term users (SIR=0.31, 95% CI 0.30 to 0.33 for 5.5–7.7 years), but an increased risk for short-term users (SIR=2.77, 95% CI 2.69 to 2.85), and stronger protective effect for low-dose aspirin (SIR=0.86, 95% CI 0.85 to 0.88). Users of non-selective NSAIDs showed an overall decreased risk of gastrointestinal cancer (SIR=0.79, 95% CI 0.77 to 0.82), in particular for cancer of the stomach, colorectum and oesophagus, and the SIRs were further decreased among long-term users. Users of selective COX-2 inhibitors showed a SIR=0.89 (95% CI 0.73 to 1.09) for gastrointestinal cancers. Both aspirin and unselective NSAIDs users who also were using PPIs, had higher risks for all gastrointestinal cancer types; and lower risk if using statins.ConclusionLong-term use of (low-dose) aspirin and non-selective NSAIDs was associated with a decreased risk of all gastrointestinal cancer types.

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Are COX-2 inhibitors preferable to non-selective non-steroidal anti-inflammatory drugs in patients with risk of cardiovascular events taking low-dose aspirin?

The Lancet ◽

10.1016/s0140-6736(07)61909-6 ◽

2007 ◽

Vol 370 (9605) ◽

pp. 2138-2151 ◽

Cited By ~ 88

Author(s):

Vibeke Strand

Keyword(s):

Cardiovascular Events ◽

Low Dose ◽

Dose Aspirin ◽

Low Dose Aspirin ◽

Inflammatory Drugs ◽

Cox 2 ◽

Anti Inflammatory ◽

Cox 2 Inhibitors

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Low-dose Aspirin, Nonsteroidal Anti-inflammatory Drugs, Selective COX-2 Inhibitors and Breast Cancer Recurrence

Epidemiology ◽

10.1097/ede.0000000000000480 ◽

2016 ◽

Vol 27 (4) ◽

pp. 586-593 ◽

Cited By ~ 15

Author(s):

Deirdre P. Cronin-Fenton ◽

Uffe Heide-Jørgensen ◽

Thomas P. Ahern ◽

Timothy L. Lash ◽

Peer Christiansen ◽

...

Keyword(s):

Breast Cancer ◽

Low Dose ◽

Cancer Recurrence ◽

Breast Cancer Recurrence ◽

Dose Aspirin ◽

Low Dose Aspirin ◽

Inflammatory Drugs ◽

Cox 2 ◽

Anti Inflammatory ◽

Cox 2 Inhibitors

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Effects of Combining Aspirin with Non-Steroidal Anti-Inflammatory Drugs or COX-2 Inhibitors on Shear-Induced Platelet Aggregation.

Blood ◽

10.1182/blood.v104.11.1853.1853 ◽

2004 ◽

Vol 104 (11) ◽

pp. 1853-1853

Author(s):

Angela Bergeron ◽

Carol Sun ◽

Jennifer Wood ◽

Jo Ellen Schweinle ◽

Frank L. Lanza ◽

...

Keyword(s):

Platelet Aggregation ◽

Naproxen Sodium ◽

Low Dose ◽

Closure Time ◽

Dose Aspirin ◽

Low Dose Aspirin ◽

Inflammatory Drugs ◽

The Mean ◽

Cox 2 ◽

Cox 2 Inhibitors

Abstract Aspirin has been widely used as a cardiac protective drug, often with hemostasis inhibition and bleeding risks. This concern becomes even more significant when it is used in combination with non-steroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors, both of which may have independent effects on platelets. To study how hemostasis may be affected by these drugs, we conducted a multiple-dose, single-blind, parallel-group study to determine the effects of aspirin combined with over-the-counter NSAIDs or COX-2 inhibitors on shear-induced platelet aggregation (SIPA). For this study, 87 healthy individuals (age 40 to 75) who met inclusion and exclusion criteria were recruited. All subjects received 81 mg of aspirin (non-enteric coated and chewable) daily for eight days. In addition, beginning 2 hours after low-dose aspirin, the subjects also received one of the following drugs: acetaminophen (4 doses of 1000 mg daily), ibuprofen (3 doses of 400 mg daily), naproxen sodium (440 mg morning and 220 mg evening), additional aspirin (4 doses of 650 mg daily), celecoxib (2 doses of 200 mg daily) and rofecoxib (1 dose of 25 mg daily). The second drugs were given 2 hrs after initial aspirin intake. The control group received only 81 mg of aspirin. Blood was drawn before the treatment and at 24 hr and 7 days (before any medications on Day 8) after the initial drug intake. Shear-induced platelet aggregation (SIPA) on a collagen matrix with either ADP or epinephrine was measured in citrated whole blood using a platelet function analyzer. The aggregation was defined as closure time (sec) under a constant shear rate of 1500 −s, a level of pathological high shear stress. We found that the closure time with the collagen/ADP cartridge was not affected by any of the treatments (83 – 108 sec). In contrast, SIPA with the collagen/epinephrine cartridge showed a time-dependent inhibition by 81 mg of aspirin with the mean closure times being 118, 138, and 222 sec before drug administration, 24 hr and 7 day after treatments, respectively. The course of low-dose aspirin inhibition of SIPA was not changed by acetaminophen, celecoxib, or rofecoxib. In contrast, the mean closure time at 24 hr after the treatment was 249 and 264 sec for samples from individuals on a combined treatment of low-dose aspirin with either naproxen sodium or a high dose of aspirin (2600 mg), significantly longer than those of other treatment groups (P< 0.001). It has been demonstrated that SIPA, which is primarily initiated by the GP Ib-VWF interaction, is insensitive to aspirin. Our results suggest that aspirin inhibits SIPA induced in the presence of collagen and epinephrine, but not collagen and ADP. Furthermore, this effect was significantly enhanced by either naproxen sodium or a higher dose of aspirin (2600 mg), suggesting that the simultaneous intake of low-dose aspirin and either analgesic doses of aspirin or naproxen may enhance the risk of aspirin-induced bleeding tendency.

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Effects of Non-Steroidal Anti-Inflammatory Drugs and COX-2 Inhibitors on Aspirin-Induced Platelet Inhibition.

Blood ◽

10.1182/blood.v104.11.531.531 ◽

2004 ◽

Vol 104 (11) ◽

pp. 531-531

Author(s):

Carol Sun ◽

Angela Bergeron ◽

Jennifer Wood ◽

Jo Ellen Schweinle ◽

Frank L. Lanza ◽

...

Keyword(s):

Platelet Aggregation ◽

Naproxen Sodium ◽

Low Dose ◽

Dose Aspirin ◽

Low Dose Aspirin ◽

Inflammatory Drugs ◽

Cox 2 ◽

Enteric Coated ◽

Cox 2 Inhibitors ◽

Initial Drug

Abstract Low dose aspirin has been widely used as a cardiac protective drug. It acts by inhibiting platelet activation and aggregation through the cyclooxygenase-1 pathway. However, such effects may be affected by short-term use of other drugs such as non-steroidal anti-inflammatory drugs (NSAIDs). We have conducted a multiple-dose, single-blind, parallel-group study to investigate the effects of over-the-counter NSAIDs and COX-2 inhibitors on arachidonic-induced platelet aggregation and thromboxane B2 (TxB2) production. We recruited 87 healthy individuals of 40-75 years of age, who met the inclusion and exclusion criteria by pretest screening. All subjects received 81 mg of aspirin (non-enteric coated and chewable) daily for eight days. Two hours after the 81 mg aspirin dose, the subjects received one of following drugs: acetaminophen (4 doses of 1000 mg daily), ibuprofen (3 doses of 400 mg daily), naproxen sodium (440 mg morning and 220 mg evening), a higher dose of aspirin (4 doses of 650 mg daily), celecoxib (2 doses of 200 mg daily) and rofecoxib (1 dose of 25 mg daily). Control individuals received only 81 mg of aspirin. Citrated blood was obtained before the treatment and at 2, 6, 12, and 24 hr during the first day and an identical schedule after 7 days of dosing (Day 8 of treatment). Platelet function was measured by arachidonic acid-induced platelet aggregation and serum levels of TxB2. We found that the maximal inhibitory effect (more than 85% reduction in aggregation) of 81 mg aspirin was reached more than 24 hr after initial drug intake; whereas it was observed within 6 hr in subjects receiving randomized 2600 mg of aspirin (but only took 1300 mg at time of blood draw). Similar to the higher dose of aspirin, both ibuprofen and naproxen sodium also significantly accelerated the inhibitory effects of low dose aspirin on platelet aggregation (Paired Student t test, p < 0.01). In comparison, acetaminophen and two COX-2 inhibitors showed no additive effects with 81 mg of aspirin. Consistent with aggregation studies, the inhibition of TxB2 production was significantly greater than those with 81 mg of aspirin only at 6, 12, and 24 hr after initial drug intake for 2600 mg of aspirin, ibuprofen, and naproxen, but not for acetaminophen, celecoxib, and rofecoxib. Contrary to a report by Catella-Lawson et al, we found that ibuprofen did not interfere, but rather slightly enhanced, aspirin-induced inhibition of platelet aggregation. The reason for the discrepancy remains unknown, but may be attributed to the type of aspirin used (enteric-coated vs. non-enteric-coated) and different schedules of drug intakes between the two studies. Finally, it may also be due to the fact that our subjects were in their normal environments and not in a clinical research unit. In conclusion, we found that acetaminophen and COX-2 inhibitors did not affect the course of the low-dose aspirin action on platelets. Although ibuprofen and naproxen have had no additive effects, they accelerated the action of 81 mg of aspirin on platelet aggregation.

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Long-Term Use of Low-Dose Aspirin can Reduce Multiple Gastrointestinal Cancer Incidence and Mortality: A 10-Year Population-Based Study

Gastroenterology ◽

10.1016/s0016-5085(17)30803-x ◽

2017 ◽

Vol 152 (5) ◽

pp. S142

Author(s):

Kelvin Tsoi ◽

Felix C.H. Chan ◽

Hoyee W. Hirai ◽

Joseph J. Sung

Keyword(s):

Cancer Incidence ◽

Gastrointestinal Cancer ◽

Low Dose ◽

Population Based ◽

Population Based Study ◽

Dose Aspirin ◽

Incidence And Mortality ◽

Low Dose Aspirin

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Comparing mortality of colorectal cancer and gastrointestinal bleeding among patients with long-term use of low dose aspirin: A population-based study of 689,209 patients.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.527 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 527-527

Author(s):

Joseph Sung ◽

Kelvin Kf Tsoi

Keyword(s):

Colorectal Cancer ◽

Gastrointestinal Bleeding ◽

Large Scale ◽

Low Dose ◽

Population Based ◽

Dose Aspirin ◽

Increased Risk ◽

Incidence And Mortality ◽

Low Dose Aspirin

527 Background: Aspirin, commonly used for prevention of cardiovascular and cerebrovascular diseases, is well-known to protect against colorectal cancer (CRC) development but increase risk of gastrointestinal bleeding (GIB). Few large-scale studies have compared the benefit and risk of long-term aspirin usage. This cohort study aims to evaluate the use of low-dose aspirin to prevent CRC and the risk of GIB associated with the aspirin use. Methods: A population-based clinical dataset was used to compare incidence and mortality of CRC and GIB patients receiving low-dose aspirin with sex-and-age matched controls (in 1:2 ratio). Patients with aspirin≤6 months were excluded. Clinical data of 206,243 aspirin users (mean dose 80 mg/day, mean duration 7.7 years) and 482,966 non-users were included. All patients must have at least 10-year follow up on clinical outcome. Results: Among aspirin users 5,776 (2.80%) were diagnosed with CRC; 2,097 (1.02%) died of the malignancy. 16,483 (3.41%) non-users were diagnosed with CRC; 7,963 (1.65%) died of CRC. Using the cox-proportional hazard regression, aspirin usage showed a modest but significant reduction in CRC mortality (HR = 0.65; 95% CI = 0.62 to 0.69). On the other hand, 11,187 (5.42%) aspirin users developed GIB, and 841 (0.41%) died. 15,186 (3.14%) non-users developed GIB, and 1,682 patients (0.35%) died. Aspirin users showed modest but significant increased risk of GIB-related mortality (HR = 1.24; 95% CI = 1.14 to 1.35). Conclusions: The long-term use of low dose aspirin shows preventive effect on CRC, but also increases the associated GIB risk. Considerations of prophylactic use of aspirin should balance the benefit and the risk of this treatment to the target population. [Table: see text]

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Association Between Aspirin Use and Decreased Risk of Pneumonia in Patients With Cardio-Cerebra-Vascular Ischemic Disease: A Population-Based Cohort Study

Frontiers in Public Health ◽

10.3389/fpubh.2021.625834 ◽

2021 ◽

Vol 9 ◽

Author(s):

Ying-Cheng Chen ◽

Yin-Yang Chen ◽

Han Wei Yeh ◽

Tung-Ying Yeh ◽

Jing-Yang Huang ◽

...

Keyword(s):

Cohort Study ◽

Low Dose ◽

Population Based ◽

Hazard Ratio ◽

Cumulative Probability ◽

Research Database ◽

Cox Regression Analysis ◽

Dose Aspirin ◽

Low Dose Aspirin

This study evaluated the association between long-term low-dose aspirin use and decreased risk of pneumonia in patients with cardio-cerebra-vascular ischemic diseases (CCVDs). This retrospective cohort study used records from Taiwan's National Health Insurance Research Database of claims made between 1997 and 2013. After propensity score matching (PSM), patients who took a low dose of aspirin for more than 90 days within 1 year of diagnosis with CCVDs were identified as the exposure group (n = 15,784). A matched total of 15,784 individuals without aspirin use were selected for the non-aspirin group. The main outcome was the development of pneumonia after the index date. Multivariable Cox regression analysis and Kaplan–Meier survival analysis were performed to estimate the adjusted hazard ratio (aHR) and cumulative probability of pneumonia. The result after PSM indicated a lower hazard ratio for pneumonia in aspirin users (aHR = 0.890, 95% confidence interval = 0.837–0.945). Therefore, patients with CCVDs who took aspirin had a lower risk of developing pneumonia than those who did not. In conclusion, this population-based cohort study demonstrated that long-term low-dose aspirin use is associated with a slightly decreased risk of pneumonia in patients with CCVDs.

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Review of the selective COX-2 inhibitors celecoxib and rofecoxib: focus on clinical aspects

CJEM ◽

10.1017/s1481803500007508 ◽

2002 ◽

Vol 4 (04) ◽

pp. 268-275 ◽

Cited By ~ 7

Author(s):

Peter S. Loewen

Keyword(s):

Similar Efficacy ◽

Clinical Aspects ◽

Cardiovascular Risk Reduction ◽

Dose Aspirin ◽

Concurrent Use ◽

Low Dose Aspirin ◽

Postoperative Dental Pain ◽

Inflammatory Drugs ◽

Cox 2 ◽

Cox 2 Inhibitors

ABSTRACT:The selective cyclooxygenase-2 (COX-2) inhibitors celecoxib and rofecoxib were designed to have similar efficacy but less gastrointestinal toxicity than traditional nonsteroidal anti-inflammatory drugs (NSAIDs). Their efficacy has been demonstrated in the treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, postoperative dental pain and dysmenorrhea. These agents produce fewer endoscopic ulcers, symptomatic ulcers and gastrointestinal bleeds than traditional NSAIDs; although the absolute benefit is small and the gastropreserving effect is negated by concurrent use of low-dose aspirin for cardiovascular risk reduction. Nephrotoxicity and hyptertension remain concerns with COX-2 inhibitors, as they are with traditional NSAIDs. COX-2 inhibitors may be safe alternatives to traditional NSAIDs for patients with aspirin-sensitive asthma.

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