Studies included in the review
| Study name | Study site | Study design | n | Duration of follow-up (maximum) (years) | Participants | Measure of effect | Outcomes | Exposure (no-use versus:) | Results |
|---|---|---|---|---|---|---|---|---|---|
| Chan et al10 | USA | Cohort | 70 971 | 12 | Female registered nurses aged 30–55 years | Risk ratio | Cardiovascular AEs (confirmed or probable non-fatal myocardial infarction, non-fatal stroke, fatal coronary heart disease or fatal stroke) | 1–4 days/month use 5–14 days/month use 15–21 days/month use >22 days/month use | 0.98 (0.84 to 1.14) 1.09 (0.91 to 1.30) 1.22 (0.95 to 1.56) 1.35 (1.14 to 1.59) |
| Curhan et al11 | USA | Cohort | 80 020 | 2 | Female registered nurses aged 30–55 years | Relative risk | Incidence of hypertension | 1–4 days/month use 5–14 days/month use 15–21 days/month use >22 days/month use | 1.19 (1.04 to 1.36) 1.37 (1.15 to 1.64) 1.62 (1.22 to 2.16) 2.00 (1.52 to 2.62) |
| Dedier et al12 | USA | Cohort | 57 935 | 2 | Female registered nurses aged 30–55 years | Relative risk | Incidence of hypertension | 1–4 days/month use 5–14 days/month use 15–21 days/month use >22 days/month use | 1.07 (1.02 to 1.13) 1.22 (1.14 to 1.32) 1.31 (1.16 to 1.48) 1.20 (1.08 to 1.33) |
| Curhan et al13 | USA | Cohort | 1697 | 11 | Female registered nurses aged 30–55 years | OR | Decrease in eGFR of at least 30 mL/min/1.73 m2 | 100–499 g lifetime intake 500–2999 g lifetime intake >3000 g lifetime intake | 1.80 (1.02 to 3.17) 2.23 (1.36 to 3.63) 2.04 (1.28 to 3.24) |
| ≥ 30% decrease in eGFR | 100–499 g lifetime intake 500–2999 g lifetime intake >3000 g lifetime intake | 1.40 (0.79 to 2.49) 1.64 (1.00 to 2.69) 2.19 (1.40 to 3.45) | |||||||
| De Vries et al8 | UK | Cohort | 382 404 | 20 | Patients aged ≥18 received a prescription for paracetamol or ibuprofen | Relative rate | All-cause mortality | First prescription Long gap (patients with at least 12 months between prescriptions) Low MPR Medium MPR High MPR Very High MPR | 1.95 (1.87 to 2.04) 1.18 (1.14 to 1.23) 0.95 (0.92 to 0.97) 1.08 (1.05 to 1.12) 1.27 (1.21 to 1.33) 1.63 (1.58 to 1.68) |
| Incidence of myocardial infarction | First prescription Long gap (patients with at least 12 months between prescriptions) Low MPR Medium MPR High MPR Very High MPR | 1.42 (1.22 to 1.65) 0.98 (0.86 to 1.11) 1.11 (1.02 to 1.19) 1.17 (1.05 to 1.29) 1.04 (0.89 to 1.23) 1.17 (1.04 to 1.32) | |||||||
| Incidence of stroke | First prescription Long gap (patients with at least 12 months between prescriptions) Low MPR Medium MPR High MPR Very High MPR | 1.17 (1.02 to 1.35) 1.14 (1.03 to 1.25) 1.03 (0.97 to 1.10) 1.17 (1.08 to 1.27) 1.02 (0.89 to 1.15) 1.30 (1.19 to 1.41) | |||||||
| Upper GI AEs (gastroduodenal ulcers and complications such as upper GI haemorrhages) | First prescription Long gap (patients with at least 12 months between prescriptions) Low MPR Medium MPR High MPR Very High MPR | 1.74 (1.53 to 1.59) 1.30 (1.17 to 1.46) 1.11 (1.04 to 1.21) 1.25 (1.12 to 1.38) 1.49 (1.29 to 1.71) 1.49 (1.34 to 1.66) | |||||||
| Incidence of acute renal failure | First prescription Long gap (patients with at least 12 months between prescriptions) Low MPR Medium MPR High MPR Very High MPR | 1.31 (1.03 to 1.68) 1.21 (1.02 to 1.43) 1.16 (1.04 to 1.29) 1.27 (1.10 to 1.47) 1.44 (1.18 to 1.75) 1.34 (1.15 to 1.57) | |||||||
| Evans et al14 | Sweden | Cohort | 801 | 7 | People diagnosed with incident CKD aged ≥18 | Regression coefficient | Differences in estimated progression rates, (change in eGFR in mL/min/1.73 m2 per year) | <99 g lifetime intake 100–499 g lifetime intake 500–2999 g lifetime intake >3000 g lifetime intake | −0.17 (−0.9 to 0.6) 0.60 (−0.3 to 1.5) 0.65 (−0.7 to 2.0) 0.24 (−1.2 to 1.7) |
| HR | Time to renal replacement therapy | Regular use (at least twice a week for 2 months prior to inclusion) | 1.1 (0.9 to 1.4) | ||||||
| Kurth et al15 | USA | Cohort | 22 071 | 14 | Healthy male physicians | OR | Increased creatinine concentration of ≥ 0.3 mg/dL | 12–1499 pills/14 years 1500–2499 pills/14 years >2500 pills/14 years | 0.68 (0.48 to 0.98) 0.69 (0.31 to 1.54) 1.11 (0.52 to 2.37) |
| Decrease in eGFR of at least 30 mL/min/1.73 m2 | 12–1499 pills/14 years 1500–2499 pills/14 years >2500 pills/14 years | 0.53 (0.36 to 0.78) 0.65 (0.29 to 1.45) 1.28 (0.61 to 2.69) | |||||||
| Lipworth et al9 | Denmark | Cohort | 49 890 | 7 | People prescribed paracetamol aged over 16 | Standardised mortality ratio | All-cause mortality | Prescribed paracetamol during lifetime | 1.9 (1.88 to 1.94) |
| Renal failure | 1.8 (1.3 to 2.5) | ||||||||
| Ischemic heart disease | 1.6 (1.5 to 1.6) | ||||||||
| Other heart disease | 1.6 (1.5 to 1.8) | ||||||||
| Cerebrovascular disease | 1.6 (1.5 to 1.7) |
MPR is defined as the ratio of duration of the previous prescription to the time between that prescription and the current prescription. Low MPR = <0.40; medium MPR = 0.40–0.59; high MPR = 0.60–0.79 and very high MPR = >0.8.
AE, adverse event; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; GI, gastrointestinal; MPR, medication possession ratio.