Objective To examine the cardiovascular risks of diclofenac initiation compared with initiation of other traditional non-steroidal anti-inflammatory drugs, initiation of paracetamol, and no initiation.
Design Series of 252 nationwide cohort studies, each mimicking the strict design criteria of a clinical trial (emulated trial design).
Setting Danish, nationwide, population based health registries (1996-2016).
Participants Individuals eligible for inclusion were all adults without malignancy; schizophrenia; dementia; or cardiovascular, kidney, liver, or ulcer diseases (that is, with low baseline risk). The study included 1 370 832 diclofenac initiators, 3 878 454 ibuprofen initiators, 291 490 naproxen initiators, 764 781 healthcare seeking paracetamol initiators matched by propensity score, and 1 303 209 healthcare seeking non-initiators also matched by propensity score.
Main outcome measures Cox proportional hazards regression was used to compute the intention to treat hazard ratio (as a measure of the incidence rate ratio) of major adverse cardiovascular events within 30 days of initiation.
Results The adverse event rate among diclofenac initiators increased by 50% compared with non-initiators (incidence rate ratio 1.5, 95% confidence interval 1.4 to 1.7), 20% compared with paracetamol or ibuprofen initiators (both 1.2, 1.1 to 1.3), and 30% compared with naproxen initiators (1.3, 1.1 to 1.5). The event rate for diclofenac initiators increased for each component of the combined endpoint (1.2 (1.1 to 1.4) for atrial fibrillation/flutter, 1.6 (1.3 to 2.0) for ischaemic stroke, 1.7 (1.4 to 2.0) for heart failure, 1.9 (1.6 to 2.2) for myocardial infarction, and 1.7 (1.4 to 2.1) for cardiac death) as well as for low doses of diclofenac, compared with non-initiators. Although the relative risk of major adverse cardiovascular events was highest in individuals with low or moderate baseline risk (that is, diabetes mellitus), the absolute risk was highest in individuals with high baseline risk (that is, previous myocardial infarction or heart failure). Diclofenac initiation also increased the risk of upper gastrointestinal bleeding at 30 days, by approximately 4.5-fold compared with no initiation, 2.5-fold compared with initiation of ibuprofen or paracetamol, and to a similar extent as naproxen initiation.
Conclusions Diclofenac poses a cardiovascular health risk compared with non-use, paracetamol use, and use of other traditional non-steroidal anti-inflammatory drugs.
Reference: BMJ 2018;362:k3426
Question Is there an association between cardiovascular health level in older age and risk of incident dementia?
Findings In this French population-based cohort study involving 6626 individuals, an increased number of optimal cardiovascular health metrics (defined using a 7-item tool from the American Heart Association) were significantly associated with lower risk of incident dementia (hazard ratio, 0.90 for each additional metric at recommended optimal level).
Meaning These findings may support the promotion of cardiovascular health to prevent development of risk factors associated with dementia.
Patients with diabetes are at higher risk for death and cardiovascular outcomes than the general population. We investigated whether the excess risk of death and cardiovascular events among patients with type 2 diabetes could be reduced or eliminated.
In a cohort study, we included 271,174 patients with type 2 diabetes who were registered in the Swedish National Diabetes Register and matched them with 1,355,870 controls on the basis of age, sex, and county. We assessed patients with diabetes according to age categories and according to the presence of five risk factors (elevated glycated hemoglobin level, elevated low-density lipoprotein cholesterol level, albuminuria, smoking, and elevated blood pressure). Cox regression was used to study the excess risk of outcomes (death, acute myocardial infarction, stroke, and hospitalization for heart failure) associated with smoking and the number of variables outside target ranges. We also examined the relationship between various risk factors and cardiovascular outcomes.
The median follow-up among all the study participants was 5.7 years, during which 175,345 deaths occurred. Among patients with type 2 diabetes, the excess risk of outcomes decreased stepwise for each risk-factor variable within the target range. Among patients with diabetes who had all five variables within target ranges, the hazard ratio for death from any cause, as compared with controls, was 1.06 (95% confidence interval [CI], 1.00 to 1.12), the hazard ratio for acute myocardial infarction was 0.84 (95% CI, 0.75 to 0.93), and the hazard ratio for stroke was 0.95 (95% CI, 0.84 to 1.07). The risk of hospitalization for heart failure was consistently higher among patients with diabetes than among controls (hazard ratio, 1.45; 95% CI, 1.34 to 1.57). In patients with type 2 diabetes, a glycated hemoglobin level outside the target range was the strongest predictor of stroke and acute myocardial infarction; smoking was the strongest predictor of death.
Patients with type 2 diabetes who had five risk-factor variables within the target ranges appeared to have little or no excess risk of death, myocardial infarction, or stroke, as compared with the general population. (Funded by the Swedish Association of Local Authorities and Regions and others.)