Prescriber responsibility, predictors for initiation, and 20-year trends in use of non-aspirin non-steroidal anti-inflammatory drugs in patients with cardiovascular contraindications: a nationwide cohort study

Eur Heart J Cardiovasc Pharmacother. 2021 Nov 3;7(6):496-506. doi: 10.1093/ehjcvp/pvaa073.


Aims: To examine whether prescription patterns complied with recommendations not to use non-steroidal anti-inflammatory drugs (NSAIDs) in patients with cardiovascular contraindications. Moreover, we examined predictors for initiation and prescriber responsibility.

Methods and results: We used Danish medical databases to identify all patients with first-time cardiovascular disease during 1996-2017 (n = 628 834). We assessed standardized prevalence proportions, predictors from logistic regression, and prescriber identifiers. One-year prevalence of NSAID initiation increased 3.4% from 1996 (19.4%) to 2001 (22.7%) and declined by 2.7% thereafter until 2017 (13.5%). Trends were independent of age, sex, and disease subtype, although larger annual declines occurred for heart failure (3.9%) and ischaemic heart disease (3.5%) since 2002. One-year prevalence remained highest among patients with venous thromboembolism (16.6%) and angina (13.8%), and lowest for ST-segment elevation myocardial infarction (7.0%) and heart failure (8.8%). Initiators were predominantly prescribed ibuprofen (59%), diclofenac (23%), and etodolac (6%). Diclofenac and coxib use declined, while ibuprofen and naproxen use increased. Median prescribed pill dose of ibuprofen declined after 2008 from moderate/high (600 mg) to low (400 mg). Treatment duration declined for all NSAIDs, except celecoxib. Rheumatic, obesity, and pain-related conditions predicted NSAID initiation. General practitioners issued 86-91% of all NSAID prescriptions, followed by hospital prescribers (7.3-12%).

Conclusions: Initiation of NSAIDs in patients with cardiovascular disease declined since 2002. Shorter treatment duration, declining COX-2 inhibition, and increasing use of naproxen and low-dose ibuprofen suggest adherence to guidelines when NSAIDs cannot be avoided. Still, NSAID use remained prevalent despite cardiovascular contraindications, warranting awareness of appropriateness of use among general practitioners in particular.

Keywords: Cardiovascular diseases; Epidemiology; NSAIDs; Trends.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal* / adverse effects
  • Cohort Studies
  • Cyclooxygenase 2 Inhibitors / adverse effects
  • Diclofenac / adverse effects
  • Humans
  • Ibuprofen* / adverse effects


  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2 Inhibitors
  • Diclofenac
  • Ibuprofen