The Validity of Danish Prescription Data to Measure Use of Aspirin and Other Non-Steroidal Anti-Inflammatory Drugs and Quantification of Bias Due to Non-Prescription Drug Use

Figures & data

Figure 1 Prevalence of true NSAID use misclassified as non-use in the apparent NSAID non-user group dependent on values of (A) non-prescription NSAID use (over-the-counter use + hospital use) and (B) prevalence of true NSAID use. Note different scales of y-axes.

Figure 2 The proportion of the total Danish population using non-steroidal anti-inflammatory drugs (NSAIDs) in Denmark, 1999–2019.

Figure 3 Proportion of non-prescribed non-steroidal anti-inflammatory drug (NSAID) use in the (A) hospital sector and (B) primary sector (over-the-counter use) in Denmark, 1999–2019. Note different scales of y-axes.

Figure 4 Misclassification of true NSAID use as apparent non-use from non-prescribed drug use in the (A) hospital sector and (B) primary sector (over-the-counter use) and (C) total population (hospital sector + primary sector). Denmark, 1999–2019. Note different scales of y-axes.

Table 1 Prevalence of True Non-Aspirin NSAID Use Misclassified as Apparent Non-Use in Subgroups of Patients with Cardiac Disease

	Prevalence of NSAID Use (Prescribed)*	OTC NSAID Use†	Hospital-Sector Misclassification of NSAID Use as Non-Use‡	Prevalence of True NSAID Use (Total)§	Misclassification of True NSAID Use as Non-Use||
2002
Overall	22.7%	15%	0.6%	26.7%	4.6%
Ischemic heart disease	20.9%	15%	0.6%	24.6%	4.3%
Angina pectoris	24.7%	15%	0.6%	29.1%	5.0%
Myocardial infarction	18.0%	15%	0.6%	21.2%	3.8%
NSTEMI	20.3%	15%	0.6%	23.9%	4.2%
STEMI	16.3%	15%	0.6%	19.2%	3.5%
Atrial fibrillation/flutter	20.4%	15%	0.6%	24.0%	4.2%
Heart failure	21.0%	15%	0.6%	24.7%	4.3%
Venous thromboembolism	24.1%	15%	0.6%	28.4%	4.9%
Ischemic stroke	20.6%	15%	0.6%	24.2%	4.2%
Valvular heart disease	22.5%	15%	0.6%	26.5%	4.6%
Infective endocarditis	18.6%	15%	0.6%	21.9%	3.9%
2017
Overall	13.5%	19%	0.4%	16.7%	3.6%
Ischemic heart disease	9.9%	19%	0.4%	12.2%	2.7%
Angina pectoris	13.8%	19%	0.4%	17.0%	3.6%
Myocardial infarction	8.7%	19%	0.4%	10.7%	2.4%
NSTEMI	9.6%	19%	0.4%	11.9%	2.7%
STEMI	7.0%	19%	0.4%	8.6%	2.0%
Atrial fibrillation/flutter	10.9%	19%	0.4%	13.5%	3.0%
Heart failure	8.8%	19%	0.4%	10.9%	2.5%
Venous thromboembolism	16.6%	19%	0.4%	20.5%	4.3%
Ischemic stroke	10.4%	19%	0.4%	12.8%	2.8%
Valvular heart disease	15.3%	19%	0.4%	18.9%	4.0%
Infective endocarditis	11.8%	19%	0.4%	14.6%	3.2%

Notes: *Based on prescribed prevalence of non-aspirin NSAIDs in specific cardiac patient groups.¹⁹ †Assumed proportion of OTC non-aspirin NSAID use based on total population OTC proportion in 2002 and 2017. ‡Assumed prevalence of true non-aspirin NSAID use misclassified as apparent non-use based on hospital-sector use (total population). §Calculated as: Prevalence of NSAID use/ OTC NSAID use. ||Calculated as: OTC NSAID use × prevalence of true NSAID use + hospital sales misclassification of true NSAID use as non-use.

Abbreviations: NSAID, non-steroidal anti-inflammatory drug; OTC, over-the-counter; NSTEMI, non-ST-elevation myocardial infarction; STEMI, ST-elevation myocardial infarction.

Table 2 Magnitude of Bias in Drug Outcome Studies, Illustrated from Case–Control Studies with Varying Prevalence of NSAID Exposure Among Cases and Controls and Varying Proportion of True NSAID Use Misclassified as Apparent Non-Use

Proportion of True NSAID Use Misclassified as Non-Use*	Prevalence of NSAID Exposure		Odds Ratio† (95% Confidence Interval)	Bias (%)‡
	Controls	Cases
0% (true value)§	15%	20%	1.42 (0.68–2.96)	0.00
2%	14.70%	19.60%	1.41 (0.67–2.97)	0.15
5%	14.25%	19.00%	1.41 (0.67–2.99)	0.36
10%	13.50%	18.00%	1.41 (0.65–3.03)	0.72
0% (true value)§	10%	30%	3.86 (1.77–8.42)	0.00
2%	9.80%	29.40%	3.83 (1.74–8.42)	0.63
5%	9.50%	28.50%	3.80 (1.71–8.43)	1.57
10%	9.00%	27.00%	3.74 (1.66–8.45)	3.09
0% (true value)§	5%	15%	3.35 (1.17–9.62)	0.00
2%	4.90%	14.70%	3.34 (1.15–9.69)	0.24
5%	4.75%	14.25%	3.33 (1.13–9.80)	0.62
10%	4.50%	13.50%	3.31 (1.10–10.01)	1.22
0% (true value)§	6%	25%	5.22 (2.04–13.39)	0.00
2%	5.88%	24.50%	5.19 (2.01–13.43)	0.54
5%	5.70%	23.75%	5.15 (1.97–13.49)	1.33
10%	5.40%	22.50%	5.09 (1.90–13.63)	2.64
0% (true value)§	5%	35%	10.23 (3.81–27.49)	0.00
2%	4.90%	34.30%	10.13 (3.74–27.47)	0.96
5%	4.75%	33.25%	9.99 (3.63–27.45)	2.39
10%	4.50%	31.50%	9.76 (3.47–27.48)	4.72

Notes: *Color change indicate new example. †Odds ratio = (exposed cases × non-exposed controls)/(exposed controls × non-exposed cases). ‡Bias = ln(true OR/biased OR). Translates to the approximate percentage change shown as: 100 × ln(true OR/biased OR). §0% represent the scenario in each hypothetical example where no NSAID use is misclassified as non-use.

Abbreviation: NSAID, non-steroidal anti-inflammatory drug.

Schmidt M, Pottegård A. 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. 2020. doi:10.1093/ehjcvp/pvaa073

 Web of Science ®Google Scholar