Adverse drug events associated with vitamin K antagonists: factors of therapeutic imbalance

Figures & data

Table 1 Characteristics of patients on treatment with vitamin K antagonists

Variables	Cases (n = 67)	Controls (n = 81)	P*
Age over 75 years	39 (58.2%)	33 (40.7%)	0.049
Recent infection	27 (40.3%)	5 (6.2%)	<0.0001
Hypertension	52 (77.6%)	51 (62.9%)	0.054
Low level of hemoglobin	48 (71.6%)	19 (23.5%)	<0.0001
Low albumin	25 (37.3%)	5 (6.1%)	<0.0001
High creatininemia	32 (47.7%)	20 (24.7%)	0.002

Note: ^*Chi-square test used.

Table 2 Comparison of drug–drug interactions between cases and controls

Variables	Cases (n = 67)	Controls (n = 81)	P*
Drug–drug interaction	61 (91%)	63 (77.7%)	0.029
Contraindication	1 (1.49%)	1 (1.23%)	0.892
Discouraged	10 (14.9)	15 (18.5%)	0.561
Precaution for use	60 (89.5%)	61 (75.3%)	0.026
Take into account	1 (1.49%)	0 (0%)	0.361
Antibiotics	24 (35.8%)	9 (11.1%)	<0.0001
Penicillins	10 (14.9%)	4 (4.9%)	0.039
Quinolones	9 (13.4%)	3 (3.7%)	0.031
Anti-inflammatory drugs	18 (26.8%)	1 (1.2%)	<0.0001
Paracetamol	1 (1.5%)	5 (6.1%)	0.056
Antifungals	5 (7.5%)	3 (3.7%)	0.324
Statins	18 (28.9%)	22 (27%)	0.986
Anticoagulants/antiplatelet agents	32 (47.7%)	20 (24.7%)	0.002
Aspirin	10 (14.9%)	2 (2.5%)	0.006
Amiodarone	19 (28.3%)	3 (3.7%)	<0.0001

Note: ^*Chi-square test used.

Table 3 Comparison of signs of bleeding between cases and controls

Variables	Cases (n = 67)	Controls (n = 81)	P*
Hemorrhage	36 (53%)	5 (6.2%)	<0.0001
Hematuria	18 (27%)	3 (3.7%)	<0.0001
Hematoma	10 (15%)	0 (0%)	<0.0001
Intracranial bleeding	4 (5.9%)	0 (0%)	0.026
Decreased hemoglobin level	15 (22%)	2 (2.5%)	<0.0001
Internal bleeding	30 (45%)	1 (1.2%)	<0.0001
Fatigue	13 (19%)	1 (1.2%)	<0.0001
Pallor	9 (13%)	1 (1.2%)	0.003
Palpitations	6 (8.9%)	1 (1.2%)	0.018
Syncope	7 (10%)	0 (0%)	0.003
Dizziness	7 (8.6%)	1 (1.5%)	0.014

Note: ^*Chi-square test used.

Figure 1 Management of bleeding or nonbleeding patients with a high INR.

Abbreviations: INR, international normalized ratio; AVK, vitamin K antagonists; FFP, fresh frozen plasma.

Table 4 Logistic regression coefficient for values of INR higher than the therapeutic range

Variables	P	ORa [95% CI]
Recent infection	0.003	1.76 [2.77–27.67]
Low level of albumin	0.0005	4.50 [1.76–8.08]
Concomitant use of amiodarone	0.008	4.73 [1.18–5.23]
Concomitant use of aspirin	0.0074	5.20 [1.78–6.35]
Presence of drug–drug interactions	0.0065	5.70 [0.45–5.67]

Abbreviations: INR, international normalized ratio; ORa, adjusted Odds Ratio; CI, confidence interval.