Is the multinational, surveillance PRO-E2 study informative for all countries? The Italian data on VTE and contraceptive effectiveness

Figures & data

Table 1. Selected baseline characteristics by user cohort.

	NOMAC-E2	COCLNG	Total
Number (%) of women	11,179 (56.8)	8,504 (43.2)	19,683 (100)
WY (%)	12,360 (35.4)	9,653 (27.7)	34,869 (100)^a
Age (years)
Mean (SD)	31.8 (9.53)	30.7 (9.30)	31.3 (9.45)
Age category, n (%)
<20 years	1,127 (10.1)	1,059 (12.5)	2,186 (11.1)
20–<25 years	2,267 (20.3)	1,818 (21.4)	4,085 (20.8)
25–<30 years	1,967 (17.6)	1,607 (18.9)	3,574 (18.2)
30–<35 years	1,608 (14.4)	1,312 (15.4)	2,920 (14.8)
35–<40 years	1,493 (13.4)	1,052 (12.4)	2,545 (12.9)
≥40 years	2,717 (24.3)	1,656 (19.5)	4,373 (22.2)
Weight (kg)
Mean (SD)	60.6 (11.18)	60.9 (11.70)	60.7 (11.41)
BMI (kg/m^2)
Mean (SD)	22.51 (3.98)	22.64 (4.13)	22.57 (4.05)
BMI category, n (%)
<20	2,988 (26.7)	2,244 (26.4)	5,232 (26.6)
20–<25	5,688 (50.9)	4,214 (49.6)	9,902 (50.3)
25–<30	1,756 (15.7)	1,441 (16.9)	3,197 (16.2)
30–<35	431 (3.9)	382 (4.5)	813 (4.1)
≥35	137 (1.2)	115 (1.4)	252 (1.3)
Education level, n (%)
Less than university entrance level	2,482 (22.2)	2,136 (25.1)	4,618 (23.5)
University entrance level	5,874 (52.5)	4,448 (52.3)	10,322 (52.4)
More than university entrance level	2,805 (25.1)	1,915 (22.5)	4,720 (24.0)

^a Describes WY from the whole study population, including women who stopped using hormonal contraceptives (ex-user) or switched to other contraceptives (i.e., progestin-only method, injections, implants, LNG-releasing intrauterine devices, contraceptive patches) during the follow-up period.

NOMAC-E2: nomegestrol acetate and 17β-oestradiol; COC_LNG: levonorgestrel-containing combined oral contraceptives; WY: women-years; SD: standard deviation; BMI: body mass index.

Table 2. Selected cardiovascular risk factors at study entry by user cohort.

	NOMAC-E2	COCLNG	Total
Number (%) of women	11,179 (56.8)	8,504 (43.2)	19,683 (100)
DVT, n (%)	9 (0.08)	8 (0.09)	17 (0.09)
PE, n (%)	0 (0.00)	2 (0.02)	2 (0.01)
Myocardial infarction, n (%)	0 (0.00)	4 (0.05)	4 (0.02)
Stroke, n (%)	0 (0.00)	1 (0.01)	1 (0.005)
Treated high blood pressure, n (%)	123 (1.1)	67 (0.8)	190 (1.0)
Thrombophilia, n (%)	27 (0.2)	33 (0.4)	60 (0.3)
Other severe diseases, n (%)	290 (2.6)	219 (2.6)	509 (2.6)
Any surgery, n (%)	3,548 (31.7)	2,765 (32.5)	6,313 (32.1)
Current smokers, n (%)	3,208 (28.7)	2,625 (30.9)	5,833 (29.6)
Heavy smokers^a, n (%)	381 (3.4)	248 (2.9)	629 (3.2)
Family history of VTE, n (%)	273 (2.4)	201 (2.4)	474 (2.4)
Family history of ATE, n (%)	281 (2.5)	196 (2.3)	477 (2.4)

^a >15 cigarettes per day.

NOMAC-E2: nomegestrol acetate and 17β-oestradiol; COC_LNG: levonorgestrel-containing combined oral contraceptives; DVT: deep venous thrombosis; PE: pulmonary embolism; VTE: venous thromboembolism; ATE: arterial thromboembolism.

Table 3. Confirmed DVT of the lower extremities and PE in women without pre-defined risk factors^a at study entry by user (sub-)cohort.

	NOMAC-E2	COCLNG^b	COCother^c	OHC^c	Ex-user^c	Total
Number of WY	11,680	9,065	1,854	550	9,642	32,791
Confirmed DVT of the lower extremities and PE
Number	2	6	0	1	0	9
Incidence per 10,000 WY (95% CI)	1.7 (0.21–6.2)	6.6 (2.4–14.4)	0.00 (0.00–19.9)	18.2 (0.46–100.9)	0.00 (0.00–3.8)	2.7 (1.3–5.2)
Confirmed DVT of the lower extremities
Number	1	5	0	0	0	6
Incidence per 10,000 WY (95% CI)	0.86 (0.02–4.8)	5.5 (1.8–12.9)	0.00 (0.00–19.9)	0.00 (0.00–66.9)	0.00 (0.00–3.8)	1.8 (0.67–4.0)
Confirmed PE
Number	1	2	0	1	0	4
Incidence per 10,000 WY (95% CI)	0.86 (0.02–4.8)	2.2 (0.27–8.0)	0.00 (0.00–19.9)	18.2 (0.46–100.9)	0.00 (0.00–3.8)	1.2 (0.33–3.1)

^a Pregnant within 3 months of study entry, history of cancer/chemotherapy, increased genetic risk of VTE (e.g., Factor V Leiden, Protein S or C deficiency).

^b COC_LNG cohort includes 4 WY of >40μg EE use.

^c Data on these sub-cohorts are reported for completeness of information, but were not subjected to the present subgroup analysis.

NOMAC-E2: nomegestrol acetate and 17β-oestradiol; COC_LNG: levonorgestrel-containing combined oral contraceptives; COC_Other: combined oral contraceptives other than NOMAC-E2 or COC_LNG; OHC: other hormonal contraceptives; WY: women-years; DVT: deep venous thrombosis; PE: pulmonary embolism; CI: confidence interval.

Note. One woman in the COC_LNG cohort experienced both a DVT and a PE.

Table 4. All confirmed VTE by user (sub-)cohort.

	NOMAC-E2	COCLNG^a	COCother^c	OHC^c	Ex-user^c	Total
Number of WY	12,360	9,653	1,951	590	10,314	34,869
All confirmed VTEs
Number	4	7	1	1	1	14
Incidence per 10,000 WY (95% CI)	3.2 (0.88–8.3)	7.3 (2.9–14.9)	5.1 (0.13–28.5)	16.9 (0.43–94.0)	0.97 (0.02–5.4)	4.0 (2.2–6.7)
Idiopathic VTE^b
Number	3	7	1	1	1	13
Incidence per 10,000 WY (95% CI)	2.4 (0.50–7.1)	7.3 (2.9–14.9)	5.1 (0.13–28.5)	16.9 (0.43–94.0)	0.97 (0.02–5.4)	3.7 (2.0–6.4)

^a COC_LNG cohort includes 4 WY of >40μg EE use.

^b VTEs excluding those cases with acute risk factors such as pregnancy, delivery, trauma, immobilisation, long-haul travel, surgery, chemotherapy.

^c Data on these sub-cohorts are reported for completeness of information, but were not subjected to the present subgroup analysis.

NOMAC-E2: nomegestrol acetate and 17β-oestradiol; COC_LNG: levonorgestrel-containing combined oral contraceptives; COC_Other: combined oral contraceptives other than NOMAC-E2 or COC_LNG; OHC: other hormonal contraceptives; WY: women-years; VTE: venous thromboembolism; CI: confidence interval.

Table 5. Confirmed unintended pregnancies (contraceptive failure) by user (sub-)cohort.

	NOMAC-E2	COCLNG^a	COCother^c	OHC^c	Total
Number of WY	10,677	8,430	1,775	541	34,829
Confirmed unintended pregnancies
Number	13	13	5	1	32
Incidence per 100 WY (95% CI)	0.12 (0.06–0.21)	0.15 (0.08–0.26)	0.28 (0.09–0.66)	0.18 (0.005–1.0)	0.09 (0.06–0.13)
'Perfect HC use’^b
Number	3	5	1	1	10
Incidence per 100 WY (95% CI)	0.03 (0.006–0.08)	0.06 (0.02–0.14)	0.06 (0.001–0.31)	0.18 (0.005–1.0)	0.03 (0.01–0.05)
'Non-perfect HC use’ ^b
Number	10	8	4	0	22
Incidence per 100 WY (95% CI)	0.09 (0.04–0.17)	0.09 (0.04–0.19)	0.23 (0.06–0.58)	0.00 (0.00–0.68)	0.06 (0.04–0.10)

^a COC_LNG cohort includes 3 WY of >40 μg EE use.

^b ‘Perfect HC use’ – the reported use was compliant with the instructions on the package insert and no extenuating circumstances were present (e.g., diarrhoea, vomiting or the use of antibiotics). ‘Non-perfect HC use’ – the reported use was not compliant with the instructions on the package insert.

^c Data on these sub-cohorts are reported for completeness of information, but were not subjected to the present subgroup analysis.

NOMAC-E2: nomegestrol acetate and 17β-oestradiol; COC_LNG: levonorgestrel-containing combined oral contraceptives; COC_Other: combined oral contraceptives other than NOMAC-E2 or COC_LNG; OHC: other hormonal contraceptives; WY: women-years; CI: confidence interval.

Figure 1. Contraceptive failure by user (sub-)cohort and age category.

Data availability statement

The data supporting the findings of this study cannot be made available as containing proprietary information.