Extemporaneous combination therapy with nebivolol/ramipril for the treatment of hypertension: a real-world evidence study in Europe

Figures & data

Table 1. Attrition table for the inclusion in the cohorts of prevalent and incident users of the extemporaneous combination of nebivolol/ramipril (NR-EXC).

	Italian LPD	Italian LRx	German LRx	French LRx	Polish LRx	Hungarian NHIF
Patients with at least one prescription of NR-EXC during the selection period, n	13,467	230,527	177,402	60,471	272,376	58,476
Patients without hypertension diagnosis, n (%)	1624 (12.1)	n/a	n/a	n/a	n/a	n/a
Underage patients, n (%)	1 (0.0)	336 (0.1)	211 (0.1)	17 (0.1)	192 (0.1)	76 (0.1)
Prevalent users of NR-EXC, n (%)^a	11,842 (6.2)	230,191 (6.0)	177,191 (2.3)	60,454 (3.0)	272,184 (8.5)	58,412 (5.5)
Patients with a prescription of NR-EXC during the pre-selection period, n (%)	1953 (16.5)	61,094 (26.5)	69,549 (39.3)	15,335 (25.3)	48,077 (17.7)	21,794 (37.3)
Incident users of NR-EXC, n (%)^a	9889 (5.2)	169,097 (4.4)	107,642 (1.4)	45,119 (2.2)	224,107 (7.0)	36,618 (3.5)

Abbreviations. LPD, longitudinal patient database; LRx, longitudinal prescription database; NIHF, National Hospital Insurance Fund database; n/a, not available.

^a Percentages are calculated over the total number of patients with at least one prescription of “5 mg nebivolol” and/or “2.5/5/10 mg ramipril” during the selection period.

Figure 1. Distribution of incident users of the extemporaneous combination of nebivolol/ramipril (NR-EXC) by sex and country/database. Abbreviations. LPD, longitudinal patient database; LRx, longitudinal prescription database; NIHF, National Hospital Insurance Fund database.

Figure 2. Distribution of incident users of the extemporaneous combination of nebivolol/ramipril (NR-EXC) by age group and country/database. Abbreviations. LPD, longitudinal patient database; LRx, longitudinal prescription database; NIHF, National Hospital Insurance Fund database.

Figure 3. Distribution of incident users of the extemporaneous combination of nebivolol/ramipril (NR-EXC) by ramipril dosage. Abbreviations. LPD, longitudinal patient database; LRx, longitudinal prescription database; NIHF, National Hospital Insurance Fund database.

Table 2. Clinical characteristics of the incident users of the extemporaneous combination of nebivolol and ramipril (NR-EXC) from the Italian longitudinal patient database (LPD).

Patients’ characteristics	NR-EXC (N = 9889)
BMI (kg/m^2)
Mean (SD)	28.34 (5.35)
Median (p25, p75)	27.68 (24.72, 31.23)
Missing, n (%)	3434 (34.7)
BMI class, n (%)^a
Underweight (BMI < 20)	195 (3.0)
Norm weight (20 ≤ BMI < 25)	1579 (24.5)
Overweight (25 ≤ BMI < 30)	2581 (40.0)
Obese—Class I (30 ≤ BMI < 35)	1407 (21.8)
Obese—Class II (35 ≤ BMI < 40)	497 (7.7)
Obese—Class III (BMI ≥ 40)	196 (3.0)
Comorbidities, n (%)^b
Diabetes mellitus	1903 (19.2)
Dyslipidemia	1797 (18.2)
Cardiac dysrhythmias	780 (7.9)
Other forms of chronic ischemic heart disease	583 (5.9)
Acquired hypothyroidism	527 (5.3)
Gout	485 (4.9)
Asthma	334 (3.4)
Chronic kidney disease	323 (3.3)
Occlusion and stenosis of precerebral arteries	320 (3.2)
Nontoxic nodular goiter	283 (2.9)
Chronic bronchitis	242 (2.4)
Other and ill-defined cerebrovascular disease	228 (2.3)
Chronic airway obstruction, not elsewhere classified	223 (2.3)
Overweight and obesity	209 (2.1)
Heart failure	207 (2.1)
Co-prescriptions during pre-selection period, n (%)^c
Antithrombotics	3140 (31.8)
Lipid-lowering agents	2936 (29.7)
(Other) Agents acting on the renin-angiotensin system	2886 (29.2)
Calcium-channel blockers	2392 (24.2)
Nonsteroidal anti-inflammatory drugs	2377 (24.0)
Diuretics	1940 (19.6)
Antihyperglycemic drugs	1668 (16.9)
(Other) Beta-blocking agents	1322 (13.4)
Antidepressants	1118 (11.3)
Corticosteroids	954 (9.6)
Thyroid therapy	871 (8.8)
Antigout preparations	697 (7.0)
Antihypertensive	662 (6.7)
Organic nitrates	271 (2.7)
Antiarrhythmics	183 (1.9)
Number of co-prescriptions during pre-selection period, n (%)
0	1907 (19.3)
1	1984 (20.1)
2	1869 (18.9)
3	1447 (14.6)
4	1144 (11.6)
5	739 (7.5)
6	429 (4.3)
≥7	370 (3.7)
Co-prescriptions during follow-up period, n (%)^c
Antithrombotics	3846 (38.9)
Lipid-lowering agents	3547 (35.9)
(Other) Agents acting on the renin-angiotensin system	2804 (28.4)
Calcium-channel blockers	2548 (25.8)
Diuretics	2367 (23.9)
Nonsteroidal anti-inflammatory drugs	2251 (22.8)
Antihyperglycemic drugs	1790 (18.1)
Antidepressants	1276 (12.9)
(Other) Beta-blocking agents	1157 (11.7)
Corticosteroids	1048 (10.6)
Thyroid therapy	943 (9.5)
Antigout preparations	868 (8.8)
Antihypertensive	804 (8.1)
Organic nitrates	339 (3.4)
Antiarrhythmics	266 (2.7)
Cardiologic visit request, n (%)
No requests at all	5833 (59.0)
During baseline only	1940 (19.6)
During follow-up only	1325 (13.4)
Both during baseline and follow-up	791 (8.0)

Abbreviations. SD, standard deviation; P25, 25th percentile; P75, 75th percentile; BMI, body mass index.

Note: Comorbidities were measured during baseline period (6 months before the index date) while treatments measured during baseline and follow-up period (6 months following the index date); BMI was measured in the 12 months before the index date.

^aProportions calculated over the total number of patients with an available BMI value (n = 6455).

^bFor each comorbidity, % of patients with at least one registration; only frequencies ≥2% were reported.

^cFor each treatment, % of patients with at least one prescription; only frequencies ≥2% were reported.

Table 3. Treatment adherence of the incident users of the extemporaneous combination of nebivolol and ramipril (NR-EXC) from the Italian longitudinal patient database (LPD).

Characteristics	NR-EXC (N = 9889)
PDC by prescriptions
Mean (SD)	38.88 (27.62)
Median (p25, p75)	31.11 (15.56, 61.11)
Adherence level, n (%)
Low (PDC < 40%)	5572 (56.3)
Intermediate (40% ≤ PDC < 80%)	3224 (32.6)
High (PDC ≥ 80%)	1093 (11.1)

Abbreviations. PDC, proportion of days covered; SD, standard deviation; P25, 25th percentile; P75, 75th percentile.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article and its Supplementary Materials.