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

Figures & data

Table 1. Patient attrition for inclusion in the european cohorts of prevalent and incident users of the extemporaneous combination of nebivolol and amlodipine (NA-EXC).

	Italian LPD	German DA	Italian LRx	German LRx	French LRx	Polish LRx	Hungarian NHIF
Patients with at least one prescription of NA-EXC during the selection period, n	13,616	6,633	257,578	155,373	84,456	186,651	131,458
Patients without hypertension diagnosis, n (%)	1,212 (8,9%)	1,345 (20,3%)	n/a	n/a	n/a	n/a	n/a
Underage Patients, n (%)	3 (0,0%)	0 (0,0%)	344 (0,1%)	168 (0,1%)	28 (0,0%)	190 (0,1%)	66 (0,1%)
Prevalent users of NA-EXC, n	12,401	5,288	257,234	155,205	84,428	186,461	131,392
Patients with a prescription of NA-EXC during the pre-selection period, n (%)	2,179 (17,6%)	684 (12,9%)	70,763 (27,5%)	58,110 (37,4%)	19,664 (23,3%)	31,309 (16,8%)	46,210 (35.2%)
Incident users of NA-EXC, n	10,222	4,604	186,471	97,095	64,764	155,152	85,182

Table 2. Clinical characteristics of incident users of the extemporaneous combination of nebivolol and amlodipine in Italy and Germany.

Patients Characteristics	ITALIAN LPD (N = 10,222)		GERMAN DA (N = 4,604)
BMI (Kg/m^2)
mean (SD)	28.75	(5.33)	29.52	(5.67)
median	28.08		28.93
p25, p75	25.18	31.62	25.65	32.66
missing, n (%)	3,495	(34.2)	2,430	(52.8)
BMI Class, n (%)^1
Underweight: BMI < 20	178	(2.6)	55	(2.5)
Normoweight: 20 ≤ BMI < 25	1,397	(20.8)	393	(18.1)
Overweight: 25 ≤ BMI < 30	2,742	(40.8)	806	(37.1)
Obese - Class I: 30 ≤ BMI < 35	1,591	(23.7)	583	(26.8)
Obese - Class II: 35 ≤ BMI < 40	582	(8.7)	228	(10.5)
Obese - Class III: BMI > 40	237	(3.5)	109	(5.0)
Comorbidities, n (%)^2
Diabetes mellitus	2,266	(22.2)	1,062	(23.1)
Dyslipidemia	1,943	(19.0)	988	(21.5)
Cardiac dysrhythmias	759	(7.4)	579	(12.6)
Other forms of chronic ischemic heart disease	670	(6.6)	608	(13.2)
Gout	660	(6.5)	129	(2.8)
Chronic kidney disease	543	(5.3)	277	(6.0)
Acquired hypothyroidism	542	(5.3)	240	(5.2)
Occlusion and stenosis of precerebral arteries	461	(4.5)	205	(4.5)
Asthma	363	(3.6)	279	(6.1)
Nontoxic nodular goiter	301	(2.9)	101	(2.2)
Chronic bronchitis	280	(2.7)	75	(1.6)
Chronic airway obstruction, not elsewhere classified	265	(2.6)	573	(12.4)
Other and ill-defined cerebrovascular disease	259	(2.5)	78	(1.7)
Atherosclerosis	226	(2.2)	115	(2.5)
Transient cerebral ischemia	211	(2.1)	58	(1.3)
Thyroiditis	205	(2.0)	52	(1.1)
Heart failure	182	(1.8)	371	(8.1)
Simple and unspecified goiter	106	(1.0)	216	(4.7)
Overweight and obesity	159	(1.6)	199	(4.3)
Other peripheral vascular disease	93	(0.9)	188	(4.1)
Edema (includes Peripheral Edema)	83	(0.8)	167	(3.6)
Coronary artery spasm	113	(1.1)	116	(2.5)
Old myocardial infarction	64	(0.6)	106	(2.3)
Late effects of cerebrovascular disease	14	(0.1)	97	(2.1)
Acute myocardial infarction	160	(1.6)	90	(2.0)
Co-prescriptions during pre-selection period, n (%)^3
Agents acting on the renin-angiotensin system	7,509	(73.5)	3,221	(70.0)
Antithrombotics	3,937	(38.5)	1,459	(31.7)
Lipid-lowering agents	3,539	(34.6)	1,395	(30.3)
Nonsteroidal anti-inflammatory drugs	2,560	(25.0)	801	(17.4)
Diuretics	2,287	(22.4)	1,355	(29.4)
Antihyperglycemic drugs	2,030	(19.9)	925	(20.1)
(Other) β-blocking agents	1,440	(14.1)	843	(18.3)
Antidepressants	1,226	(12.0)	510	(11.1)
(Other) Calcium-channel blockers	1,184	(11.6)	331	(7.2)
Antihypertensive	1,097	(10.7)	462	(10.0)
Corticosteroids	1,043	(10.2)	297	(6.5)
Antigout preparations	976	(9.5)	473	(10.3)
Thyroid therapy	949	(9.3)	817	(17.7)
Organic nitrates	342	(3.3)	298	(6.5)
Antiarrhythmics	263	(2.6)	81	(1.8)
Cardiac therapy	83	(0.8)	110	(2.4)
Number of co-prescriptions during pre-selection period, n (%)
0	961	(9.4)	650	(14.1)
1	1,673	(16.4)	675	(14.7)
2	1,897	(18.6)	807	(17.5)
3	1,850	(18.1)	766	(16.6)
4	1,548	(15.1)	642	(13.9)
5	1,131	(11.1)	461	(10.0)
6	645	(6.3)	339	(7.4)
≥7	517	(5.1)	264	(5.7)
Co-prescriptions during follow-up period, n (%)^3
Agents acting on the renin-angiotensin system	7,551	(73.9)	3,623	(78.7)
Antithrombotics	4,543	(44.4)	1,932	(42.0)
Lipid-lowering agents	4,078	(39.9)	1,786	(38.8)
Diuretics	2,692	(26.3)	1,832	(39.8)
Nonsteroidal anti-inflammatory drugs	2,390	(23.4)	771	(16.7)
Antihyperglycemic drugs	2,188	(21.4)	1,061	(23.0)
Antidepressants	1,357	(13.3)	608	(13.2)
Antihypertensive	1,335	(13.1)	624	(13.6)
Antigout preparations	1,179	(11.5)	538	(11.7)
Corticosteroids	1,170	(11.4)	375	(8.1)
(Other) β-blocking agents	1,130	(11.1)	333	(7.2)
Thyroid therapy	1,039	(10.2)	964	(20.9)
(Other) Calcium-channel blockers	811	(7.9)	258	(5.6)
Organic nitrates	380	(3.7)	288	(6.3)
Antiarrhythmics	325	(3.2)	97	(2.1)
Other cardiac preparations	129	(1.3)	97	(2.1)
Cardiac therapy	94	(0.9)	124	(2.7)
Cardiologic visit request, n (%)
No requests at all	6,160	(60.3)	n/a	n/a
During baseline only	1,969	(19.3)	n/a	n/a
During follow-up only	1,229	(12.0)	n/a	n/a
Both during baseline and follow-up	864	(8.5)	n/a	n/a

¹Proportions calculated over the total number of patients with an available BMI value, which was 6,727 (Italian LPD) and 2,174 (German DA). ²For each comorbidity, % of patients with at least one registration; only frequencies ≥2% in at least one DB were reported. ³For each treatment, % of patients with at least one prescription for that treatment; only frequencies ≥2% in at least one DB were reported. Age and Sex measured at Index Date; comorbidities measured during baseline period (6 months before the index date); other treatments measured during baseline period (6 months before the index date) and follow-up period (6 months following the index date); BMI measured in the 12 months before the index date. SD: Standard Deviation. p25: 25^th percentile. P75: 75^th percentile. BMI: Body Mass Index.

Figure 1. Visual representation of the extemporaneous combination and of the index date.

Figure 2. Incident users of the extemporaneous combination of nebivolol and amlodipine stratified by sex.

Figure 3. Incident users of the extemporaneous combination of nebivolol and amlodipine stratified by age group.

Figure 4. Incident users of the extemporaneous combination of nebivolol and amlodipine stratified by amlodipine dosage.

Table 3. Adherence to treatment of incident users of the extemporaneous combination of nebivolol and amlodipine in Italy and Germany.

	ITALIAN LPD (N = 10,222)		GERMAN DA (N = 4,604)
PDC by prescriptions
mean (SD)	41.91	(29.12)	62.21	(28.79)
median	31.11		55.56
p25, p75	15.56	65.56	43.33	91.67
Adherence level, n (%)
Low (PDC < 40%)	5,575	(54.5)	1,064	(23.1)
Intermediate (40% ≤ PDC < 80%)	3,051	(29.8)	1,930	(41.9)
High (PDC ≥ 80%)	1,596	(15.6)	1,610	(35.0)

PDC: Proportion of days covered. SD: Standard Deviation. p25: 25th percentile. P75: 75th percentile.