Evaluating the Effectiveness of an Additional Risk Minimization Measure to Reduce the Risk of Prescribing Mirabegron to Patients with Severe Uncontrolled Hypertension in Four European Countries

Figures & data

Figure 1 Number of mirabegron initiations per quarter year between January 2013 and December 2016 per country. Total number of initiations are shown for the pre-DHPC period, the DHPC intervention month (September 2015), and for the post-DHPC period.

Figure 2 Observed, predicted and counterfactual proportions of patients with severe or non-severe uncontrolled hypertension at mirabegron initiation, by country. EAC = Estimated absolute change, i.e. projected counterfactual proportion – predicted proportion based on the best fit model at mid-point of post-DPHC period (denoted with dashed vertical lines). The DHPC intervention month is denoted with solid vertical lines.

Table 1 Patient Characteristics

	Netherlands		Spain		UK		Finland
	Pre-DHPC N = 4,418 n (%)	Post-DHPC N = 3,124 n (%)	Pre-DHPC N = 12,584 n (%)	Post-DHPC N = 7,124 n (%)	Pre-DHPC N = 9,951 n (%)	Post-DHPC N = 7,497 n (%)	Pre-DHPC N = 3,412 n (%)	Post-DHPC N = 3,968 n (%)
Age, mean ± SD	66 ± 15	66 ± 15	69 ± 13	69 ± 13	65 ± 15	67 ± 15	71 ± 14	70 ± 14
Gender, Male	1,912 (43)	1,420 (45)	5,498 (44)	3,168 (44)	3,071 (31)	2,625 (35)	1,129 (33)	1,343 (34)
Hypertension status
Severe uncontrolled hypertension	27 (0.6)	8 (0.3)	42 (0.3)	30 (0.4)	46 (0.5)	33 (0.4)	44 (1.3)	74 (1.9)
Non-severe uncontrolled hypertension	700 (16)	431 (14)	1,578 (13)	811 (11)	1,488 (15)	1,173 (16)	442 (13)	534 (13)
Controlled hypertension	545 (12)	423 (14)	3,477 (28)	1,921 (27)	2,235 (22)	1,762 (24)	333 (10)	388 (10)
Normal blood pressure	1,836 (42)	1,274 (41)	4,623 (37)	2,686 (38)	4,202 (42)	2,971 (40)	1,190 (35)	1,325 (33)
Unconfirmed hypertension status	1,310 (30)	988 (32)	2,864 (23)	1,676 (24)	1,980 (20)	1,558 (21)	1,403 (41)	1,647 (42)
Comorbid conditions
Acute myocardial infarction (MI)^a	90 (2)	76 (2)	314 (2)	179 (3)	63 (1)	87 (1)	143 (4)	158 (4)
Ischemic heart diseases (excl. MI)^a	208 (5)	158 (5)	911 (7)	506 (7)	320 (3)	360 (5)	517 (15)	647 (16)
Cardiac arrhythmias^a	232 (5)	181 (6)	1,093 (9)	694 (10)	281 (3)	384 (5)	673 (20)	842 (21)
Congestive heart failure^a	104 (2)	75 (2)	414 (3)	249 (3)	118 (1)	139 (2)	212 (6)	258 (7)
Cerebrovascular events^a	267 (6)	204 (7)	1,209 (10)	699 (10)	489 (5)	542 (7)	558 (16)	587 (15)
Peripheral artery disease (PAD)^a	170 (4)	124 (4)	552 (4)	330 (5)	80 (1)	87 (1)	164 (5)	196 (5)
Chronic kidney disease (CKD)^a	230 (5)	209 (7)	965 (8)	615 (9)	682 (7)	666 (9)	79 (2)	101 (3)
Diabetes^ab	598 (14)	409 (13)	2,692 (21)	1,483 (21)	1,486 (15)	1,276 (17)	566 (17)	770 (19)
Hyperlipidaemia^ab	1,491 (34)	1,054 (34)	5,413 (43)	2,897 (41)	3,632 (36)	2,931 (39)	1,099 (32)	1,495 (38)
Chronic respiratory disease^ab	664 (15)	490 (16)	1,867 (15)	989 (14)	2,173 (22)	1,557 (21)	422 (12)	564 (14)

Notes: ^aAny time before starting mirabegron; ^bbased on treatment or diagnosis.

Table 2 Proportion of Mirabegron Initiations with Severe and Non-Severe Uncontrolled Hypertension Relative to DHPC Dissemination

		Netherlands	Spain	UK	Finland
Severe uncontrolled hypertension	Pre-DHPC % (95% CI)	0.61 (0.40–0.89)	0.33 (0.24–0.45)	0.46 (0.34–0.62)	1.29 (0.94–1.73)
	Post-DHPC % (95% CI)	0.26 (0.11–0.50)	0.42 (0.28–0.60)	0.44 (0.30–0.62)	1.86 (1.47–2.34)
	Estimated absolute % change^a	−0.36 (p=0.053)	0.12 (p=0.301)	−0.15 (p=0.251)	0.73 (p=0.016)
Non-severe uncontrolled hypertension	Pre-DHPC % (95% CI)	15.84 (14.78–16.95)	12.54 (11.97–13.13)	14.95 (14.26–15.67)	12.95 (11.84–14.13)
	Post-DHPC % (95% CI)	13.80 (12.61–15.06)	11.38 (10.66–12.14)	15.65 (14.83–16.49)	13.46 (12.41–14.56)
	Estimated absolute % change^a	−2.02 (p=0.038)	−1.04 (p=0.071)	0.75 (p=0.188)	−1.91 (p=0.219)^b

Notes: ^aEstimated absolute change is calculated as the projected counterfactual proportion – predicted proportion based on the best fit model at the mid-point of post-DPHC period (as indicated in Figure 2). ^bp-value pertains to change in level; time trend was retained in the model with p=0.034

Abbreviations: BP, blood pressure; IQR, interquartile range.

Table 3 Frequency of Blood Pressure Recordings Before and During Mirabegron Treatment

	Netherlands		Spain		UK		Finland
	Pre-DHPC	Post-DHPC	Pre-DHPC	Post-DHPC	Pre-DHPC	Post-DHPC	Pre-DHPC	Post-DHPC
All mirabegron initiations	N = 4,418	N = 3,124	N = 12,584	N = 7,124	N = 9,951	N = 7,497	N = 3,412	N = 3968
n (%) with BP record before initiation	1,747 (40)	1,228 (39)	7,135 (57)	3,909 (55)	5,720 (57)	4,505 (60)	1,133 (33)	1,331 (34)
Duration (months) of total mirabegron treatment^a, median (IQR)	5 (1–17)	2 (1–6)	8 (2–21)	3 (1–8)	10 (2–23)	4 (1–9)	8 (1–20)	3 (1–7)
Number of BP records per person-quarter year of treatment, median (IQR)	0.0 (0.0–0.4)	0.0 (0.0–0.4)	0.0 (0.0–0.9)	0.0 (0.0–0.9)	0.0 (0.0–0.6)	0.0 (0.0–0.7)	0.0(0.0–0.2)	0.0 (0.0–0.2)
Documented hypertension at mirabegron initiation^b	N = 1,272	N = 862	N = 5,097	N = 2,762	N = 3,769	N = 2,968	N = 819	N = 996
Duration (months) of total mirabegron treatment^a, median (IQR)	6 (1–18)	2 (1–6)	10 (3–22)	3 (1–8)	11 (3–23)	4 (1–8)	9 (3–19)	4 (1–8)
Number of BP records/per person-quarter year of treatment, median (IQR)	0.4 (0.0–1.1)	0.3 (0.0–1.3)	0.5 (0.0–1.2)	0.4 (0.0–1.2)	0.4 (0.0–0.9)	0.4 (0.0–1.1)	0.0 (0.0–2.3)	0.0 (0.0–2.4)

Notes: ^aMirabegron treatment including gaps < 12 months. ^bExcluding hypertension with unconfirmed blood pressure; Pre-DHPC person time was censored at DHPC dissemination date.

Abbreviations: BP, blood pressure; IQR, interquartile range.