Adherence to heart failure management medications following cardiac resynchronization therapy

Figures & data

Table 1. Baseline demographics and characteristics of patients in 6-, 12-, and 24- month pre- and post-index periods.

	6-Months pre- and post-index	12-Months pre- and post- index	24-Months pre- and post- index
Patient characteristics at baseline^a	N = 4500	N = 2603	N = 829
Demographic characteristics
Age, mean ± SD [median]	56.1 ± 7.3 [58.0]	56.0 ± 7.3 [58.0]	56.2 ± 7.1 [58.0]
Female, n (%)	1422 (31.6)	847 (32.5)	282 (34.0)
Year of index date
2008	379 (8.4)	14 (0.5)	0.0 (0.0)
2009	825 (18.3)	525 (20.2)	12 (1.4)
2010	844 (18.8)	567 (21.8)	284 (34.3)
2011	902 (20.0)	635 (24.4)	298 (35.9)
2012	674 (15.0)	451 (17.3)	230 (27.7)
2013	589 (13.1)	407 (15.6)	5 (0.6)
2014	287 (6.4)	4 (0.2)	0.0 (0.0)
Clinical characteristics
Related cardiovascular conditions
Any cardiac dysrhythmia^b	2496 (55.5)	1518 (58.3)	517 (62.4)
Atrial fibrillation and flutter	1330 (29.6)	799 (30.7)	252 (30.4)
Ventricular fibrillation and flutter	195 (4.3)	111 (4.3)	42 (5.1)
Atrioventricular Block	500 (11.1)	317 (12.2)	89 (10.7)
Cardiomyopathy^c
Ischemic	1025 (22.8)	631 (24.2)	231 (27.9)
Non-Ischemic	3485 (77.4)	2112 (81.1)	679 (81.9)
Conduction disorders	1916 (42.6)	1220 (46.9)	386 (46.6)
Hypertensive heart disease	286 (6.4)	202 (7.8)	87 (10.5)
Left bundle branch block	1243 (27.6)	801 (30.8)	262 (31.6)
Right bundle branch block	155 (3.4)	110 (4.2)	33 (4.0)
Comorbidities^d
Quan-Charlson Comorbidity Index, mean ± SD [median]	2.3 ± 1.6 [2.0]	2.5 ± 1.6 [2.0]	2.6 ± 1.6 [2.0]
Cerebrovascular disease	442 (9.8)	324 (12.4)	129 (15.6)
Chronic kidney disease	426 (9.5)	246 (9.5)	74 (8.9)
Coronary heart disease	1152 (25.6)	719 (27.6)	254 (30.6)
Depression	175 (3.9)	148 (5.7)	56 (6.8)
Diabetes	1617 (35.9)	975 (37.5)	330 (39.8)
Dyslipidemia	2165 (48.1)	1456 (55.9)	525 (63.3)
Hypertension	2548 (56.6)	1687 (64.8)	590 (71.2)
Concomitant medications during pre-index period^e
Anticoagulants	1127 (25.0)	709 (27.2)	233 (28.1)
Antiplatelet agents	700 (15.6)	428 (16.4)	141 (17.0)
Calcium channel blockers	431 (9.6)	310 (11.9)	124 (15.0)
Digoxin	915 (20.3)	582 (22.4)	198 (23.9)
Statins	2234 (49.6)	1388 (53.3)	465 (56.1)

Abbreviation. SD, Standard deviation.

a n (%) were reported for categorical variables; mean ± SD [median] were reported for continuous variables.

b Patients may have other types of idysrhythmia than atrial or ventricular fibrillation or flutter (e.g. tachycardia).

c It is possible for patients to have both ischemic and non-ischemic cardiomyopathy.

d See Quan et al., “Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 Administrative Data.” Medical Care, vol. 43, no. 11, Nov. 2005.

e Medication use was determined based on the respective claims observed during the pre-index period only.

Figure 1. Adherence to HF medication classes for the 12 months pre-index and post-index periods. *Indicates p-value <.05. Abbreviations. ACE-I, Angiotensin-converting enzyme inhibitor; ARB, Angiotensin receptor blocker.

Table 2. Adherence to HF GDMT classes during the pre-index and post-index periods.

	Pre-index	Post-index	Percent change relative to pre-index (%)	p-Value^a
ACE-I
6-Month pre-index and post-index periods
Number of patients with ≥1 day on medication for both pre and post, n	2423	2423
Proportion of days covered^b
PDC, mean ± SD [median]	0.67 ± 0.29 [0.76]	0.75 ± 0.26 [0.86]	11.9	<.001
PDC ≥ 0.80, n (%)	1128 (46.6)	1440 (59.4)	27.7	<.001
12-Month pre-index and post-index periods
Number of patients with ≥1 day on medication for both pre and post, n	1497	1497
Proportion of days covered^b
PDC, mean ± SD [median]	0.58 ± 0.32 [0.63]	0.71 ± 0.28 [0.83]	22.4	<.001
PDC ≥ 0.80, n (%)	557 (37.2)	817 (54.6)	46.7	<.001
24-Month pre-index and post-index periods
Number of patients with ≥1 day on medication for both pre and post, n	517	517
Proportion of days covered^b
PDC, mean ± SD [median]	0.48 ± 0.34 [0.43]	0.66 ± 0.30 [0.77]	37.5	<.001
PDC ≥ 0.80, n (%)	148 (28.6)	239 (46.2)	61.5	<.001
ARB
6-Month pre-index and post-index periods
Number of patients with ≥1 day on medication for both pre and post, n	618	618
Proportion of days covered^b
PDC, mean ± SD [median]	0.66 ± 0.30 [0.76]	0.75 ± 0.28 [0.88]	13.6	<.001
PDC ≥ 0.80, n (%)	290 (46.9)	379 (61.3)	30.7	<.001
12-Month pre-index and post-index periods
Number of patients with ≥1 day on medication for both pre and post, n	354	354
Proportion of days covered^b
PDC, mean ± SD [median]	0.59 ± 0.32 [0.64]	0.73 ± 0.27 [0.84]	23.7	<.001
PDC ≥ 0.80, n (%)	132 (37.3)	194 (54.8)	47.0	.006
24-Month pre-index and post-index periods
Number of patients with ≥1 day on medication for both pre and post, n	104	104
Proportion of days covered^b
PDC, mean ± SD [median]	0.47 ± 0.33 [0.38]	0.65 ± 0.31 [0.77]	38.3	<.001
PDC ≥ 0.80, n (%)	26 (25.0)	42 (40.4)	61.5	.003
BB
6-Month pre-index and post-index periods
Number of patients with ≥1 day on medication for both pre and post, n	3224	3224
Proportion of days covered^b
PDC, mean ± SD [median]	0.67 ± 0.29 [0.74]	0.77 ± 0.24 [0.87]	14.9	<.001
PDC ≥ 0.80, n (%)	1422 (44.1)	1992 (61.8)	40.1	<.001
12-Month pre-index and post-index periods
Number of patients with ≥1 day on medication for both pre and post, n	1921	1921
Proportion of days covered^b
PDC, mean ± SD [median]	0.57 ± 0.31 [0.60]	0.75 ± 0.25 [0.85]	31.6	<.001
PDC ≥ 0.80, n (%)	653 (34.0)	1119 (58.3)	71.4	<.001
24-Month pre-index and post-index periods
Number of patients with ≥ 1 day on medication for both pre and post, n	632	632
Proportion of days covered^b
PDC, mean ± SD [median]	0.47 ± 0.33 [0.41]	0.72 ± 0.26 [0.82]	53.2	<.001
PDC ≥ 0.80, n (%)	162 (25.6)	337 (53.3)	108.0	<.001
Furosemide
6-Month pre-index and post-index periods
Number of patients with ≥1 day on medication for both pre and post, n	1986	1986
Proportion of days covered^b
PDC, mean ± SD [median]	0.60 ± 0.30 [0.63]	0.70 ± 0.28 [0.79]	16.7	<.001
PDC ≥ 0.80, n (%)	685 (34.5)	970 (48.8)	41.6	<.001
12-Month pre-index and post-index periods
Number of patients with ≥ 1 day on medication for both pre and post, n	1195	1195
Proportion of days covered^b
PDC, mean ± SD [median]	0.50 ± 0.32 [0.44]	0.64 ± 0.29 [0.71]	28.0	<.001
PDC ≥ 0.80, n (%)	316 (26.4)	488 (40.8)	54.4	<.001
24-Month pre-index and post-index periods
Number of patients with ≥ 1 day on medication for both pre and post, n	398	398
Proportion of days covered^b
PDC, mean ± SD [median]	0.38 ± 0.32 [0.24]	0.57 ± 0.31 [0.60]	50.0	<.001
PDC ≥ 0.80, n (%)	76 (19.1)	122 (30.7)	60.5	.003

Abbreviations. AA, aldosterone antagonists; ACE-I, Angiotensin-converting enzyme inhibitor; ARB, Angiotensin receptor blocker; BB: Beta-blocker; DRI, Direct renin inhibitors; PDC, Proportion of days covered; SD, Standard deviation.

a Comparisons of adherence between pre-index and post-index periods were conducted for paired data using the Wilcoxon sign-rank test for continuous variables and McNemar's test for categorical variables.

b Proportion of days covered (PDC) was calculated as the sum of the number of unique days during which the patient had all medications on hand, divided by a fixed time interval of either 6, 12, or 24 months as applicable.

Figure A1. Adherence to medication regimens 1 and 2 during the 12 months pre- and post-CRT implantation. On an average, mean PDC was lower for regimens 1 and 2 over the total course of the 12 months pre- versus 12-months post-CRT implantation. Though an increasing trend in PDC is observed leading up to CRT implantation and a slight decrease in PDC is observed following this point, PDC is observed to remain higher than observed pre-index levels (seen ≥3–4 months prior to CRT implantation) through the end of the post-CRT 12-month period.

Table A1. Adherence to HF medication regimens during the pre-index and post-index periods.

	Pre-index	Post-index	Percent change relative to pre-index (%)	p-Value^a
Medication regimen 1
(ACE-I/ARB/DRI + BB)
6-Month pre-index and post-index periods
Number of patients with ≥1 day on regimen for both pre and post, n	2597	2597
Proportion of days covered^b
PDC, mean ± SD [median]	0.59 ± 0.29 [0.62]	0.67 ± 0.27 [0.76]	14.8	<.001
PDC ≥ 0.80, n (%)	824 (31.7)	1178 (45.4)	43.0	<.001
12-Month pre-index and post-index periods
Number of patients with ≥1 day on regimen for both pre and post, n	1602	1602
Proportion of days covered^b
PDC, mean ± SD [median]	0.49 ± 0.30 [0.44]	0.64 ± 0.28 [0.72]	31.9	<.001
PDC ≥ 0.80, n (%)	371 (23.2)	639 (39.9)	72.2	<.001
24-Month pre-index and post-index periods
Number of patients with ≥1 day on regimen for both pre and post, n	540	540
Proportion of days covered^b
PDC, mean ± SD [median]	0.38 ± 0.30 [0.29]	0.60 ± 0.29 [0.67]	57.5	<.001
PDC ≥ 0.80, n (%)	88 (16.3)	178 (33.0)	102.3	<.001
Medication regimen 2
(ACE-I/ARB/DRI + BB + Furosemide)
6-Month pre-index and post-index periods
Number of patients with ≥1 day on regimen for both pre and post, n	1375	1375
Proportion of days covered^b
PDC, mean ± SD [median]	0.48 ± 0.29 [0.46]	0.55 ± 0.29 [0.57]	16.2	<.001
PDC ≥ 0.80, n (%)	266 (19.3)	379 (27.6)	42.5	<.001
12-Month pre-index and post-index periods
Number of patients with ≥1 day on regimen for both pre and post, n	860	860
Proportion of days covered^b
PDC, mean ± SD [median]	0.38 ± 0.29 [0.30]	0.50 ± 0.30 [0.51]	30.7	<.001
PDC ≥ 0.80, n (%)	117 (13.6)	179 (20.8)	53.0	<.001
24-Month pre-index and post-index periods
Number of patients with ≥1 day on regimen for both pre and post, n	298	298
Proportion of days covered^b
PDC, mean ± SD [median]	0.27 ± 0.27 [0.15]	0.43 ± 0.29 [0.41]	59.5	<.001
PDC ≥ 0.80, n (%)	22 (7.4)	43 (14.4)	95.5	.003

Abbreviations. ACE-I, angiotensin-converting enzyme inhibitor; ARB, Angiotensin receptor blocker; BB, Beta blocker; DRI, Direct renin inhibitors; PDC, Proportion of days covered; SD, Standard deviation.

a Comparisons of adherence between pre-index and post-index periods were conducted for paired data using the Wilcoxon sign-rank test for continuous variables and McNemar's test for categorical variables.

b Proportion of days covered (PDC) was calculated as the sum of the number of unique days during which the patient had all medications in the regimen on hand, divided by a fixed time interval of either 6, 12, or 24 months as applicable.