Identifying prescribing cascades in Alzheimer's disease and related dementias: The calcium channel blocker‐diuretic prescribing cascade

Abstract

Purpose: Prescribing cascades occur when a physician prescribes a new drug to address the side-effect of another drug. Persons with Alzheimer's disease and related dementias (ADRD) are at increased risk for prescribing cascades. Our objective was to develop an approach to estimating the proportion of calcium channel blockerdiuretic (CCB-diuretic) prescribing cascades among persons with ADRD in two U.S. health plans. Methods:We identified patients aged ≥50 on January 1, 2017, dispensed a drug to treat ADRD in the 365-days prior to/on cohort entry date. Patients had medical/ pharmacy coverage for 1 year before and through cohort entry. We excluded individuals with an institutional stay encounter in the 45 days prior to cohort entry and censored patients based on: disenrollment from coverage, death, or end of data. We identified incident and prevalent CCB use in the 183-days following cohort entry, and identified subsequent incident diuretic use among incident and prevalent CCBusers within 365-days from cohort entry.Results: There were 121 538 eligible patients. Approximately 62% were female, with a mean age of 79.5 (SD ±8.6). Overall 2.1% of the cohort experienced a prevalent CCB-diuretic prescribing cascade with 1586 incident diuretic-users among 36 462 prevalent CCB-users (4.3%, 95% CI 4.1-4.6%]); and there were161 incident diureticusers among 3304 incident CCB-users (4.9%, 95% CI 4.2-5.7%) (incident CCBdiuretic cascade).

Evaluation of the key prescription sequence symmetry analysis assumption using the calcium channel blocker: Loop diuretic prescribing cascade

“…These results also reaffirm the necessity of using a control group either by incorporating pre‐index prescribing of a marker drug (i.e., a PSSA) 10 or using of alternative medication not associated with the outcome using a cohort design 21 as a lack of a control group could result in an overestimation of attributing the marker drug to a prescribing cascade 22 …”

“…20 These results also reaffirm the necessity of using a control group either by incorporating pre-index prescribing of a marker drug (i.e., a PSSA) 10 or using of alternative medication not associated with the outcome using a cohort design 21 result in an overestimation of attributing the marker drug to a prescribing cascade. 22 There are a few limitations to note. First, findings of the prescribing cascade validation may not be generalizable to other health systems or other prescribing cascades, thus, while we demonstrate proof of concept of the symmetry assumption, explicit testing using similar methods as described here should be conducted for other PSSAs.…”

Prescribing cascades in community‐dwelling adults: A systematic review

“…Most studies ( n = 88) were retrospective cohort studies, 5 , 7 , 18 , 21 , 23 , 24 , 25 , 26 , 27 , 29 , 30 , 31 , 32 , 33 , 34 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , …”

Prescribing cascades in community-dwelling adults: a systematic review

“…In one study examining the CCB-loop diuretic prescribing cascade, an additional medical chart review was also conducted. 107 The suspected ADRs, symptoms or new diagnoses explored were broad-ranging (see Table 2) most commonly depression (n=13) 33,37,40,45,52,55,57,73,95,99,100,112,114 ; peripheral oedema (n=11) [5][6][7]28,36,64,81,98,[105][106][107]118 ; urinary incontinence (n=9). 24,26,41,44,50,53,75,81,119 and parkinsonism (n=9) 27,29,31,46,57,81,84,123,124…”

“…91,93,103 No association between drug pairs could be determined for several studies, largely due to either a crosssectional study design examining concurrent drug use, insufficient drug-pair sample size to determine a sequence ratio or reporting of incidence rates with no incidence rate ratio (labelled N/A in Figure 2). 6,21,25,43,46,53,55,64,81,114,116,117,123,125,126 Several studies reported at least one negative association between drug pairs, indicating a reduced likelihood of the second medication being initiated (see eTable 3 Supplementary materials). 33,60,[68][69][70]75,83,89,91,95,113 Modifiers of identified associations Older people (aged [?…”