Dataset Information

Association of Low-Dose Triple Combination Therapy With Therapeutic Inertia and Prescribing Patterns in Patients With Hypertension: A Secondary Analysis of the TRIUMPH Trial.

ABSTRACT:

Importance

Fixed-dose combination (FDC) therapies are being increasingly recommended for initial or early management of patients with hypertension, as they reduce treatment complexity and potentially reduce therapeutic inertia.

Objective

To investigate the association of antihypertensive triple drug FDC therapy with therapeutic inertia and prescribing patterns compared with usual care.

Design, setting, and participants

A post hoc analysis of the Triple Pill vs Usual Care Management for Patients With Mild-to-Moderate Hypertension (TRIUMPH) study, a randomized clinical trial of 700 patients with hypertension, was conducted. Patients were enrolled from 11 urban hospital clinics in Sri Lanka from February 2016 to May 2017; follow-up ended in October 2017. Data were analyzed from September to November 2019.

Interventions

Once-daily FDC antihypertensive pill (telmisartan, 20 mg; amlodipine, 2.5 mg; and chlorthalidone, 12.5 mg) or usual care.

Main outcomes and measures

Therapeutic inertia, defined as not intensifying therapy in those with blood pressure (BP) above target, was assessed at baseline and during follow-up visits. Prescribing patterns were characterized by BP-lowering drug class and treatment regimen potency. Predictors of therapeutic inertia were assessed with binomial logistic regression.

Results

Of the 700 included patients, 403 (57.6%) were female, and the mean (SD) age was 56 (11) years. Among patients who did not reach the BP target, therapeutic inertia was more common in the triple pill group compared with the usual care group at the week 6 visit (92 of 106 [86.8%] vs 124 of 194 [63.9%]; P < .001) and week 12 visit (81 of 90 [90%] vs 116 of 179 [64.8%]; P < .001). At the end of the study, 221 of 318 patients in the triple pill group (69.5%) and 182 of 329 patients in the usual care group (55.3%) reached BP targets. Among those who received treatment intensification, the increase in estimated regimen potency was greater in the triple pill group compared with the usual care group at baseline (predicted mean [SD] increase in regimen potency: triple pill, 15 [6] mm Hg; usual care, 10 [5] mm Hg; P < .001), whereas there were no significant differences at the week 6 or at week 12 visit. Clinic systolic BP level was the only consistent predictor of treatment intensification during follow-up. During follow-up, there were 23 vs 54 unique treatment regimens per 100 treated patients in the triple pill vs usual care groups, respectively (P < .001).

Conclusions and relevance

Triple pill FDC therapy was associated with greater rates of therapeutic inertia compared with usual care. Despite this, triple pill FDC therapy substantially simplified prescribing patterns and improved 6-month BP control rates compared with usual care. Further improvements in hypertension control could be achieved by addressing therapeutic inertia among the minority of patients who do not achieve BP control after initial FDC therapy.

Trial registration

ANZCTR Identifier: ACTRN12612001120864.

SUBMITTER: Wang N

PROVIDER: S-EPMC7376473 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of Low-Dose Triple Combination Therapy With Therapeutic Inertia and Prescribing Patterns in Patients With Hypertension: A Secondary Analysis of the TRIUMPH Trial.

Wang Nelson N Salam Abdul A Webster Ruth R de Silva Asita A Guggilla Rama R Stepien Sandrine S Mysore Jayanthi J Billot Laurent L Jan Stephen S Maulik Pallab K PK Naik Nitish N Selak Vanessa V Thom Simon S Prabhakaran Dorairaj D Patel Anushka A Rodgers Anthony A

JAMA cardiology 20201101 11

<h4>Importance</h4>Fixed-dose combination (FDC) therapies are being increasingly recommended for initial or early management of patients with hypertension, as they reduce treatment complexity and potentially reduce therapeutic inertia.<h4>Objective</h4>To investigate the association of antihypertensive triple drug FDC therapy with therapeutic inertia and prescribing patterns compared with usual care.<h4>Design, setting, and participants</h4>A post hoc analysis of the Triple Pill vs Usual Care Ma ...[more]

PMID: 32717045

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Project description:ImportanceCumulative exposure to high blood pressure (BP) is an adverse prognostic marker. Assessments of BP control over time, such as time at target, have been developed but assessments of the effects of BP-lowering interventions on such measures are lacking.ObjectiveTo evaluate whether low-dose triple combination antihypertensive therapy was associated with greater rates of time at target compared with usual care.Design, setting, and participantsThe Triple Pill vs Usual Care Management for Patients With Mild-to-Moderate Hypertension (TRIUMPH) trial was a open-label randomized clinical trial of low-dose triple BP therapy vs usual care conducted in urban hospital clinics in Sri Lanka from February 2016 to May 2017. Adults with hypertension (systolic BP >140 mm Hg and/or diastolic BP >90 mm Hg or in patients with diabetes or chronic kidney disease, systolic BP >130 mm Hg and/or diastolic BP >80 mm Hg) requiring initiation (untreated patients) or escalation (patients receiving monotherapy) of antihypertensive therapy were included. Patients were excluded if they were currently taking 2 or more blood pressure-lowering drugs or had severe or uncontrolled blood pressure, accelerated hypertension or physician-determined need for slower titration of treatment, a contraindication to the triple combination pill therapy, an unstable medical condition, or clinically significant laboratory values deemed by researchers to be unsuitable for the study. All 700 individuals in the original trial were included in the secondary analysis. This post hoc analysis was conducted from December 2020 to December 2021.InterventionOnce-daily fixed-dose triple combination pill (telmisartan 20 mg, amlodipine 2.5 mg, and chlorthalidone 12.5 mg) therapy vs usual care.Main outcomes and measuresBetween-group differences in time at target were compared over 24 weeks of follow-up, with time at target defined as percentage of time at target BP.ResultsThere were a total of 700 randomized patients (mean [SD] age, 56 [11] years; 403 [57.6%] women). Patients allocated to the triple pill group (n = 349) had higher time at target compared with those in the usual care group (n = 351) over 24 weeks' follow-up (64% vs 43%; risk difference, 21%; 95% CI, 16-26; P < .001). Almost twice as many patients receiving triple pill therapy achieved more than 50% time at target during follow-up (64% vs 37%; P < .001). The association of the triple pill with an increase in time at target was seen early, with most patients achieving more than 50% time at target by 12 weeks. Those receiving the triple pill achieved a consistently higher time at target at all follow-up periods compared with those receiving usual care (mean [SD]: 0-6 weeks, 36.3% [30.9%] vs 21.7% [28.9%]; P < .001; 6-12 weeks, 55.2% [31.9%] vs 33.7% [33.0%]; P < .001; 12-24 weeks, 66.0% [31.1%] vs 43.5% [34.3%]; P < .001).Conclusions and relevanceTo our knowledge, this analysis provides the first estimate of time at target as an outcome assessing longitudinal BP control in a randomized clinical trial. Among patients with mild to moderate hypertension, treatment with a low-dose triple combination pill was associated with substantially higher time at target compared with usual care.

Project description:Importance: The prescription of generic (non-proprietary) compared to brand-name drugs is increasing worldwide. In many developing and emerging countries, generics companies market products at similar costs as brand-name competitors benefiting from more flexible compliance rules and regulations for marketing their products in the health system. Together, this phenomenon may influence prescriber's behavior (e.g., maintaining the same treatment despite guideline's recommendations or despite evidence of disease progression). Objectives: To compare the prevalence of therapeutic inertia (TI) between primary prescription of brand-name vs. generic drugs in the management of MS in Argentina. Design: We conducted a population-based online study comprising 117 neurologists with expertise in MS. Participants answered questions regarding their clinical practice, most commonly prescribed disease modifying agents, and therapeutic choices of 10 simulated case-scenarios that assessed TI. Inertia was defined as the lack of treatment initiation or escalation despite evidence of clinical and radiological activity (8 case-scenarios, 720 individual responses). We created the generic-brand name score (GBS) according to the 5 most frequently prescribed generic (n = 16) vs. brand-name (n = 9) drugs for MS, where scores higher than 1 indicated higher prescription of generic drugs and scores lower than 1 indicated higher prescription of brand-name agents. Candidate predictors of prescribing generic drugs included demographic data, MS specialist vs. general neurologist, practice setting, years of practice, volume of MS patients, risk preferences, costs of annual treatment. Participants and setting: population-based prospective study using including neurologists who care for patients with multiple sclerosis across Argentina. Exposure: prescription of generic vs. brand-name MS drugs Main outcome of interest: Therapeutic inertia (TI), defined as lack of treatment escalation when goals are unmet. Secondary outcomes included factors associated with generic drug prescription and costs of MS treatment. Results: Ninety participants completed the study (completion rate 76.9%). TI was observed in 153 (21.3%) of participants' responses. The evaluation of aggregate responses revealed a mean GBS score (SD) of 3.44 (2.1), with 46 (51.1%) participants having a GBS equal to or higher than 1. Older age (OR 1.19; 95% CI 1.00-1.42), being a general neurologist (OR 3.91; 95% CI 1.19-12.8), and being more willing to take risks in multiple domains (SOEP score OR 1.06, 95% CI 1.01-1.12) were associated with higher prescription of generic drugs in MS care. Costs of treatment were not associated with prescribing generic drugs. There was no difference in the annual costs of MS treatment for primary prescribers of brand-name vs. generic drugs (67,500 US$ vs. 67,496 US$; p = 0.99). The evaluation of individual responses revealed that participants with higher prescription of generics-reflected by a higher GBS-had higher incident risk of TI (mean GBS 3.61 for TI vs. 2.96 for no TI; p < 0.001). Multivariate analysis revealed that a prescription of generic agents was associated with an increased incident risk of TI (OR 1.56; 95%CI 1.07-2.29). There was no difference in the annual costs of MS treatment for participants that exhibited TI vs. those without TI (67,426 US$ vs. 67,704 US$; p = 0.66). Conclusions: General neurologist, older age, and willingness to take risks were associated with increased prescription of generic drugs despite similar costs compared to brand-name agents. In our study, the prescription of generic-MS drugs was associated with a higher incident risk of therapeutic inertia.

Project description:BACKGROUND: Therapeutic inertia has been defined as the failure of health-care provider to initiate or intensify therapy when therapeutic goals are not reached. It is regarded as a major cause of uncontrolled hypertension. The exploration of its causes and the interventions to reduce it are plagued by unclear conceptualizations and hypothesized mechanisms. We therefore systematically searched the literature for definitions and discussions on the concept of therapeutic inertia in hypertension in primary care, to try and form an operational definition. METHODS: A systematic review of all types of publications related to clinical inertia in hypertension was performed. Medline, EMbase, PsycInfo, the Cochrane library and databases, BDSP, CRD and NGC were searched from the start of their databases to June 2013. Articles were selected independently by two authors on the basis of their conceptual content, without other eligibility criteria or formal quality appraisal. Qualitative data were extracted independently by two teams of authors. Data were analyzed using a constant comparative qualitative method. RESULTS: The final selection included 89 articles. 112 codes were grouped in 4 categories: terms and definitions (semantics), "who" (physician, patient or system), "how and why" (mechanisms and reasons), and "appropriateness". Regarding each of these categories, a number of contradictory assertions were found, most of them relying on little or no empirical data. Overall, the limits of what should be considered as inertia were not clear. A number of authors insisted that what was considered deleterious inertia might in fact be appropriate care, depending on the situation. CONCLUSIONS: Our data analysis revealed a major lack of conceptualization of therapeutic inertia in hypertension and important discrepancies regarding its possible causes, mechanisms and outcomes. The concept should be split in two parts: appropriate inaction and inappropriate inertia. The development of consensual and operational definitions relying on empirical data and the exploration of the intimate mechanisms that underlie these behaviors are now needed.

Project description:Aim Selexipag is an oral selective prostacyclin receptor agonist approved for treatment of patients with pulmonary arterial hypertension (PAH). In the present study, we aim to assess the safety and efficacy of selexipag in triple combination therapy with endothelial receptor antagonists (ERAs) and PDE5is for Chinese PAH patients. Methods and results A single center retrospective study was performed on group 1 PAH patients (n = 68) initiating triple combination therapy with selexipag from 1 February 2020 to 31 August 2021 in Qilu Hospital of Shandong University (Shandong, China). Adolescents, children, and PAH patients with unrepaired congenital heart disease were excluded. The French pulmonary hypertension network (FPHN) non-invasive risk assessment, echocardiogram parameters, and clinical data, including tolerability, safety, and death/hospitalization events associated with PAH, were collected. Of the 68 patients, 31 (45.6%) patients had tolerable side effects while only a single patient discontinued selexipag due to severe diarrhea. In the analysis of the efficacy set of 62 patients, the median selexipag treatment time from selexipag initiation to last risk assessment was 27 (21, 33) weeks. Compared to baseline parameters, the percentage of WHO FC III/IV decreased from 77.4% (48) to 24.2% (15) (p = 0.000), median 6-min walk distance (6MWD) increased 82 m [from 398 (318, 450) to 480 (420, 506) m; p = 0.000], and NT-proBNP levels decreased from 1,216 (329, 2,159) to 455 (134, 1,678) pg/mL (p = 0.007). Patients who improved to three low-risk criteria increased from 9.7 to 38.7%. Right ventricular diameter (RV) diameter also decreased and was accompanied by an improved tricuspid annular plane systolic excursion (TAPSE). Patients transitioning from subcutaneous treprostinil to selexipag continued to show improvements in WHO FC, 6MWD (404 ± 94 vs. 383 ± 127 m) and NT-proBNP levels (2,319 ± 2,448 vs. 2,987 ± 3,770 pg/mL). Finally, the 1-year event free survival rate was 96.7% for patients initiating the triple combination therapy within 3 years of PAH diagnosis. Conclusion Triple combination therapy with selexipag was safe and effective in Chinese PAH patients, which was confirmed by acceptable tolerability, and improved exercise capacity, right heart function, risk assessment, and prognosis.

Dataset Information

Association of Low-Dose Triple Combination Therapy With Therapeutic Inertia and Prescribing Patterns in Patients With Hypertension: A Secondary Analysis of the TRIUMPH Trial.

Importance

Objective

Design, setting, and participants

Interventions

Main outcomes and measures

Results

Conclusions and relevance

Trial registration

Publications

Association of Low-Dose Triple Combination Therapy With Therapeutic Inertia and Prescribing Patterns in Patients With Hypertension: A Secondary Analysis of the TRIUMPH Trial.

Similar Datasets

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