RESUMEN
New approaches are needed to lower blood pressure (BP) given persistently low control rates. QUARTET USA sought to evaluate the effect of four-drug, quarter-dose BP lowering combination in patients with hypertension. QUARTET USA was a randomized (1:1), double-blinded trial conducted in federally qualified health centers among adults with hypertension. Participants received either a quadpill of candesartan 2 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg or candesartan 8 mg for 12 weeks. If BP was >130/>80 mm Hg at 6 weeks in either arm, then participants received open label add-on amlodipine 5 mg. The primary outcome was mean change in systolic blood pressure (SBP) at 12 weeks, controlling for baseline BP. Secondary outcomes included mean change in diastolic blood pressure (DBP), and safety included serious adverse events, relevant adverse drug effects, and electrolyte abnormalities. Among 62 participants randomized between August 2019-May 2022 (n = 32 intervention, n = 30 control), mean (SD) age was 52 (11.5) years, 45% were female, 73% identified as Hispanic, and 18% identified as Black. Baseline mean (SD) SBP was 138.1 (11.2) mmHg, and baseline mean (SD) DBP was 84.3 (10.5) mmHg. In a modified intention-to-treat analysis, there was no significant difference in SBP (-4.8 mm Hg [95% CI: -10.8, 1.3, p = 0.123] and a -4.9 mmHg (95% CI: -8.6, -1.3, p = 0.009) greater mean DBP change in the intervention arm compared with the control arm at 12 weeks. Adverse events did not differ significantly between arms. The quadpill had a similar SBP and greater DBP lowering effect compared with candesartan 8 mg. Trial registration number: NCT03640312.
Asunto(s)
Amlodipino , Antihipertensivos , Bencimidazoles , Compuestos de Bifenilo , Bisoprolol , Presión Sanguínea , Hipertensión , Tetrazoles , Humanos , Femenino , Masculino , Hipertensión/tratamiento farmacológico , Persona de Mediana Edad , Antihipertensivos/uso terapéutico , Antihipertensivos/efectos adversos , Antihipertensivos/administración & dosificación , Método Doble Ciego , Bencimidazoles/uso terapéutico , Bencimidazoles/efectos adversos , Bencimidazoles/administración & dosificación , Amlodipino/administración & dosificación , Amlodipino/efectos adversos , Amlodipino/uso terapéutico , Tetrazoles/uso terapéutico , Tetrazoles/efectos adversos , Tetrazoles/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Anciano , Resultado del Tratamiento , Bisoprolol/uso terapéutico , Bisoprolol/administración & dosificación , Indapamida/uso terapéutico , Indapamida/administración & dosificación , Indapamida/efectos adversos , Adulto , Quimioterapia CombinadaRESUMEN
BACKGROUND: In China, the prevalence of hypertension is high and the use of combination antihypertensive therapy is low, which contributes to inadequate blood pressure (BP) control. The availability of simplified treatments combining complementary BP-lowering agents may help more patients achieve their goals. METHODS: This Phase III, multicenter, randomized, double-blind, noninferiority study included Chinese adults with mild-to-moderate hypertension. Following a 1-month run-in on perindopril/indapamide bi-therapy, patients with uncontrolled systolic/diastolic BP (≥140/90âmmHg) were randomized to perindopril 5âmg/indapamide 1.25 mg/amlodipine 5âmg (Per/Ind/Aml) single-pill combination (SPC) or perindopril 4âmg/indapamide 1.25 mg plus amlodipine 5âmg (Per/Ind + Aml) for 6âmonths. Uptitration was permitted from month 2 onwards. The primary efficacy objective was the noninferiority of Per/Ind/Aml in lowering office systolic BP at 2âmonths. The secondary objectives included the effectiveness of SPC on diastolic BP, uptitration efficacy, and office BP control (systolic/diastolic <140/90âmmHg). A subgroup of patients participated in 24-h ambulatory BP monitoring (ABPM). RESULTS: A total of 532 patients were randomized: Per/Ind/Aml ( n â=â262) and Per/Ind + Aml ( n â=â269). Overall, the mean (±SD) age was 55.7â±â8.8âyears, 60.7% were male, and the mean office systolic/diastolic BP at baseline on Per/Ind was 150.4/97.2âmmHg. Systolic BP decreased in both groups at 2âmonths from baseline: -14.99â±â14.46âmmHg Per/Ind/Aml versus -14.49â±â12.87âmmHg Per/Ind +Aml. A predefined noninferiority margin of 4âmmHg was observed ( P â<â0.001). The effectiveness of the Per/Ind/Aml SPC was also demonstrated for all secondary endpoints. ABPM demonstrated sustained BP control over 24âh. Both treatments were well tolerated. CONCLUSIONS: Per/Ind/Aml is an effective substitute for Per/Ind + Aml, providing at least equivalent BP control over 24âh in a single pill, with comparable safety.
Asunto(s)
Amlodipino , Antihipertensivos , Hipertensión , Indapamida , Perindopril , Humanos , Amlodipino/administración & dosificación , Amlodipino/efectos adversos , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Indapamida/administración & dosificación , Indapamida/uso terapéutico , Masculino , Persona de Mediana Edad , Método Doble Ciego , Perindopril/administración & dosificación , Perindopril/uso terapéutico , Femenino , Antihipertensivos/administración & dosificación , Antihipertensivos/uso terapéutico , Antihipertensivos/efectos adversos , Anciano , Resultado del Tratamiento , Presión Sanguínea/efectos de los fármacos , China , Adulto , Combinación de Medicamentos , Quimioterapia Combinada , Pueblos del Este de AsiaRESUMEN
BACKGROUND: A combination of four ultra-low-dose blood pressure (BP) medications lowered office BP more effectively than initial monotherapy in the QUARTET trial. The effects on average ambulatory BP changes at 12âweeks have not yet been reported in detail. METHODS: Adults with hypertension who were untreated or on monotherapy were eligible for participation. Overall, 591 participants were randomized to either the quadpill (irbesartan 37.5âmg, amlodipine 1.25âmg, indapamide 0.625âmg, and bisoprolol 2.5âmg) or monotherapy control (irbesartan 150âmg). The difference in 24-h, daytime, and night-time systolic and diastolic ambulatory BP at 12âweeks along further metrics were predefined secondary outcomes. RESULTS: Of 576 participants, 289 were randomized to the quadpill group and 287 to the monotherapy group. At 12âweeks, mean 24-h ambulatory SBP and DBP were 7.7 [95% confidence interval (95% CI) 9.6-5.8] and 5.3 (95% CI: 6.5-4.1) mmHg lower in the quadpill vs. monotherapy group ( P â<â0.001 for both). Similar reductions in the quadpill group were observed for daytime (8.1/5.7âmmHg lower) and night-time (6.3/4.0âmmHg lower) BP at 12âweeks (all P â<â0.001) compared to monotherapy. The rate of BP control (24-h average BPâ<â130/80âmmHg) at 12âweeks was higher in the quadpill group (77 vs. 50%; P â<â0.001). The reduction in BP load was also more pronounced with the quadpill. CONCLUSION: A quadruple quarter-dose combination compared with monotherapy resulted in greater ambulatory BP lowering across the entire 24-h period with higher ambulatory BP control rates and reduced BP variability at 12âweeks. These findings further substantiate the efficacy of an ultra-low-dose quadpill-based BP lowering strategy.
Asunto(s)
Antihipertensivos , Monitoreo Ambulatorio de la Presión Arterial , Presión Sanguínea , Quimioterapia Combinada , Hipertensión , Humanos , Antihipertensivos/administración & dosificación , Antihipertensivos/uso terapéutico , Monitoreo Ambulatorio de la Presión Arterial/métodos , Masculino , Presión Sanguínea/efectos de los fármacos , Femenino , Persona de Mediana Edad , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Anciano , Bisoprolol/administración & dosificación , Bisoprolol/uso terapéutico , Amlodipino/administración & dosificación , Adulto , Indapamida/administración & dosificación , Indapamida/uso terapéuticoRESUMEN
Two recent large trials showed the potential of single pill combinations (SPCs) with ≥3 low-dose components among people with hypertension who were untreated or receiving monotherapy. In both trials, these 'hypertension polypills' were superior to usual care, achieving >80% BP control without increasing withdrawal due to side effects. However, there are no such products available for prescribers. To address this unmet need, George Medicines developed GMRx2 with telmisartan/amlodipine/indapamide in three strengths (mg): 10/1.25/0.625, 20/2.5/1.25; 40/5/2.5. Two pivotal trials are ongoing to support FDA submission for the treatment of hypertension, including initial treatment. These assess efficacy and safety of GMRx2 compared to: placebo, and each of the three possible dual combinations. Regulatory submissions are planned for 2024, with the aim of providing access to GMRx2 in developed and developing regions. Wider implementation of GMRx2-based treatment strategies will be guided by further research to inform access and appropriate scale up.
Asunto(s)
Hipertensión , Indapamida , Humanos , Antihipertensivos/uso terapéutico , Hipertensión/tratamiento farmacológico , Indapamida/farmacología , Indapamida/uso terapéutico , Presión Sanguínea , Resultado del TratamientoRESUMEN
OBJECTIVES: This analysis compared adherence, cardiovascular (CV) events and all-cause mortality incidence, and healthcare costs among hypertensive patients treated with perindopril (PER)/indapamide (IND)/amlodipine (AML) in single-pill combination (SPC) vs. multiple-pill combination, in a real-world setting in Italy. METHODS: In this observational retrospective analysis of Italian administrative databases, adult patients treated with PER/IND/AML between 2010 and 2020 were divided into two cohorts: single-pill vs. multiple-pill. Patient data were available for at least one year before and after index date. Propensity score matching (PSM) was applied to reduce selection bias. Adherence was defined as proportion of days covered: non-adherence, <40%; partial adherence, 40-79%, and adherence ≥80%. Mortality incidence and CV events as single, or composite, endpoints were evaluated after first year of follow-up. Healthcare cost analyses were performed from the perspective of the Italian National Health Service. RESULTS: Following PSM, the single-pill cohort included 12 150 patients, and the multiple-pill cohort, 6105. The SPC cohort had a significantly higher percentage of adherent patients vs. the multiple-pill cohort (59.9% vs. 26.9%, P â<â0.001). Following the first year of follow-up, incidence of all-cause mortality, and combined endpoint of all-cause mortality and CV events were lower in the SPC cohort compared with multiple-pill cohort. Average annual direct healthcare costs were lower in the single-pill cohort (2970) vs. multiple-pill cohort (3642); cost of all drugs and all-cause hospitalizations were major contributors. CONCLUSION: The SPC of PER/IND/AML, compared with multiple-pill combination, is associated with higher adherence to medication, lower incidence of CV events and mortality, and reduced healthcare costs.