Single-pill Combination Therapy Research Articles

Participants' views of ultra-low dose combination therapy for high blood pressure: a mixed-methods study from the QUARTET trial.

Single-pill combination therapy containing four quarter-dose medications for high blood pressure improves BP control compared to monotherapy, however patient-reported acceptance of the quadpill as a treatment strategy remains undescribed. We collected within-trial feedback and interviewed participants from the quadruple ultra-low-dose treatment for hypertension (QUARTET) trial to characterise patient attitudes to this intervention. All trial participants were asked about ease and preference for the quadpill and provided an opportunity to give further comments on the trial at 12 weeks (trial primary endpoint) and 52 weeks extended follow-up. Separately, we used purposive and quota sampling for the semi-structured telephone interviews, with the resultant verbatim transcripts analysed using an inductive thematic analysis approach. Themes were re-evaluated after each successive interview, and at suspected data saturation, an additional interview conducted for confirmation. At 12 weeks follow-up, 502 of 591 (85%) participants responded to acceptability questions, and 359 of 417 (86%) responded at week 52. Most reported the trial capsule easy or very easy to take. From eight sites, 16 participants were interviewed between 5 August 2020 and 19 November 2020. All described a positive experience, preferred once-daily morning dosing and found routine facilitated adherence. Participants valued individual responsibility for adherence, and involvement of the general practitioner in blood-pressure management. Most reported capsule size did not deter adherence but desired a smaller capsule. Participants described a preference for minimising number and dosage of medications, reduced capsule size, and once-daily morning dosing. These findings suggest a preference for single-pill combination therapy for blood pressure lowering.

SINGLE-PILL, TRIPLE ANTIHYPERTENSIVE THERAPY IN RURAL SUB-SAHARAN AFRICA: PRELIMINARY EXPERIENCE

Objective: Arterial hypertension is worldwide the leading modifiable cardiovascular risk factor. Beside life-style changes, strong evidence supports the efficacy of pharmacological treatment in reducing the complications of hypertension. International guidelines have recommended single-pill, low-dose combinations as initial treatment strategy. We investigated whether management of hypertension through this approach is feasible and effective in a rural sub-Saharan Africa setting. Design and method: Diagnosis of hypertension was established over three sets of blood pressure measurements: during a community-based, house-to-house screening in 2020 and in 2022, and at the hypertension outpatient clinic. Blood pressure measurements were performed according to the ESH recommendations by trained personnel, using a validated, oscillometric device OMRON M7 IT-HEM-7322-E. In 98 individuals diagnosed to have arterial hypertension, once-daily, single-pill combination of olmesartan, amlodipine, and hydrochlorothiazide was prescribed at a dose suitable to their blood pressure values and clinical characteristics. They were instructed on its administration and potential side effects and encouraged towards lifestyle modifications. Treatment regimen was adjusted, if needed, at each outpatient clinic visit scheduled after 4, 8, 12, and 16 weeks Results: 79 patients (aged 61 [53-70] years; median and interquartile range) strictly adhered to the treatment schedule, while overall 19 individuals dropped-out (aged 70 [65-80] years) because of different reasons. About 20% were tobacco smokers and nearly all consumed alcohol. Blood pressure was <140/90 mm Hg after 4 weeks in 44 (56%), after 8 weeks in 62 (78%), after 12 weeks in 69 (87%), and after 16 weeks in 74 (94%) participants. Excellent tolerance was widely reported. Conclusions: Management of hypertension with once-daily, single-pill combination of olmesartan, amlodipine, and hydrochlorothiazide as initial treatment was feasible and effective also in a rural sub-Saharan setting, with very high rate of hypertension control in patients adherent to treatment. Our results provide real life evidence in favor of extensive implementation of single-pill combination therapy also in low- and middle-income countries where local Health Care Systems should include recommendation on their usage in national guidelines and should make them available also in rural and remote areas at low or no cost as reliable first-line treatment strategy

Uncontrolled hypertension and hypertensive urgency: One-year single-center emergency department experience.

The prevalence of uncontrolled hypertension remains a significant concern in public healthcare systems, including daily practices of emergency departments (ED). We aimed to characterize patients admitted to an ED for elevated blood pressure (BP) and to identify factors leading to hospitalization. This retrospective analysis included all patients admitted to an ED in a tertiary hospital in 2022 due to an acute BP rise without hypertensive emergencies. The studied group (n = 570) constituted 1.5% of all ED admissions in 2022. The median age was 67 years (Q1-Q3) (52-75), 68.9% were females. Systolic BP (200 mm Hg [180-212]) and diastolic BP (105 mm Hg [100-115]) at home were higher than during triage (173 mm Hg [160-190] and 95 mm Hg [84-103], respectively [P <0.0001]). Thirty-nine percent of the studied population had taken BP-lowering agents before ED admission (captopril in 91.8% of cases). In the ED, nitrendipine (54.2%), captopril (38.1%), furosemide (16.3%), urapidil (10.0%), and nitroglycerine (1.9%) were administered. Eventually, a median of 140/82 mm Hg BP was reached in the median time of 288 minutes (202-400). Hospitalization was necessary in 5.4% of patients. The need for furosemide or urapidil administration in the ED doubled the risk of hospitalization (OR, 2.0; P <0.01). Before ED admission, only 17.0% of patients received guidelines-recommended single-pill combination therapy, and 17.6% had already visited ED for uncontrolled hypertension (median of 388 days earlier). Elevated BP is a common reason for admission to the ED. Crucially, improvements in long-term hypertension treatment and education are needed to reduce the number of patients seeking ED care for elevated BP.

Abstract P318: Provider Barriers and Facilitators to Treatment Intensification for Patients With Uncontrolled Blood Pressure

Background: Hypertension is the leading cause of cardiovascular disease and premature death worldwide, however, therapeutic inertia, failure to intensify pharmacotherapy when blood pressure (BP) is not at goal, is a key obstacle to hypertension control. We aimed to identify barriers and facilitators to increasing the dose or adding a different antihypertensive medication class for patients with uncontrolled BP. Methods: We conducted a qualitative study of healthcare providers from Kaiser Permanente Southern California (KPSC). Using a stratified purposeful sampling approach, we identified 300 providers across 15 medical centers and specialties and with a mix of treatment intensification rates. In 2 separate waves, we emailed a letter of invitation to 150 eligible providers followed by 2 reminder emails each two weeks apart. We sought to conduct 30 semi-structured interviews about management of patients newly diagnosed with hypertension including use of single-pill combination therapy (SPC) (the recommended first-line therapy within KPSC), barriers to therapeutic intensification and use of home BP monitoring for treatment intensification decision making. We used rapid analysis methods to code responses and develop themes. Results: A total of 11 interviews were completed with providers from family medicine (n=7), internal medicine (n=3) and cardiology (n=1) who had an average of 6 years of practice within KPSC. The majority of providers reported using monotherapy as first-line treatment while SPC therapy was reserved for younger patients and those with baseline systolic BP &gt;160 mm Hg. Monotherapy was often preferred to help providers determine if the first-line medication is causing side effects. Nearly all providers reported maximizing the dose of one medication before adding another medication class. Providers ranked the barriers to intensifying patients’ treatment in order of importance as 1) side effects such as frequent urination, hyperkalemia, and hypotension, 2) nonadherence to the current antihypertensive medication regimen and patient preference/hesitancy, 3) comorbidities (e.g., kidney function), and 4) age-related factors such as memory loss and ability to complete follow-up labs. All providers reported using patients’ home BP readings for treatment decision-making with most recognizing that patients’ out-of-clinic BP may be lower than clinic BP. Conclusion: Providers embraced stepped-care treatment for newly diagnosed patients with hypertension with most preferring monotherapy as first-line treatment. Concerns with side effects, nonadherence to the medication regimen and shared decision-making are key factors in providers’ decisions to intensify therapy for patients with uncontrolled BP. Targeted interventions to address provider barriers to treatment intensification may be needed.

Optimizing antihypertensive care: exploring the therapeutic merits of single-pill combination therapy in antihypertensive management

Optimizing antihypertensive care: exploring the therapeutic merits of single-pill combination therapy in antihypertensive management

Effectiveness of Valsartan's Single-Pill Combination Therapies on Blood Pressure Control in Hypertensive Patients: Malaysian Single-Centre Real-World Experience.

Uncontrolled hypertension can cause cardiovascular disease and is an important public health issue. Single-pill combination (SPC) therapies possess combined blood pressure (BP)-lowering effect and may improve compliance to treatment. This study assessed the effectiveness of valsartan (Val)-based SPC therapies in achieving BP control in hypertensive patients. This was a retrospective study. Data were extracted from the hybrid medical records of patients from the Institut Jantung Negara (IJN), Malaysia. Adults with established diagnosis of hypertension and on prescription of Val-based SPC therapies as part of routine medical care from 1 January 2013 to 31 December 2018, with ≥ 1 year of follow-up were included. Primary endpoint was proportion of patients achieving therapeutic BP control (BP < 140/90 mmHg). Secondary outcomes included change from baseline (CFB) in systolic BP (SBP) and diastolic BP (DBP), and subgroup analysis was based on baseline SBP categories and presence of diabetes. Study included 409 hypertensive patients. The mean (standard deviation [SD]) age of the population was 65.1 (10.6) years old, with male predominance (61.6%). Proportion of patients achieving target BP between baseline and follow-up were 57.0% (P < 0.001). Mean CFB in SBP and DBP were recorded as 19.52 mmHg and 7.47 mmHg, respectively. Over half of the patients achieved the target BP in all subgroups categorised by SBP at baseline, except the subgroup of SBP 160 mmHg-179 mmHg. SPC therapies were continued in 97.3% of patients at 1-year follow-up. Patients using Val-based SPC therapies had significant reduction in BP with good tolerability, with 57% of patients achieving target BP over a prolonged 1-year follow-up period. Uptake of SPC therapy is warranted to improve patient care and outcomes in hypertension.

Ultra-Low Dose Multi-Drug Quadruple Single-Pill Combination For Hypertension.

Respected Madam, Patients with hypertension require a multi-drug regimen to manage hypertension. But, multi-drug management may lead to patients’ lower cohesion to drugs and multiple adverse effects. (1) On the contrary a single pill containing four drugs (calcium channel blockers, beta-blockers, angiotensin II receptor blockers, and thiazide diuretics) of low dosages may deliver the same outcomes with lesser inauspicious effects. Current hypertension guidelines of the American Heart Association categorically recommend using a combination of four drugs in to manage and control hypertension, preferably in single-pill preparations. (2) Most patients remain on a single-drug therapy with insubordinate control, despite the recommendations that most require single-pill combination therapy of four drugs for blood pressure management (3) A recent randomized control trial demonstrated that a combination of four blood pressure-reducing agents in a single-pill at lower doses provided a simple, safe and potent treatment that improved the patient’s cohesion to the drug. The quadruple combination consists of four drugs: calcium channel blockers, beta-blockers, angiotensin II receptor blockers, and thiazide diuretics. Quadruple therapy is proven to have many benefits, namely higher efficacy, fewer adverse effects, and fast acting. It is found to be cost-effective as compared to monotherapy of multi-drugs. It is also known that patients taking high doses of multiple drugs to control blood pressure would be at higher risk of facing adverse effects such as bradycardia, hypokalemia, metabolic alkalosis, and constipation being the most common ones. In contrast, quadruple therapy consists of low dosages and it’s a combination of drugs to be taken together which helps the patient to surpass the adverse effects and effectively lower the blood pressure. It is also noted that quadruple therapy has proved effective in primary hypertension as a trial on a quadruple single-pill combination showed that the single-pill combination effectively reduced blood pressure in patients with stage 1 hypertension (4). In light of the above evidence, healthcare professionals should know the benefits of using a single-pill quadruple therapy for managing hypertension instead of traditional monotherapy. Moreover, additional studies should be performed on the effectiveness of using quadruple therapy.

Estimating the impact of single pill combination therapy for hypertension: projections of patient outcomes in Italy.

Hypertension affects almost a third of the Italian population and is a major risk factor for cardiovascular disease. Management of hypertension is often hindered by poor adherence to complex treatment regimens. This analysis aimed to estimate the 10-year clinical outcomes associated with single pill combination (SPC) therapies compared with other treatment pathways for the management of hypertension in Italy. A microsimulation modeling approach was used to project health outcomes over a 10-year period for people with hypertension. Input data for four treatment pathways [current treatment practices (CTP), single drug with dosage titration then sequential addition of other agents (start low and go slow, SLGS), free choice combination with multiple pills (FCC) and SPC] were sourced from the Global Burden of Disease 2017 data set. The model simulated clinical outcomes for 1 000 000 individuals in each treatment pathway, including mortality, chronic kidney disease (CKD), stroke, ischemic heart disease (IHD) and disability-adjusted life years (DALYs). Through improved adherence, SPC was projected to improve clinical outcomes versus CTP, SLGS, and FCC. SPC was associated with reductions in mortality, incidence of clinical events, and DALYs versus CTP of 5.4%, 11.5%, and 5.7%, respectively. SLGS and FCC were associated with improvements in clinical outcomes versus CTP, but smaller improvements than those associated with SPC. Over 10 years, combination therapies (including SPC and FCC) were projected to reduce the burden of hypertension compared with conventional management approaches in Italy. Due to higher adherence, SPC was associated with the greatest overall benefits versus other regimens.

PRESCRIPTION OF SINGLE-PILL ANTIHYPERTENSIVE COMBINATION THERAPY

Objective: The need for polytherapy is common among people affected by arterial hypertension (AH). A single-pill combination is a response to decreased medication adherence, especially in elderly people often suffering from more than one disease, which tends to improve blood pressure control and cardiovascular outcomes. The aim of our study was to determine the frequency of use of a single-pill antihypertensive combination (SPC) therapy and possible differences in presence of comorbidities. Design and method: 324 hypertensive participants on pharmacological treatment were included in this research, of which 51.2% were men, and with an overall median age of 64 years (IQR = 17). For each participant undergoing 24-hour ambulatory blood pressure measurement, data about pharmacological therapy, weight, height and comorbidities such as chronic kidney disease (CKD) and diabetes mellitus (DM) were obtained from their most recent medical records combined with self reports. Body mass index (BMI) was calculated. Results: 148 (45.7%) participants were prescribed a SPC. Participants taking a SPC had lower presence of CKD (23.7% with CKD vs. 76.3% without CKD, p&lt;0.001). No significant difference was found in the presence of DM (p = 0.496). Another interesting finding was more frequent use of SPC therapy among patients with higher BMI (p = 0.029). Conclusions: The results show that less than half of the participants in our study were prescribed an SPC. From this we can conclude that more attention should be paid to educating people about the options for antihypertensive treatment and simplifying therapy regimen. Another point we should highlight is the limited availability of SPCs in the treatment of hypertension in patients suffering from CKD.

Age-specific differences in hypertension combination management and associated factors influencing treatment choice.

The current hypertension guideline emphasizes combination therapy, especially single-pill combination therapy (SPC). However, few studies compared the prevalence and factors associated with initial therapy choice across heterogeneous age groups in a current population. First, the authors consecutively identified 964 treatment naïve hypertensive patients in a large academic hospital from 01/31/2019 to 01/31/2020. All patients were grouped into (1) young aged, age<55; (2) middle-aged, 55≤age<65; and (3) older aged, age ≥65. The multivariable regression model examined the factors associated with the combination therapy by age group. Overall, 80 (8.3%) were young, 191 (19.8%) were middle, and 693 (71.9%) were older aged. Compared with older age, younger patients were more likely to be male, highly educated, regularly exercised, have metabolic syndrome, and less likely to have cardiovascular-related comorbidities, with a lower systolic but higher diastolic pressure. Only one in five patients used SPC, and the prevalence decreased with age. Besides hypertension grade, young patients without catheterization or echo test were less likely to receive multiple therapies, while older patients who were male with lower weight and lower risk levels were less likely to receive multiple therapies. In conclusion, combination therapy, especially SPC, was underused in the targeted hypertensive population. Our contemporary population study showed that young patients (<55) without a history of catheterization or echo examination and male older-aged (≥65) patients with low-risk classification were the population most likely to be neglected. Such information can help triage medical care resources in improving SPC use.

Adherence to Triple Single-Pill Combination of Perindopril/Indapamide/Amlodipine: Findings from Real-World Analysis in Italy.

Single-pill combination therapy for hypertension is recognized to improve adherence to treatment. However, less is known about the benefits of triple single-pill combinations. This retrospective observational analysis aimed to assess changes in adherence when treatment was switched from perindopril (PER)/indapamide (IND) + amlodipine (AML) to PER/IND/AML single-pill combination, in Italian clinical practice. This analysis used data extracted from administrative databases of Italian healthcare entities. Adult patients receiving PER/IND/AML were selected, and the prescription date was considered as the index date. Among them, those who had a prescription for PER/IND + AML during the 12months before the index date and a prescription of PER/IND/AML during 6months of follow-up were included. Adherence was calculated as the proportion of days covered (PDC: PDC < 40%, non-adherent; PDC = 40-79%, partially adherent; PDC ≥ 80%, adherent). Among the identified patients, 158 were exposed users and were included in the analysis. When patients were compared before and after switch to triple single-pill combination, the proportion of adherent patients was significantly higher with PER/IND/AML single-pill combination (75.3%) than with PER/IND + AML combination (44.3%) (P < 0.05). Conversely, the proportion of non-adherent patients was lower with the PER/IND/AML single-pill combination (14.6%) vs PER/IND + AML (17.7%) (P < 0.001). This real-world analysis showed that switching to a triple single-pill combination could offer an opportunity to improve adherence to antihypertensive treatment in real-life clinical practice.

Efficacy and safety of single pill combination of amlodipine and valsartan in hypertensive Saudi patients.

A significant global health issue that affects 25.5% of Saudi people is hypertension (HTN). According to international recommendations, most HTN patients require more than one therapy to reach their blood pressure targets (BP). Therefore, it would be preferable to utilize two medications from distinct classes separately or in a predetermined combination. According to recent studies, a single-pill combination (SPC) may be more efficient. This study evaluated the safety and tolerability of Amlodipine/Valsartan (Aml/Val) SPC in Saudi hypertensive patients, as well as the effectiveness of the medication. Observational research was done prospectively at the King Fahad Armed Forces Hospital in Jeddah, Saudi Arabia. The effectiveness of the treatment and the percentage of 159 hypertensive patients who achieved the target blood pressure values (140/90; 130/80 mmHg) among those with diabetes mellitus (DM), chronic kidney disease (CKD), other cardiovascular disorders, and responders were assessed from the beginning to the endpoint (week 23). According to the results, taking Aml/Val SPC significantly lowered all patients' baseline systolic and diastolic blood pressure readings by -17.97 and 8.58 mmHg, respectively. 43.4% of patients successfully met their BP therapeutic objectives by bringing their blood pressure levels back to normal, including 51.4% of patients under 65, 39.3% of patients with chronic kidney disease, and 26.2% of diabetic patients. Aml/Val 10/160 mg significantly lowers SBP, more than Aml/Val 5/160 mg (-13.32% vs. -9.00%, p<0.050). Vertigo (6.30%), respiratory tract infections (4.0%), and ankle edema (2.50%) were the most frequent adverse events. Aml/Val SPC therapy effectively lowered BP and had few side effects while being well-tolerated in people with hypertension.

Review of Long-Term Blood Pressure Control After Intracerebral Hemorrhage: Challenges and Opportunities.

Blood pressure (BP) is the most important modifiable risk factor for intracerebral hemorrhage (ICH). Elevated BP is associated with an increased risk of ICH, worse outcome after ICH, and in survivors, higher risks of recurrent ICH, ischemic stroke, myocardial infarction, and cognitive impairment/dementia. As intensive BP control probably improves the chances of recovery from acute ICH, the early use of intravenous or oral medications to achieve a systolic BP goal of <140 mm Hg within the first few hours of presentation is reasonable for being applied in most patients. In the long-term, oral antihypertensive drugs should be titrated as soon as possible to achieve a goal BP <130/80 mm Hg and again in all ICH patients regardless of age, location, or presumed mechanism of ICH. The degree of sustained BP reduction, rather than the choice of BP-lowering agent(s), is the most important factor for optimizing risk reduction, with varying combinations of thiazide-type diuretics, long-acting calcium channel blockers, ACE (angiotensin-converting enzyme) inhibitors or angiotensin receptor blockers, being the mainstay of therapy. As most patients will require multiple BP-lowering agents, and physician inertia and poor adherence are major barriers to effective BP control, single-pill combination therapy should be considered as the choice of management where available. Increased population and clinician awareness, and innovations to solving patient, provider, and social factors, have much to offer for improving BP control after ICH and more broadly across high-risk groups. It is critical that all physicians, especially those managing ICH patients, emphasize the importance of BP control in their practice.

TELMISARTAN/AMLODIPINE SINGLE-PILL COMBINATION THERAPY TO ACHIEVE BLOOD PRESSURE GOAL VALUES IN HYPERTENSIVE PATIENTS IN GPS’ PRACTICE – AN OBSERVATIONAL STUDY

Objective: Current ESC/ESH Guidelines suggests a simple therapeutic strategy to increase treatment effectiveness: the application of single pill combination (SPC) of a RAS inhibitor with a calcium channel antagonist or a diuretic as a first step. Our primary goal was to assess the percentage of patients reaching optimal BP goal (130/80 mmHg) after 12 weeks of SPC therapy with telmisartan/amlodipine according to office BP measurements in hypertensive patients treated by general practitioners (GPs) in regular clinical practice. We also examined the percentage of patients achieving primary target BP (&lt;140/90 mmHg). Design and method: After given informed consent, 729 patients with primary hypertension from 120 GP’s offices participated in this multicentre, observational, non-interventional, prospective study. Results: The average age of the patients was 62 ± 12 years, 357 patients (49.8%) of the population was male. The average office BP at baseline was 150 ± 17/88 ± 10 mmHg, and decreased to 130 ± 8.1/78 ± 6.1 mmHg at 12 week (p &lt; 0.05). Pulse rate has decreased as well (from 80 ± 9.8/min to 75 ± 6.3/min). At baseline, 10.1 % of the patients were at optimal systolic BP goal (&lt;130 mmHg), 15.8% at optimal diastolic BP goal (&lt;80 mmHg) and only 5.5% simultaneously at systolic and diastolic BP goal (&lt;130/80 mmHg). By the end of the observational period the percentage of patients reaching these optimal BP goal values increased to 51.6%, 54.1% and 33.0%, respectively. At baseline 19.2% of patients had BP less than 140/90 mmHg, which increased to 87.1% by the end of the study. Dose adjustments during the study were made in only 3 % of patients (n = 22). Patients tolerated SPC telmisartan/amlodipine well, 95% of the patients continued medication after study conclusion. Conclusions: The introduction of a SPC therapy of telmisartan/amlodipine increases the success rate of treatment during a relative short period. High proportion of patients were able to lower within 3 months their BP levels under 140/90 mmHg, however, only one third of the patients reached optimal target BP. Main possible reasons for this was the low rate of dose adjustment during the study. The study was sponsored by KRKA Hungary Ltd.

Use of fixed-dose combination antihypertensives in Germany between 2016 and 2020: an example of guideline inertia

BackgroundThe 2018 European Society of Cardiology (ESC)/European Society of Hypertension (ESH) guidelines for the management of hypertension highlight the importance of fixed-dose combinations (FDC) for the treatment of hypertension and recommend initial single-pill combination therapy in almost all patients. However, data on the implementation of these recommendations in clinical practice are scarce.MethodsData from the German Institute for Drug Use Evaluation (DAPI) were analyzed and extrapolated accounting for approximately 88% of Germany’s population (approximately 73.3 million subjects). All antihypertensive (AHT) FDC products available on the German market were included in the analyses. We examined the time course of dispensed packages between January 2016 and December 2020.ResultsFDCs accounted for 15.4% of all AHT in 2016 and for 10.9% in 2020. While dispensing of all AHT increased slightly from year to year (2016: 143.8 million, 2020: 153.2 million packs), dispensing of FDCs decreased from 22.2 million (2016) to 16.6 million (2020) packs. Dispensing of FDCs containing hydrochlorothiazide (HCT) declined considerably from 2016 to 2020 (Q1 2016: 4.65 million, Q4 2020: 3.13 million packs). Accordingly, the proportion of HCT-containing combinations in all FDCs decreased from 85.3 to 74.2% from Q1 2016 to Q4 2020. Patients younger than 80 years were prescribed FDCs more frequently (14.6% of all AHT, based on the entire evaluation period) than patients 80 years and older (10.0%). In both age groups, this proportion decreased continuously over time.ConclusionsAlmost 2 years following the release of the 2018 ESC/ESH guidelines, only 10.9% of the prescribed packs of antihypertensive drugs in 2020 were FDC products, documenting underutilization of current guideline recommendations on pharmacotherapy in hypertension. Structured programs to evidence-based decision support are required to improve guideline inertia and patient outcomes, eventually.Graphical abstract

Are We There Yet? Exploring the Use of Single-Pill Combination Therapy in the Management of Raised Blood Pressure in Australia

Single-pill combination (SPC) therapy is recommended as first-line therapy for most patients in global hypertension guidelines due to benefits of improved adherence and blood pressure (BP) control. We aimed to understand factors affecting SPC use in the management of raised BP in Australia. A mixed-method study comprising of qualitative (policy review and interviews) and quantitative (Pharmaceutical Benefits Scheme [PBS] data) approaches. Australian and international hypertension guideline recommendations regarding SPC use; the Australian registration and subsidy approval processes of SPCs; use of SPCs on the PBS; cost-analysis of PBS-listed SPCs compared to free-drug combinations; perceptions of healthcare providers towards SPCs. The 2016 Australian Heart Foundation's "Guideline for the diagnosis and management of hypertension in adults" does not recommend combination therapy (including SPCs) as first-line treatment. Additional challenges in the uptake of SPCs include: (1) the additional PBS requirements and barriers imposed for the listing of SPCs. (2) Script volumes for SPCs have not matched the rise in the number of SPCs listed for subsidy, have plateaued since 2016 and remained significantly lower than single constituent scripts. (3) SPCs are not subsidised by the PBS for initial treatment. Most SPCs provided substantial cost savings for individual patients compared to free-drug combinations. Health care providers were positive about the cost-saving and convenience of SPCs, however perceived negatives included inflexibility of SPCs during dose titration, medicine shortages, and potential adverse effects when initiating treatment with multiple drugs. The safety, efficacy and cost-saving potential of SPCs have been established in the literature but several roadblocks in the existing health system in Australia impede uptake. Interventions addressing these barriers may facilitate improved uptake, which may in turn improve blood pressure control in Australia.

Implementing Single-Pill Combination Therapy for Hypertension: A Scoping Review of Key Health System Requirements in 30 Low- and Middle-Income Countries.

Objective:The World Health Organization (WHO) included single-pill combination (SPC) antihypertensive medications on their 2019 essential medicines list (EML) to encourage uptake and improved hypertension control. We documented key national-level facilitators (SPCs on national EMLs, recommendation for SPCs in national hypertension guidelines and availability of SPCs on the market) supporting uptake of SPCs in the 30 most populous low- and middle-income countries (LMICs).Methods:A hierarchical information gathering strategy was used including literature and web searches, the use of organisational databases and personal communications with colleagues to obtain information on (1) whether SPC antihypertensives are on national EMLs, (2) whether SPC antihypertensives are recommended in national hypertension guidelines and (3) whether SPCs are available on the market.Results:Eleven of 30 LMICs had all facilitators in place being Egypt, Kenya, Nigeria, Sudan, China, the Philippines, Thailand, Iran, Argentina, Colombia and Mexico. Twenty-six countries had national hypertension guidelines (or similar) in place with SPCs being recommended in 18 of these. Apart from Afghanistan, SPCs were available on the market in all countries. The facilitator least present was the inclusion of SPC antihypertensives on national EMLs at 12 of 29 (Turkey does not have an EML).Conclusion:This study demonstrated that many LMICs have made significant progress in their uptake of SPC antihypertensives and several had included SPCs on their EMLs and guidelines prior to their inclusion on the WHO EML. Despite this progress, the uptake of SPC antihypertensives in LMICs could be improved including through their further inclusion on EMLs.

The Effects of Single Pill Combinations on Adherence and Blood Pressure Control in Hypertensive Patients.

Background:Hypertension is the most important risk factor for cardiovascular morbidity and mortality. Blood pressure control rates are as low as 17% to 31% in patients diagnosed with hypertension in high-income countries; control rates are likely poorer in low- to middle- and low-income countries. Blood pressure control rates are as low as 17% to 31% in patients diagnosed with hypertension in high-income countries; control rates are likely poorer in low- to middle- and low- income countries. Overall, 43% to 66% of patients fail to adhere to their prescribed antihypertensive medications, and after 1 year, ≈40% of patients with hypertension may stop their initial drug treatment.Objective:The aim of the study was to evaluate the effects of single pill combination antihypertensive drugs on the adherence to treatment, blood pressure control and cardiovascular events vs. free-combination therapy.Methods:We enrolled 192 adult hypertensive patients not older than 79 years, with untreated or uncontrolled hypertension despite previously receiving free combination antihypertensive therapy, between November 2020 and March 2022. Patients treated with single pill combination (SPC) were compared with an arm of the same size (n = 96) and matched by age and gender who received a standard free combination (FC) antihypertensive therapy.Results:There were significant reductions from baseline to month 6 of follow-up in office SBP in the SPC group vs. reduction in FC group (21.9 vs. 13.1 mmHg; p < 0.0001). There were significant reductions from baseline to month 6 of follow-up in office DBP in the SPC group vs. group with free-combination therapy (13.7 vs. 8.0 mmHg; p < 0.0001). At 6 months, 94 participants (98%) were still prescribed the SPC therapy. At the final 6-month study visit, 84.2% of patients in the SPC therapy group were adherent to the prescribed antihypertensive therapy vs. 52% of patients in the FC group. Target BP values (mean 24h ambulatory systolic/diastolic BP < 130/80 mmHg) were reached by more recipients of SPC than free-combination therapy (78.2% vs. 46.3%, p < 0.05) at month 6 of follow-up.Conclusion:Treatment with single pill combinations (SPC), is the emerging best practice for safe, effective, rapid, and convenient hypertension control. It improves the affordability, adherence and control of arterial hypertension.

Improving the Management of Hypertension by Tackling Awareness, Adherence, and Clinical Inertia: A Symposium Report.

Hypertension remains the leading cause of global mortality, with elevated systolic blood pressure (BP) leading to 10.8 million deaths each year. Despite this, only around 50% of individuals with hypertension are aware of their condition. Alongside low awareness rates, lack of patient adherence to medication and therapeutic inertia have been identified as factors contributing to the lack of hypertension control worldwide. This report summarizes presentations from the “one of a kind” Servier-sponsored symposium, Improving the Management of Hypertension: Acting on Key Factors, which was conducted as part of the European Society of Hypertension (ESH)-International Society of Hypertension (ISH) 2021 ON-AIR meeting. The symposium focused on how low awareness, therapeutic inertia, and nonadherence can be addressed by combining the experience of a patient with the expertise of physicians. May Measurement Month, the ongoing global BP measurement program, is raising awareness of hypertension in over 90 countries, and the 2018 European Society of Cardiology/ESH guidelines and the 2020 ISH guidelines now include recommendations that specifically address low adherence and therapeutic inertia, including involving patients in a shared decision-making process and the use of single-pill combination therapy. Understanding the role of emotion in decision making and addressing the different psychological states and attitudes in the patient’s “cycle of change” are key to effective shared decision making and improving adherence.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40256-021-00505-6.

Projecting the long-term benefits of single pill combination therapy for patients with hypertension in five countries

ObjectiveTo project the 10-year clinical outcomes associated with single pill combination (SPC) therapies compared with multi-pill regimens for the management of hypertension in five countries (Italy, Russia, China, South Korea and Mexico). MethodsA microsimulation model was designed to project health outcomes between 2020 and 2030 for populations with hypertension managed according to four different treatment pathways: current treatment practices (CTP), single drug with dosage titration then sequential addition of other agents (start low and go slow, SLGS), free choice combination with multiple pills (FCC) and combination therapy in the form of a single pill (SPC). Model inputs were derived from the Global Burden of Disease 2017 dataset. Simulated outcomes of mortality, chronic kidney disease (CKD), stroke, ischemic heart disease (IHD), and disability-adjusted life years (DALYs) were estimated for 1,000,000 patients on each treatment pathway. ResultsSPC therapy was projected to improve clinical outcomes over SLGS, FCC and CTP in all countries. SPC reduced mortality by 5.4% in Italy, 4.9% in Russia, 4.5% in China, 2.3% in South Korea and 3.6% in Mexico versus CTP and showed greater reductions in mortality than SLGS and FCC. The projected incidence of clinical events was reduced by 11.5% in Italy, 9.2% in Russia, 8.4% in China, 4.9% in South Korea and 6.7% in Mexico for SPC versus CTP. ConclusionsTen-year projections indicated that combination therapies (FCC and SPC) are likely to reduce the burden of hypertension compared with conventional management approaches, with SPC showing the greatest overall benefits due to improved adherence.