Use Of Single-pill Combinations Research Articles

New advances in the treatment and diagnosis of hypertension in primary care: a literature review

Background: Despite the availability of safe and effective antihypertensive drugs, hypertension continues to be a major risk factor for cardiovascular death and morbidity worldwide. This review explores the contemporary landscape of advances in hypertension (HTN) diagnosis and treatment, examining the discordant diagnostic thresholds proposed by American and European guidelines. Methods: An integrative approach was employed, analyzing pertinent literature from sources such as ScienceDirect, Google Scholar, and PubMed. Inclusion criteria encompassed studies on new advances in HTN diagnosis and treatment in primary care, published in English within the last five years (2018-2023). Results: Diagnostic innovations focus on the preference for automated sphygmomanometers and technological advancements, enhancing precision and reliability. Treatment advancements span neurovascular dimensions, including neuromodulation, and innovations in the renin-angiotensin-aldosterone system, showcasing promising drugs like finerenone and esaxerenone. Sodium-glucose cotransporter-2 inhibitors demonstrate efficacy beyond antidiabetic effects. The complexities of renal denervation and its challenges are scrutinized, emphasizing the need for further research. Clinical decision-making underscores risk stratification, lifestyle modifications, and the emerging use of single-pill combinations and individualized treatment plans. Conclusion: The review highlights the multidimensional approach required for optimal HTN management in primary care, encompassing diagnostic innovations, treatment advancements, and individualized strategies. Ongoing research is pivotal for refining diagnostic and therapeutic paradigms in hypertension management.

Therapy and guideline adherence at a multidisciplinary hypertension clinic: A prospective, observational study

BackgroundHypertension is highly prevalent and remains one of the most frequent and preventable causes of cardiovascular morbidity and mortality. Yet, suboptimal blood pressure control is common. Hypertension clinics might play an important role in improving target attainment, by targeting drug therapy adherence, improving guideline compliance and by involving pharmacists. ObjectivesWe aimed to characterize patient drug therapy adherence, prescriber guideline compliance and pharmacist interventions at the hypertension clinic. MethodsA prospective observational study was performed at the hypertension clinic of a large, academic hospital. Adult Dutch-speaking patients were eligible for inclusion. Following data were collected: patient demographics, medication use, patient adherence to prescribed antihypertensive drug therapies according to the BAASIS tool and prescriber compliance to the 2018 European Society of Cardiology (ESC) hypertension guidelines. ResultsA cohort of 108 patients was included with 51.9% male and aged 65 (IQR: 52–75) years. In total, 104 patients took at least 1 antihypertensive drug and 46 patients (44.2%) were classified as non-adherent with regard to their antihypertensive treatment; 82 patients (78.8%) had suboptimal blood pressure control. Compliance with the ESC guidelines was 66.3% prior to the consultation at the clinic and significantly increased to 77.9% thereafter (p = 0.0015). The clinical pharmacist performed a medication review for 27 patients with a total of 44 recommendations and an acceptance rate of 59.1%. ConclusionA visit to the multidisciplinary hypertension clinic improved prescriber guideline compliance and the use of single pill combinations. Involvement of a clinical pharmacist could be beneficial to further improve patient drug therapy adherence and guideline compliance.

Practical use of single pill combinations in the treatment of hypertension — an analysis focused on perindopril-based combinations

Practical use of single pill combinations in the treatment of hypertension — an analysis focused on perindopril-based combinations

USE OF ANTIHYPERTENSIVE COMBINATION THERAPY DURING THE COVID-19 PANDEMIC - A CROSS-SECTIONAL, NATION-WIDE STUDY 2019-2021

Objective: To assess changes in the use of antihypertensive drug combinations during the COVID-19 pandemic and the degree of adherence to the recommendations of more frequent use of combination therapy by ESC/ESH 2018 guidelines, data of all patients who filled a prescription for an antihypertensive drug in Poland were analyzed. Design and method: Patients who filled at least one prescription from ATC groups C02, C03, C07-10, C10BX in each of the years 2019, 2020 and 2021 were extracted from the obligatory prescription database of the National Health Service in Poland. This database covers all filled prescriptions in Poland. We have excluded from the analysis patients with diagnosis of heart failure. Combination therapy was assumed if prescriptions of two drugs overlapped for at least 40 days. In the case of the use of single pill combinations (SPC), the combined use of the individual substances included in the SPC was automatically recognized by the database. The frequencies were analyzed for the years 2019, 2020 and 2021 respectively. Results: In years 2019, 2020 and 2021 – 10,328,341, 9,478,949 and 9,637,595 patients fulfilled the inclusion criteria. One antihypertensive drug was used by 28.5, 28.0 and 28.3% of patients. The remaining patients used two antihypertensive drugs 27.4, 28.1 and 28.0%, three antihypertensive drugs 21.6, 22.2 and 22.1%, four antihypertensive drugs 12.7, 12.8 and 12.7% and 5 or more antihypertensive drugs 9.8, 9.0 and 9.0%. There was a modest increase in two drug SPC, which were used by 28.0, 28.7 and 29.8% of patients. There was an increase in the use of three drug SPC – 2.6%, 2.9% and 3.4% of patients. Conclusions: Although a modest, significant increase in the frequency of SPC use, both based on two and three antihypertensive drugs, was found, the COVID-19 pandemic and the ESC/ESH 2018 recommendations supporting the use of combination treatments, have had little impact on the prevalence of combination treatment in Poland.

REAL VS PERCEIVED BLOOD PRESSURE AND LDL-CHOLESTEROL CONTROL IN HYPERTENSIVE PATIENTS WITH DYSLIPIDEMIA: A CROSS-SECTIONAL EPIDEMIOLOGICAL STUDY IN ROMANIA (SNAPSHOT-1)

Objective: To assess cardiovascular (CV) risk measurement, blood pressure (BP) and LDL-cholesterol (LDL) control rates, in hypertensive patients with dyslipidemia, based on current recommendations of guidelines, and compare them with assessment provided by physicians. Design and method: Cross-sectional, observational, multicenter epidemiological study (SNAPSHOT-1), conducted in Romania, involved 130 investigators (general practitioners, cardiologists, and diabetologists), and included 2469 hypertensive patients with dyslipidemia. Results: Study population (65±10 years; 40.9% men) had the following characteristics: 12.1% smokers; 40.9% overweight and 45.2% obese (BMI 30.1±5.2 kg/m2); 80.0% had comorbidities, most frequently diabetes mellitus (45.0%), angina (28.8%), and chronic kidney disease (18.8%). Mean systolic / diastolic BP were 137.6±17.1 / 81.0±10.4 mmHg, total cholesterol was 199.1±54.3 mg/dL, HDL-C 51.2±15.9 mg/dL, LDL-C 118.4±46.4 mg/dL, and triglycerides 162.1±92.4 mg/dL. CV risk was estimated by the investigators as “high” or “very high” for 34.3% and 35.4% of patients, respectively, whereas calculated CV risk according to the SCORE chart 1 was “high” or “very high” for 12.6% and 81.8% of patients. Thus, only 41.5% of the investigators estimated CV risk accurately, while 54.2% underestimated it. Hypertension was treated in 98.1% of patients. BP was considered controlled by investigators in 71.2% of patients, whereas BP control based on European recommendations was achieved by only 25.0% of patients. Dyslipidemia was treated in 90.9% of patients. LDL-C was considered controlled by investigators in 46.1% of patients, whereas LDL-C control based on European recommendations was achieved by only 8.8% of patients. Both BP and LDL-C were considered controlled by investigators in 39.6% of patients, whereas both targets were controlled based on European recommendations in only 3.3% of patients (Figure). 44.7% of patients were treated with a single-pill combination for hypertension, and only 9.0% received treatment for both hypertension and dyslipidemia in a single pill. Conclusions: This study showed that CV risk is underestimated by physicians in more than half of patients. BP and LDL-C control is markedly overestimated by physicians, while real control rates remain very low. Use of single-pill combinations is still low.

Improved Persistence to Medication, Decreased Cardiovascular Events and Reduced All-Cause Mortality in Hypertensive Patients With Use of Single-Pill Combinations: Results From the START-Study.

Single-pill combination improves adherence and persistence to medication in hypertension. It remains unclear whether this also reduces cardiovascular outcomes and all-cause mortality. We analyzed whether single-pill combinations are superior to identical multiple pills on persistence to medication, cardiovascular outcomes, and all-cause mortality. This was a retrospective claims data (German AOK PLUS) analysis. Data from hypertensive patients ≥18 years treated with renin-angiotensin system combinations given as single pill or identical multipills covering the years 2012 to 2018 were analyzed and followed up to at least 1 year. After 1:1 propensity score matching, persistence to medication, cardiovascular events, and all-cause mortality were compared using non-parametric tests. Results were reported as incidence rate ratios and hazard ratios. After propensity score matching data from 57 998 patients were analyzed: 10 801 patients received valsartan/amlodipine, 1026 candesartan/amlodipine, 15 349 ramipril/amlodipine, and 1823 amlodipine/valsartan/hydrochlorothiazide as single pill or identical multipill. No relevant differences in patient characteristics were observed within the 4 groups. In all groups, a significant lower all-cause mortality, a significant a higher persistence to medication, a significant lower event rate in 15 out of 20 comparisons, and a tendency in the remaining 5 comparisons was observed under single pills compared with multipill combinations. Antihypertensive combination therapy reduces all-cause mortality and cardiovascular events when provided as single pill compared to identical drugs as multipills. This strongly supports the European Society of Cardiology/European Society of Hypertension and International Society of Hypertension guidelines recommending the use of a single-pill combination and thus should be more rigorously implemented into daily clinical practice.

PS-BPP05-3: ESTIMATED IMPACT OF MEDICATION DISPENSING REFORMS FOR PUBLIC HYPERTENSION TREATMENT COVERAGE IN INDIA

Background: Reforms to scale up hypertension treatment are needed in India, where < 20% of individuals with hypertension have controlled blood pressure. Limited medication supply and short prescription periods are two key barriers to increase hypertension treatment coverage in the public health system. Objective and Design: We estimated the benefits on medication coverage of three medication dispensing reforms to increase hypertension medication coverage in India's public health system. The reforms included: 1) Increased use of single pill combinations (SPC, i.e., multiple medication classes within a pill); 2) Focused procurement by reducing the number of antihypertensive medication classes (from n = 5 to n = 3) and selecting one medication within class (e.g., amlodipine for calcium channel blockers) to be procured; and 3) Extended prescription duration (from one to three months) to reduce medication refill frequency. The alternative scenarios assuming implementation of individual or combined reforms were compared to a base case scenario (no use of SPC, current procurement of multiple medications across classes, and 1-month prescription duration). For each scenario, the maximal number of patients that could receive adequate medication was estimated using constrained optimization with a fixed budget (i.e., the cost of procuring and dispensing medication for n = 1,000 patients in the base case scenario). Microsimulation was utilized to simulate medication dispensation for individual patients, each with a specific medication requirement. Key input data on prescription patterns and medication costs were derived from publicly available sources. Results: We estimated that, at the same total costs as the base case scenario, ∼25% more patients could receive sufficient medication if either the use of SPC increased or if the number of medication types procured and dispensed was restricted (Figure). Even greater medication coverage was estimated if both reforms were combined (+63%,) or if all patients were dispensed SPC (+80%). Extending the prescription duration from one to three months was estimated to alone increase the medication coverage by ∼40% and could substantially enhance the effects of the other reforms when combined (e.g., Figure). The combination of only SPC and 3-month prescription can almost triple the number of patients able to receive antihypertensive medication. Conclusion: In India's public health care system, without additional costs to the health system, three reforms (increasing SPC use, restricting the number of medication types, and extending prescription periods) could substantially increase the number of patients to receive hypertension medications. Our study encourages the combination of these reforms to improve hypertension management coverage in India.

Implementation of the 2018 ESC/ESH Guidelines for the management of hypertension in primary care: the HYPEDIA study

The HYPEDIA study aimed at evaluating the implementation of the 2018 European guidelines for treating hypertension in primary care. A nationwide prospective non-interventional cross-sectional study was performed in consecutive untreated or treated hypertensives recruited mainly in primary care in Greece. Participants’ characteristics, office blood pressure (BP) (triplicate automated measurements, Microlife BPA3 PC) and treatment changes were recorded on a cloud platform. A total of 3,122 patients (mean age 64 ± 12.5 [SD] years, 52% males) were assessed by 181 doctors and 3 hospital centers. In 772 untreated hypertensives (25%), drug treatment was initiated in the majority, with monotherapy in 53.4%, two-drug combination in 36.3%, and three drugs in 10.3%. Angiotensin receptor blocker (ARB) monotherapy was initiated in 30%, ARB/calcium channel blocker (CCB) 20%, ARB/thiazide 8%, angiotensin converting enzyme inhibitor (ACEi)-based 19%. Of the combinations used, 97% were in single-pill. Among 977 treated hypertensives aged <65 years, 79% had BP ≥ 130/80 mmHg (systolic and/or diastolic), whereas among 1,373 aged ≥65 years, 66% had BP ≥ 140/80 mmHg. ARBs were used in 69% of treated hypertensives, CCBs 47%, ACEis 19%, diuretics 39%, beta-blockers 19%. Treatment modification was decided in 53% of treated hypertensives aged <65 years with BP ≥ 130/80 mmHg and in 62% of those ≥65 years with BP ≥ 140/80 mmHg. Renin-angiotensin system blocker-based therapy constitutes the basis of antihypertensive drug treatment in most patients in primary care, with wide use of single-pill combinations. In almost half of treated uncontrolled hypertensives, treatment was not intensified, suggesting suboptimal implementation of the guidelines and possible physician inertia.

Use of single pill combinations in the treatment of arterial hypertension in Poland: The current practice and guidelines, the impact on reimbursement spending and patient co-payment.

BackgroundClinical guidelines recommend using single pill combinations (SPC) when initiating and intensifying the treatment of arterial hypertension (AH), which is not reflected in the Summaries of Product Characteristics (SMPC) for individual preparations. The drug reimbursement system in Poland (with a few exceptions) does not provide for reimbursement outside the indications specified in the SMPC. Therefore, it excludes the use of SPC under reimbursement. In 2020 the share of SPC in the treatment of AH amounted to 12.8% of unit volume and was lower than the 80% based on the guidelines of the Polish Society of Hypertension.MethodsUsing the data from a sample of pharmacies in Poland over the period November–December 2020, the potential was assessed of switching from existing AH therapy with monocomponent drugs containing selected combinations of active ingredients to the equivalent SPC.ResultsThe potential of switching from AH treatment in the analyzed period using monocomponent drugs with the equivalent SPC amounted to 19% of unit volume (a reduction of 212M units), with the highest switch potential (43.9%) for drugs containing amlodipine. The public payer’s savings would be EUR 12.3 million and patient savings would amount to EUR 5.0 million.ConclusionsEnabling reimbursement of SPC in Poland in line with the clinical guidelines can significantly increase the share of SPC in the treatment of AH, which will result in better health outcomes and a significant reduction in the payer’s drug reimbursement spending and will lower the financial barrier for patients to access this type of treatment.

Use of single pill anti-hypertensive combination medications in Cardiology Clinic of a Tertiary Health Institution in Nigeria

Background: Majority of patients with hypertension require 2 or more medications to provide adequate blood pressure (BP) control. In addition, contemporary guidelines on the management of hypertension favor the use of single-pill combinations (SPCs) as they simplify the treatment regimen and decrease the daily pill burden for patients, both of which are associated with improved adherence. In spite of this, there is a lack of data in sub-Saharan Africa on the frequency of use of SPC anti-hypertensive medications. Method: We prospectively collected detailed clinical data from 373 patients with primary diagnosis of hypertension attending the cardiology clinic of University of Abuja Teaching Hospital between 2016 and 2017. Results: Three hundred and seventy three patients with mean age of 50.6 ± 12.3 years and mean body mass index of 31.2 ± 6.5kg/m2 on anti-hypertensive treatment were evaluated. Baseline mean systolic and diastolic BPs were 161.1 ± 3.1mmHg and 95.4 ± 15.6mmHg respectively, while the mean pulse pressure was 56.6 ± 18.1mmHg. 212 (56.8%) where on SPCs, with 32.5% on angiotensin receptor blockers (ARBs) plus hydrochlorothiazide (HCTZ), 18.9% on angiotensin converting enzyme inhibitors (ACEIs) plus HCTZ, 9.9% on amlodipine (AML) plus ARB, 3.3% on AML plus ACEI, 3.8% on thiazide-like diuretic plus atenolol, 29.2% on HCTZ plus amiloride, and 2.4% on triple combination of AML+ARB+HCTZ. Conclusion: Our study has shown that over 50% of our patients were on SPC anti-hypertensive medications, with the most prescribed single pill combination being angiotensin receptor blocker plus thiazide diuretic.

Hypertension and Drug Adherence in the Elderly.

Hypertension is highly prevalent after the age of 65 years affecting more than 60% of individuals in developed countries. Today, there is sufficient evidence from clinical trials that treating elderly subjects with hypertension with antihypertensive medications has a positive benefit/risk ratio even in very elderly patients (>80 years). In recent years, partial or total non-adherence has been recognized as major issues in the long-term management of hypertension in all age categories. However, whether non-adherence is more frequent in hypertensive patients older than 65 years or not is still a matter of debate and the common belief is that adherence is lower in older than in younger patients. Are clinical data supporting this belief? In this brief review, we discuss the topic of drug adherence in elderly in the context of the medical treatment of hypertension. Studies show that drug adherence is actually better in patients aged 65 to 80 years when compared to younger hypertensive patients (<50 years). However, in very old patients (>80 years) the prevalence of non-adherence does increase. In this patients' group, there are specific risk factors for non-adherence such as cognitive ability, depression, and health believes, in addition to classical risk factors for non-adherence. One important aspect in the elderly is the prescription of potentially inappropriate medications that will interfere with the adherence to necessary treatments. In this context, an interesting new concept was developed few years ago, i.e., the process of deprescribing. Thus, today, in addition to conventional guidelines recommendations (use of single pill combinations, individualization of treatments), the evaluation of cognitive abilities, the regular assessment of potentially inappropriate medications, and the process of deprescribing appear to be three new additional steps to improve drug adherence in the elderly and thereby ameliorate the global management of hypertension.

Medication adherence in hypertension.

: Suboptimal adherence to antihypertensive medication is a major contributor to poor blood pressure control. Several methods, direct or indirect, are available for measuring adherence, including the recently developed biochemical screening, although there is no gold-standard method routinely used in clinical practice to accurately assess the different facets of adherence. Adherence to treatment is a complex phenomenon and several of the barriers to adherence will need to be addressed at the healthcare system level; however, when looking at adherence from a more practical side and from the practitioner's perspective, the patient-practitioner relationship is a key element both in detecting adherence and in attempting to choose interventions tailored to the patient's profile. The use of single-pill combinations enabling simplification of treatment regimen, the implementation of a collaborative team-based approach and the development of electronic health tools also hold promise for improving adherence, and thus impacting cardiovascular outcomes and healthcare costs.

Facing the Challenge of Lowering Blood Pressure and Cholesterol in the Same Patient: Report of a Symposium at the European Society of Hypertension.

A symposium held at the 29th European Meeting on Hypertension and Cardiovascular Protection in Milan, Italy, discussed the potential impact and long-term benefits of early active management of cardiovascular disease (CVD) risk in patients with hypertension, and potential barriers to this strategy. Hypertension often aggregates with other cardiovascular risk factors, exponentially increasing morbidity and mortality. While effective therapies to treat hypertension exist, a substantial number of patients still experience major cardiovascular events. Two major issues account for these disappointing results: interventions initiated too late in the disease trajectory and lack of effective translation of the research findings into daily clinical practice. Results from genetic studies suggest that lifetime exposure to lower blood pressure (BP) and cholesterol levels due to protective gene mutations, can provide greater cardiovascular benefits than middle-/late-age interventions. Clinical guidelines suggest adding statins to BP-lowering therapies for further cardiovascular benefits in most hypertensive patients; however, real-world data show that physicians’ compliance with these recommendations and patients’ adherence to BP- and lipid-lowering treatments remain poor, resulting in poor risk factor control and an increased risk of adverse outcomes. The use of single-pill combinations (SPC) can partially mitigate these issues, as they are associated with increased patient adherence and improved BP control. Treatment with SPC has been recommended in the European Hypertension Guidelines, but optimization of the total CVD risk may need adoption of more ambitious treatment strategies aimed to deliver single pills that control multiple CVD risk factors. Amlodipine, perindopril and atorvastatin have been shown to improve BP and lipid levels to a great extent when given separately, and this combination has also been shown to improve cardiovascular outcomes. Overall, early intervention in patients with hypertension with use of an effective, high-intensity cardiovascular risk reduction regimen and attention to medication adherence through reducing pill burden are likely to result in optimal outcomes.

Single-pill combinations (SPCs) and treatment of arterial hypertension in Poland. Expert consensus statement of the Polish Society of Hypertension and Polish Cardiac Society Working Group on Cardiovascular Pharmacotherapy.

The reasons for the publication of current expert consensus statement after 4 years from the previous one are: the growing number of evidence on the benefits of the use of single-pill combinations (SPCs) in hypertension (also with concomitant dyslipidaemia), the extension of indications for their use in the hypertension management algorithm and the emergence in recent years after the publication of Polish Society of Hypertension experts' position statement in 2013 of new types of SPCs available to doctors in Poland, including triple-drug combinations of antihypertensives and the so-called "hybrids" SPCs containing not only antihypertensive drugs but also statins. The current position statement of experts summarizes the progress of knowledge and practical application of SPCs of antihy-pertensives in Poland. It seems that there will be a long gap in the introduction of new classes of antihypertensive drugs. The only noticeable progress in the pharmacotherapy of hypertension in the last 15 years, which may explain some increase in the effectiveness of blood pressure control in patients, is more common use of SPCs of antihypertensive drugs. Analysis of European Society of Hypertension (ESH) experts' lectures during this year's ESH 2017 Annual Meeting in Milan suggests that the next edition of the 2018 ESH Guidelines may include major changes in the antihypertensive therapy algorithm, suggesting the need for initiation of pharmacologic treatment with combination therapy, i.e. SPCs, in most patients with hypertension. Combination of an angiotensin converting enzyme (ACE) inhibitor + calcium antagonist should be considered optimal in patients with high and very high cardiovascular risk. Undoubtedly, the position of this combination is due to the ACCOM-PLISH trial in which such SPCs werefound to be more effective in reducing cardiovascular risk than SPCs composed of an ACE-inhibitor + thiazide diuretic. As a result of gradually increasing popularity of combined drugs, further SPCs that meet the criteria for optimal combination of antihypertensive drugs emerged in Poland between 2012 and 2017. Two of them provided the possibility of using SPCs in patients who do not need or should not use renin-angiotensin-aldosterone inhibitors. An interesting alternative is the SPC which contains antihypertensive agents along with other drugs used in cardiovascular prevention: statins and acetylsalicylic acid. This direction in the evolution of pharmacotherapy of hypertension is approaching the concept of "polypill". In the opinion of the authors, the use of SPCs in antihypertensive therapy will increase in Poland, which may contribute to further improvement of pressure control in our country. At present, almost all useful anti-hypertensive agents are available in the form of two-drug SPCs. The combination of a sartan with beta-blocker for hypertensive patients with cardiac hypertrophy who do not tolerate ACE inhibitors and a "hybrid" SPCs of an ACE inhibitor + statin are still expected. Three-drug combinations: ACE inhibitor + beta-blocker + calcium antagonist, for patients with hypertension and coronary artery disease requiring intensive therapy, and ACE inhibitor + beta-blocker + statin, which will enable SPCs therapy for most patients, would also be useful.

PP.01.08] SINGLE-PILL VERSUS FREE ANTIHYPERTENSIVE COMBINATION USE BY GENERAL PRACTITIONERS IN IN BELGIUM AND LUXEMBURG

Objective: Studies suggest that the use of single-pill combinations could improve therapeutic adherence and blood pressure (BP) control in hypertensive patients. We examined the use of single-pill or free antihypertensive drug combinations, BP control, and attitude towards prescription of single-pill combinations in current general practice. Design and method: Between January 2015 and September 2016, 742 general practitioners in Belgium and Luxemburg retrospectively collected data from 8006 consecutive hypertensive patients recently seen in their routine practice and taking at least two antihypertensive drugs. Results: Patients (mean age 67 ± 22 years [SD], 54% men, 37% with diabetes mellitus, 37% with a previous cardiovascular event) were treated with two (n = 4549), three (n = 2470) or more than three (n = 987) antihypertensive drugs. Combinations were free (n = 3089), single-pill (n = 2713) or mixed (n = 2204) (93 missing data). Blood pressure was 141/82 ± 21/11 mm Hg (mean ± SD). According to the 2013 ESH/ESC Guidelines, control rates were: systolic BP 47%, diastolic BP 70%, and both systolic and diastolic BP 42%. Estimation by the GPs of both systolic and diastolic BP control rate was 61%. Actual control rates were comparable whatever the type of combination. Blood pressure control was better in patients with low cardiovascular risk compared to patients with high risk (respectively 43% vs 33% for systolic BP control and 63% vs 47% for diastolic BP control). Patients treated with single-pill combinations were younger and had a low cardiovascular risk. In 54% (n = 4361) of the patients, physicians considered to prescribe a single-pill combination. In 1452 (18%) patients, they were willing to switch to a single-pill 2-drug combination, and in 2508 (31%) patients, they were willing to switch to a single-pill 3-drug combination. Reasons were improved adherence (71%) and better BP control (69%). Conclusions: In patients requiring at least two antihypertensive drugs, BP control rate remains low and is overestimated by GPs. Free combinations remain largely used although many GPs seem prone to switch free to single-pill combinations. Treatment simplification could improve adherence and BP control rate, which has in turn been shown to lead to reduced morbidity and mortality.

Antihypertensive Combination Treatment: State of the Art.

An adequate control of blood pressure is essential to reduce the risk of target organ damages and cardiovascular events in patients with hypertension. Yet, it is well recognized that a substantial proportion of treated patients remain hypertensive despite treatment. Several reasons have been evoked to explain why so many patients are not adequately controlled. Among them, medical inertia, a poor long-term adherence, and the need to prescribe several antihypertensive drugs to reach the target blood pressure have been identified as major limitations to the success of antihypertensive therapy. In this context, the use of single-pill combinations (SPC) containing two or three drugs in one pill has an important role in reducing the impact of some of these issues. Indeed, the use of SPC enables to reduce the pill burden and to improve the treatment efficacy without increasing the incidence of side effects. However, besides their major advantages, SPC have also some limitations such as a possible lack of flexibility or a higher cost. The purpose of this review is to discuss the place of SPC in the actual management of hypertension. The active development of new single-pill combinations in last years can be considered as a significant improvement in the physicians' capacity to treat hypertension effectively.

Simplified therapeutic intervention to control hypertension and hypercholesterolemia

Notwithstanding improving rates of hypertension control in North America, management of patients with both hypertension and dyslipidemia remains problematic. Based on evidence of improved control utilizing a simplified algorithm for management of hypertension (STITCH), we questioned whether a simplified comprehensive treatment algorithm featuring initial use of single-pill combinations (SPCs) would improve management of participants with both hypertension and dyslipidemia. We randomized 35 primary care practices in Ontario to either Guidelines-care (following current Canadian guidelines) or STITCH2-care (following a treatment algorithm featuring SPCs). Practices each enrolled up to 50 participants with at least one risk factor above target at entry based on Canadian guidelines for BP and LDL-cholesterol control. The primary endpoint was achieving targets for both hypertension and dyslipidemia control after 6 months, assessed at the practice level. The primary endpoint was achieved in 31.3% of participants in STITCH2-care practices, compared with 28.1% in Guidelines-care practices, yielding a difference of 3.2% (P = 0.63). Notably, STITCH2-care practices had a significantly greater reduction in SBP while LDL-cholesterol reduction was only marginally greater in STITCH2 practices. The STITCH2 algorithm resulted in significantly greater use of any SPC compared with Guidelines-care and greater use of the SPC of calcium channel blocker/statin. Unwillingness of the prescribing physician to advance treatment beyond a monotherapy threshold was found to be an important determinant for failing to achieve blood pressure control. In contrast, the more important determinant for failing to achieve LDL control appeared to be the unwillingness of the prescribing physician to initiate therapy with a statin.

A review of the benefits of early treatment initiation with single-pill combinations of telmisartan with amlodipine or hydrochlorothiazide.

This review discusses the rationale for earlier use of single-pill combinations (SPCs) of antihypertensive drugs, with a focus on telmisartan/amlodipine (T/A) and telmisartan/hydrochlorothiazide (T/H) SPCs. Compared with the respective monotherapies, the once-daily T/A and T/H SPCs have been shown to result in significantly higher blood pressure (BP) reductions, BP goal rates, and response rates in patients at all stages of hypertension. As expected, BP reductions are highest with the highest dose (T80/A10 and T80/H25) SPCs. Subgroup analyses of the telmisartan trials have reported the efficacy of both SPCs to be consistent, regardless of the patients’ age, race, and coexisting diabetes, obesity, or renal impairment. In patients with mild-to-moderate hypertension, the T/A combination provides superior 24-hour BP-lowering efficacy compared with either treatment administered as monotherapy. Similarly, the T/H SPC treatment provides superior 24-hour BP-lowering efficacy, especially in the last 6 hours relative to other renin–angiotensin system inhibitor-based SPCs. The T/A SPC is associated with a lower incidence of edema than amlodipine monotherapy, and the T/H SPC with a lower incidence of hypokalemia than hydrochlorothiazide monotherapy. Existing evidence supports the use of the T/A SPC for the treatment of hypertensive patients with prediabetes, diabetes, or metabolic syndrome, due to the metabolic neutrality of both component drugs, and the use of the T/H SPC for those patients with edema or in need of volume reduction.

Initial Monotherapy and Combination Therapy and Hypertension Control the First Year

Initial antihypertensive therapy with single-pill combinations produced more rapid blood pressure control than initial monotherapy in clinical trials. Other studies reported better cardiovascular outcomes in patients achieving lower blood pressure during the first treatment year. We assessed the effectiveness of initial antihypertensive monotherapy, free combinations, and single-pill combinations in controlling untreated, uncontrolled hypertensives during their first treatment year. Electronic record data were obtained from 180 practice sites; 106 621 hypertensive patients seen from January 2004 to June 2009 had uncontrolled blood pressure, were untreated for ≥ 6 months before therapy, and had ≥ 1 one-year follow-up blood pressure data. Control was determined by the first follow-up visit with blood pressure <140/<90 mm Hg for patients without diabetes mellitus or chronic kidney disease and <130/<80 mm Hg for patients with either or both conditions. Multivariable hazards regression ratios (HRs) and 95% CIs for time to control were calculated, adjusting for age, sex, baseline blood pressure, body mass index, diabetes mellitus, chronic kidney disease, cardiovascular disease, initial therapy, final blood pressure medication number, and therapeutic inertia. Patients on initial single-pill combinations (N = 9194) were more likely to have stage 2 hypertension than those on free combinations (N = 18 328) or monotherapy (N = 79 099; all P<0.001). Initial therapy with single-pill combinations (HR, 1.53 [95% CI, 1.47-1.58]) provided better hypertension control in the first year than free combinations (HR, 1.34; [95% CI, 1.31-1.37]) or monotherapy (reference) with benefits in black and white patients. Greater use of single-pill combinations as initial therapy may improve hypertension control and cardiovascular outcomes in the first treatment year.

Target blood pressure attainment with antihypertensive therapy in Swiss primary care

Introduction: The control of high blood pressure (BP) remains insufficient in developed as well as in developing countries. We conducted a cross-sectional survey to investigate the management of hypertension and the achievement of target BPs in a large population of hypertensive patients treated by Swiss primary care physicians. Methods. Data from 4594 hypertensive patients were collected and assessed for demographic data, mode of treatment and BP achievements for the overall population and for high-risk patients such as diabetics and patients with impaired renal function (CKD patients). Furthermore, we analysed the achieved BP in patients receiving single pill combinations or dual free combinations for the three most commonly prescribed substances. Results. In this large patient population, 84% of patients were receiving an antihypertensive treatment of which 54% showed BP control (< 140/90 mmHg or < 130/80 mmHg for diabetics and patients with CKD). Considering the higher BP target in the elderly, 60.6% of treated patients were on target. In contrast, 28.8% of treated diabetics and 29.7% of patients with impaired renal function met BP goals. Diuretics and blockers of the renin–angiotensin system were the most commonly prescribed substances. High-risk patients and patients at advanced age (≥ 80 years) received dual free combination more frequently than younger patients. The use of diuretics was particularly high because of the prescription of single pill formulations. Differences in the pattern of drug prescription were found according to the linguistic areas. Conclusion. The control of hypertension in the Swiss hypertensive population is relatively high but still insufficient particularly among high cardiovascular risk patients such as diabetics and patients with impaired renal function. A further improvement of BP control could perhaps be achieved with a greater use of single pill combinations particularly in patients with complicated hypertension.