Fixed-dose Combination Medication Research Articles

Patient Profiling and Outcome Assessment of Vildagliptin and Dapagliflozin FDC in Persons with Type 2 Diabetes Mellitus

Introduction: Type 2 Diabetes Mellitus (T2D) is a condition characterized by rapid progression, and in certain instances, managing glucose levels may not be adequately achieved with a single pill. Vildagliptin and dapagliflozin in a Fixed-Dose Combination (FDC) complement each other’s actions, aiding in the control of glycemia. The primary goal of this retrospective investigation was to gain insight into the patient characteristics, safety profile, and efficacy of the FDC in reducing weight and glycated hemoglobin levels. Methods: Retrospective data from T2D patients who were prescribed the FDC and had two follow-up visits between May 1, 2022, and January 31, 2023, were enrolled in the study. Results: The average age of the study sample was 55.8 years, with nearly two-thirds being male (65.5%). At 6 months after FDC medication, glycated hemoglobin (HbA1c) significantly decreased by 1.2% (Baseline: 8.4%, Follow-up: 7.2%, p-value <0.001), indicating improved glycemic control. An average weight decrease of 4.3 kg (Baseline: 76.9Kg, Follow-up: 72.5Kg, p-value <0.001), was noted in patients receiving the FDC. Weight loss was higher in males (4.5 kg) than in females (4.0 kg). Safety analysis was carried out for all randomized patients and no major AEs were noted. No patients were withdrawn from the study due to safety concerns. No episode of hypoglycemia occurred during the study time. There were no statistical differences in the hepatic enzymes at the end of six months in the study groups. Conclusion: The Fixed Dose Combination of Vildagliptin and Dapagliflozin effectively enhances glycemic control by demonstrating a significant reduction in mean HbA1c levels after six months compared to baseline. However, further multicenter studies are necessary to substantiate these findings.

Abstract 13591: Utilization and Spending on Fixed-Dose Combination Treatment for Hypertension in Medicare and Medicaid, 2016-2020

Introduction: ACC/AHA hypertension guidelines recommend fixed-dose combination (FDC) medications for Stage 2 hypertension to improve adherence and blood pressure control. However, utilization, total spending, and generic availability of FDC antihypertensives among U.S. adults are unknown. Methods: We evaluated total claims in millions (M) and inflation-adjusted spending for all first-line single and FDC antihypertensive medications consisting of ACEi/ARBs, calcium channel blockers, and/or thiazide diuretics in Medicare Part D and Medicaid from 2016 to 2020. We also evaluated use of generic vs. brand-name first-line antihypertensives. Results: Though total antihypertensive claims increased from 2016 to 2020 in Medicare and Medicaid, use of FDC antihypertensives decreased from 20.6M to 16.9M claims in Medicare (12.6% to 9.4% of all first-line hypertension treatment claims), and from 4.6M to 3.4M claims in Medicaid (12.3% to 8.8%), respectively ( Figure ). Total spending on FDC antihypertensives decreased from $823.3M to $670.9M in Medicare and from $58.9M to $46.9M in Medicaid over this time period. Generically available medications constituted >96% of all Medicare and Medicaid claims in 2016 and >99% of all Medicare and Medicaid claims in 2020 for both single and FDC antihypertensives. Spending on FDC brand-name medications decreased by 87.6% in Medicare ($385.5M to $47.7M) and by 94.1% ($24.9M to $1.5M) in Medicaid. Conclusions: Though FDC medications are widely recommended for treatment of hypertension and almost exclusively generic, use of these agents in Medicare and Medicaid has decreased from 2016 to 2020. Further efforts are needed to understand the decrease in FDC use and to increase adoption of FDC antihypertensives in clinical practice.

Disruption in Blood Pressure Control With the COVID-19 Pandemic: The PCORnet Blood Pressure Control Laboratory

ObjectiveTo explore trends in blood pressure (BP) control before and during the COVID-19 pandemic. Patients and MethodsHealth systems participating in the National Patient-Centered Clinical Research Network (PCORnet) Blood Pressure Control Laboratory Surveillance System responded to data queries, producing 9 BP control metrics. Averages of the BP control metrics (weighted by numbers of observations in each health system) were calculated and compared between two 1-year measurement periods (January 1, 2019, through December 31, 2019, and January 1, 2020, through December 31, 2020). ResultsAmong 1,770,547 hypertensive persons in 2019, BP control to <140/<90 mm Hg varied across 24 health systems (range, 46%-74%). Reduced BP control occurred in most health systems with onset of the COVID-19 pandemic; the weighted average BP control was 60.5% in 2019 and 53.3% in 2020. Reductions were also evident for BP control to <130/<80 mm Hg (29.9% in 2019 and 25.4% in 2020) and improvement in BP (reduction of 10 mm Hg in systolic BP or achievement of systolic BP <140 mm Hg; 29.7% in 2019 and 23.8% in 2020). Two BP control process metrics exhibited pandemic-associated disruption: repeat visit in 4 weeks after a visit with uncontrolled hypertension (36.7% in 2019 and 31.7% in 2020) and prescription of fixed-dose combination medications among those with 2 or more drug classes (24.6% in 2019 and 21.5% in 2020). ConclusionBP control decreased substantially during the COVID-19 pandemic, with a corresponding reduction in follow-up health care visits among persons with uncontrolled hypertension. It is unclear whether the observed decline in BP control during the pandemic will contribute to future cardiovascular events.

Use of Contrave, Naltrexone with Bupropion, Bupropion, or Naltrexone and Major Adverse Cardiovascular Events: A Systematic Literature Review.

Naltrexone/Bupropion extended release (ER; Contrave) is an extended-release, fixed-dose combination medication of naltrexone (8 mg) and bupropion (90 mg) for patients with obesity or overweight with at least one weight-related comorbidity. Obese and overweight patients with or without comorbidities are at increased cardiovascular (CV) risk. Due to the increased CV risk profile in this patient population, this systematic literature review was conducted to assess human studies reporting major adverse CV events (MACE) and other CV events. A priori eligibility criteria included clinical studies (randomized and observational) published from January 1, 2012, to September 30, 2021, with data comparing users of naltrexone/bupropion ER, naltrexone with bupropion, bupropion without naltrexone, or naltrexone without bupropion versus comparator groups (placebo or other treatments), and with sufficient information to determine the frequency of MACE or other CV adverse events by treatment group. Among 2539 English-language articles identified, 70 articles met the eligibility criteria: seven studies of naltrexone/bupropion ER or naltrexone with bupropion, 32 studies of bupropion, and 31 studies of naltrexone. No studies reported an increased risk of MACE among users of naltrexone/bupropion ER, naltrexone with bupropion, or bupropion or naltrexone individually compared with nonusers. One-half of the available studies (n = 35) reported no (zero) CV events and the other half (n = 35) reported that a non-zero frequency of CV events occurred. Four studies reported data on MACE, including three studies of bupropion and one study of naltrexone/bupropion ER. For composite MACE and its components, the difference in proportions between naltrexone/bupropion ER-, bupropion-, or naltrexone-treated patients compared with active comparators or placebo-treated patients did not exceed 2.5%. In conclusion, the available human evidence does not indicate an increased risk of CV events or MACE following use of naltrexone/bupropion ER, naltrexone with bupropion, or the individual components.

Simultaneous Estimation of Sacubitril and Valsartan Combination of Drug in Tablet Dosage Form Using Hydrotropy by UV Spectrophotometry

Sacubitril/valsartan, traded under the brand name Entresto between others, is a fixed-dose combination medication for use heart failure. Sacubitril is a neprilysin inhibitor (A prodrug) and is used in combination with valsartan to reduce the risk of cardiovascular events in patients with chronic heart failure. It is anti - hypertensive drug. Valsartan is an Angiotensin Receptor Blocker (ARB) that may be used to treat a variety of cardiac conditions including hypertension, diabetic nephropathy and heart failure. Two UV-spectrophotometric methods have been developed and validated for simultaneous estimation of Sacubitril and Valsartan in a tablet dosage form. The first method employed solving of simultaneous equations based on the measurement of absorbance at two wavelengths, 226.0 nm and 254.0 nm, 𝜆max for Sacubitril and Valsartan, respectively. The second method was absorbance ratio method, which involves formation of Q-absorbance equation at 240 nm (isoabsorptive point) and also at 254 nm (𝜆max of Valsartan). The methods were found to be linear between the range of 4-12 𝜇g/mL for Sacubitril and 2-10 𝜇g/mL for Valsartan using Methanol as solvent. The mean percentage recovery was found to be 96.68%and 101.89% for the simultaneous equation method and 100.2% and 104.53% for the absorbance ratio method, for sacubitril and valsartan respectively. It could be concluded from the results obtained in the present investigation that the two methods for simultaneous estimation of sacubitril and valsartan in tablet dosage form are simple, rapid, accurate, precise and economical and can be used, successfully, in the quality control of pharmaceutical formulations and other routine laboratory analysis. The reviewed highlights various analytical techniques such as high-performance liquid chromatography (HPLC), ultra- performance liquid chromatography (UPLC), UV Spectroscopy, high per-formance thin layer chromatography (HPTLC), liquid chromatography coupled to tandem mass spectrometry (LC- MS), RP-HPLC and other chromatographic method used. The combination of these drugs with different method was examine and the commonly use of the drugs in hypertensive.

Fixed-Dose Combination Medications for Treating Hypertension: A Review of Effectiveness, Safety, and Challenges.

To summarize the recent evidence on the effectiveness and safety of antihypertensive fixed-dose combination (FDC) medications, and to describe the facilitators and barriers to implementing FDCs in US clinical practice. Recent clinical practice guidelines include FDC use for treating high BP. Clinical trials in recent years support the use of antihypertensive FDCs including low-dose triple- and quadruple-therapy FDCs. Initiating a low-to-standard dose dual-therapy FDCs showed better BP control than initiating treatment with a standard-dose monotherapy, and triple-therapy FDCs produced better BP control rates than dual-therapy FDCs. Retrospective cohort studies showed that FDCs are associated with increased medication adherence, reduced clinical inertia, decreased time to BP control, and improved cardiovascular outcomes. We further discussed barriers and facilitators of wider implementation of antihypertensive FDCs in clinical practice. FDC treatment for hypertension is not commonly used despite historical and recent data which support the effectiveness, safety, and benefits of FDCs. Simplified and protocolized treatment algorithms, team-based care, shared decision-making principles are crucial to successful utilization and implementation of FDC in clinical practice.

Hypertension management in MSF programmes in Jordan and Zimbabwe: opportunities for simplification and use of fixed-dose combination medications

Hypertension management in MSF programmes in Jordan and Zimbabwe: opportunities for simplification and use of fixed-dose combination medications

Abstract 56: Blood Pressure Control in the Real World - Early Evidence From a National Blood Pressure Surveillance System

Background: The Patient-Centered Outcomes Research Institute (PCORI) funded National Blood Pressure Surveillance System (BP Track) is a new national system that generates quarterly metrics of blood pressure (BP) control and BP-related quality metrics for participating healthcare systems from electronic health record (EHR) data. Methods: Queries against standardized EHR data in the national Patient-Centered Clinical Research Network (PCORnet) Common Data Model format produce a set of quality metrics relevant to improving BP control, including Controlling High BP (NQF 0018) and Improvement in BP (CMS65v7), and eight process measures specific to clinical management and treatment practices for improving BP control ( Table ). The metrics, aggregated overall and by health system are reported back to health systems via user-friendly Tableau dashboards, and allow for observation of metric trends. Results: To date, 19 datamarts have contributed EHR data from 1,177,232 patients who met the eligibility criteria for the BP Control measure and 4,454,729 encounters that included a BP measurement during the measurement period. Average age was 62 years; 10% were young adults (&lt;45 years), 17% were African American, 52% female, 28% had diabetes, 15% had coronary heart disease, and 14% had depression. Results demonstrate substantial opportunity for improvement in overall BP control (60% with BP&lt;140/&lt;90 mmHg, range: 42-72%), and many healthcare processes, including medication intensification (12%, 0.6-22%) and use of fixed dose combination medications (24%, 0-88%, Table ). Conclusion: Major opportunities exist for improving BP control, especially in improving the frequency and quality of BP medication prescribing for patients with high BP. The BP Track National BP Surveillance System will track these metrics, by demographic subgroup and over time, and will generate data that can guide and focus quality improvement initiatives aimed at effective BP management.

National Rates of Nonadherence to Antihypertensive Medications Among Insured Adults With Hypertension, 2015.

Despite the importance of antihypertensive medication therapy for blood pressure control, no single data system provides estimates of medication nonadherence rates across age groups and health insurance plans types. Using multiple administrative datasets and national survey data, we determined health insurance plan-specific and overall weighted national rates of nonadherence to antihypertensive medications among insured hypertensive US adults in 2015. We used 2015 prescription claims data from Medicare Part D and 3 IBM MarketScan databases (Commercial, Medicaid, Medicare Supplemental) to calculate medication nonadherence rates among hypertensive adults aged ≥18 years with public or private health insurance using the proportion of days covered algorithm. These findings, in combination with National Health Interview Survey findings, were used to project national weighted estimates of nonadherence. We included 23.8 million hypertensive adults who filled 265.8 million prescriptions for antihypertensive medications. Nonadherence differed by health insurance plan type (highest for Medicaid members, 55.4%; lowest for Medicare Part D members, 25.2%). The overall weighted national nonadherence rate was 31.0%, with greater nonadherence among women versus men, younger versus older adults (aged 18-34 years, 58.1%; aged 65-74 years, 24.4%), fixed-dose combination medication nonusers (31.2%) versus users (29.4%), and by pharmacy outlet type (retail only, 30.7%; any mail order, 19.8%). In 2015, almost one-third (≈16.3 million) of insured US adults with diagnosed hypertension were considered nonadherent to their antihypertensive medication regimen, and considerable disparities were evident. Public health and healthcare professionals can use available evidence-based interventions to address nonadherence and improve blood pressure control.

Barriers and Facilitators to the Use of Cardiovascular Fixed-Dose Combination Medication (Polypills) in Andhra Pradesh, India: A Mixed-Methods Study

BackgroundPolypills, fixed-dose combinations of blood pressure–lowering drug(s), and statin, with or without aspirin, improve the use of these recommended drugs in patients with or at high risk of cardiovascular disease. However, in India, there has been poor uptake of polypills despite market availability. ObjectivesThis study sought to assess availability and cost of polypills and explore barriers and facilitators to their use in the state of Andhra Pradesh in India. MethodsA mixed-methods study was conducted. Availability and cost of polypills as well as individual component drugs was assessed through a survey of pharmacies across urban, urban slum, and rural regions in state of Andhra Pradesh in India. In-depth interviews with stakeholders at each level of the health system explored barriers and facilitators to use of polypills. ResultsOverall, 30 pharmacies were surveyed (10 in each of urban, urban slum, and rural region). In urban region, 2 pharmacies stocked polypills (without aspirin) costing 121 Indian rupees (INR) per 10 pills, and 1 other pharmacy stocked a polypill (with aspirin) costing 24 INR per 10 pills. All pharmacies stocked a wide range of component drugs as separate pills with combined cost of the cheapest angiotensin-converting enzyme inhibitor, statin, and aspirin INR 124 per 10 pills. Patients were willing to use polypills if prescribed by their doctor, and pharmacies were willing to stock polypills if there was market demand. For prescribers, key barriers included perceptions that current polypills contained outdated drugs and inadequate flexibility in prescribing. ConclusionsIn a market in which polypill use is licensed, their availability and use is very low. Lack of prescription of polypills was the predominant barrier to polypill use; therefore, making polypills with drugs that are more acceptable and at different available strengths, in conjunction with broader prescriber education and training, may improve their use.

Adapting and Evaluating a Health System Intervention From Kaiser Permanente to Improve Hypertension Management and Control in a Large Network of Safety-Net Clinics.

Nearly half of Americans with diagnosed hypertension have uncontrolled blood pressure (BP) while some integrated healthcare systems, such as Kaiser Permanente Northern California, have achieved control rates upwards 90%. We adapted Kaiser Permanente's evidence-based treatment protocols in a racially and ethnically diverse population at 12 safety-net clinics in the San Francisco Health Network. The intervention consisted of 4 elements: a hypertension registry, a simplified treatment intensification protocol that included fixed-dose combination medications containing diuretics, standardized BP measurement protocol, and BP check visits led by registered nurse and pharmacist staff. The study population comprised patients with hypertension who made ≥1 primary care visits within the past 24 months (n=15 917) and had a recorded BP measurement within the past 12 months. We conducted a postintervention time series analysis from August 2014 to August 2016 to assess the effect of the intervention on BP control for 24 months for the pilot site and for 15 months for 11 other San Francisco Health Network clinics combined. Secondary outcomes were changes in use of guideline-recommended medication prescribing. Rates of BP control increased at the pilot site (68%-74%; P<0.01) and the 11 other San Francisco Health Network clinic sites (69%-74%; P<0.01). Statistically significant improvements in BP control rates (P<0.01) at the 11 San Francisco Health Network clinic sites occurred in all racial and ethnic groups (blacks, 60%-66%; whites, 69%-75%; Latinos, 67%-72%; Asians, 78%-82%). Use of fixed-dose combination medications increased from 10% to 13% (P<0.01), and the percentage of angiotensin-converting enzyme inhibitor prescriptions dispensed in combination with a thiazide diuretic increased from 36% to 40% (P<0.01). Evidence-based system approaches to improving BP control can be implemented in safety-net settings and could play a pivotal role in achieving improved population BP control and reducing hypertension disparities.

Abstract 178: Byvalson Fixed-Dose Combination for the Treatment of Hypertension: A Comprehensive Review

Purpose: Byvalson (nebivolol and valsartan), FDA approved in June 2016 for the treatment of hypertension, is the first combination beta blocker and ARB fixed-dose combination medication available. Two-thirds of patients with hypertension require more than one drug to achieve BP control. The combination of two antihypertensive medications has been associated with greater BP control, compliance, and reduced adverse effects. Nebivolol is a highly selective β1-adrenergic receptor antagonist with vasodilator properties and valsartan is an ARB. The objective of this study is to evaluate clinical efficacy and safety of this combination of BP-lowering medications in the treatment of hypertension. Methods: A comprehensive literature search was conducted to date utilizing MEDLINE and PUBMED with the following search terms: “nebivolol”, “valsartan”, and “hypertension” to retrieve clinical trials. The following three studies were found: a phase I randomized, open-label study investigating pharmacokinetic and pharmacodynamic interactions between nebivolol and valsartan; and two phase III studies evaluating the safety and efficacy of combination treatment: one is an open-label, single-arm study over 52 weeks and the other is a phase III randomized, placebo-controlled study comparing fixed-dose combination to nebivolol and valsartan alone over 8 weeks. Analysis of the study designs, methods, results, statistical analyses, and conclusions were properly conducted for appropriateness and validity. Results: The pharmacokinetic and pharmacodynamics parameters in the phase I study involving 30 patients had statistically significant steady-state PK interactions deemed not clinically significant, significant reductions in blood pressure (p≤0.005) and other PD interactions. A phase III trial (n=4161) showed significantly greater reductions from baseline at 8 weeks in DBP in the fixed-dose combination group than both nebivolol 40 mg (mean difference –1.2 mm Hg [95% CI, –2.3 to –0.1; p=0.030] and valsartan 320 mg (–4.4 mm Hg [95% CI, –5.4 to –3.3]; p&lt;0.0001). SBP reductions were also significant (p&lt;0.01). Another phase III trial (n=810) showed significant reductions from baseline at 52 weeks for SBP (-25.5±15.9 mm Hg) and for DBP (-19.0±8.7 mm Hg). 75.7% of nebivolol/valsartan and 57.8% of nebivolol/valsartan/HCTZ patients achieved a BP goal of &lt;140/90. Conclusion: Both phase III trials evaluating the combination treatment of nebivolol and valsartan demonstrated long term safety, efficacy, and tolerability with significant reductions in systolic and diastolic blood pressure compared with monotherapy. The phase I study showed limited PK interactions, additive PD effects, and tolerability in healthy volunteers. As an initial therapy in patients with inadequately controlled blood pressure, Byvalson 5/80 mg taken orally once daily is a safe and effective treatment for the hypertension.

Grazoprevir/elbasvir fixed-dose combination for hepatitis C.

Hepatitis C virus (HCV) infection is an increasing public health concern with an estimated 184 million people infected worldwide and approximately 350,000 deaths yearly from HCV-related complications. There is a compelling medical need for new anti-HCV therapeutic agents that are potent, tolerable, safe, completely oral and with shorter treatment duration. To this end, a plethora of direct-acting antivirals have been developed and regulatory authorities have approved nine new molecules for the treatment of chronic hepatitis C (CHC). In January 2016, the U.S. Food and Drug Administration approved the fixed-dose combination medication incorporating the NS3/NS4A inhibitor grazoprevir (formerly MK-5172) and the NS5A inhibitor elbasvir (formerly MK-8742), with or without ribavirin, for the treatment of CHC genotypes 1 and 4 infection in adult patients. This all-oral combination has proven potent and safe even in patients with advanced kidney disease. Herein, we review the pharmacokinetics, clinical efficacy and safety profile pertaining to grazoprevir/elbasvir fixed-dose combination for CHC.

Bronchodilatory and Anti-Inflammatory Effects of ASM-024, a Nicotinic Receptor Ligand, Developed for the Treatment of Asthma

Conventional asthma and COPD treatments include the use of bronchodilators, mainly β2-adrenergic agonists, muscarinic receptor antagonists and corticosteroids or leukotriene antagonists as anti-inflammatory agents. These active drugs are administered either separately or given as a fixed-dose combination medication into a single inhaler. ASM-024, a homopiperazinium compound, derived from the structural modification of diphenylmethylpiperazinium (DMPP), has been developed to offer an alternative mechanism of action that could provide symptomatic control through combined anti-inflammatory and bronchodilator properties in a single entity. A dose-dependent inhibition of cellular inflammation in bronchoalveolar lavage fluid was observed in ovalbumin-sensitized mice, subsequently treated for 3 days by nose-only exposure with aerosolized ASM-024 at doses up to 3.8 mg/kg (ED50 = 0.03 mg/kg). The methacholine ED250 values indicated that airway hyperresponsivenness (AHR) to methacholine decreased following ASM-024 administration by inhalation at a dose of 1.5 mg/kg, with a value of 0.145±0.032 mg/kg for ASM 024-treated group as compared to 0.088±0.023 mg/kg for untreated mice. In in vitro isometric studies, ASM-024 elicited dose-dependent relaxation of isolated mouse tracheal, human, and dog bronchial preparations contracted with methacholine and guinea pig tracheas contracted with histamine. ASM-024 showed also a dose and time dependant protective effect on methacholine-induced contraction. Overall, with its combined anti-inflammatory, bronchodilating and bronchoprotective properties, ASM-024 may represent a new class of drugs with a novel pharmacological approach that could prove useful for the chronic maintenance treatment of asthma and, possibly, COPD.

Physician Underutilization of Effective Medications for Resistant Hypertension at Office Visits in the United States: NAMCS 2006–2010

The American Heart Association (AHA) published guidelines for treatment of resistant hypertension in 2008 recommending use of thiazide diuretics (particularly chlorthalidone), aldosterone antagonists, and fixed-dose combination medications, but it is unclear the extent to which these guidelines are being followed. To describe trends in physician use of recommended medications for resistant hypertension and assess variations in medication use based on geography, physician specialty and patient characteristics. Cross-sectional analysis using the National Ambulatory Medical Care Survey from 2006 to 2010. We analyzed visits of hypertension patients to family physicians, general internists, and cardiologists. Resistant hypertension was defined as concurrent use of ≥ 4 classes of blood pressure (BP) medications or elevated BP despite the use of ≥ 3 medications. Pregnant patients and visits with diagnosed heart failure or end-stage renal disease were excluded. Use of AHA-recommended medications for management of resistant hypertension. Of 19,500 patient visits with hypertension, 1,567 or 7.1 % CI (6.6-7.7 %) met criteria for resistant hypertension. Thiazide diuretic use was reported in 58.9 % of visits pre-guidelines vs. 54.8 % post-guidelines (p = 0.37). Use of aldosterone antagonists was low and also did not change significantly after guideline publication (3.1 % vs. 4.5 %, p = 0.27). Fixed-dose combinations use was 42.0 % before and 37 % after guideline publication (p = 0.29). Each 10-year increase in patient age was associated with lower thiazide use (OR 0.87, CI 0.77-0.97), as was presence of comorbid ischemic heart disease (OR 0.62, CI 0.41-0.94). Medication use did not vary by geography or physician specialty. Use of AHA-recommended medications for resistant hypertension remains low after publication of guidelines. Healthcare systems should encourage more frequent prescribing of these medications to improve care in this high-risk population.

MECHANISMS OF COMBINED ACTION OF ACE INHIBITORS AND CALCIUM ANTAGONISTS IN ARTERIAL HYPERTENSION

This review presents the modern views on the effectiveness of water-soluble angiotensin-converting enzyme (ACE) antagonists and calcium antagonists (CA), as monotherapy or as fixed-dose combination therapy, in the treatment of arterial hypertension (AH). The results of the X-ray structural analysis of crystal ACE-lisinopril complexes suggest a highly selective, strong inhibitory effect of lisinopril on various ACE forms of the hormonal renin-angiotensin-aldosterone system and tissue renin-angiotensin systems. The association between specific action mechanisms and therapeutic effects in hypertension is analysed for a third-generation CA amlodipine. The benefits of a fixed-dose combination medication Ekvator (amlodipine 5 mg plus lisinopril 10 mg) in hypertension are described, including its synergetic protective effects.

The Importance of Managing Hypertension and Dyslipidemia to Decrease Cardiovascular Disease

Clinical management of two key modifiable risk factors for cardiovascular disease (CVD), hypertension and dyslipidemia, has evolved considerably over the past 40 years, in terms of the focus of therapy, available pharmacologic agents, and therapeutic targets. A brief review of the epidemiology of hypertension and hyperlipidemia and of controlled clinical trials of pharmacologic therapy of these conditions in decreasing cardiovascular events is presented. Risk factors for CVD generally do not occur in isolation, and the co-occurrence of hypertension and dyslipidemia, with or without other additional risk factors, greatly increases the risk of CVD. Clinical trials performed in the last 40 years have demonstrated the clinical benefit of treating hypertension and dyslipidemia. Recent trials have shown that intensive, early management of these risk factors provide the greatest clinical benefits. Emerging evidence suggests that lipid management provides clinical benefit in patients at high risk of CVD, regardless of their baseline cholesterol levels, and that lipid-lowering with statin therapy provides additional benefits over antihypertensive therapy alone in high-risk patients with hypertension. It has become evident that the most effective means of reducing CVD risk is the simultaneous management of all modifiable risk factors. Treatment of an individual risk factor can reduce CVD events by approximately 30%, whereas treatment of multiple risk factors can reduce the risk of CVD by more than 50%. However, a large number of patients are not treated or receive suboptimal treatment. Overwhelming controlled clinical trial evidence supports the clinical benefit of treating hypertension and hypercholesterolemia. Fixed-dose combination medications for hypertension, and integrative combination therapies containing antihypertensive and lipid-lowering medications in a single pill contribute to better risk factor management with the potential for greater adherence and improved clinical outcomes.