A Prospective Randomized, Double-Blind, Multi-Center, Phase III Clinical Trial Evaluating the Efficacy and Safety of Olmesartan/Amlodipine plus Rosuvastatin Combination Treatment in Patients with Concomitant Hypertension and Dyslipidemia: A LEISURE Study

Background: This study was a multicenter, randomized, double-blinded, placebo-controlled phase III clinical trial to investigate the efficacy and safety of an olmesartan/amlodipine single pill plus rosuvastatin combination treatment for patients with concomitant hypertension and dyslipidemia. Methods: Patients with both hypertension and dyslipidemia aged 20–80 were enrolled from 36 tertiary hospitals in Korea from January 2017 to April 2018. Patients were randomized to three groups in a 1:1:0.5 ratio, olmesartan/amlodipine single pill plus rosuvastatin (olme/amlo/rosu) or olmesartan plus rosuvastatin (olme/rosu) or olmesartan/amlodipine single pill (olme/amlo) combination. The primary endpoints were change of sitting systolic blood pressure (sitSBP) from baseline in the olme/amlo/rosu vs. olme/rosu groups and the percentage change of low-density lipoprotein cholesterol (LDL-C) from baseline in the olme/amlo/rosu vs. olme/amlo groups after 8 weeks of treatment. Results: A total of 265 patients were randomized, 106 to olme/amlo/rosu, 106 to olme/rosu and 53 to olme/amlo groups. Baseline characteristics among the three groups did not differ. The mean sitSBP change was significantly larger in the olme/amlo/rosu group with −24.30 ± 12.62 mmHg (from 153.58 ± 10.90 to 129.28 ± 13.58) as compared to the olme/rosu group, −9.72 ± 16.27 mmHg (from 153.71 ± 11.10 to 144.00 ± 18.44 mmHg). The difference in change of sitSBP between the two groups was −14.62± 1.98 mmHg with significance (95% CI −18.51 to −10.73, p < 0.0001). The mean LDL-C reduced significantly in the olme/amlo/rosu group, −52.31 ± 16.63% (from 154.52 ± 30.84 to 72.72 ± 26.08 mg/dL) as compared to the olme/amlo group with no change, −2.98 ± 16.16% (from 160.42 ± 32.05 to 153.81 ± 31.57 mg/dL). Significant difference in change was found in LDL-C between the two groups with −50.10 ± 2.73% (95% CI −55.49 to −44.71, p < 0.0001). Total adverse drug reaction rates were 10.48%, 5.66% and 3.7% in the olme/amlo/rosu, olme/rosu and olme/amlo groups, respectively with no statistical significance among the three groups. Serious adverse drug reactions did not occur. Conclusions: Olmesartan/amlodipine single pill plus rosuvastatin combination treatment for patients with both hypertension and dyslipidemia is effective and safe as compared to either olmesartan plus rosuvastatin or olmesartan plus amlodipine treatment.

Reduction of blood pressure fluctuations by telmisartan molecule especially in combination with calcium channel antagonist

1.28 billion people suffer from hypertension, and its complications cause 10 million deaths each year. Effective antihypertensive therapy is therefore one of the priority tasks of health care. Achieving good BP control depends on many factors, but one of the primary ones is the use of maximally effective therapy in the simplest possible regimen. Amlodipine in combination with telmisartan in the single-pill combination, through its high smoothness index, makes it possible to achieve a satisfactory hypotensive effect lasting 24 h when taken once daily. This combination is also a good alternative for cardiovascularly burdened patients who cannot use angiotensin-converting enzyme inhibitors and for elderly patients, especially after stroke

Pill Detection Model for Medicine Inspection Based on Deep Learning

This paper proposes a deep learning algorithm that can improve pill identification performance using limited training data. In general, when individual pills are detected in multiple pill images, the algorithm uses multiple pill images from the learning stage. However, when there is an increase in the number of pill types to be identified, the pill combinations in an image increase exponentially. To detect individual pills in an image that contains multiple pills, we first propose an effective database expansion method for a single pill. Then, the expanded training data are used to improve the detection performance. Our proposed method shows higher performance improvement than the existing algorithms despite the limited imaging and data set size. Our proposed method will help minimize problems, such as loss of productivity and human error, which occur while inspecting dispensed pills.

Real-world evidence on the strategy of olmesartan-based triple single-pill combination in Korean hypertensive patients: a prospective, multicenter, observational study (RESOLVE-PRO)

Background In this prospective, multicenter, non-comparative observational study, the effectiveness and safety of the triple single-pill combination (SPC) of olmesartan/amlodipine/hydrochlorothiazide (OM/AML/HCTZ) were evaluated in a real clinical practice setting in Korean patients with essential hypertension. Methods A total of 3752 patients were enrolled and followed for 12 months after administration of OM/AML/HCTZ. Primary endpoint was change from baseline to month 6 in the mean systolic blood pressure (SBP). Secondary endpoints included changes from baseline in the mean SBP at month 3, 9, 12 and the mean diastolic blood pressure (DBP) at month 3, 6, 9, 12; changes in the mean SBP/DBP according to age and underlying risk factors; and blood pressure control rate (%) at different time points. Adherence to and satisfaction with OM/AML/HCTZ treatment among patients and physicians were assessed by medication possession ratio (MPR) and numeric rating scale, respectively, as exploratory endpoints. Safety was evaluated by the incidence and severity of adverse events (AEs) as well as the discontinuation rate due to AEs. Results OM/AML/HCTZ administration led to significant reductions in the mean SBP/DBP by 11.5/6.6, 12.3/7.0, 12.3/7.2, and 12.8/7.4 mmHg from baseline to month 3, 6, 9 and 12, respectively (P < 0.0001). The BP reductions were maintained throughout the 1-year observation period in all patients with different age groups and risk factors (diabetes mellitus, cardiovascular disease, and renal disease). The BP control rate (%) of < 140/90 mmHg was 65.9, 67.9, 68.9, and 70.6% at month 3, 6, 9, and 12, respectively. The mean MPR during the observation period was 0.96. The safety results were consistent with the previously reported safety profile of OM/AML/HCTZ. Conclusions Treatment with the triple SPC of OM/AML/HCTZ demonstrated significant effectiveness in reducing SBP/DBP and achieving target BP control with high adherence over the 1-year observation period in Korean hypertensive patients and was well-tolerated. Trial registration CRIS, KCT0002196, Registered 3 May 2016.

The Combination of Beta-Blockers and ACE Inhibitors Across the Spectrum of Cardiovascular Diseases

Cardiovascular disease is the leading cause of mortality worldwide, affecting a wide range of patients at different stages across the cardiovascular continuum. Hypertension is one of the earliest risk factors in this continuum and can be controlled in most patients with currently available antihypertensive agents. However, goals are often not met because treatments are not optimized in terms of tailoring therapy to individual patients based on their hypertension subclass and cardiovascular risk profile and initiating early use of adapted-dose, single-pill combinations. In this context, beta-blockers in combination with angiotensin-converting enzyme (ACE) inhibitors are of special interest as a result of their complementary actions on the sympathetic nervous system and renin–angiotensin–aldosterone system, two interlinked pathways that influence cardiovascular risk and disease outcomes. In addition to their antihypertensive actions, beta-blockers are used to manage arrhythmias and treat angina pectoris and heart failure, while ACE inhibitors provide cardioprotection in patients with acute coronary syndromes and treat congestive heart failure. A broad range of patients may therefore receive the combination in routine clinical practice. This paper examines the supporting evidence for beta-blockers and ACE inhibitors in each of the above indications and considers the rationale for combining these agents into a single pill, using data from bisoprolol and perindopril randomized controlled trials as supporting evidence. Combining these established antihypertensive agents into a single pill continues to provide effective blood pressure lowering and improved cardiovascular outcomes while allowing a greater proportion of patients to rapidly achieve treatment targets.

Epidemiological Observational Study on the Assessment of the Comorbidity and the Efficacy of the Treatment of Hypertensive Patients with Single Pill Combination of Lysinopril, Amlodipine and Rosuvastatin "PHENOTYPE-AG"

Aim. To study the prevalence of comorbidity affecting the choice of antihypertensive treatment, as well as the efficacy and safety of the application of a single pill combination of lysinopril, amlodipine and rosuvastatin (SPC LAR) in hypertensive patients.Material and methods. Observational epidemiological study with the participation of 626 doctors and 13037 hypertensive patients with high cardiovascular risk and dyslipidemia treated with SPC LAR were held in 24 cities of Russia from November 2020 to March 2021. Prevalence and types of comorbidity, changes of blood pressure (BP), of total cholesterol (TC) and blood glucose levels and adverse events were studied during observation. Patients had 3 visits – initially, after 4 and 12 weeks. The obtained data was recorded by doctors through a web portal.Results. Concominant cardiovascular diseases found in all patients (in 38.7% of cases – from 2 to 5 diseases). The most commonly diseases were coronary artery disease (43.1%), metabolic syndrome (36.6%), diabetes (25.2%), chronic heart failure (24.9%), cerebrovascular diseases (12.3%) and chronic obstructive pulmonary disease (0.5%). SPC LAR with minimal doses of components (in 41.1% of patients) or with reinforced antihypertensive or hypocholesterolemic effects, based on the experience of treatment, the patient was prescribed as starting treatment with doctors. Reducing the level of systolic and diastolic BP, as well as the level Tc, respectively, by 20.9%, 16.9% and 29.7% found during the study. Target levels of systolic BP were achieved in 97.6% of patients, diastolic BP – in 99.6%, and target levels TC ≤5 mmol/l, ≤4 mmol/l and ≤3 mmol/l were achieved, respectively, in 94.5%, 68.6% and 23.5% patients. No significant dynamics of the level of glycemia were not found. The treatment was well tolerated by patients. Side effects found in 0.53% of patients (more often there was a dry cough, feet edema and headache). Commitment to treatment was 92.7%.Conclusion. The modern hypertension phenotype has cardiovascular atherosclerosis-associated diseases, which justifies the need to combine antihypertensive and hypolipidemic therapy. Triple SPC LAR, which effectively controlled the blood pressure and improved the violation of lipid metabolism was prescribed to patients in this observational study. The low frequency of side effects and good tolerance of treatment was accompanied by a high adherence of patients to treatment.