Status of home blood pressure measurement in treated hypertensive patients. Results of a survey from two cities in Korea.

Knowledge of the status of real-world home blood pressure (BP) measurements is crucial for establishing policies promoting hypertension treatment through home BP monitoring. However, only a few studies have investigated the status of home BP measurements in real-world settings. This study investigated the practice of Korean patients in measuring BP at home. This study recruited participants aged ≥20 years who were taking antihypertensives and conducted a questionnaire-based survey on home BP measurements. Of 701 participants recruited between August 2018 and April 2020, 673 were included in the analysis. Of these, 359 (53.3%) possessed home BP measurement devices. The devices used by 184 (51.3%) participants were validated, 110 (30.6%) were nonvalidated, and 65 (18.1%) had an unknown validation status. Only 18 patients (5.0%) with home BP devices were aware of the validation tests for home BP measurement devices. Of the 673 participants, 278 (41.3%) measured BP at home (77.4% of the patients owned home BP measurement devices). Among them, at least 74 (26.6%) performed proper measurements (at least once a month, at least twice a day or twice at a time, after at least 1 minute of rest, with at least a 1-min interval between each measurement, and 30 min after drinking coffee, exercising, or smoking). In conclusion, our community-based survey in the nonpresentive Korean population revealed a low rate of home BP measurement, a high rate of using nonvalidated devices, and a high rate of inappropriate measurements, suggesting that more efforts toward patient education regarding home BP measurements are needed.

The Efficacy and Tolerability of Irbesartan/Amlodipine Combination Therapy in Patients With Essential Hypertension Whose Blood Pressure Were not Controlled by Irbesartan Monotherapy.

PURPOSE: This study aimed to evaluate the efficacy and tolerability of irbesartan (IRB) and amlodipine (AML) combination therapy in patients with essential hypertension whose blood pressure (BP) was not controlled by IRB monotherapy. METHODS: Two multicenter, randomized, double-blind, placebo-controlled, phase III studies were conducted in Korea (the I-DUO 301 study and the I-DUO 302 study). After a 4-week run-in period with either 150 mg IRB (I-DUO 301 study) or 300 mg IRB (I-DUO 302 study), patients with uncontrolled BP (ie, mean sitting systolic BP [MSSBP] ≥140 mmHg to <180 mmHg and mean sitting diastolic BP <110 mmHg) were randomized to the placebo, AML 5 mg, or AML 10 mg group. A total of 428 participants were enrolled in the 2 I-DUO studies. In the I-DUO 301 study, 271 participants were randomized in a 1:1:1 ratio to receive either IRB/AML 150/5 mg, IRB/AML 150/10 mg, or IRB 150 mg/placebo. In the I-DUO 302 study, 157 participants were randomized in a 1:1 ratio to receive IRB/AML 300/5 mg or IRB 300 mg/placebo. The primary endpoint was the change in MSSBP from baseline to week 8. Tolerability was assessed according to the development of treatment-emergent adverse events (TEAEs) and clinically significant changes in physical examination, laboratory tests, pulse, and 12-lead electrocardiography. FINDINGS: In I-DUO 301, the mean (SD) changes of MSSBP at week 8 from baseline were -14.78 (12.35) mmHg, -21.47 (12.78) mmHg, and -8.61 (12.19) mmHg in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively. In I-DUO 302, the mean (SD) changes of MSSBP at week 8 from baseline were -13.30 (12.47) mmHg and -7.19 (15.37) mmHg in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively. In both studies, all combination groups showed a significantly higher reduction in MSSBP than the IRB monotherapy groups (P < 0.001 for both). TEAEs occurred in 10.00%, 10.99%, and 12.22% of participants in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively, in I-DUO 301 and in 6.33% and 10.67% of participants in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively, in I-DUO 302, with no significant between-group differences. Overall, there was one serious adverse event throughout I-DUO study. IMPLICATIONS: The combination of IRB and AML has superior antihypertensive effects compared with IRB alone over an 8-week treatment period, with placebo-like tolerability. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05476354 (I-DUO 301), NCT05475665 (I-DUO 302).

Efficacy and safety of standard dose triple combination of telmisartan 80 mg/amlodipine 5 mg/chlorthalidone 25 mg in primary hypertension: A randomized, double-blind, active-controlled, multicenter phase 3 trial.

The authors evaluated the efficacy, safety, and characteristics of patients who respond well to standard dose triple combination therapy including chlorthalidone 25 mg with telmisartan 80 mg plus amlodipine 5 mg in hypertensive patients. This is a multicenter, double-blind, active-controlled, phase 3, randomized trial. Patients are randomized to triple combination (telmisartan 40 mg/amlodipine 5 mg/chlorthalidone 12.5 mg, TEL/AML/CHTD group) or dual combination (telmisartan 40 mg/amlodipine 5 mg, TEL/AML group) treatment and then dose up titration to TEL 80/AML5/CHTD25mg and TEL80/AML5, respectively. The primary endpoint is the change of mean sitting systolic blood pressure (MSSBP) at week 8. A Target BP achievement rate, a response rate, and the safety endpoints are also evaluated. Total 374 patients (mean age = 60.9 ± 10.7 years, male = 78.3%) were randomized to the study. The baseline MSSBPs/diastolic BPs were 149.9 ± 12.2/88.5 ± 10.4 mm Hg. After 8 weeks treatment, the change of MSSBPs at week 8 are -19.1 ± 14.9 mm Hg (TEL/AML/CHTD) and -11.4 ± 14.7 mm Hg (TEL/AML) (p < .0001). The achievement rates of target BP (53.8% vs. 37.8%, p = .0017) and responder rate (54.8% vs. 35.6%, p = .0001) at week 8 were significantly higher in TEL/AML/CHTD. There are no serious adverse event and no one discontinued medication due to adverse event. Among the TEL 80/AML5/CHTD25mg treatment group, patients of female or age ≥ 65 years old showed higher rate of target BP achievement than relatively young male. (61.4 vs. 46.8%, p = .042) Our study showed standard dose triple combination of telmisartan 80 mg/amlodipine 5 mg/chlorthalidone 25 mg is efficacious and safe in treatment of primary hypertension. Target BP achievement with triple therapy would be facilitated in female or old age.

Randomized, multicenter, parallel, open, phase 4 study to compare the efficacy and safety of rosuvastatin/amlodipine polypill versus atorvastatin/amlodipine polypill in hypertension patient with dyslipidemia.

The authors performed this study to investigate the efficacy and safety of a rosuvastatin (RSV)/amlodipine (AML) polypill compared with those of atorvastatin (ATV)/AML polypill. We included 259 patients from 21 institutions in Korea. Patients were randomly assigned to 1 of 3 treatment groups: RSV 10 mg/AML 5 mg, RSV 20 mg/AML 5 mg, or ATV 20 mg /AML 5 mg. The primary endpoint was the efficacy of the RSV 10.20 mg/AML 5 mg via percentage changes in LDL-C after 8 weeks of treatment, compared with the ATV 20 mg /AML 5 mg. There was a significant difference in the mean percentage change of LDL-C at 8 weeks between the RSV 10 mg/AML 5 mg and the ATV 20 mg/AML 5 mg (full analysis set [FAS]: -7.08%, 95% CI: -11.79 to -2.38, p = .0034, per-protocol analysis set [PPS]: -6.97%, 95% CI: -11.76 to -2.19, p = .0046). Also, there was a significant difference in the mean percentage change of LDL-C at 8 weeks between the RSV 20 mg/AML 5 mg and the ATV 20 mg/AML 5 mg (FAS: -10.13%, 95% CI: -15.41 to -4.84, p = .0002, PPS: -10.96%, 95% CI: -15.98 to -5.93, p < .0001). There was no significant difference in the adverse events rates between RSV 10 mg/AML 5 mg, RSV 20 mg/AML 5 mg, and ATV 20 mg/AML 5 mg. In conclusion, while maintaining safety, RSV 10 mg/AML 5 mg and the RSV 20 mg/AML 5 mg more effectively reduced LDL-C compared with the ATV 20 mg /AML 5 mg (Clinical trial: NCT03951207).

A Randomized, Multicenter, Double-blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of a Quadruple Combination of Amlodipine, Losartan, Rosuvastatin, and Ezetimibe in Patients with Concomitant Essential Hypertension and Dyslipidemia.

BACKGROUND: Few data are available regarding the efficacy and safety of a single-pill combination (SPC) consisting of four medications in patients with concomitant hypertension and dyslipidemia. OBJECTIVE: We aimed to determine the efficacy and tolerability of a fixed-dose SPC consisting of 5 mg amlodipine, 100 mg losartan, 20 mg rosuvastatin, and 10 mg ezetimibe (A/L/R/E) in patients with concomitant hypertension and dyslipidemia. METHODS: This was a 14-week, randomized, multicenter, double-blind, placebo-controlled, phase III clinical trial. In total, 145 patients were randomized to receive A/L/R/E, A/L, or L/R/E. The primary endpoints were the average change in the low-density lipoprotein cholesterol (LDL-C) level in the A/L/R/E and A/L groups and the sitting systolic blood pressure (sitSBP) in the A/L/R/E and L/R/E groups. The numbers of patients with adverse drug reactions (ADRs) were compared as safety variables. RESULTS: The average percentage change in the LDL-C level as the least squares mean (LSM) from the baseline LDL-C level at the end of the 8-week treatment was - 59.0% in the A/L/R/E group and 0.2% in the A/L group (LSM difference - 59.2, 95% confidence interval [CI] - 68.1 to - 50.4; p < 0.0001). The average change in the sitSBP as the LSM was - 15.8 mmHg in the A/L/R/E group and -4.7 mmHg in the L/R/E group (LSM difference - 11.1, 95% CI - 16.8 to - 5.4; p = 0.0002). No ADRs occurred in the A/L/R/E group. CONCLUSIONS: A/L/R/E as an SPC could be an effective treatment for patients with hypertension and dyslipidemia without significant safety issues. CLINICAL TRIALS REGISTRATION: NCT04074551 (registered 30 August 2019).

Comparison of efficacy and safety between third-dose triple and third-dose dual antihypertensive combination therapies in patients with hypertension.

We compared the efficacy and safety of third-standard-dose triple and third-standard-dose dual antihypertensive combination therapies in patients with mild to moderate hypertension. This was a phase II multicenter, randomized, double-blind, parallel-group trial. After a 4-week placebo run-in period, 245 participants were randomized to the third-dose triple combination (ALC group; amlodipine 1.67 mg + losartan potassium 16.67 mg + chlorthalidone 4.17 mg) or third-dose dual combination (AL group; amlodipine 1.67 mg + losartan potassium 16.67 mg, LC group; losartan potassium 16.67 mg + chlorthalidone 4.17 mg, AC group; amlodipine 1.67 mg + chlorthalidone 4.17 mg) therapy groups and followed up for 8 weeks. The mean systolic blood pressure (BP) reduction was -18.3 ± 13.2, -13.0 ± 13.3, -16.3 ± 12.4, and -13.8 ± 13.2 mmHg in the ALC, AL, LC, and AC groups, respectively. The ALC group showed significant systolic BP reduction compared to the AL and AC groups at weeks 4 (P = .010 and P = .018, respectively) and 8 (P = .017 and P = .036, respectively). At week 4, the proportion of systolic BP responders was significantly higher in the ALC group (42.6%) than in the AL (22.0%), LC (23.3%), and AC (27.1%) groups (P = .013, P = .021, and P = .045, respectively). At week 8, the proportion of systolic and diastolic BP responders was significantly higher in the ALC group (59.7%) than in the AL (39.3%) and AC (42.4%) groups (P = .022 and P = .049, respectively) at week 8. Third-standard-dose triple antihypertensive combination therapy demonstrated early effective BP control compared to third-standard-dose dual combination therapies, without increasing adverse drug reactions in patients with mild-to-moderate hypertension.

Efficacy and Safety of Coadministered Ezetimibe-Rosuvastatin plus Telmisartan in South Korean Patients with Dyslipidemia and Hypertension: A Multicenter, Randomized, Double-Blind, Active-Controlled, Phase III Trial.

BACKGROUND: The introduction of a fixed-dose combination (FDC) is expected to improve treatment compliance. METHODS: There were 181 subjects who were randomized to three groups: ezetimibe-rosuvastatin 10/20 mg + telmisartan 80 mg, ezetimibe-rosuvastatin 10/20 mg, and telmisartan 80 mg. The primary outcomes were change in mean sitting systolic blood pressure (MSSBP) and percentage change in low-density-lipoprotein cholesterol (LDL-C) compared to baseline at week 8. RESULTS: The least-square mean (SE) in MSSBP changes between the ezetimibe-rosuvastatin 10/20 mg + telmisartan 80 mg group and the ezetimibe-rosuvastatin 10/20 mg group were -25.81 (2.34) mmHg and -7.66 (2.45) mmHg. There was a significant difference between the two groups (-18.15 (2.83) mmHg, 95% CI -23.75 to -12.56, p < 0.0001). Changes in least-square mean (SE) in LDL-C between the ezetimibe-rosuvastatin 10/20 mg + telmisartan 80 mg group and the telmisartan 80 mg group were -63.82 (2.87)% and -2.48 (3.12)%. A significant difference was observed between the two groups (-61.34 (3.33)%, 95% CI -67.91 to -54.78, p < 0.0001). No serious adverse events were observed. CONCLUSIONS: Ezetimibe-rosuvastatin plus telmisartan treatment is effective and safe when compared to either ezetimibe-rosuvastatin or telmisartan.

Home blood pressure measurement for hypertension management in the real world: Do not just measure, but share with your physician.

Introduction: Studies of the effectiveness of home blood pressure (BP) measurement on the treatment of hypertension in the real world are sparse, and the results are controversial. There is an efficacy-effectiveness gap in the treatment of hypertension using home BP measurements. We aimed to investigate the effect of reporting home BP to physicians on ambulatory BP control as a factor contributing to the efficacy-effectiveness gap in treating patients with hypertension. Methods: We recruited patients ≥20 years of age taking antihypertensive drugs. Office and 24-h ambulatory BP were measured. A questionnaire to the measurement of home BP was conducted. Participants were divided into an HBPM(-) group, home BP was not measured (n = 467); HBPM(+)-R(-) group, home BP was measured but not reported (n = 81); and HBPM(+)-R(+) group, home BP was measured and reported (n = 125). Results: The HBPM(+)-R(+) group had significantly lower office systolic BP (SBP, p = 0.035), 24-h SBP (p = 0.009), and daytime SBP (p = 0.016) than the HBPM(-) group, and lower nighttime SBP (p = 0.005) and diastolic BP (DBP, p = 0.008) than the HBPM(+)-R(-) group. In the multivariate analysis, the differences in 24-h SBP, daytime SBP, and nighttime DBP remained significant. There was a significant difference between groups in the target achievement rate of 24-h SBP (p = 0.046), nighttime SBP (p = 0.021), and nighttime DBP (p = 0.023). The nighttime SBP and DBP target achievement rates in the HBPM(+)-R(+) group were higher than those in the HBPM(+)-R(-) group (p = 0.006 and 0.010, respectively). Among patients measuring home BP, the adjusted odds ratio for 24-h and nighttime BP target achievement in the HBPM(+)-R(+) group were 2.233 and 3.658, respectively. Conclusion: Home BP measurements should be reported to the treating physician to effectively manage hypertension. Clinical trial registration: https://clinicaltrials.gov, identifier NCT03868384.

Body Mass Index and Major Adverse Events During Chronic Antiplatelet Monotherapy After Percutaneous Coronary Intervention With Drug-Eluting Stents　- Results From the HOST-EXAM Trial.

BACKGROUND: This study evaluated the association of body mass index (BMI) with adverse clinical outcomes during chronic maintenance antiplatelet monotherapy after percutaneous coronary intervention (PCI) with drug-eluting stents (DES).Methods and Results: Overall, 5,112 patients were stratified (in kg/m2) into underweight (BMI ≤18.4), normal weight (18.5-22.9), overweight (23.0-24.9), obesity (25.0-29.9) and severe obesity (≥30.0) categories with randomized antiplatelet monotherapy of aspirin 100 mg or clopidogrel 75 mg once daily for 24 months. The primary endpoint was the composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome and major bleeding of Bleeding Academic Research Consortium type ≥3. Compared with normal weight, the risk of primary composite outcomes was higher in the underweight (hazard ratio [HR] 2.183 [1.199-3.974]), but lower in the obesity (HR 0.730 [0.558-0.954]) and severe obesity (HR 0.518 [0.278-0.966]) categories, which is partly driven by the difference in all-cause death. The risk of major bleeding was significantly higher in the underweight (HR 4.140 [1.704-10.059]) than in the normal weight category. A decrease in categorical BMI was independently associated with the increased risk of primary composite outcomes. CONCLUSIONS: Lower BMI is associated with a higher risk of primary composite outcomes, which is primarily related to the events of all-cause death or major bleeding during chronic maintenance antiplatelet monotherapy after PCI with DES.

Association of the magnitude of the difference in blood pressure between office and ambulatory measurements with blood pressure variability in untreated individuals.

OBJECTIVES: We evaluated the association between cardiovascular risk factors and the magnitude of the difference in systolic blood pressure (SBP) between office and ambulatory measurements (masked effect) in untreated individuals without apparent hypertension-mediated organ damage (HMOD). METHODS: The inclusion criteria were 1) age ≥ 20 years, 2) blood pressure ≥ 140/90 mmHg at the outpatient clinic, and 3) not receiving antihypertensive medications. The difference between office and ambulatory SBP was calculated by subtracting the ambulatory daytime SBP from the office SBP. The association between the masked effect and SBP variability was analyzed in individuals without HMOD (no electrocardiographic left ventricular hypertrophy, spot urine albumin-to-creatinine ratio < 30 mg/g, and estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2, n = 296). RESULTS: Among the cardiovascular risk factors, ambulatory BP variability was significantly correlated with the SBP difference. The standard deviation (SD) and coefficient of variation (cv) of 24-h SBP exhibited a significant negative linear association with the SBP difference in univariate and multivariate analyses adjusted for age, sex, presence of diabetes, and 24-h ambulatory SBP. A significant association was observed in patients with ambulatory daytime hypertension. In the multivariate analysis, individuals with a negative SBP difference > -5 mmHg exhibited a higher SD and cv of 24-h SBP than those with a negative SBP difference ≤ -5 mmHg or a positive SBP difference. CONCLUSIONS: The results of our study suggest that the magnitude of the negative difference in office and ambulatory SBP may be a potential risk factor, even in individuals without apparent HMOD. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov ( NCT03855605 ).

A randomized, double-blind, multicenter, phase III study on the efficacy and safety of a combination treatment involving fimasartan, amlodipine, rosuvastatin in patients with essential hypertension and dyslipidemia who fail to respond adequately to fimasartan monotherapy.

BACKGROUND: To assess the efficacy and safety of a combination therapy involving fimasartan, amlodipine, and rosuvastatin in patients with essential hypertension and dyslipidemia who fail to respond to fimasartan monotherapy. METHODS: This phase III, randomized, double-blind, multicenter study was conducted in adults aged 19-70 years. Patients who voluntarily consented were screened for eligibility to enroll in the study. Patients who failed to respond to 4 weeks of fimasartan monotherapy were randomized with a 1:1:1 ratio to the fimasartan 60 mg/amlodipine 10 mg + rosuvastatin 20 mg (FMS/ALD + RSV) as study group, fimasartan 60 mg/amlodipine 10 mg (FMS/ALD) as control 1 group, and fimasartan 60 mg + rosuvastatin 20 mg (FMS + RSV) as control 2 group. The primary efficacy endpoints were the change in the sitting systolic blood pressure and the rate of change in the low-density lipoprotein cholesterol (LDL-C) level from baseline to 8 weeks. The adverse events, adverse drug reactions, physical examination findings, laboratory test results, electrocardiograms, and vital signs were evaluated to assess safety in the study. RESULTS: Of 138 randomized patients, 131 were conducted efficacy analysis, and 125 completed the study. For the change in LDL-C and sitting SBP (SiSBP) as primary efficacy assessments, the change in LDL-C at week 8 was significantly reduce in the FMS/ALD + RSV group than in the control 1 group (P < 0.001). The change in SiSBP at week 8 were greater reduce in the FMS/ALD + RSV group than in the FMS + RSV group (both P < 0.001). For the safety evaluation, there were no differences among the treatment groups in the incidence of adverse drug reactions. CONCLUSIONS: The fimasartan/amlodipine + rosuvastatin combination therapy can effectively and safely lower blood pressure and improve lipid levels in patients with essential hypertension and dyslipidemia who fail to respond adequately to fimasartan monotherapy. TRIAL REGISTRATION: NCT03156842, Registered 17 May 2017.

Association of periodontitis, missing teeth, and oral hygiene behaviors with the incidence of hypertension in middle-aged and older adults in Korea: A 10-year follow-up study.

BACKGROUND: The relationship between periodontitis and hypertension remains controversial. This study aimed to investigate the association of periodontitis, missing teeth, and oral hygiene behaviors with the incidence of hypertension. METHODS: A total of 104,349 participants were selected from the National Health Insurance System-Health Screening (NHIS-HEALS) cohort. Incident hypertension and periodontitis were diagnosed based on the patients' clinical records and health examinations. A multivariable Cox proportional hazards regression analysis was performed after adjusting for socioeconomic factors, coexisting disease, and health behaviors. RESULTS: The mean age of the participants was 51.1 years (range, 40-79 years) at baseline, and 55.1% were men. A total of 52,855 incident hypertension cases were identified during the median follow-up period of 9.6 years. Among the participants, periodontitis (hazard ratio [HR]: 1.02; 95% confidence interval [95% CI]: 1.00-1.04), number of missing teeth (for ≥15 group, HR: 1.40; 95% CI: 1.29-1.52), dental scaling (HR: 0.93; 95% CI: 0.91-0.95), and toothbrushing frequency (for ≥3 group, HR: 0.85; 95% CI: 0.83-0.88) were significantly associated with incident hypertension after full adjustments for covariates. While periodontitis was significantly associated with incident hypertension (HR: 1.04; 95% CI: 1.02-1.06) in the middle-aged group (40-64 years), the effect was insignificant in the older group (≥65 years). CONCLUSIONS: Oral inflammation could contribute to the incidence of hypertension; thus, efforts to reduce oral inflammation should be encouraged. Future intervention studies are warranted to determine whether oral health care could be beneficial in the management of hypertension.

Algorithm for diagnosing hypertension using out-of-office blood pressure measurements.

The authors developed and validated a diagnostic algorithm using the optimal upper and lower cut-off values of office and home BP at which ambulatory BP measurements need to be applied. Patients presenting with high BP (≥140/90 mm Hg) at the outpatient clinic were referred to measure office, home, and ambulatory BP. Office and home BP were divided into hypertension, intermediate (requiring diagnosis using ambulatory BP), and normotension zones. The upper and lower BP cut-off levels of intermediate zone were determined corresponding to a level of 95% specificity and 95% sensitivity for detecting daytime ambulatory hypertension by using the receiver operator characteristic curve. A diagnostic algorithm using three methods, OBP-ABP: office BP measurement and subsequent ambulatory BP measurements if office BP is intermediate zone; OBP-HBP-ABP: office BP, subsequent home BP measurement if office BP is within intermediate zone and subsequent ambulatory BP measurement if home BP is within intermediate zone; and HBP-ABP: home BP measurement and subsequent ambulatory BP measurements if home BP is within intermediate zone, were developed and validated. In the development population (n = 256), the developed algorithm yielded better diagnostic accuracies than 75.8% (95%CI 70.1-80.9) for office BP alone and 76.2% (95%CI 70.5-81.3) for home BP alone as follows: 96.5% (95%CI: 93.4-98.4) for OBP-ABP, 93.4% (95%CI: 89.6-96.1) for OBP-HBP-ABP, and 94.9% (95%CI: 91.5-97.3%) for HBP-ABP.  In the validation population (n = 399), the developed algorithm showed similarly improved diagnostic accuracy. The developed algorithm applying ambulatory BP measurement to the intermediate zone of office and home BP improves the diagnostic accuracy for hypertension.

A Randomized, Double-blind, Active-controlled, Two Parallel-Group, Optional Titration, Multicenter, Phase IIIb Study to Evaluate the Efficacy and Safety of Fimasartan Versus Perindopril Monotherapy With and Without a Diuretic Combination in Elderly Patients With Essential Hypertension.

PURPOSE: The efficacy and tolerability of fimasartan in elderly patients have not been fully evaluated. This study was therefore conducted to determine the efficacy and tolerability of fimasartan compared with perindopril in elderly Korean patients aged >70 years with essential hypertension (defined by a mean sitting systolic blood pressure [SBP] ≥140 mm Hg). METHODS: This randomized, double-blind, active-controlled, 2 parallel-group, optional titration, multicenter, Phase IIIb trial (FITNESS [Fimasartan in the Senior Subjects]) enrolled 241 patients from 23 cardiac centers in the Republic of Korea between August 2017 and December 2019. After the placebo run-in period, treatment started with fimasartan 30 mg or perindopril arginine 2.5 mg once daily at a 1:1 ratio; if BP was not controlled at week 4, the dose was doubled. If BP was not controlled at week 8, a diuretic combination (fimasartan 60 mg/hydrochlorothiazide 12.5 mg or perindopril arginine 5 mg/indapamide 1.25 mg) was administered. After 16 weeks of the double-blind treatment, the patients with controlled BP participated in an 8-week open-label extension study, with the 2 groups unified by fimasartan 60 mg with or without hydrochlorothiazide 12.5 mg for 8 weeks. The primary outcome was a change in SBP for 8 weeks. The secondary outcomes included a change in sitting diastolic BP (DBP) for 8 weeks and changes in SBP and DBP for 4, 16, and 24 weeks. FINDINGS: At week 8, mean SBP significantly decreased from baseline in both groups: -14.2 (14.4) mm Hg in the fimasartan group and -9.0 (16.1) mm Hg in the perindopril group. The difference between the 2 groups was 5.4 (2.1) mm Hg, indicating the noninferiority of fimasartan to perindopril. Moreover, fimasartan exhibited a higher BP-lowering effect than perindopril (P = 0.0108). In addition, reductions in SBP and DBP from baseline to weeks 4, 8, and 16 were significantly greater in the fimasartan group than in the perindopril group, although the SBP reduction was comparable at week 16. Both groups reported an excellent mean compliance rate of 97.4% (4.7%) through week 16. During the study period, 82 adverse events were reported in 52 patients, 40 in the fimasartan group and 42 in the perindopril group (P = 0.4647). Dizziness was the most commonly reported adverse event (7 cases). Remarkably, only 1 case of orthostatic hypotension was reported during the study period. IMPLICATIONS: In elderly patients with essential hypertension, fimasartan 30 to 60 mg with a possible hydrochlorothiazide 12.5-mg combination was noninferior to perindopril 2.5 to 5 mg with a possible indapamide 1.25-mg combination. Furthermore, fimasartan exhibited higher BP-lowering efficacy than perindopril. There was no difference in tolerability between the 2 groups. Clinicaltrials.gov Identifier: NCT03246555.

Prevalence and characteristics of isolated nocturnal hypertension in the general population.

BACKGROUND/AIMS: Ascertaining the prevalence of isolated nocturnal hypertension (INHT) in the general population and identifying the characteristics of patients with INHT may be important to determine patients who should receive 24- hour ambulatory blood pressure (BP) measurements. This study aimed to evaluate the prevalence and characteristics of INHT in the general population. METHODS: Of 1,128 participants (aged 20 to 70 years), we analyzed 823 who had valid 24-hour ambulatory BP measurements and were not on antihypertensive drug treatment. RESULTS: The prevalence of INHT in the study was 22.8%. Individuals with INHT had a higher office, 24-hour, and daytime and nighttime ambulatory systolic and diastolic BPs compared to individuals with sustained day-night normotension. INHT was more prevalent in individuals with masked hypertension (MH) than in those with sustained hypertension (59.8% vs. 15.6%, p < 0.001). Among individuals with INHT, 92.6% had MH. Among individuals with office BP-based prehypertension, 34.5% had both INHT and MH. The prevalence of INHT was highest in individuals with office BP-based prehypertension. INHT was an independent determinant of MH after adjustment for age, sex, body mass index, diabetes, low-density-lipoprotein cholesterol, 24-hour systolic and diastolic BP, systolic and diastolic BP dipping, and systolic and diastolic BP non-dipping. CONCLUSION: The present study showed that INHT is not uncommon and is a major determinant of MH. Our findings strongly suggest the use of 24-hour ambulatory BP measurement for individuals within the prehypertension range of office BP owing to the high prevalence of INHT and MH in this population.

Effects of Fixed-dose Combination of Low-intensity Rosuvastatin and Ezetimibe Versus Moderate-intensity Rosuvastatin Monotherapy on Lipid Profiles in Patients With Hypercholesterolemia: A Randomized, Double-blind, Multicenter, Phase III Study.

PURPOSE: We investigated whether the combination therapy of low-intensity rosuvastatin and ezetimibe is an useful alternative to moderate-intensity rosuvastatin monotherapy in patients requiring cholesterol-lowering therapy. METHODS: This was a multicenter randomized, double-blind study to investigate the safety and efficacy of a fixed-dose combination of rosuvastatin 2.5 mg and ezetimibe 10 mg (R2.5+E10) compared to those of ezetimibe 10 mg monotherapy (E10), rosuvastatin 2.5 mg (R2.5), and rosuvastatin 5 mg monotherapy (R5) in patients with hypercholesterolemia. A total of 348 patients at 15 centers in Korea were screened, and 279 patients were randomized to different groups in the study. Clinical and laboratory examinations were performed at baseline and 4 and 8 weeks after intervention. The primary endpoint was the percentage change of low-density lipoprotein (LDL) cholesterol levels at the 8-week follow-up. FINDINGS: Baseline characteristics were similar among the four groups. There were significant changes in lipid profiles at the 8-week follow-up. A greater decrease in the LDL cholesterol levels (primary endpoint) were found in the R2.5+E10 group (-45.7±18.6%) than in the E10 group (-16.7±14.7%, p<0.0001), R2.5 group (-32.6±15.1%, p<0.0001), and R5 group (-38.9±13.9%, p=0.0003). Similar outcomes were observed regarding the decrease in total cholesterol, non-high-density lipoprotein (HDL) cholesterol, and apolipoprotein B protein. In addition, changes in the triglyceride and HDL levels in the R2.5+E10 group were significantly different compared with those in the E10 group; however, the changes were similar to those in the other treatment groups. In patients with low and moderate risk, all patients achieved the target LDL cholesterol levels in the R2.5+E10 group (100%) compared to 13.0% in the E10 group, 47.6% in the R2.5 group, and 65.2% in the R5 group. Adverse effects were rare and similar in the four groups. IMPLICATIONS: Fixed-dose combination of low-intensity rosuvastatin and ezetimibe was more effective in lowering LDL cholesterol and achieving LDL cholesterol goals than moderate-intensity rosuvastatin monotherapy. These findings suggest that the combination therapy of low-intensity rosuvastatin and ezetimibe is an useful alternative to moderate-intensity rosuvastatin monotherapy for cholesterol management, particularly in patients with low and moderate risk. ClinicalTrials.gov identifier: NCT04652349.

Effect of angiotensin receptor blockers on the development of cancer: A nationwide cohort study in korea.

The potential cancer risk associated with long-term exposure to angiotensin receptor blockers (ARBs) is still unclear. We assessed the risk of incident cancer among hypertensive patients who were treated with ARBs compared with patients exposed to angiotensin-converting enzyme inhibitors (ACEIs), which are known to have a neutral effect on cancer development. Using the Korean National Health Insurance Service database, we analyzed the data of patients diagnosed with essential hypertension from January 2005 to December 2012 who were aged ≥40 years, initially free of cancer, and were prescribed either ACEI or ARB (n = 293,962). Cox proportional hazard model adjusted for covariates was used to evaluate the risk of incident cancer. During a mean follow-up of 10 years, 24,610 incident cancers were observed. ARB use was associated with a decreased risk of overall cancer compared with ACEI use (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.72-0.80). Similar results were obtained for lung (HR 0.73, 95% CI 0.64-0.82), hepatic (HR 0.56, 95% CI 0.48-0.65), and gastric cancers (HR 0.74, 95% CI 0.66-0.83). Regardless of the subgroup, greater reduction of cancer risk was seen among patients treated with ARB than that among patients treated with ACEIs. Particularly, the decreased risk of cancer among ARB users was more prominent among males and heavy drinkers (interaction P < .005). Dose-response analyses demonstrated a gradual decrease in risk with prolonged ARB therapy than that with ACEI use. In conclusion, ARB use was associated with a decreased risk of overall cancer and several site-specific cancers.

Determination of candesartan or olmesartan in hypertensive patient plasma using UPLC-MS/MS.

Candesartan and olmesartan are angiotensin II receptor blockers (ARBs) used for the treatment of hypertension and heart failure. Quantitation methods for candesartan and olmesartan were developed using ultra-high performance liquid chromatography-tandem mass spectrometry following protein precipitation. Candesartan was separated using 5 mM ammonium formate (A) and 100% acetonitrile (B) and olmesartan was separated using 2 mM ammonium formate with 0.1% formic acid (A) and 100% acetonitrile (B). Separation was performed using an isocratic method with a Thermo hypersil GOLD C18 column. Electrospray ionization was used for analyte ionization and detection of candesartan, olmesartan, and the internal standards by multiple reaction monitoring. Developed method showed excellent linearity (r > 0.99) in the concentration range of 2-500 ng/mL for candesartan and 5-2,500 ng/mL for olmesartan. Accuracies were 86.70-108.8% for candesartan and 87.87-112.6% for olmesartan. These methods were able to successfully measure plasma candesartan or olmesartan concentrations in hypertensive patients. This study can be used for pharmacokinetic studies of candesartan or olmesartan in humans.

Office blood pressure threshold of 130/80 mmHg better predicts uncontrolled out-of-office blood pressure in apparent treatment-resistant hypertension.

The objective of this study was to compare the diagnostic accuracy of office blood pressure (BP) threshold of 140/90 and 130/80 mmHg for correctly identifying uncontrolled out-of-office BP in apparent treatment-resistant hypertension (aTRH). We analyzed 468 subjects from a prospectively enrolled cohort of patients with resistant hypertension in South Korea (clinicaltrials.gov: NCT03540992). Resistant hypertension was defined as office BP ≥ 130/80 mmHg with three different classes of antihypertensive medications including thiazide-type/like diuretics, or treated hypertension with four or more different classes of antihypertensive medications. We conducted different types of BP measurements including office BP, automated office BP (AOBP), home BP, and ambulatory BP. We defined uncontrolled out-of-office BP as daytime BP ≥ 135/85 mmHg and/or home BP ≥ 135/85 mmHg. Among subjects with office BP < 140/90 mmHg and subjects with office BP < 130/80 mmHg, 66% and 55% had uncontrolled out-of-office BP, respectively. The prevalence of controlled and masked uncontrolled hypertension was lower, and the prevalence of white-coat and sustained uncontrolled hypertension was higher, with a threshold of 130/80 mmHg than of 140/90 mmHg, for both office BP and AOBP. The office BP threshold of 130/80 mmHg was better able to diagnose uncontrolled out-of-office BP than 140/90 mmHg, and the net reclassification improvement (NRI) was 0.255. The AOBP threshold of 130/80 mmHg also revealed better diagnostic accuracy than 140/90 mmHg, with NRI of 0.543. The office BP threshold of 130/80 mmHg showed better than 140/90 mmHg in terms of the correspondence to out-of-office BP in subjects with aTRH.

GENetic characteristics and REsponse to lipid-lowering therapy in familial hypercholesterolemia: GENRE-FH study.

Among the 146 patients enrolled in the Korean FH registry, 83 patients who had undergone appropriate LLT escalation and were followed-up for ≥ 6 months were analyzed for pathogenic variants (PVs). The achieved percentage of expected low-density lipoprotein-cholesterol (LDL-C) reduction (primary variable) and achievement rates of LDL-C < 70 mg/dL were assessed. The correlations between the treatment response and the characteristics of PVs, and the weighted 4 SNP-based score were evaluated. The primary variables were significantly lower in the PV-positive patients than in the PV-negative patients (p = 0.007). However, the type of PV did not significantly correlate with the primary variable. The achievement rates of LDL-C < 70 mg/dL was very low, regardless of the PV characteristics. Patients with a higher 4-SNP score showed a lower primary variable (R2 = 0.045, p = 0.048). Among evolocumab users, PV-negative patients or those with only defective PVs revealed higher primary variable, whereas patients with at least one null PV showed lower primary variables. The adjusted response of patients with FH to LLT showed significant associations with PV positivity and 4-SNP score. These results may be helpful in managing FH patients with diverse genetic backgrounds.