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).

Fifteen-Year Nationwide Trend in Antiplatelet Treatment among Drug-Eluting Stent Recipients in Korea: Many Patients Receive Very Prolonged Dual-Antiplatelet Treatment, and Newer Drugs Are Replacing the Older Ones.

Drug-eluting stent (DES) recipients require 6-12 months of dual antiplatelet treatment (DAPT) and long-term aspirin mono-antiplatelet treatment (MAPT). Given the diversity of contemporary antiplatelet agents, antiplatelet treatment (APT) selection is becoming more complicated. We evaluated 15-year APT trends based on nationwide prescription data of 79,654 patients who underwent percutaneous coronary intervention (PCI) using DESs from 2002 to 2018 in Korea. DAPT (80.7%) was the most preferred initial APT post-PCI. Many DES recipients received prolonged DAPT (post-PCI 3 years: 41.0%; 10 years: 27.7%). There was a noticeable delay in DAPT-to-MAPT conversion from the mid to late 2000s (after the late-stent thrombosis concerns of first-generation DESs raised); the conversion after that was similar during the 2010s, occurring most robustly at 12-18 months post-PCI. Clopidogrel had long and increasingly been used for MAPT, surpassing aspirin. The recent increase in newer P2Y12 inhibitor prescriptions was noted. The patients treated with newer P2Y12 inhibitors were more likely younger men and presented with acute myocardial infarction. Real-world APT is evolving, and guideline-practice gaps exist. Further studies exploring the impact of diverse APT strategies on patient outcomes are expected to provide insights into optimal APT that can sophisticatedly balance the ischemic and bleeding risks.

A Multicenter, Randomized, Double-blind, Active-controlled, Factorial Design, Phase III Clinical Trial to Evaluate the Efficacy and Safety of Combination Therapy of Pitavastatin and Ezetimibe Versus Monotherapy of Pitavastatin in Patients With Primary Hypercholesterolemia.

PURPOSE: Pitavastatin is a unique lipophilic statin with moderate efficacy in lowering LDL-C levels by 30% to 50% with a tolerable safety profile. However, the efficacy of adding ezetimibe to pitavastatin in patients with dyslipidemia has not been well investigated. Therefore, the objective of this double-blind, multicenter, randomized, Phase III study was to compare the efficacy and safety of pitavastatin and ezetimibe combination therapy with those of pitavastatin monotherapy in Korean patients with primary hypercholesterolemia. METHODS: Korean men and women aged >19 and <80 years with primary hypercholesterolemia requiring medical treatment were included in this study. During the 8-week screening period, all patients were instructed to make therapeutic lifestyle changes. The screening period consisted of a 4-week washout period and a placebo run-in period (4-8 weeks). During treatment period I, patients were randomly assigned to receive 1 of 4 treatments: pitavastatin 2 mg plus ezetimibe 10 mg, pitavastatin 2 mg, pitavastatin 4 mg plus ezetimibe 10 mg, or pitavastatin 4 mg. The 8-week double-blind treatment period then commenced. Adverse events (AEs), clinical laboratory data, and vital signs were assessed in all patients. FINDINGS: The percentages in LDL-C from baseline after 8 weeks of double-blind treatment decreased significantly in the pooled pitavastatin/ezetimibe (-52.8% [11.2%]) and pooled pitavastatin (-37.1% [14.1%]) groups. Treatment with pitavastatin/ezetimibe resulted in a significantly greater LDL-C-lowering effect than that with pitavastatin (difference, -15.8 mg/dL; 95% CI, -18.7 to -12.9; P < 0.001). The precentages of achieving LDL-C goal in pooled pitavastatin/ezetimibe and pooled pitavastatin groups were 94.2% and 69.1%, respectively (P < 0.001). There were no significant differences in the incidence of overall AEs and adverse drug reactions. Serious AEs were comparable between the groups. IMPLICATIONS: Pitavastatin and ezetimibe combinations effectively and safely decreased LDL-C levels by >50% in patients with dyslipidemia. The safety and tolerability of pitavastatin and ezetimibe combination therapy were comparable with those of pitavastatin monotherapy. CLINICALTRIALS: gov identifier: NCT04584736.

Efficacy and safety of low-dose antihypertensive combination of amlodipine, telmisartan, and chlorthalidone: A randomized, double-blind, parallel, phase II trial.

The aim of this clinical trial was to assess the efficacy and safety of low-dose triple combinations of amlodipine, telmisartan, and chlorthalidone in patients with essential hypertension. After a 2-week placebo run-in period, 176 patients were randomized to seven treatment groups (placebo, quarter-dose combination, third-dose combination, half-dose combination, amlodipine 5 mg, amlodipine 10 mg, and telmisartan 80 mg) and administered the assigned study drug orally for 8 weeks. The primary efficacy endpoint was the change in the mean sitting systolic blood pressure (BP) (MSSBP) at Week 8. The MSSBP and mean sitting diastolic BP in the quarter-dose and half-dose groups were significantly lower compared to the placebo and amlodipine 5 mg groups, with similar BP-lowering effects observed compared to the amlodipine 10 mg and telmisartan 80 mg groups. However, the third-dose group showed significant BP improvement only compared to the placebo group. A similar pattern was observed for the control rate of hypertension and response rates. Additional analysis was conducted after correcting for gender and age effects, and, as a result, the third-dose group showed similar results with regard to the BP-lowering effect as the quarter-dose and half-dose groups. In terms of safety, no special adverse events and clinically significant results were noted, and all dose groups of the triple combination are considered safe for use in essential hypertension patients. The current findings indicated that low-dose triple combination of amlodipine, telmisartan, and chlorthalidone over 8 weeks effectively improved the BP-lowering effect in patients with essential hypertension without any safety concerns.

Favorable Vasomotor Function after Drug-Coated Balloon-Only Angioplasty of De Novo Native Coronary Artery Lesions.

Balloon-injured coronary segments are known to harbor abnormal vasomotion. We evaluated whether de novo coronary lesions treated using drug-coated balloon (DCB) are prone to vasospasm and how they respond to ergonovine and nitrate. Among 132 DCB angioplasty recipients followed, 89 patients underwent ergonovine provocation test at 6-9 months follow-up. Within-subject ergonovine- and nitrate-induced diameter changes were compared among three different sites: DCB-treated vs. angiographically normal vs. segment showing prominent vasoreactivity (spastic). No patient experienced clinically refractory vasospastic angina or symptom-driven revascularization during follow-up. Ergonovine induced vasospasm in seven patients; all were multifocal spasm either involving (n = 2) or rather sparing DCB-treated segments (n = 5). None showed focal spasm that exclusively involved DCB-treated lesions. Among 27 patients with vasospastic features, DCB-treated segments showed less vasoconstriction than spastic counterparts (p < 0.001). A total of 110 DCB-treated lesions were analyzed to assess vasomotor function. Vasomotor function, defined as a combined constrictor and dilator response, was comparable between DCB-treated and angiographically normal segments (p = 0.173), while significant differences were observed against spastic counterparts (p < 0.001). In our study, DCB-treated lesions were not particularly vulnerable to vasospasm and were found to have vasomotor function similar to angiographically normal segments, supporting safety of DCB-only strategy in treating de novo native coronary lesions.

Clinical and central hemodynamic characteristics of early adulthood isolated diastolic hypertension: a comparison with isolated systolic hypertension.

OBJECTIVES: Knowledge on early adulthood isolated diastolic hypertension (IDH) is limited. We compared the clinical and central hemodynamic characteristics of early adulthood IDH, isolated systolic hypertension (ISH) and normotension. METHODS: A total of 509 untreated young adults (18-35 years) who underwent ambulatory blood pressure monitoring (ABPM; ABPM cohort), 148 who underwent both ABPM and applanation tonometry (ABPM-tonometry cohort) and 26 newly recruited normotensives were analyzed. Their pulse wave images were analyzed after categorizing them into type A vs. B vs. C. RESULTS: In the ABPM cohort (men, 86.6%), systolic-diastolic hypertension was the most common subtype (68.0%), while IDH was the rarest (5.1%). The subtype composition showed age-dependency; the proportion of IDH and systolic-diastolic hypertension increased across the age tertiles, while that of ISH declined. Patients with IDH were significantly older and shorter than those with ISH. Despite having a significantly lower 24-h average systolic blood pressure (SBP), patients with IDH exhibited discordantly high central systolic blood pressures at levels comparable to those of patients with ISH. Pulse pressure amplification was the lowest in patients with IDH and highest in those with ISH (P < 0.001), accounting for the discordance. Augmentation index differed significantly between them (P < 0.016). The waveform composition differed across the subtypes (type A vs. B/C: IDH = 61.5 vs. 38.5%; ISH = 3.0 vs. 97.0%; normotension = 30.8 vs. 69.2%, P < 0.001); the averaged waveform plots demonstrated a clear morphological disparity between IDH (type A) and ISH (type B/C). CONCLUSIONS: Early adulthood IDH is a unique entity clearly distinguishable from ISH in terms of clinical and central hemodynamic characteristics.

Effect of body mass index and abdominal obesity on mortality after percutaneous coronary intervention: a nationwide, population-based study.

BACKGROUND/AIMS: We investigated the impact of obesity on the clinical outcomes following percutaneous coronary intervention (PCI). METHODS: We included South Koreans aged > 20 years who underwent the Korean National Health Screening assessment between 2009 and 2012. Obesity was defined using the body mass index (BMI), according to the World Health Organization's recommendations. Abdominal obesity was defined using the waist circumference (WC), as defined by the Korean Society for Obesity. The odds and hazard ratios in all-cause mortality were calculated after adjustment for multiple covariates. Patients were followed up to the end of 2017. RESULTS: Among 130,490 subjects who underwent PCI, the mean age negatively correlated with BMI. WC, hypertension, diabetes, dyslipidemia, fasting glucose, total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels correlated with the increased BMI. The mortality rates were higher in the lower BMI and WC groups than the higher BMI and WC groups. The non-obese with abdominal obesity group showed a mortality rate of 2.11 per 1,000 person-years. Obese with no abdominal obesity group had the lowest mortality rate (0.88 per 1,000 person-years). The mortality showed U-shaped curve with a cut-off value of 29 in case of BMI and 78 cm of WC. CONCLUSION: The mortality showed U-shaped curve and the cut-off value of lowest mortality was 29 in case of BMI and 78 cm of WC. The abdominal obesity may be associated with poor prognosis in Korean patients who underwent PCI.

Efficacy and safety of co-administered telmisartan/amlodipine and rosuvastatin in subjects with hypertension and dyslipidemia.

Single risk factors, such as hypertension and dyslipidemia, can combine to exacerbate the development and severity of cardiovascular disease. Treatment goals may be more effectively achieved if multiple disease factors are targeted with combination treatment. We enrolled 202 patients who were randomly divided into the following three groups: telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg, telmisartan 80 mg + rosuvastatin 20 mg, and telmisartan/amlodipine 80/5 mg. The primary efficacy variables were changes from baseline in mean sitting systolic blood pressure (MSSBP) between telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan 80 mg + rosuvastatin 20 mg at 8 weeks, and the percent changes from baseline in low-density lipoprotein (LDL) cholesterol between telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan/amlodipine 80/5 mg at 8 weeks. The secondary efficacy variables were changes in MSSBP, mean sitting diastolic blood pressure (MSDBP), LDL cholesterol and other lipid levels at 4 weeks and 8 weeks, as well as observed adverse events during follow-up. There were no significant differences between the three groups in demographic characteristics and no significant difference among the three groups in terms of baseline characteristics for the validity evaluation variables. The mean overall treatment compliance in the three groups was, respectively, 98.42%, 96.68%, and 98.12%, indicating strong compliance for all patients. The Least-Square (LS) mean (SE) for changes in MSSBP in the two (telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan 80 mg + rosuvastatin 20 mg) groups were -19.3 (2.68) mm Hg and -6.69 (2.76) mm Hg. The difference between the two groups was significant (-12.60 (2.77) mm Hg, 95% CI -18.06 to -7.14, P < .0001). The LS Mean for the percent changes from baseline in LDL cholesterol in the two (telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan/amlodipine 80/5 mg) groups were -52.45 (3.23) % and 2.68 (3.15) %. The difference between the two groups was significant (-55.13 (3.20) %, 95% CI -61.45 to -48.81, P < .0001). There were no adverse events leading to discontinuation or death. Combined administration of telmisartan/amlodipine 80/5 mg and rosuvastatin 20 mg for the treatment of hypertensive patients with dyslipidemia significantly reduces blood pressure and improves lipid control. ClinicalTrials.gov identifier: NCT03067688.

A randomized, double-blind clinical trial to evaluate the efficacy and safety of a fixed-dose combination of amlodipine/rosuvastatin in patients with dyslipidemia and hypertension.

This multicenter, randomized, double-blind, parallel-group phase III clinical trial aimed to investigate the efficacy and safety of a rosuvastatin + amlodipine combination compared with that of rosuvastatin or amlodipine monotherapy in hypertensive patients with dyslipidemia. A total of 106 patients of 15 institutions in Korea were randomly assigned to 1 of 3 treatment groups: rosuvastatin 20 mg + amlodipine 10 mg, amlodipine 10 mg, or rosuvastatin 20 mg. After 8 weeks of treatment, the mean ± SD of change in mean sitting systolic blood pressure (msSBP) was -22.82 ± 12.99 mm Hg in the rosuvastatin + amlodipine group, the most decreased among the treatment groups. The percentage of patients whose msSBP decreased ≥20 mm Hg or msDBP decreased ≥10 mm Hg was also highest in this group (74.29%). The mean ± SD percentage change in low-density lipoprotein cholesterol (LDL-C) level from baseline after 8 weeks was -52.53% ± 11.21% in the rosuvastatin + amlodipine group, the most decreased among the treatment groups. More patients in the rosuvastatin + amlodipine group achieved their target LDL-C goal at 8 weeks, compared with the other treatment groups (97.14%). No serious adverse events or adverse drug reactions were observed in all groups. In hypertensive patients with dyslipidemia, combination treatment with rosuvastatin 20 mg + amlodipine 10 mg effectively reduced blood pressure and LDL-C levels while maintaining safety.

Central hemodynamic characteristics of young adults with isolated systolic hypertension: an ambulatory blood pressure monitoring-based study of real-world clinical patients.

The central hemodynamic characteristics of young adults with isolated systolic hypertension (ISH) remain controversial, particularly regarding the extent of pulse pressure amplification (PPamp) compared with that of normotensives (NTs). Given the lack of ambulatory blood pressure monitoring (ABPM)-based data, this study evaluated 509 untreated young adults (18-35 years) who had undergone ABPM during the last decade, 109 who had undergone both ABPM and SphygmoCor analysis, and 26 newly recruited NTs. The agreement rate between office BP- and ABPM-based subtype classification was alarmingly low (50.7%). ISH was distinguishable from systolic-diastolic hypertension, the predominant subtype characterized by increased central BPs and stiffened arteries. The central hemodynamic parameters were all similar between patients with ISH and white-coat hypertension (WC). ISH patients had central BPs that were, albeit higher than those of NTs, at an upper-normal level that was comparable to those of WC patients. ISH patients had similar cfPWV but significantly higher PPamp than NTs (p = 0.032). The central hemodynamic parameters of the participants were further analyzed according to central pressure waveform types (A vs. B vs. C). Type C waves were associated with the highest PPamp and lowest cfPWV, whereas type A waves were associated with the lowest PPamp and highest cfPWV. Subjects with type B waves, an intermediate form, also had considerably high PPamps. Waveform composition differed significantly across hypertension subtypes (p < 0.001). ISH patients mostly had type B or C waves (96.7%), with only 3.3% having type A waves. This study based on a refined diagnosis showed that the ambulatory ISH of young adults arises from highly elastic arteries and related robustness of PPamp and shares similar central hemodynamic characteristics with WC patients.