Chang-Gyu Park

Efficacy and tolerability of fimasartan, a new angiotensin receptor blocker, compared with losartan (50/100 mg): a 12-week, phase III, multicenter, prospective, randomized, double-blind, parallel-group, dose escalation clinical trial with an optional 12-week extension phase in adult Korean patients with mild-to-moderate hypertension.

BACKGROUND Angiotensin receptor blockers (ARBs) is an effective and well tolerated first-line antihypertensive drug. Fimasartan is a newly developed ARB that has not been compared with other ARBs with regard to its efficacy and tolerability. OBJECTIVE The goal of this study was to determine the noninferiority of fimasartan to losartan with regard to its efficacy and tolerability in adult Korean patients with mild-to-moderate hypertension. METHODS This was a randomized, multicenter, double-blind, parallel group, dose escalation, Phase III, noninferiority clinical trial. Patients aged 18 to 70 years with mild-to-moderate hypertension were randomized to receive either fimasartan 60/120 mg daily or losartan 50/100 mg daily with optional titration. Antihypertensive efficacy and tolerability were evaluated for 12 weeks. The primary end point was noninferiority of improvement in mean siDBP from baseline to week 12 for fimasartan compared with losartan. The incidence and severity of adverse events (AEs) and adverse drug reactions (ADRs) were evaluated to assess their tolerability. In addition, some patients whose blood pressure reached goal levels participated in a 24-week extension study for additional assessment of tolerability and efficacy. RESULTS Five hundred six patients were randomly allocated to receive fimasartan (n = 256) or losartan (n = 250). There was no significant difference in baseline demographic characteristics between the 2 treatment groups (fimasartan-treated group-mean age, 53.96 [8.79] years; mean weight, 70.58 [11.73] kg; male, 68.02%; losartan-treated group-mean age, 53.58 [9.61] years; mean weight, 69.80 [11.08] kg; male, 70.17%). At week 12, siDBP was significantly decreased from baseline in both groups (-11.26 [7.53] mm Hg in the fimasartan group and -8.56 [7.72] mm Hg in the losartan group [P < 0.0001]). The between-group difference was 2.70 mm Hg (P = 0.0002), and the lower limit of the 2-sided 95% CI (1.27 mm Hg) was higher than the prespecified noninferiority margin (-2.5 mm Hg). The incidence of ADRs were 7.84% and 10.40% in the fimasartan and losartan groups, respectively (χ(2) test, P = 0.3181). The efficacy of fimasartan was maintained over 24 weeks, and its tolerability was comparable with losartan in the extension study. CONCLUSIONS In this study with eligible adult Korean patients who had mild-to-moderate hypertension, the reduction of siDBP after 12 weeks of treatment with fimasartan 60/120 mg was noninferior to that of losartan 50/100 mg. By post hoc comparison, between-group differences in siDBP were significant in favor of fimasartan, suggesting superiority to losartan. There was no statistically significant difference in tolerability between the groups. This efficacy and tolerability were maintained throughout the additional 12-week extension study.

Unrestricted Use of 2 New-Generation Drug-Eluting Stents in Patients With Acute Myocardial Infarction : A Propensity Score-Matched Analysis

OBJECTIVES This study sought to compare everolimus-eluting stents (EES) with zotarolimus-eluting stents (ZES) in patients with acute myocardial infarction (AMI). BACKGROUND There is a paucity of data to exclusively evaluate the safety and efficacy of second-generation drug-eluting stents (DES) in the setting of AMI. METHODS The present study enrolled 3,309 AMI patients treated with ZES (n = 1,608) or EES (n = 1,701) in a large-scale, prospective, multicenter registry-KAMIR (Korea Acute Myocardial Infarction Registry). Propensity score matching was applied to adjust for differences in baseline clinical and angiographic characteristics, producing a total of 2,646 patients (1,343 receiving ZES, and 1,343 receiving EES). Target lesion failure (TLF) was defined as the composite of cardiac death, recurrent nonfatal myocardial infarction, or target lesion revascularization. Major clinical outcomes at 1 year were compared between the 2 propensity score-matched groups. RESULTS After propensity score matching, baseline clinical and angiographic characteristics were similar between the 2 groups. Clinical outcomes of the propensity score-matched patients showed that, despite similar incidences of recurrent nonfatal myocardial infarction and in-hospital and 1-year mortality, patients in the EES group had significantly lower rates of TLF (6.5% vs. 8.7%, p = 0.029) and probable or definite stent thrombosis (0.3% vs. 1.6%, p < 0.001), compared with those in the ZES group. Furthermore, there was a numerically lower rate of target lesion revascularization (1.2% vs. 2.2%, p = 0.051) in the EES group than in the ZES group. CONCLUSIONS In this propensity-matched comparison, EES seems to be superior to ZES in reducing TLF and stent thrombosis in patients with AMI.

Vascular aging and hypertension: Implications for the clinical application of central blood pressure

Vascular aging may be responsible for the high residual lifetime risk for hypertension in the middle-aged and elderly individuals. Increased arterial stiffness and wave reflection has been recognized as the dominant hemodynamic manifestations of vascular aging, and both are major determinants of central blood pressure (BP) and independent predictors for incident hypertension. Because central BP is strongly linearly associated with age, it can be regarded as an integrated marker for vascular aging. Central BP can be measured noninvasively using various techniques, including the convenient cuff-based oscillometric central BP monitors. Noninvasive central BP is likely better than the conventional brachial BP in association with target organ damages and long term cardiovascular outcomes. Based on the analysis of the long-term events of derivation and validation cohorts, the central BP threshold of 130/90mmHg for defining hypertension has been proposed. Recent studies suggest that the central BP strategy for confirming a diagnosis of hypertension may be more cost-effective than the conventional brachial BP strategy, and guidance of hypertension management with central BP may result in less use of medications to achieve BP control. Vascular aging-related hypertension is expected to become the dominant phenotype in many countries, especially in the Asian regions. Although noninvasive measurement of brachial BP is inaccurate and central BP has been shown to carry superior prognostic value beyond brachial BP, the use of central BP should be justified by studies comparing central blood pressure-guided therapeutic strategies with classic guidelines-guided strategies for preventing cardiovascular events. Future randomized control trials are required to support that the diagnosis and monitoring of vascular aging-related hypertension is best managed with the central BP strategy.

Evaluation of the Dose-Response Relationship of Amlodipine and Losartan Combination in Patients with Essential Hypertension

BackgroundDespite recommendations for more intensive treatment and the availability of several effective treatments, hypertension remains uncontrolled in many patients.ObjectiveThe aim of this study was to determine the dose-response relationship and assess the efficacy and safety of amlodipine or losartan monotherapy and amlodipine camsylate/losartan combination therapy in patients with essential hypertension.MethodsThis was an 8-week, randomized, double-blind, factorial design, phase II, multicenter study conducted in outpatient hospital clinics among adult patients aged 18–75 years with essential hypertension. At screening, patients received placebo for 2–4 weeks. Eligible patients (n = 320) were randomized to one of eight treatment groups: amlodipine 5 mg or 10 mg, losartan 50 mg or 100 mg, amlodipine camsylate/losartan 5 mg/50 mg, 5 mg/100 mg, 10 mg/50 mg, or 10 mg/100 mg.Main Outcome MeasuresThe assumption of strict superiority was estimated using the mean change in sitting diastolic blood pressure (DBP) at 8 weeks. Safety was monitored through physical examinations, vital signs, laboratory test results, ECG, and adverse events.ResultsThe reduction in DBP at 8 weeks was significantly greater in patients treated with the combination therapies compared with the respective monotherapies for all specified comparisons except amlodipine camsylate/losartan 10 mg/100 mg versus amlodipine 10mg. The incidence of adverse events in the group of patients treated with the amlodipine camsylate/losartan 10 mg/50 mg combination tended to be higher than for any other group (27.9%, 12/43); however, the effect was not statistically significant.ConclusionCombination amlodipine camsylate/losartan (5 mg/50 mg, 5 mg/100 mg and 10 mg/50 mg) resulted in significantly greater BP lowering compared with amlodipine or losartan monotherapy, and was determined to be generally safe and tolerable in patients with essential hypertension.Clinical Trial RegistrationRegistered at clinicaltrials.gov: NCT00942344.

Target Blood Pressure in Patients with Diabetes: Asian Perspective

Recently, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) blood pressure (BP) trial enrolled 4733 participants with type 2 diabetes and randomized them to a target systolic blood pressure (SBP) of less than 120 mm Hg or 140 mm Hg. Despite the significant difference in the achieved SBP, there was no significant difference in the incidence of primary outcomes. Based on this evidence, the target SBP for diabetics has been revised in the majority of major guidelines. However, there is a steeper association between SBP and stroke in Asians than other ethnicities, with stroke being the leading cause of cardiovascular mortality. This suggests that target BP in the Asian region should be tailored towards prevention of stroke. In the ACCORD study, the intensive BP treatment was associated with significant reductions in both total stroke and non-fatal stroke. The results from the ACCORD study are supported by a subgroup analysis from the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) study, which showed that, in diabetic patients, the risk of stroke continues to decrease to a SBP value of 115 mm Hg with no evidence of J curve. As diabetes is highly associated with underlying coronary artery disease, there is a justified concern for adverse effects resulting from too much lowering of BP. In a post hoc analysis of 6400 diabetic subjects enrolled in the International Verapamil SR-Trandolapril (INVEST) study, subjects with SBP of less than 110 mm Hg were associated with a significant increase in all-cause mortality. In the ONTARGET study, at any levels of achieved SBP, diastolic blood pressure (DBP) below 67 mm Hg was associated with increased risk for cardiovascular outcomes. As such, a prudent approach would be to target a SBP of 130–140 mm Hg and DBP of above 60 mm Hg in diabetics with coronary artery disease. In conclusion, hypertension, in association with diabetes, has been found to be significantly correlated with an elevated risk for cardiovascular events. As the association between stroke and BP is stronger in Asians, compared to other ethnicities, consideration should be given for a target BP of 130/80 mm Hg in Asians.

Role of ambulatory blood pressure monitoring for the management of hypertension in Asian populations

Out‐of‐clinic blood pressure (BP) measurement, eg, ambulatory BP monitoring, has a strong association with target organ damage and is a powerful predictor of cardiovascular events compared with clinic BP measurement. Ambulatory BP monitoring can detect masked hypertension or various BP parameters in addition to average 24‐hour BP level. Short‐term BP variability assessed by standard deviation or average real variability, diminished nocturnal BP fall, nocturnal hypertension, and morning BP surge assessed by ambulatory BP monitoring have all been associated with target organ damage and cardiovascular prognosis. Recently, the authors compared the degree of sleep‐trough morning BP surge between a group of Japanese and a group of Western European untreated patients with hypertension and found that sleep‐trough morning BP surge in Japanese persons was significantly higher than that in Europeans. Although Asian persons have been known to have a higher incidence of stroke than heart disease, the difference in characteristics of BP indices assessed by ambulatory BP monitoring might be the cause of racial differences in stroke incidence between Asian and Western populations. This review focuses on Asian characteristics for the management of hypertension using ambulatory BP monitoring.

Management of Hypertension in Patients with Chronic Kidney Disease in Asia.

Hypertension is both a cause and consequence of chronic kidney disease (CKD). According to the Chinese national survey in 2007-2010, the prevalence of CKD was much higher in hypertensive patients (18.9%, n=16,691) than in the overall population sample (10.8%, n=47,204). CKD in hypertension confers risks to the kidneys as well as other organs. Probably because of high dietary salt intake, Asian hypertensive patients with CKD show high prevalence of non-dipping and reversed dipping blood pressure pattern, and may have even higher risks of cardiovascular disease. Therefore, out-of-office blood pressure evaluation and comprehensive cardiovascular evaluations are required. Most of current hypertension guidelines recommend intensive antihypertensive treatment in hypertensive patients with CKD. This is probably of particular relevance for cardiovascular prevention in Asia, because stroke, as a major complication of hypertension in Asia, is more closely related to blood pressure than coronary events. Intensive blood pressure control to 130/80 mmHg is often required to prevent CKD progression and cardiovascular complications. The inhibitors of the renin-angiotensin system (RAS) are recommended as the first line antihypertensive medications in patients with a glomerular filtration rate higher than 30 ml/min/1.73 m², which may more efficaciously prevent end-stage renal disease and cardiovascular events. Nonetheless, combination therapy of RAS inhibitors with other classes of antihypertensive drugs, such as calcium-channel blockers, diuretics, etc, is required to control blood pressure to the target.