Objective:
The hypertension control rate is only 16.8% in China, and superior reasonable treatment is contributive to improve the rate. This study is aimed to evaluate whether pharmacogenomics-guided ...drug therapy is superior to conventional therapy in lowering blood pressure.
Design and method:
DNA samples were collected from 93 hypertensive patients. All patients entered a 4-week conventional treatment period, and then entered a 4-week pharmacogenomics-guided drug therapy period (the antihypertensive regimen was adjusted according to the pharmacogenomic report). The hypertension control rate and reduction of blood pressure (BP) were analyzed. High-throughput targeted sequencing panel was designed to detect efficacy and adverse-related genes of 24 commonly used antihypertensive drugs (5 types) and 52 gene loci were analyzed related to drug Efficacy (E): “E-”, “E”, “E+”, Tolerance (T): “T-”, “T”, “T+” and Metabolic (M): “M-”, “M”, “M+”. Clinical drug administration was guided according to relevant judgement results.
Results:
Compared with the conventional therapy group, the hypertension control rate of office and home blood pressure in the precise treatment group increased by 14.75% and 25.81%, respectively. The reduction of BP in the precise treatment group was greater than conventional therapy group ( Table and Figure).
Conclusions:
Compared with conventional therapy, the pharmacogenomics-guided drug therapy can control blood pressure more effectively.
Table. Comparison of Reduction in Office Systolic Blood Pressure (SBP)and Home SBP between the Precise Treatment Group and the Conventional Therapy Group
Figure: Comparison of Reduction in Office SBP and Home SBP between the Precise Treatment Group and the Conventional Therapy Group
Objective:
To evaluate whether a relatively old multi-drug SPC prescription can be adapted to current treatments of hypertension.
Design and method:
1. In a retrospective, real-world study, 22148 ...patients with hypertension who visited 4 hospitals in China from 2011 to May 2016 were selected as the subjects. A comparison was conducted between treatment with compound reserpine and triamterene tablets (Reserpine/Triamterene CAS) and with four other single-pill combinations (SPCs) (losartan/hydrochlorothiazide, valsartan/hydrochlorothiazide, irbesartan/hydrochlorothiazide, and amlodipine/valsartan) for 20 days. The compliance rate was analyzed after patients’ propensity score matching analysis. 2. A meta-analysis of 7 randomized controlled trials on the safety and efficacy of compound reserpine and triamterene tablets published from 2000 to 2020 was conducted.
Results:
1. Treatment with 1 compound reserpine and triamterene tablet daily (R/L) resulted in a blood pressure compliance rate (BP < 140/90 mmHg) of 63 to 68%. Compared with valsartan/amlodipine, R/L achieved a compliance rate of 63% vs 50%; with valsartan/hydrochlorothiazide, of 64% vs 59%; with losartan/hydrochlorothiazide, of 67% vs 57%, and with irbesartan/hydrochlorothiazide, of 68% vs 59%. All P values were < 0.05 (Figure 1).
2. Seven studies were included in the meta-analysis. In five studies, the overall response rate of hypotensive treatment with compound reserpine and triamterene tablets was higher in efficacy study compared with other hypotensive drugs (OR = 2.23, 95% CI: 1.32 ∼ 3.75) (Figure 2), and there was no significant difference in the incidence of adverse reaction with compound reserpine and triamterene tablets in the 6 trials included in the safety study (OR = 0.91, 95% CI: 0.68 ∼ 1.22) (Figure 3).
Conclusions:
China is faced with high prevalence of hypertension, low control rate, and scarce medical resources and economic resources in primary medical care, but ultra-low-dose SPC (R/L) can improve the antihypertensive effect and reduce the incidence of adverse reactions (Figure 4) through the synergistic effect among different components of the drug and has good patients’ compliance and low price. We confirmed that through systematic review and meta-analysis, ultra-low-dose SPC (R/L) is suitable for the treatment of hypertension, especially those with refractory hypertension.
Microalbuminuria and hyperuricemia management are crucial for the integrated management of hypertensive patients. This retrospective post hoc analysis aims to evaluate the optimal ...allisartan‐isoproxil‐based combination regimen for hypertensive patients with microalbuminuria or hyperuricemia. A total of 460 hypertensive patients with microalbuminuria and 486 hypertensive patients with hyperuricemia were included in this study. All patients were initially treated with allisartan‐isoproxil for 4 weeks. Thereafter, patients with blood pressure (BP) < 140/90 mmHg continued the monotherapy for 8 weeks; patients with BP ≥140/90 mmHg were randomly assigned in a 1:1 ratio to receive allisartan‐isoproxil + amlodipine (Group A + C) or allisartan‐isoproxil + indapamide (Group A + D) for 8 weeks. The changes of BP, urinary albumin and serum uric acid (UA) were measured. In patients with microalbuminuria, the urinary albumin/creatinine ratio (UACR) significantly decreased by 10.4 mg/g in Group A + C (vs. baseline p = .0035) and 24.2 mg/g in Group A + D (vs baseline p < .0001), intergroup p = NS. In patients with hyperuricemia, serum UA level decreased by 44.5 µmol/L in Group A + C (vs. baseline p = .0003), but increased by 27.2 µmol/L in Group A + D (vs. baseline p = .0167), intergroup p < .0001. The results suggest that for hypertensive patients with microalbuminuria, angiotensin receptor blocker (ARB) + calcium channel blocker (CCB) or ARB+ diuretic both are good choices based on their improvement of microalbuminuria and BP. But for patients with hyperuricemia, ARB + diuretic may further increase the level of UA.
ABSTRACT—LCZ696 (Japanese adopted namesucabitril valsartan sodium hydrate), a first-in-class angiotensin receptor neprilysin inhibitor, concomitantly inhibits neprilysin and blocks angiotensin type 1 ...receptor. This randomized, double-blind, placebo-controlled study, the first in Asia for this drug, evaluated the dose-related efficacy and safety of LCZ696 in patients with hypertension using 24-hour ambulatory blood pressure (BP) monitoring. Asian patients aged ≥18 years (n=389) with hypertension were randomized to receive LCZ696 100 mg (n=100), 200 mg (n=101), 400 mg (n=96), or placebo (n=92) for 8 weeks. The primary end point was mean difference across the 3 single-dose pairwise comparisons of LCZ696 versus placebo in clinic diastolic BP after 8-week treatment. Key secondary efficacy variables included changes in clinic systolic BP and pulse pressure and changes in 24-hour, daytime, and nighttime ambulatory BPs and pulse pressure. Safety assessments included recording all adverse events and serious adverse events. A total of 362 patients completed the study. Reductions in clinic systolic BP, diastolic BP (P<0.0001), and pulse pressure (P<0.001) were significantly greater with all doses of LCZ696 than with placebo. There were also significant reductions in 24-hour, daytime, and nighttime ambulatory systolic BP, diastolic BP, and pulse pressure for all doses of LCZ696 compared with placebo (P<0.0001). LCZ696 was well tolerated, and no cases of angioedema were reported. In conclusion, LCZ696 is effective for the treatment of hypertension in Asian population and, in general, is safe and well tolerated.
CLINICAL TRIAL INFORMATION—URLhttp://www.clinicaltrials.gov. Unique identifierNCT01193101.
High sodium intake plays an important role in the onset and exacerbation of hypertension. However, the relationships between urinary electrolytes excretion and central hemodynamics and between ...urinary electrolyte excretion and arterial stiffness are still the subject of debate. This study sought to clarify the associations of salt intake with central aortic pressure and arterial stiffness indicators. A total of 431 untreated hypertensive individuals were recruited into the study. Twenty-four-hour urinary samples were collected to measure the excretion of urinary electrolytes. Central hemodynamics parameters and brachial-ankle pulse wave velocity (baPWV) were measured. We evaluated the independent relationship between urinary sodium or potassium excretion and the abovementioned indices. The mean 24-h urinary sodium of all subjects was 166.6±70.0 mmol/24 h. With increases in urinary sodium excretion, central blood pressure and baPWV values markedly increased. Multiple regression analysis showed that urinary sodium was independently associated with increases in central systolic blood pressure, central diastolic blood pressure, the augmentation index, and baPWV. Significant correlations were identified between high dietary sodium and central hemodynamics and between high dietary sodium and arterial elasticity. Prospective interventional studies in hypertensive patients may be required to determine the effect of salt intake on central hemodynamics.
Summary Background The efficacy of treatments that lower homocysteine concentrations in reducing the risk of cardiovascular disease remains controversial. Our aim was to do a meta-analysis of ...relevant randomised trials to assess the efficacy of folic acid supplementation in the prevention of stroke. Methods We collected data from eight randomised trials of folic acid that had stroke reported as one of the endpoints. Relative risk (RR) was used as a measure of the effect of folic acid supplementation on the risk of stroke with a random effect model. The analysis was further stratified by factors that could affect the treatment effects. Findings Folic acid supplementation significantly reduced the risk of stroke by 18% (RR 0·82, 95% CI 0·68–1·00; p=0·045). In the stratified analyses, a greater beneficial effect was seen in those trials with a treatment duration of more than 36 months (0·71, 0·57–0·87; p=0·001), a decrease in the concentration of homocysteine of more than 20% (0·77, 0·63–0·94; p=0·012), no fortification or partly fortified grain (0·75, 0·62–0·91; p=0·003), and no history of stroke (0·75, 0·62–0·90; p=0·002). In the corresponding comparison groups, the estimated RRs were attenuated and insignificant. Interpretation Our findings indicate that folic acid supplementation can effectively reduce the risk of stroke in primary prevention.
Sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor-neprilysin inhibitor, demonstrated significant reductions in office and 24 h ambulatory blood pressure (BP) over 8 weeks in Asian ...patients with hypertension. This 52-week extension to the 8-week core study was aimed at evaluating the long-term safety, tolerability and efficacy of sacubitril/valsartan. Patients who completed an 8-week randomized study (the core study) were enrolled in this 52-week open-label study and received sacubitril/valsartan 200 mg QD. The sacubitril/valsartan dose was uptitrated to 400 mg QD if BP was uncontrolled (>140/90 mm Hg) after 4 weeks. Subsequently, in patients with uncontrolled BP, treatment was intensified every 4 weeks with amlodipine 5-10 mg followed by hydrochlorothiazide 6.25-25 mg. Of the 341 patients enrolled, 7 (2.1%) discontinued the study drug due to adverse events (AEs). The incidence of AEs and serious AEs were 63.9 and 3.8%, respectively, and no deaths were reported in this study. The most frequent AEs were nasopharyngitis (18.2%) and dizziness (8.8%). Events that were potentially indicative of low BP were infrequent. One patient reported mild transient angioedema (lasting 2.5 h) that resolved without treatment but led to study drug discontinuation. The sacubitril/valsartan-based regimen provided clinically significant mean sitting systolic BP (msSBP) and mean sitting diastolic BP (msDBP) reductions from baseline (-24.7/-16.2 mm Hg). The overall BP control, msSBP and msDBP response rates were 75.3, 90.6 and 87.6%, respectively. Long-term use of sacubitril/valsartan was generally safe and well-tolerated in patients with hypertension and provided significant BP reductions from baseline.
BACKGROUND
The spot urine method as an alternative approach in estimating daily urine sodium excretion has been proposed for many years. Kawasaki has created an equation to predict daily urinary ...sodium excretion using second morning urine (SMU) samples which was obtained before breakfast after initial voiding upon arising. Tanaka has developed another equation by examining spot urine samples submitted at random times during the day. A newly published study proposed that the “PM sample,” collected in the late afternoon or early evening before dinner, showed a stronger relationship with actual sodium excretion. We aimed to verify the effectiveness of these methods in evaluating 24-hour urinary sodium in Chinese hypertensive patients.
METHODS
A total of 334 hypertensive participants were eligible to participate in this study. A total of 222 patients provided qualified SMU samples, Post Meridiem (PM) samples, and complete 24-hour urine collections.
RESULTS
Biases using the Kawasaki formula were 2.1 mmol/day for the SMU specimens; for the Tanaka equation, biases of SMU and PM samples were 21.1 and 30.1 mmol/day, respectively. The highest intraclass correlation coefficient (ICC) was 0.64 when the Kawasaki formula was used in PM specimens, with the lowest ICC 0.17 when it is used in SMUs.
CONCLUSIONS
Spot urine method is acceptable for estimating 24-hour urinary sodium excretion in hypertensive individuals. Kawasaki’s formula is useful for estimating population mean levels of sodium excretion from SMU, although it is not suitable for estimating individual sodium excretion.
OBJECTIVE:To examine whether a change in serum total homocysteine (tHcy) levels is associated with first stroke risk in a post hoc analysis of the China Stroke Primary Prevention Trial (CSPPT).
...METHODS:We analyzed 16,867 participants of the CSPPT with tHcy measurements at both baseline and exit visits. The primary outcome was first stroke. The secondary outcome was a composite of cardiovascular events consisting of cardiovascular death, myocardial infarction, and stroke. The percent decline in tHcy was calculated as (baseline tHcy − exit tHcy)/baseline tHcy × 100.
RESULTS:Over the median treatment duration of 4.5 years, participants who developed a first stroke had a significantly lower percent decline in tHcy (β = −5.7; 95% confidence interval CI −8.8 to −2.6) compared to their counterparts. A 20% tHcy decline was associated with a reduction in stroke risk of 7% (hazard ratio HR 0.93; 95% CI 0.90–0.97). When percent decline in tHcy was assessed as tertiles, a significantly lower stroke risk was found in those in tertiles 2–3 (HR 0.79; 95% CI 0.64–0.97) compared with participants in tertile 1. Similar results were observed for the composite of cardiovascular events. The beneficial effect associated with greater tHcy reduction was observed across strata for age, sex, treatment group (with vs without folic acid), MTHFR C677T genotypes, baseline tHcy and serum folate levels, and blood pressure control.
CONCLUSIONS:Percent lowering in tHcy was significantly associated with a reduction in first stroke risk in Chinese adults with hypertension, and if further confirmed, may serve as a useful indicator for folic acid treatment efficacy on stroke prevention.
CLINICALTRIALS.GOV IDENTIFIER:NCT00794885.
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