A Japan nationwide web‐based survey of estimation on patients for renal denervation based on blood pressure level and the number of antihypertensives (J‐NEEDs survey)

Catheter‐based renal denervation (RDN) is currently being developed as a new complementary treatment option for hypertension. RDN has not yet received approval in Japan and so the number of possible candidates for RDN in Japan also remains unknown. A total of 10 756 hypertensive patients who regularly visit medical institutions and reported their latest home blood pressure (BP) values were identified from registrants at an online research company. They filled out a survey regarding their prescribed antihypertensives and latest BP values in March 2020 in Japan. The mean age of the patients was 61.3 years old (83.5% male). According to JSH 2019, the prevalence of resistant hypertension (RHT) was estimated to be 1.4% (0.52% having an office BP of 140/90 mm Hg or more while taking three antihypertensives, including diuretics; 0.84% taking four or more antihypertensives regardless of BP level). Assuming the indication for RDN was RHT with morning home systolic BP (HSBP) ≥ 135 mm Hg and office systolic BP (OSBP) ≥ 140 mm Hg, the number of candidates for RDN was estimated to be approximately 340 000 and 372 000, respectively. When hypertensive patients prescribed three or more, two, one, and no antihypertensives were included, the estimated number based on uncontrolled HSBP and OSBP cumulatively increased 2.6, 14.2, 40.6, and 58.0‐fold; 1.8, 8.6, 25.3, and 36.4‐fold, respectively. These findings revealed that a substantial number of hypertensive patients are unable to adequately control their BP level with existing treatments, and new complemental therapies, such as RDN, would alleviate the burden of hypertension in this population.     

Japan Society of Hepatology guidelines for the management of hepatitis C virus infection: 2019 update

The Drafting Committee for Hepatitis Management Guidelines established by the Japan Society of Hepatology (JSH) drafted the first version of the clinical practice guidelines for the management of hepatitis C virus (HCV) infection in 2012. Since then, we have been publishing updates as new drugs for hepatitis C become available and new indications for existing drugs are added. The new approval of sofosbuvir/velpatasvir prompted us to publish the seventh version of the guidelines in Japanese in March 2019. We also published the first English‐language version of the JSH guidelines in 2013 and English versions of updates made to the Japanese‐language guidelines in 2014 and 2016. In 2020, the Committee has decided to publish a new English version, covering general information about treatment for hepatitis C, drugs used, recommended treatments for chronic hepatitis and cirrhosis, and special populations, such as patients who have renal impairment, are on dialysis, or have developed recurrence of hepatitis C after liver transplantation. Furthermore, the Committee has released a separate publication covering the protective effect of antiviral therapy against hepatocarcinogenesis.     

Diuretic induced hyponatraemia in elderly hypertensive women

Diuretics are recommended as first-line antihypertensive treatment in elderly patients. Although attention is usually paid to prevent hypokalaemia with diuretic therapy, risk of hyponatraemia is often ignored. We performed this study to characterise hypertensive patients at increased risk to develop hyponatraemia. We reviewed charts of hypertensive patients hospitalised in Chaim Sheba Medical Center for hyponatraemia from 1990 to 1997. Patients with other causes of hyponatraemia were excluded. The General Practice Maccabi database was used to estimate age and sex distribution of patients prescribed diuretics for hypertension. We identified 180 hypertensive patients (149 F, 31 M; mean age 76.4 +/- 9.2 years) hospitalised because of hyponatraemia. Across all age groups, odds ratio (OR) to develop hyponatraemia was three times higher for women vs men (OR 3.10, 95% confidence interval (CI): 2.07-4.67). One hundred and sixty-two patients (90%) were older than 65 years. Patients of both sexes older than 65 years were 10 times (and if they were older than 75 years 16 times) more likely to develop hyponatraemia than those younger than 65 years (OR 9.87, 95%, CI: 5.93-16.64). Most patients (74.5%) used a thiazide-based diuretic; only 10% used a low dose (<25 mg/day). In 37% of patients diuretics were used for more than 1 year before hyponatraemia developed. Diuretic-induced hyponatraemia may be insidious and appear even after prolonged diuretics use. Elderly women seem to be at particularly high risk. In this population diuretic use should be associated with close monitoring of sodium and potassium levels.     

Control of blood pressure as measured at home and office, and comparison with physicians' assessment of control among treated hypertensive patients in Japan: First Report of the Japan Home versus Office Blood Pressure Measurement Evaluation (J-HOME) study.

The Japan Home versus Office Blood Pressure Measurement Evaluation (J-HOME) study was conducted to measure the control of blood pressure (BP) as evaluated by home BP measurement among 3,400 patients with essential hypertension (mean age: 66 years; females: 55%) receiving antihypertensive treatment in primary care settings in Japan. The purpose of this first report was to compare characteristics of BP control as measured at home and in the clinic (office) and define their association with BP control as evaluated by physicians. Mean systolic/diastolic BP (SBP/DBP) values were 140/82 mmHg for home BP and 143/81 mmHg for office BP. BP levels were not adequately controlled among approximately 60% of the patients, according to reference values described in the national guidelines (office BP: <140/90 mmHg; home BP: <135/85 mmHg). Even among patients evaluated by physicians as having excellent or fairly good BP control, office and home SBP values were insufficiently controlled in approximately 50%. Although the tendency was more remarkable among older patients, whose recommended target BP levels are higher than those of middle-aged patients in the Japanese Hypertension Society 2000 criteria, office and home BP values were not adequately controlled in approximately 50% of the middle-aged patients whose BP control was evaluated as good. Our findings suggest that an important reason why home and office BP values are not adequately controlled is that physicians approve relatively higher BP levels under treatment, even among middle-aged patients.     

The effect of combination therapy with an L/N-Type Ca(2+) channel blocker, cilnidipine, and an angiotensin II receptor blocker on the blood pressure and heart rate in Japanese hypertensive patients: an observational study conducted in Japan.

Recently, the use of combination therapy with a calcium channel blocker (CCB) and an angiotensin II receptor blocker (ARB) has been rapidly increasing. Although this combination therapy is accepted as a standard treatment hypertension, there have been few large-scale, multicenter studies examining its safety and efficacy. The present study was designed to investigate the safety and efficacy of adding cilnidipine, a dual L/N-type CCB, to the regimen of patients whose blood pressure had been poorly controlled (systolic blood pressure [SBP] >140 mmHg or diastolic blood pressure [DBP] >90 mmHg) by antihypertensive monotherapy with an ARB. The percentage achievement of the blood pressure goals recommended by the JSH 2000 guidelines was also assessed for at least 12 weeks of treatment. A total of 2,920 patients were enrolled in the study at 471 institutions in Japan from February 2003 to July 2004. The incidence of adverse reactions related to cilnidipine was as low as 2.5%. A significant reduction from the baseline was found both in SBP (from 164.1 +/- 15.3 to 139.2 +/- 15.3 mmHg, p<0.0001) and DBP (from 91.7 +/- 11.4 to 79.3 +/- 10.7 mmHg, p<0.0001). A total of 31.5% of the patients achieved the blood pressure goals recommended by the JSH 2000 guidelines. Moreover, the heart rate also significantly decreased in these patients, particularly in those with a higher baseline heart rate. Our results indicate that cilnidipine can be used in combination with an ARB to control blood pressure without any significant adverse effects, and also that cilnidipine successfully reduces elevated heart rate, which is a possible risk factor for cardiovascular events.     

Heart failure due to left ventricular systolic dysfunction: treatment at discharge from hospital and at one year

BACKGROUND: The treatment of heart failure (HF) due to left ventricular systolic dysfunction has been defined in recent guidelines, but these guidelines are not always applied in routine clinical practice. One of the objectives of the ETICS study was to evaluate medical treatment at discharge and after 1 year in patients hospitalised for a first episode of congestive HF due to left ventricular systolic dysfunction in 2000. METHODS: One hundred and seventy nine patients (63% males, mean age of 69+/-13 years) with an ejection fraction < or = 40% were prospectively included. The main aetiology was ischaemic heart disease (44%). RESULTS: The drugs prescribed at discharge and at one year, respectively, were loop diuretics in 95% and 91% of cases, angiotensin-converting enzyme (ACE) inhibitors in 82% and 75%, spironolactone in 35% and 37%, beta-blockers in 25% and 41%, digitalis glycosides in 34% and 30% of cases, and nitrates in 20% and 16% of cases. ACE inhibitors were prescribed at discharge and at 1 year at dosages reaching 64+/-29% and 72+/-30% of the recommended doses, respectively, and beta-blockers were prescribed at 26+/-16% and 35+/-25% of recommended doses, respectively. CONCLUSION: Diuretics and ACE inhibitors are largely prescribed in HF due to left ventricular systolic dysfunction, followed by spironolactone. Beta-blockers are still underused both in terms of the rate of patients receiving them and the daily doses. These results highlight the value of continuing to widely circulate official practice guidelines in order to improve the management of HF due to left ventricular systolic dysfunction.     

Management of hepatocellular carcinoma in Japan: Consensus-Based Clinical Practice Guidelines proposed by the Japan Society of Hepatology (JSH) 2010 updated version

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death not only in Japan but also worldwide. Clinical practice guidelines for HCC were first published in 2001 by the European Society of Study of the Liver (EASL) followed by the American Association for the Study of Liver Disease (AASLD) published in 2005 and updated in 2010. However, these guidelines have proven to be somewhat unsuitable for Japanese patients. In 2005, supported by the Japanese Ministry of Health, Labour and Welfare, evidence-based clinical practice guidelines for HCC were compiled in Japan. In 2009, a revised version of evidence-based guidelines was published. Based on both 'evidence-based' guidelines and the consensus of an expert panel on HCC, the Japan Society of Hepatology (JSH) published the Consensus-Based Clinical Practice Manual in 2007 and updated in 2010. In this article, the 2010 updated version of this manual, especially issues on prevention, surveillance, pathology, diagnosis, staging, and treatment algorithm are summarized.     

Loop Diuretics in the Treatment of Hypertension

Loop diuretics are not recommended in current hypertension guidelines largely due to the lack of outcome data. Nevertheless, they have been shown to lower blood pressure and to offer potential advantages over thiazide-type diuretics. Torsemide offers advantages of longer duration of action and once daily dosing (vs. furosemide and bumetanide) and more reliable bioavailability (vs. furosemide). Studies show that the previously employed high doses of thiazide-type diuretics lower BP more than furosemide. Loop diuretics appear to have a preferable side effect profile (less hyponatremia, hypokalemia, and possibly less glucose intolerance). Studies comparing efficacy and side effect profiles of loop diuretics with the lower, currently widely prescribed, thiazide doses are needed. Research is needed to fill gaps in knowledge and common misconceptions about loop diuretic use in hypertension and to determine their rightful place in the antihypertensive arsenal.     

Hypertension Guideline Adherence Among Nursing Home Patients

Background  Adherence to hypertension guidelines in the outpatient setting is low. Objective  To evaluate adherence to JNC VII guidelines in nursing home patients. Design  Data were obtained from the 2004 National Nursing Home Survey (NNHS), a nationally representative sample of US nursing homes. Patients with hypertension were identified using ICD-9 codes. Adherence to JNC VII guidelines was defined as the use of a thiazide diuretic in patients without a compelling indication for a different class of antihypertensive medication, such as diabetes, chronic kidney disease, coronary artery disease, congestive heart failure, or a history of stroke. Participants  There were 13,507 patients in the 2004 NNHS survey, of whom 7,129 had hypertension. Main Results  Of these 7,129 hypertensive patients, only 12.6% were on a thiazide. Out of the 7,129 hypertensive patients, 3,113 did not have diabetes, chronic kidney disease, coronary artery disease, congestive heart failure, or a history of stroke. Of these 3,113 patients, only 13.9% were on a thiazide. After excluding patients with a potential contraindication to a diuretic, such as hospice care or incontinence, only 18% were prescribed a thiazide. Of the 3,113 patients, 1,148 were on a single class of antihypertensive and more were prescribed a beta blocker, ACE inhibitor, calcium channel blocker, loop diuretic, and ARB than a thiazide diuretic. Conclusions  Adherence to hypertension guidelines among nursing home patients is low. The appropriate use of thiazide diuretics could reduce costs and improve blood pressure control and patient outcomes.     

Austrian survey of treating heart failure--AUSTRIA

BACKGROUND: Treatment of chronic heart failure is based on the results of large clinical trials, which form the basis of treatment guidelines, such as those from the European Society of Cardiology (ESC). The aim of this study was to record treatment-modalities and the implementation of guidelines of chronic heart failure in clinical practice in Austria. METHODS: Overall 96 general physicians, specialists for internal medicine in private practice or in hospital outpatient departments participated in the survey. Physicians were asked to prospectively document 30 consecutive patients with chronic heart failure. RESULTS: 1880 patients were documented. The majority of patients were treated by general physicians (57%). Coronary artery disease was the most frequent aetiology for heart failure (47%). The most frequently used drugs were blockers of the renin-angiotensin-system (RAS-blocker including ACE-inhibitors and angiotensin-receptor-blockers, 78%), diuretics (76%) and beta-blockers (49%). Other drugs like digitalis and spironolactone were used infrequently. Average doses of ACE-inhibitors were approximately 90% of those recommended by the ESC, average doses of beta-blockers were approximately 50% of those recommended. Treatment among the three classes of physicians differed with respect to RAS-blockers and beta-blockers, which were used infrequently by general practitioners. Both groups of drugs were given more frequently to younger patients (<70 years) while digitalis was given more often to elderly patients. CONCLUSIONS: Results from this survey suggest that Austrian physicians treating patients with heart failure use the appropriate drugs in dosages that are suggested by recently published guidelines (ACE-inhibitors and beta-blockers). However, dosages of spironolactone clearly differed from current recommendations.     

Effects of clonidine on diuretic response in ascitic patients with cirrhosis and activation of sympathetic nervous system

The effects of the addition of clonidine to diuretics on the mobilization of ascites in the short term (diuretic response and requirement of diuretics) and the long term (readmissions for tense ascites and requirement of diuretics) were examined in patients with cirrhosis and with increased sympathetic nervous system (SNS) activity. We also studied neurohormonal, hemodynamic effects and side effects of clonidine and diuretics. Patients were randomized to receive placebo (group 1, n = 32) or clonidine (0.075 mg) twice daily (group 2, n = 32) for 3 months. After 8 days and for 10 days duration, spironolactone (200 mg/day) was added in both groups. After this period, the dosages of diuretics were individually increased until diuretic response. Responding patients were discharged and followed at the outpatient clinic. During the first hospitalization, the time needed for diuretic response was shorter in group 2 than in group 1. The mean requirement for diuretics was significantly higher in group 1 than in group 2, and the diuretic complications (hyperkalemia and renal impairment) were significantly lower in group 2. Clonidine induced a permanent decrease in SNS activity and delayed decrease in renin/aldosterone levels. During the follow-up, the time to the first readmission for tense ascites was shorter in group 1 than in group 2. Readmissions related to tense ascites or diuretic complications were significantly lower in group 2. The mean requirement for diuretics was significantly higher in group 1 than in group 2. In conclusion, the additional administration of clonidine to diuretics induced an earlier diuretic response associated with fewer diuretic requirements and complications.     

Pharmacologic treatment of hypertension in the Department of Veterans Affairs during 1995 and 1996

Patterns of antihypertensive drug use, the cost of this care and potential savings with changes of treatment patterns, were studied for all hypertensives treated at US Veterans Affairs (VA) medical facilities for fiscal years 1995 and 1996. Data was aggregated by individual medication as well as by antihypertensive drug class. Cost estimates were based on median cost and number of units for each dosage form of each medication dispensed at all facilities. Potential savings were estimated by substituting β-blockers or diuretics for calcium antagonists. In a subset of patients the prevalence of hypertension, and among hypertensives the prevalence of coronary artery disease, congestive heart failure, and diabetes mellitus, was determined. For these patients, patterns of treatment by antihypertensive drug class was examined.For all VA facilities, of the 10 most frequently prescribed antihypertensives in 1995, four were calcium antagonists, two angiotensin converting enzyme (ACE) inhibitors, two β-blockers, and two diuretics. In 1996, this was changed by the addition of an ACE inhibitor and the subtraction of a diuretic combination. Calcium antagonists accounted for 37% of treatment days in 1995 and 35% in 1996, ACE inhibitor use went from 34% to 36%, β-blockers from 17% to 18%, and diuretic use remained at 12%. In 1996, approximately 86.6 million dollars were spent on calcium antagonists, 51.8 million on ACE inhibitors, 7.9 million on β-blockers, and 3.6 million on diuretics. The estimated annual cost savings for each 1% conversion of calcium antagonists to β-blockers would be $713,000 and to diuretics $758,000. In a subset of 7526 hypertensive patients with known comorbid conditions, calcium antagonists and ACE inhibitors were also the most commonly used drug classes for all categories of patients, including those without coronary artery disease, congestive heart failure, and diabetes mellitus.Calcium antagonists and ACE inhibitors were the most commonly dispensed antihypertensives at VA facilities for both 1995 and 1996, with a small decrease in calcium antagonist use from 1995 to 1996. The cost implications of these practice patterns as compared with the primary use of diuretics and β-blockers are enormous.     

Effects of initial antihypertensive drug class on patient persistence and compliance in a usual-care setting in the United States

Antihypertensive treatment regimen persistence and compliance were measured using a retrospective cohort study of pharmacy claims data. Newly treated patients receiving monotherapy with angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs), calcium channel blockers (CCBs), beta-blockers (BBs), or diuretics were followed for 1 year (N=242,882). A higher proportion of ARB patients (51.9%) were persistent in taking prescribed medication compared with those in the ACEI (48.0%), BB (40.3%), CCB (38.3%), and diuretic groups (29.9%). Compared with patients receiving diuretics, those receiving ARBs (hazard ratio [HR], 0.593; P<.0001), ACEIs (HR, 0.640; P<.0001), CCBs (HR, 0.859; P<.0001), and BBs (HR, 0.819; P<.0001) were all less likely to discontinue therapy. Compliance was similar in ACEI and ARB patients, but patients receiving ARBs and ACEIs had better compliance than those receiving BBs, CCBs, or diuretics. The lesser degree of compliance and persistence observed in patients receiving diuretics compared with other antihypertensive medications may have public health as well as cost implications.     

Management of hepatitis C; Report of the Consensus Meeting at the 45th Annual Meeting of the Japan Society of Hepatology (2009)

The consensus meeting for the diagnosis, management and treatment for hepatitis C was held in 45^th annual meeting for the Japan Society of Hepatology (JSH) in June 2009 where the recommendations and informative statements were discussed including organizers and presenters. The Several important informative statements and recommendations have been shown. This was the fourth JSH consensus meeting of hepatitis C, however, the recommendations have not been published in English previously. Thus, this is the first report of JSH consensus of hepatitis C. The rate of development of hepatocellular carcinoma (HCC) in HCV‐infected patients in Japan is higher than in the USA, because the average age of the HCV‐infected patients is greater and there are more patients with severe fibrosis of the liver than in the USA. In Japan, more than 60% of HCV‐infected patients are genotype 1b infection, and they show lower response to perinterferon and ribavirin combination treatment. To improve the response rate is also an important issue in our country. To establish the original recommendations and informative statements to prevent the development of HCC is a very important issue in Japan.     

JSH Guidelines for the Management of Hepatitis C Virus Infection, 2019 Update; Protective Effect of Antiviral Therapy against Hepatocarcinogenesis

The Drafting Committee for Hepatitis Management Guidelines established by the Japan Society of Hepatology (JSH) drafted the first version of the clinical practice guidelines for the management of hepatitis C virus (HCV) infection in 2012. Since then, we have been publishing updates as new drugs for hepatitis C become available and new indications for existing drugs are added. The new approval of sofosbuvir/velpatasvir prompted us to publish the seventh version of the guidelines in Japanese in March 2019. We also published the first English‐language version of the JSH guidelines in 2013 and English versions of updates made to the Japanese‐language guidelines in 2014 and 2016. In 2020, the committee has decided to publish a new English version, covering general information about treatment for hepatitis C, drugs used, recommended treatments for chronic hepatitis and cirrhosis, and special populations, such as patients who have renal impairment, are on dialysis, or have developed recurrence of hepatitis C after liver transplantation. Furthermore, the committee has released a separate publication covering the protective effect of antiviral therapy against hepatocarcinogenesis.