Objective: To evaluate the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOAC) in patients with atrial fibrillation (AF) and hypertrophic cardiomyopathy (HCM). Methods: This study was a prospective cohort study. The data of this study were based on the Chinese Atrial Fibrillation Registry (CAFR) Study, which was a prospective, multicenter registry study. The CAFR Study enrolled inpatients and outpatients with AF from 31 hospitals. Patients with AF and HCM were selected from August 2011 to December 2018. The patients were divided into NOAC-treated group and warfarin-treated group. General clinical data, echocardiographic results and treatment options were collected and compared between the two groups. Patients were followed up every 6 months; outcome events included effective endpoint events(thromboembolism)and safety endpoint events(major bleeding). The incidence of endpoint events in both groups was calculated and compared. Cox proportional hazards regression models and Kaplan-Meier survival analysis were performed to determine the association between NOAC use and endpoint events. Results: A total of 393 patients were included (average age: (60.5±11.8) years, 252 men (64.1%)). There were 133 (34.0%) patients in the NOAC-treated group and 260 (66.0%) patients in the warfarin-treated group. Compared with the warfarin-treated group, the patients in the NOAC-treated group had a higher proportion of paroxysmal AF, catheter ablation of AF, a lower proportion of hypertension, ischemic stroke/transient ischemic attack (TIA), lower heart rate, lower usage rate of angiotensin-converting enzyme inhibitors(ACEI)/angiotensin receptor blockers(ARB), β-blockers, non-dihydropyridine calcium channel blockers(NDH-CCB)(P<0.05). There were no significant differences on the echocardiographic results, including interventricular septal thickness, left ventricular posterior wall thickness, left ventricular end-diastolic diameter, left atrial diameter, left ventricular ejection fraction(P>0.05). After a follow-up of 42 (24, 60)months, the incidence rates of thromboembolism were 1.63 and 2.10 events per 100 person-years for NOAC-and warfarin-treated group, and those of major bleeding were 0.66 and 1.03 events per 100 person-years. Kaplan-Meier survival analysis showed survival rates free from endpoint events were similar between NOAC-treated group and warfarin-treated group(thromboembolism-free survival comparison, P=0.476; major bleeding-free survival comparison, P=0.855). Cox multivariate regression analysis revealed that there was no significant difference on risk of thromboembolism(HR=1.21, 95%CI: 0.42-3.50, P=0.720) and major bleeding(HR=1.50, 95%CI: 0.27-8.41, P=0.642) between NOAC-treated and warfarin-treated group. Conclusion: Patients with AF and HCM can be safely and effectively treated with NOAC.
Administration, Oral ; Aged ; Angiotensin Receptor Antagonists/therapeutic use* ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use* ; Anticoagulants/therapeutic use* ; Atrial Fibrillation/drug therapy* ; Cardiomyopathy, Hypertrophic/drug therapy* ; Humans ; Male ; Middle Aged ; Prospective Studies ; Stroke ; Stroke Volume ; Treatment Outcome ; Ventricular Function, Left

BACKGROUNDCombination of angiotensin-converting enzyme inhibitors and calcium channel blockers has been successfully used in the antihypertensive therapy for many years. Fixed dose combinations of ramipril/amlodipine have a benefit effect for patients to achieve target blood pressure (BP). This study aimed to assess the efficacy and safety of fixed dose combinations of ramipril and amlodipine (Egiramlon®) in hypertensive diabetic patients.

METHODSHypertensive diabetic patients who were enrolled into the RAMONA trial were included in this open, prospective, Phase IV observational clinical study. Patients had mild-to-moderate hypertension and failed to reach target BP levels through their previous therapy. During the four months of observation, patients took part in three visits (1st day = visit 1, 1st month = visit 2, and 4th month = visit 3) where they received a fixed dose combination of 5/5, 5/10, 10/5, or 10/10 mg ramipril/amlodipine, respectively, with the possibly required dose titrations, based on the decision of their attending physician. Target BP for diabetic patients was <140/85 mmHg. BP levels were measured in all visits, by taking two readings at 2-min interval. Laboratory tests including full blood count, renal function test, electrolytes, blood glucose, serum cholesterol, uric acid, triglycerides, liver function test, creatinine kinase, and midstream urinalysis were performed at visit 1 and visit 3.

RESULTSThe 6423 patients completed the study. Among these patients, 1276 (19.9%) patients suffered from type 2 diabetes mellitus. The mean age of these diabetic patients was 64.2 ± 10.0 years; 707 (55.4%) patients were males. Target BP was achieved by 891 (69.8%) of diabetic patients at visit 3 (primary endpoint). BP decreased from 157.5/91.3 ± 9.6/7.6 mmHg (visit 1) to 130.9/79.6 ± 7.4/5.8 mmHg (visit 3). As for the secondary endpoint of the study, total cholesterol decreased from 5.50 ± 1.13 mmol/L (visit 1) to 5.20 ± 0.95 mmol/L (P = 0.000), low-density lipoprotein cholesterol decreased from 3.20 ± 0.93 mmol/L to 3.00 ± 0.77 mmol/L (P = 0.000), triglyceride decreased from 2.20 ± 1.14 mmol/L to 2.00 ± 1.97 mmol/L (P = 0.000), while high-density lipoprotein cholesterol increased from 1.30 ± 0.42 to 1.35 ± 0.30 mmol/L (P = 0.001) until the end of the 4th month (visit 3). Fasting blood glucose of the hypertensive diabetic patients decreased from 7.20 ± 1.88 mmol/L to 6.70 ± 1.38 mmol/L (P = 0.000), while HbA1c decreased from 7.90 ± 1.78% to 7.60 ± 1.83% (P = 0.000). Various fixed dose combinations of ramipril/amlodipine were well tolerated and no adverse event related to the use of the medicine has appeared.

CONCLUSIONSThe fixed dose combination of ramipril/amlodipine was effective in hypertensive diabetic patients who failed to reach target BP previously.

Aged ; Amlodipine ; administration & dosage ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; administration & dosage ; therapeutic use ; Antihypertensive Agents ; administration & dosage ; therapeutic use ; Blood Pressure ; drug effects ; Diabetes Mellitus, Type 2 ; drug therapy ; Female ; Humans ; Hypertension ; drug therapy ; Male ; Middle Aged ; Ramipril ; administration & dosage ; therapeutic use

To systematically evaluate the efficacy and safety of tripterygium glycosides (TG) combined with ACEI/ARB preparation in treating diabetic nephropathy stage IV. The computer retrievals were made in Cochrane Libarary, PubMed, Embase, SCI, Sinnomed, CNKI, Chinainfo and VIP, and hand retrievals were conducted for meeting and academic papers (updated to December 30, 2014), in order to collect randomized controlled trials and quasi-randomized control trials for TG combined with ACEI/ARB preparation in treating diabetic nephropathy stage IV and set the literature inclusion and elimination standards. Eligible literatures were included and evaluated according to standards in Cochrane Handbook. RevMan 5.3 and Stata 12.0 were used for a Meta-analysis. A total of 13 randomized controlled trials and quasi-randomized control trials involving 1119 patients with diabetic nephropathy were included. The Meta analysis result showed that compared with the control group, the combination group showed better effects in reducing the 24-hour urinary protein [MD = -0.84, 95% CI (-1.02, -0.66)], raising albumin [SMD = 0.98, 95% CI (0.81, 1.16)], the total efficiency [OR = 4.23, 95% CI (2.77, 6.46)] and the significant efficiency [OR = 5.35, 95% CI (2.70, 10.60)], with no statistical difference in Serum Creatinine between Both groups [MD = -0.82, 95% CI (-4.30, 2.66), P = 0.64]. However, the risk of adverse reactions increased by 7% [RD = 0.07, 95% CI (0.03, 0.12)]. The Egger's test showed no publication bias. Tripterygium Glycosides combined with ACEI/ARB in treating diabetic nephropathy stage IV is supper than the single administration of ACEI/ARB, with a good prospect in clinical application. Nevertheless, due to the small-size and low-quality samples in this study, more high-quality and large sample-size randomized controlled trials shall be conducted to verify the findings.
Angiotensin Receptor Antagonists ; administration & dosage ; Angiotensin-Converting Enzyme Inhibitors ; administration & dosage ; Diabetic Nephropathies ; drug therapy ; Drug Therapy, Combination ; Glycosides ; administration & dosage ; Humans ; Tripterygium ; chemistry

INTRODUCTIONThe incidence of cough induced by angiotensin-converting enzyme (ACE) inhibitors has been reported to be 5%-20%, with less than half of affected patients requiring discontinuation due to persistent cough. However, the incidence in the local Asian population has not been studied. This study aimed to objectively evaluate the incidence of discontinuation of ACE inhibitors due to cough, in a primary healthcare centre in Singapore.

METHODSWe retrospectively reviewed the medical records, both electronic and written, of patients who attended Tampines Polyclinic to identify those who were newly prescribed ACE inhibitors. The written medical records were analysed to identify patients who discontinued the use of ACE inhibitors and to find out the reasons for discontinuation.

RESULTSA total of 424 patients were identified during the study period. Out of the 424 patients, 129 (30.4%) discontinued the use of ACE inhibitors due to cough. Overall, 90 (21.2%) patients who were initially started on ACE inhibitors were eventually switched to angiotensin receptor blockers (ARBs).

CONCLUSIONIn our cohort, the incidence of discontinuation of ACE inhibitors due to cough is higher than most other studies. The relationship between ethnicity and tolerance of medications should not be underestimated. As there is a high incidence of discontinuation of ACE inhibitors due to cough in the local population, ARBs may be a reasonable substitute as a first-line medication, if clinically indicated.

Angiotensin-Converting Enzyme Inhibitors ; adverse effects ; Cough ; chemically induced ; Female ; Humans ; Incidence ; Male ; Physicians ; Primary Health Care ; organization & administration ; Retrospective Studies ; Singapore ; Time Factors ; Treatment Outcome

BACKGROUNDCombination therapy is an effective method to reduce the blood pressure (BP) for patients with hypertension. This study was performed to evaluate the efficacy and safety of benazepril/lercanidipine compared with benazepril alone in patients with mild-to-moderate hypertension.

METHODSOne hundred and eighty-one patients with mild-to-moderate primary hypertension were assigned in this randomized, single-blind, parallel-group study and were randomly divided into group A (benazepril 10 mg/lercanidipine 10 mg) and group B (benazepril 10 mg) for 8 weeks. At 4 weeks, the dosage of Benazepril was titrated up to 20 mg if the diastolic blood pressure (DBP) remained ≥ 90 mmHg. BP control and side effects were evaluated at the end of 1, 4 and 8 weeks.

RESULTSThe baseline characteristics of the two groups were similar. The BP in both groups decreased from the baseline (P < 0.05). At the end of 4 and 8 weeks, Benazepril/Lercanidipine produced greater BP reduction than Benazepril alone (P < 0.05). The comparison of the rate of BP control for the benazepril/lercanidipine and benazepril groups at the end of 1, 4, and 8 weeks were 41.2% vs. 37.6% (P > 0.05), 67.1% vs. 44.7% (P < 0.05), and 71.8% vs. 45.9% (P < 0.05). There was no significant difference of side effects between the two groups.

CONCLUSIONThe benazepril/lercanidipine combination is more effective in reducing BP than benazepril alone, while it does not increase the incidence of side effects.

Aged ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Benzazepines ; administration & dosage ; adverse effects ; therapeutic use ; Blood Pressure ; drug effects ; Calcium Channel Blockers ; administration & dosage ; Dihydropyridines ; administration & dosage ; adverse effects ; Drug Therapy, Combination ; Female ; Humans ; Hypertension ; drug therapy ; Male ; Middle Aged ; Single-Blind Method

4 liters of polyethylene glycol (PEG) solution is commonly used to evacuate the colon before colonoscopy. This substance, however, is known to cause electrolyte abnormalities such as hyponatremia. Seizures caused by hyponatremia associated with bowel preparation have only rarely been reported. We report the case that a 75-year-old woman with no prior history of seizures was developed severe hyponatremia (112 mEq/L) with generalized tonic-clonic seizure and mental change after ingestion of 4L of PEG solution. Past medical history was notable for thiazide diuretics. Her symptoms are improved during intravenous administration of hypertonic saline for the correction of hyponatremia. Patients with impaired ability to excrete free water those with renal insufficiency, hypothyroidism, mineralocorticoid deficiency, liver cirrhosis, or heart failure as well as those taking drugs which including thiazide diuretics, NASIDs, and ACE inhibitors have risk of hyponatremia following bowel preparation for colonoscopy. We conclude that physicians should check patient's condition and electrolyte abnormalities before colonoscopy procedures.
Administration, Intravenous ; Angiotensin-Converting Enzyme Inhibitors ; Colon ; Colonoscopy ; Eating ; Female ; Heart Failure ; Humans ; Hyponatremia ; Hypothyroidism ; Liver Cirrhosis ; Polyethylene ; Polyethylene Glycols ; Renal Insufficiency ; Seizures ; Sodium Chloride Symporter Inhibitors ; Water

BACKGROUNDThe results from the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) indicated that the angiotensin-receptor blocker telmisartan was not inferior to the angiotensin-converting-enzyme inhibitor ramipril in reducing the composite endpoint of cardiovascular death, myocardial infarction, stroke or hospitalization for congestive heart failure in high-risk patients, and telmisartan was associated with slightly superior tolerability. The combination of the two drugs was associated with more adverse events without an increase in benefit. This study aimed to analyze the data from ONTARGET obtained from a subgroup of patients enrolled in China and to evaluate the demographic and baseline characteristics, the compliance, efficacy, and safety of the different treatment strategies in randomized patients in China.

METHODSA total of 1159 high-risk patients were randomized into three treatment groups: with 390 assigned to receive 80 mg of telmisartan, 385 assigned to receive 10 mg of ramipril and 384 assigned to receive both study medications. The median follow-up period was 4.3 years.

RESULTSThe mean age of Chinese patients was 65.6 years, 73.6% of patients were male. The proportion of patients with stroke/transient ischemic attacks at baseline in China was two times more than the entire study population (47.7% vs. 20.9%). In Chinese patients the proportion of permanent discontinuation of study medication due to cough was 0.5% in the telmisartan group, which was much less than that in the combination or the ramipril group. There were no significant differences in the incidence of primary outcome among three treatment groups of Chinese patients. More strokes occurred in Chinese patients than in the entire study population (8.5% vs. 4.5%). Greater systolic blood pressure reduction (-9.8 mmHg), and more renal function failure were noted in the combination treatment group than in the ramipril or telmisartan group (2.6% vs. 1.6% and 1.0%).

CONCLUSIONSThere was no evidence that the results of ONTARGET differed between Chinese patients and the entire study population with respect to the incidence of primary outcome, particularly safety. Compliance with study medications was good. The evidence from ONTARGET indicated that the treatment strategies in ONTARGET were applicable to patients in China.

Aged ; Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Benzimidazoles ; administration & dosage ; adverse effects ; therapeutic use ; Benzoates ; administration & dosage ; adverse effects ; therapeutic use ; China ; Drug Therapy, Combination ; Female ; Heart Failure ; drug therapy ; Humans ; Male ; Middle Aged ; Ramipril ; administration & dosage ; adverse effects ; therapeutic use

Randomized clinical trials led to the clinical recommendation that angiotensin-converting enzyme inhibitors (ACEI) should be used as standard therapy in most patients experiencing an acute myocardial infarction (AMI). However, the optimal initiation timing of treatment, as well as the exact mechanisms, have not been completely resolved, especially with the development of reperfusion strategy after AMI. Earlier initiation of ACEI might be associated with more prompt recovery of left ventricular ejection fraction due to more rapid attenuation of negative remodeling.
Angiotensin-Converting Enzyme Inhibitors ; administration & dosage ; therapeutic use ; Humans ; Myocardial Infarction ; drug therapy ; Randomized Controlled Trials as Topic ; Time Factors

To evaluate the effects of cyclosporin A (CyA) on clinical outcome and pathologic changes in children with IgA nephropathy (IgAN), we retrospectively evaluated 14 children (mean age 8.9+/-2.9 yr; eight males, six females) who were treated with CyA and steroids. The starting dose of CyA was 5 mg/kg per day, and the drug level was maintained at 100-200 ng/mL. The mean CyA level was 183.8+/-48.3 ng/mL (range 120.7-276.0 ng/mL) and the mean duration of CyA therapy was 10.9+/-1.9 months (range 8-12 months). After CyA therapy the mean 24 hr urinary protein excretion declined from 107.1+/-35.1 mg/m2/hr to 7.4+/-2.4 mg/m2/hr (P<0.001) and serum albumin increased from 3.3+/-0.6 g/dL to 4.3+/-0.3 g/dL (P<0.001). At a follow-up biopsy the histological grade of IgAN was improved in seven (50%) of the 14 patients, remained the same in three (21%), and was aggravated in four (29%). Serum creatinine, creatinine clearance, and blood pressure did not differ before and after CyA therapy. Two patients (14%) showed CyA-induced nephrotoxicity at the second biopsy. Our findings indicate that CyA therapy may be effective in reducing proteinuria and regressing renal pathology in a subset of children with IgAN.
Angiotensin-Converting Enzyme Inhibitors/*administration & dosage ; Child ; Cyclosporine/*administration & dosage ; Drug Combinations ; Female ; Glomerulonephritis, IGA/*diagnosis/*drug therapy ; Humans ; Immunosuppressive Agents/administration & dosage ; Male ; Steroids/*administration & dosage ; Treatment Outcome

Angiogenesis Inhibitors ; adverse effects ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Antibodies, Monoclonal ; adverse effects ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Aspirin ; administration & dosage ; therapeutic use ; Bevacizumab ; Hemorrhage ; chemically induced ; Humans ; Hypertension ; chemically induced ; drug therapy ; Intestinal Perforation ; chemically induced ; surgery ; Neoplasms ; drug therapy ; Proteinuria ; chemically induced ; Thromboembolism ; chemically induced ; drug therapy