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Trial to show the impact of nicorandil in angina (IONA): design, methodology, and management.

OBJECTIVE: IONA (impact of nicorandil in angina) is a randomised, double blind, placebo controlled trial that will test the hypothesis that nicorandil (target dose of 20 mg twice daily) will reduce the incidence of cardiovascular events in a cohort of men and women with effort angina and additional risk factors. METHODS: The primary composite end point of the study is coronary heart disease death, non-fatal myocardial infarction or unplanned hospital admission for cardiac chest pain, and the secondary end point is the combined outcome of coronary heart disease death or non-fatal myocardial infarction. Other cardiovascular outcomes and all cause mortality will also be reported. RESULTS: More than 5000 subjects have been randomised to receive nicorandil or placebo in addition to normal antianginal treatment. The target population, the assessments made, and the management of the trial are described in detail. CONCLUSIONS: The IONA study has achieved its first aim of randomising more than 5000 high risk subjects with effort angina. Subject follow up will be complete in the third quarter of 2001.

Angina Pectoris↗

[Low reporting of clinical characteristics of patients with diabetes mellitus included in the main clinical trials on hypertension].

BACKGROUND AND OBJECTIVE: Subjects with diabetes mellitus (DM) are at high risk of cardiovascular events. However, their cardiovascular risk varies according to several clinical characteristics like age, sex, ethnicity, type and duration of the DM, quality of glycemic control, type of hypoglycemic treatment, or the presence of nephropathy or previous cardiovascular events. It is not known if these characteristics have been sufficiently reported in clinical trials on hypertension including subjects with DM. MATERIAL AND METHOD: We analyzed randomized controlled clinical trials about treatment of hypertension published before May 2003 with the following characteristics: a) inclusion of subjects with DM and b) a primary end-point including at least one of the following events: myocardial infarction, cerebrovascular disease or total mortality. In these trials we evaluated the above-mentioned clinical characteristics concerning cardiovascular risk. RESULTS: Sixteen trials were eventually analyzed. These trials were classified into: a) trials designed only for subjects with DM (RENAAL, UKPDS 38, UKPDS 39, IDNT); b) trials with a subgroup analysis for subjects with DM (SHEP, Syst-Eur, MICRO-HOPE, HOT, STOP-2, LIFE), and c) trials without a subgroup analysis for subjects with DM (CAPP, NORDIL, INSIGHT, ALLHAT, SANBPSG, CONVINCE). All these trials included a total of 33984 subjects with DM, most of them > or = 55 years old. The percentage of women evaluated ranged from 33.5 to 71.9% although in 2 trials no data were found regarding this percentage (12.5%). There was no information on ethnicity in 10 trials (62.5%), on the type of DM in 7 (43.8%), on the duration of the disease in 13 (81.3%), on the degree of glycemic control in 10 (62.5%), on the type of hypoglycemic treatment in 11 (68.8%), on the presence or absence of nephropathy in 11 (68.8%) and on the presence or absence of previous cardiovascular events in 3 (18.8%). Trials without subgroup analysis for subjects with DM had a lower reporting of the clinical characteristics of the subjects evaluated than the rest of the trials. CONCLUSIONS: The reporting of relevant clinical characteristics of cardiovascular risk in subjects with DM in the main clinical trials on hypertension is low, diminishing their external validity. To optimize the therapeutic recommendations in the treatment of hypertension in DM these deficiencies should be overcome.

Adult↗

[An assessment of acid-base imbalance in body tissues and fluids].

Ions hydrogene concentration in fluids and tissues is one of the strict regulated physiological organism variables. Most common man and animal diseases are accompanied with compensated acid-base balance shift development. But diagnosis of metabolic acidosis and alkalosis with blood indices (pH, pCO2, HCO3) doesn't reflect true tissue condition that is connected not only with respiratory and excretion system functioning but with hypercompensation of metabolic processes. Excess organic acid formation in case of metabolic alkalosis formation in tissues directed to support pH leads to acidification, what brings an essential mistake in pathogenesis understanding of such diseases as cardiomyopathy, ischemic cardiac disease, myocardial infarction, hepatitis, collagenosis, caries, peptic ulcer, macula dystrophy, atherosclerosis, virus diseases, radiation damages. Ignorance primary tissue damages doesn't allow to conduct necessary preventive measures and to cure disease. It is suggested to assess development of metabolic acidosis and alkalosis by compensated changes of regulation acid-base homeostasis system, which is the basis of all future damages and development of different diseases against this background.

Acid-Base Imbalance↗

Results of the STOP-Hypertension-2 trial.

The second Swedish Trial in Old patients with Hypertension (STOP-Hypertension-2) was conducted to compare the effects of "newer" antihypertensive therapies (angiotensin converting enzyme [ACE] inhibitors and calcium antagonists) and established therapies (beta-blockers and diuretics) on cardiovascular mortality and morbidity in elderly hypertensive patients. A total of 6614 patients were randomized to receive conventional treatment, ACE inhibitors or calcium antagonists, and followed for a mean of 5 years. The primary endpoint was a combination of fatal stroke, fatal myocardial infarction and other fatal cardiovascular disease; secondary endpoints were a combination of fatal or non-fatal stroke or myocardial infarction, and other cardiovascular mortality. The three treatments produced similar reductions in supine systolic blood pressure. There were no significant differences in the risk of cardiovascular events between patients receiving conventional therapy and those receiving newer therapies. All three treatments were well tolerated. The STOP-Hypertension-2 results thus add to the extensive literature showing the benefits of blood pressure reduction in elderly hypertensive patients. Moreover, they are consistent with current management guidelines which emphasise the importance of the achieved blood pressure reduction in the prevention of cardiovascular events.

Aged↗

Treatable cardiomyopathies.

Cardiomyopathy is defined as primary myocardial dysfunction which is not due to hypertensive, valvular, congenital, coronary or pulmonary vascular disease. This term usually denotes a dismal prognosis short of cardiac transplantation. However, several organic diseases of the heart can result in right or left ventricular dysfunction resulting in congestive heart failure and prompting the physician to label them as cardiomyopathy; the etiological factor is overlooked as it produces very subtle features. Therefore, before labelling any child as cardiomyopathic, all possible causes of ventricular dysfunction must be excluded by clinical and investigative means. The causes of "treatable cardiomyopathy" include mechanical factors as critical aortic stenosis and pulmonic stenosis, severe coarctation of aorta in an infant and aortaarteritis is an older child. Some of the persistent arrhythmias like atrial tachycardia, fibrillation, paroxysmal junctional re-entrant tachycardia are also known for causing ventricular dysfunction producing tachycardiomyopathy. Treatment of arrhythmia improves the ventricular function. Myocardial ischemia as a result of congenital coronary anomaly (commonest being anomalous origin of left coronary artery from pulmonary artery) can also present with a cardiomyopathy like picture. Early surgical correction is very rewarding. Finally, some of the metabolic conditions like creatinine and thiamine deficiency can also produce ventricular dilatation and dysfunction. In conclusion, the so called cardiomyopathy like picture can be produced because of several reasons and an attempt must be made to identify them.

Aortic Valve Stenosis↗

[Effect of thrombolytic therapy with intravenous streptokinase on the size of myocardial infarction estimated by the ECG QRS score system].

The impact of short-term intravenous large dose streptokinase injection on the myocardial infarction size estimated by a QRS score system was studied in 57 patients with primary myocardial infarction admitted to hospital at least 6 hours following the onset of the disease. There was a lower myocardial infarction size despite its localization and the time of treatment initiation when thrombolysis was successful, as evidenced by non-invasive criteria. The reliability of the QRS score system used to estimate the myocardial infarction size increased when the patients with anterior or inferior myocardial infarction and those with successful and unsuccessful systemic streptokinase thrombolysis.

Aged↗

[Risk factors of myocardial infarction in 28 years old man].

Ischaemic heart disease in the young people is connected with family cardiovascular risk factors disease. The young 28 years old male, who was presented, has myocardial infarction treated by primary angioplasty and stent implantation. The control angiography was performed 4 month later, restenosis in stent was observed. Patient had family risk factors and arterial hypertension, dyslipoproteinemia, which was not treated before and after myocardial infarction. The doctors informed him about risk factors and modifications in patient's life style.

Adult↗

[The effect of transcardiac galvanization on the course of the physical rehabilitation of patients with an acute myocardial infarct based on the data from a measured loading test].

Transcardiac galvanization effect was assessed in 76 patients with primary noncomplicated macrofocal anterior myocardial infarction admitted to hospital within initial 6 hours of the disease. As shown by the evidence obtained at bicycle ergometry, tetrapolar rheography and clinical examination, transcardiac galvanization within 3 days of the infarction enhances hospital physical rehabilitation course, increases exercise tolerance by the disease month 6, promotes an increase in myocardial maximal oxygen consumption, increases coronary reserve and improves cardiac contractility.

Aged↗

The Japanese Trial to Assess Optimal Systolic Blood Pressure in Elderly Hypertensive Patients (JATOS): protocol, patient characteristics, and blood pressure during the first 12 months.

The benefits of a systolic blood pressure (BP) below 150-160 mmHg are well established; whether a systolic BP of less than 140 mmHg provides additional benefits remains controversial. This study was designed to compare the 2-year effect of a strict treatment to maintain systolic BP below 140 mmHg (group A) and that of a mild treatment to maintain systolic BP at between 140 and below 160 mmHg (group B). The study design followed the Prospective Randomized Open Blinded End-point (PROBE) study. The subjects were elderly patients (65-85 years old) who consistently had a systolic BP of 160 mmHg or higher. The baseline drug was efonidipine hydrochloride (efonidipine), a long-acting dihydropiridine calcium antagonist. The primary endpoints were stroke, cardiac disease, vascular disease, and renal failure. After a run-in period of 2 to 4 weeks, 2,165 patients were assigned to group A and 2,155 patients to group B. There were no significant differences between the groups in sex, age, baseline BP, or other cardiovascular risk factors. The systolic BP was 7.2 mmHg lower (p < 0.0001) and the diastolic BP 2.4 mmHg lower (p < 0.0001) in group A than in group B after 12 months of treatment. As of this interim analysis, primary endpoints have occurred in 87 patients (stroke in 58 patients, cardiac disease in 27 patients, occlusive arterial disease in 1 patient, and renal failure in 1 patient). Five patients have died of stroke and 2 patients of myocardial infarction. The primary-endpoint-related morbidity rate was 20.9/1,000 patient-years, and the mortality rate was 1.7/1,000 patient-years. Currently available results indicate that this study, one of the largest randomized trials of antihypertensive therapy in elderly patients in Japan, was conducted safely. The final results are expected to provide important and practical information for the management of hypertension in elderly patients.

Aged↗

Long-term effects on cholesterol levels and the utilization of lipid-lowering drugs of a hospital-based programme for secondary prevention of coronary artery disease.

BACKGROUND: The study was designed to determine whether a 1-year hospital-based secondary prevention programme would have any long-term effects on serum lipid levels and the use of lipid-lowering drugs in patients with coronary artery disease 4 years after referral to primary care facilities for follow-up. DESIGN/METHODS: After acute myocardial infarction or coronary bypass surgery, 241 consecutive patients were randomly assigned to conventional care (CC) by the primary health care facilities or to a 1-year hospital-based secondary prevention programme (SPP) with target levels for serum cholesterol (< 5.2 mmol/l) and triglycerides (< 1.5 mmol/l). After 1 year all patients were referred to the primary care sector for a further 4-year follow-up. RESULTS: At the 1-year follow-up there was a significant decrease in serum cholesterol, LDL-cholesterol and triglyceride levels in the SPP group but no change in the CC group, and lipid-lowering drugs were used more frequently in the SPP group. These changes were maintained after 5 years. The proportion of patients achieving target serum cholesterol and triglyceride levels were larger in the SPP group. CONCLUSIONS: Initiatives regarding cholesterol lowering and drug treatment taken by specialists within a structured hospital-based SPP have long-term impact. Accordingly, drug treatment should be initiated and adjusted to adequate doses before patients are referred to primary care for follow-up.

Aged↗

Risk factors for mortality in primary isolated coronary artery bypass grafting surgery.

BACKGROUND AND PURPOSE: Identifying the risk factors for mortality in coronary artery bypass grafting (CABG) surgery is important to improve surgical results. The purpose of this study was to identify the risk factors for mortality in primary isolated CABG in a series of Taiwanese patients. METHODS: Medical records of 914 patients who underwent primary isolated CABG surgery in Veterans General Hospital-Taipei during the period from January 1, 1991, to December 31, 1995, were reviewed. Eighteen clinical and seven operative variables were included in the univariate and multivariate analyses to identify the determinants of mortality in CABG surgery. RESULTS: Thirty-one patients (3.4%) died within 30 days after surgery; 41 (4.5%) died during hospitalization for the procedure. After univariate and multivariate analyses, emergency surgery, history of myocardial infarction, concomitant peripheral artery occlusive disease (PAOD), and prolonged cardiopulmonary bypass (CPB) were found to be significant determinants of mortality in primary isolated CABG. Other variables, including age, sex, angina class, NYHA class, diabetes mellitus, the number of anastomoses, aortic cross-clamp time, stenosis of the left main coronary artery, the number of stenotic coronary arteries, history of congestive heart failure, and a left ventricular ejection fraction less than 35%, were not significant determinants of mortality. Patients undergoing emergency surgery were found to be at highest risk of mortality. CONCLUSIONS: Patients undergoing emergency surgery who had a history of myocardial infarction, concomitant PAOD, or prolonged CPB were at higher risk of mortality in CABG surgery. More comprehensive techniques in myocardial protection, surgical procedures, and postoperative care should be used in the treatment of high-risk patients to reduce mortality.

Aged↗