A double blind comparative study of lisinopril and enalapril in patients with essential hypertension.

The efficacy and safety profiles of lisinopril (10-40 mg) and enalapril (5-20 mg) were compared in 169 hypertensive patients during 12 weeks' treatment in a randomised double-blind parallel group study. BP was measured hourly for the first 8 hours following the first dose of lisinopril 10 mg and enalapril 5 mg. The peak reduction in sitting systolic and diastolic BP occurred approximately 6 hours post dose in both groups. At 8 hours post dose lisinopril had reduced sitting systolic and diastolic BP by 2.9 mmHg and 3.5 mmHg (P = 0.02) respectively, more than enalapril with similar results for standing BP. One patient on enalapril developed first dose postural hypotension. After 12 weeks' therapy lisinopril produced a greater decrease (P less than 0.05) in BP than enalapril. Sitting BP decreased by 25/15 mmHg on lisinopril and 17/12 mmHg with enalapril. Standing BP decreased by 24/14 mmHg compared with 16/10 mmHg on enalapril. Eighteen patients did not complete the study, 8 on lisinopril (6 adverse events, 1 uncontrolled BP, 1 protocol violator) and 10 on enalapril (8 adverse events, 1 uncontrolled BP, 1 protocol violator). Overall, the results indicated that while both drugs are well tolerated, the dose range of lisinopril 10-40 mg may produce a greater antihypertensive effect than enalapril 5-20 mg.

Trial of early nifedipine in acute myocardial infarction: the Trent study.

Over 30 months 9292 consecutive patients admitted to nine coronary care units with suspected myocardial infarction were considered for admission to a randomised double blind study comparing the effect on mortality of nifedipine 10 mg four times a day with that of placebo. Among the 4801 patients excluded from the study the overall one month fatality rate was 18.2% and the one month fatality rate in those with definite myocardial infarction 26.8%. A total of 4491 patients fulfilled the entry criteria and were randomly allocated to nifedipine or placebo immediately after assessment in the coronary care unit. Roughly 64% of patients in both treatment groups sustained an acute myocardial infarction. The overall one month fatality rates were 6.3% in the placebo treated group and 6.7% in the nifedipine treated group. Most of the deaths occurred in patients with an in hospital diagnosis of myocardial infarction, and their one month fatality rates were 9.3% for the placebo group and 10.2% for the nifedipine group. These differences were not statistically significant. Subgroup analysis also did not suggest any particular group of patients with suspected acute myocardial infarction who might benefit from early nifedipine treatment in the dose studied.

The relationship of arrhythmias to walking activity during mobilization after myocardial infarction.

The extent to which everyday walking activity is responsible for ventricular arrhythmias in the first 6 weeks after suspected myocardial infarction has been studied by simultaneous 24-hour recordings of electrocardiogram and walking activity. Forty-eight recordings from 46 patients were identified which contained couplets, ventricular tachycardia or R-on-T extrasystoles. In 24 recordings (50%) all the arrhythmias occurred whilst the patient was at rest and in a further four recordings there were fewer arrhythmias during activity than would have been expected by chance. Nineteen recordings (40%) contained arrhythmias which may have been induced by activity but in only three of these was the relationship definite. Clear evidence of arrhythmias precipitated by walking was found in only a minority of patients mobilizing after suspected myocardial infarction.

Multiple Salmonella endocarditis.

A patient with known rheumatic mitral stenosis who developed infective endocarditis associated with a diarrhoeal illness is described. Dual infection with Salmonella virchow and Salmonella montevideo was identified. The illness was otherwise uncomplicated and she recovered after six weeks' treatment with parenteral antibiotics.

Factors influencing choice of a beta-blocker; should such drugs be used in combination with a calcium-channel blocking drug.

Evidence is reviewed showing that calcium-channel blockers can be added to beta-blockers in patients with ischaemic heart disease providing that the patients have a reasonable left ventricular function. The combination may prove useful in treating hypertension.

Randomised placebo-controlled trial comparing oxprenolol with disopyramide phosphate in immediate treatment of suspected myocardial infarction.

473 patients with suspected acute myocardial infarction were entered into a randomised, double-blind, placebo-controlled comparison of disopyramide phosphate, 150 mg three times a day, and oxprenolol, 40 mg three times a day. When analysed on an intension-to-treat basis there was no significant difference in 6-week mortality between the groups, but patients who were able to continue on the active medications fared better than the patients who had to be withdrawn. The withdrawal rate because of heart failure in patients randomised to receive disopyramide was significantly increased. Patients receiving this agent also showed a reduced number of arrhythmic episodes on 24-h tape recordings but this trend did not achieve statistical significance. The results show that the early use of either oxprenolol or disopyramide phosphate in patients with suspected acute myocardial infarction is unlikely to improve mortality.

Sulphinpyrazone in acute myocardial infarction: studies on cardiac rhythm and renal function.

Ninety-eight patients with acute myocardial infarction were randomly allocated to receive sulphinpyrazone 200 mg four times daily or placebo on admission to a coronary care unit. Twenty-four-hour electrocardiogram tape recordings showed no significant reduction in serious arrhythmias in the sulphinpyrazone-treated group. In addition to the expected all in serum urate concentration, patients taking sulphinpyrazone showed a persistent increase in their serum urea and creatinine concentrations when compared with those in the placebo groups (p < 0.05 and p < 0.01 respectively). These differences could not be accounted for by differences in the extent and severity of the infarction between the two groups. These results suggest that sulphinpyrazone has no discernible antiarrhythmic effect in acute myocardial infarction.

Randomised trial comparing propranolol with atenolol in immediate treatment of suspected myocardial infarction.

The value of beta-blockade for suspected acute myocardial infarction was assessed by determining the six-week and one-year mortality rates in patients started on propranolol, atenolol, or placebo immediately on entry to a coronary care unit. A total of 388 patients entered this double-blind, randomised study, and when analysed on the basis of the initial, intention-to-treat categories there was no significant difference between the three groups in respect of the mortality rate at one year. There was, however, a high withdrawal rate from the trial; the reasons for this illustrate problems of physician compliance and interpretation of data, which are common to all early-entry trials of haemodynamically active agents in acute myocardial infarction.

Effect of beta-blockers on arrhythmias during six weeks after suspected myocardial infarction.

Twenty-four-hour electrocardiographic tape-recording was used to investigate the incidence of arrhythmias in patients with suspected myocardial infarction who were receiving either propranolol, atenolol, or placebo. Recordings begun within 24 hours after admission to a coronary care unit showed that 76% of patients eventually found to have had a myocardial infarction had ventricular arrhythmias of a type generally regarded as serious, whereas of patients in whom myocardial infarction was not substantiated, only 24% had such arrhythmias. At one and six weeks after admission the incidence of arrhythmias ranged from 25% to 33% irrespective of diagnosis. Of patients monitored at both one and six weeks, however, only 5% had arrhythmias on each occasion. Patients treated with propranolol and atenolol showed a similar incidence of arrhythmias to those taking placebo. There was no difference in the incidence or type of arrhythmias recorded between patients who died and those who were still alive at six weeks.These results confirm that "serious" ventricular arrythmias occur in most patients during the acute phase of myocardial infarction and suggest that they do not constitute an independent risk factor. Beta-blockers showed little evidence of useful antiarrhythmic action in the dosage used, but increasing the dosage in suspected myocardial infarction is not practicable because of the risk of hypotension. The findings raise grave doubts about the value of studying arrhythmias to assess drugs intended to reduce mortality from myocardial infarction.

The effect of beta-adrenoceptor blockade on factors affecting exercise tolerance in normal man.

1 We have studied the effects of single oral doses of 80 mg propranolol and 100 mg metoprolol on the cardiovascular and respiratory responses to progressive exercise in nine healthy men in double-blind, placebo-controlled experiment. As judged by their effects on exercise heart rate and cardiac output the doses of the two drugs used were equivalent. 2 Beta-adrenoceptor blockade reduced oxygen consumption by 3.5% over the whole work range with an increase in the respiratory exchange ratio of 0.056 units. Carbon dioxide production and exercise ventilation were unchanged. The two drugs had similar effects. Possible mechanisms for these observations are discussed. 3 Perceived exertion during exercise was increased by both the beta-adrenoceptor blocking drugs and this may be of relevance to the symptom of fatigue reported by patients on these drugs. Endurance, assessed as either total work done or maximal work achieved, was reduced by 15%.