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Biomedical subjects

S Yusuf

Publications and source records attributed to S Yusuf.

At least 271 records · Page 15Linked to original sources
PubMed1980

The role of serum myoglobin in the detection and measurement of myocardial infarction.

The use of serum myoglobin determinations in the diagnosis and quantitation of acute myocardial infarction was studied in 53 patients. Serial blood samples collected for the first 72 h after pain were analysed for serum myoglobin using a radioimmunoassay procedure. Samples were also assayed for serum creatine kinase (CK) and its myocardial isoenzyme CK-MB, aspartate aminotransferase (AST) and alpha-hydroxybutyrate dehydrogenase (alpha HBDH). Analysis of first and second samples obtained at mean times of 7.6 and 10.7 h respectively after pain produced the following detection rate: serum myoglobin 85% and 98%; serum CK 71% and 85%; serum AST 58% and 81%; serum CK-MB 29% and 60%; serum alpha HBDH 23% and 33% respectively. Total CK-MB and myoglobin release from damaged myocardium were calculated using the method of Norris et al. [16]. A significant correlation was obtained between infarct size calculated from CK-MB and myoglobin in the whole group (n = 29, r = 0.71, p < 0.001). The correlation was even more significant for smaller infarcts with CK-MB release < 220 U/l (n = 13, r = 0.92, p < 0.001).

Adult↗
PubMed1980

Early intravenous atenolol treatment in suspected acute myocardial infarction. Preliminary report of a randomised trial.

214 patients were studied in a randomised trial to determine whether administraiton of intravenous atenolol within 12 hours of chest pain reduced eventual infarct size, as estimated by cumulative enzyme release and by ECG changes. 135 patients already had ECG evidence of infarction at entry; 72 received atenolol which significantly decreased subsequent enzyme release (atenolol and control means = 121 IU, SE +/- 10 and 177 IU, SE +/- 17; 2p < 0.005) and enhanced R-wave preservation (atenolol and control means = 46% +/- 3 and 36% +/- 3; 2p < 0.02). 79 patients had no evidence of infarction at entry; 44 did not receive atenolol and 27 of these subsequently developed infarction, whereas only 11 of 35 treated patients infarcted during their hospital stay (2p < 0.01). In hospital, fewer atenolol patients died (4 vs 9), had non-fatal cardiac arrests (2 vs 6), or required therapy for heart-failure (36 vs 47). Unlike many previous trials which had negative results, in this trial we gave the drug intravenously and promptly (median of 4 hours from onset of pain to injecton), thereby achieving early beta-blockade.

Acute Disease↗
PubMed1980

Heart rate and ectopic prematurity in relation to sustained ventricular arrhythmias.

Forty-four patients with acute myocardial infarction were studied using 24-hour electrocardiographic monitoring. A linear correlation has been shown to exist between heart rate preceding accelerated idioventricular rhythm and ventricular tachycardia and the rates of these. The prematurity index was found to be inversely related to the preceding heart rate and also to the rate of accelerated idioventricular rhythm or ventricular tachycardia. Faster heart rates preceded extrasystoles with shorter prematurity indices and a significant inverse correlation was observed between preceding heart rate and prematurity index. Patients developing ventricular tachycardia had more frequent isolated ventricular extrasystoles and faster heart rates preceding the episode as compared with patients not showing ventricular tachycardia. No association was observed between ventricular tachycardia and accelerated idioventricular rhythm. All four patients developing ventricular fibrillation showed preceding ventricular tachycardia, with three of these patients demonstrating faster rates of ventricular tachycardia (greater than 170/min) and shorter prematurity indices (less than 0.80) than patients without ventricular fibrillation. Heart rate may influence the severity of ventricular arrbythmia; the prematurity of an extrasystole is of importance in patients developing accelered idioventricular rhythm or ventricular tachycardia.

Arrhythmias, Cardiac↗
PubMed1979

Effect of atenolol on recovery of the electrocardiographic signs of myocardial infarction.

The most notable changes in the 35-lead precordial electrocardiogram in 22 subjects in the first 6--12 months after acute myocardial infarction were a reduction in the amplitude of Q waves and a significant increase in the amplitude of the R waves. Patients who, in a random trial, had been given 100 mg atenolol daily from admission showed a significantly greater recovery in R-wave amplitude and decrease in Q waves than patients given placebo. It is concluded that atenolol improves the recovery of the electrocardiographic signs of myocardial infarction.

Acute Disease↗
PubMed1979

Value of electrocardiogram in predicting and estimating infarct size in man.

The value of the electrocardiogram in assessing infarct size was studied using serial estimates of the MB isomer of creatine kinase (CK MB) in plasma, serial 35 lead praecordial maps in 28 patients with anterior myocardial infarction, and serial 12 lead electrocardiograms in 17 patients with inferior myocardial infarction. In patients with anterior infarcts, sigma ST, sigma R, sigma Q, sigma R/(Q+S), and the number of sites with ST elevation more than 2 mm or with QS waves, were obtained from each map. Correlation between both maximum sigma Q and maximum sigma ST with cumulative CK MB was highly significant. There was also a significant correlation between sigma R and sigma R/(Q+S) with cumulative CK MB. There was no significant correlation between maximum number of sites with ST elevation or with Q or QS waves and cumulative CK MB. Maximum sigma ST and number of sites with ST elevation predicted maximum sigma Q and number of sites with QS or Q waves at a time when infarction was not complete. In patients with inferior infarcts, there was a significant correlation between maximum sigma Q and maximum sigma ST in leads II, III, and a VF, and cumulative CK MB. This study shows that all the waves in the electrocardiogram are useful in assessing infarct size. The fact that maximum sigma ST predicts final sigma Q may be used to assess the efficacy of interventions designed to salvage ischaemic myocardium.

Aged↗
PubMedDate not supplied

Safety outcomes in meta-analyses of phase 2 vs phase 3 randomized trials: Intracranial hemorrhage in trials of bolus thrombolytic therapy.

CONTEXT: Recent studies have reported disagreement between meta-analysis of small trials and subsequent large trials addressing the same question. However, disagreement for uncommon but serious adverse safety outcomes has not been examined. OBJECTIVE: To explore disagreement for serious adverse safety (intracranial hemorrhage [ICH]) and efficacy outcomes between meta-analysis of phase 2 (small) vs meta-analysis of phase 3 (large) randomized controlled trials comparing the efficacy of bolus thrombolytic therapy with infusion for acute myocardial infarction (AMI). DATA SOURCES: Electronic databases (MEDLINE, Cochrane Database of Clinical Trials) between January 1980 and December 1999 using the search terms thrombolysis, thrombolytic therapy, and myocardial infarction; conference proceedings; and reference lists. STUDY SELECTION: Fifteen randomized trials comparing thrombolytic agents administered by bolus injection with standard infusion therapy in patients with AMI. DATA EXTRACTION: Data on ICH, other causes of stroke, total mortality, and reinfarction were independently extracted from each study by 2 observers. DATA SYNTHESIS: Meta-analysis of 9 phase 2 trials (n = 3956) revealed a lower risk of ICH with bolus thrombolytic therapy (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.27-1.01), which was not statistically significant. Meta-analysis of 6 phase 3 trials (n = 62 673) indicated a significant increase in risk of ICH (OR, 1.25; 95% CI, 1.06-1.49). These results were significantly different (P =.01). There was no disagreement for efficacy outcomes. Phase 2 trials included younger and heavier patients with lower baseline blood pressures, and were more often open-label. Subgroup analyses suggested that each of these factors was associated with a lower estimate of risk of ICH with bolus agents. CONCLUSIONS: Our results suggest that when therapeutic interventions are associated with a potential for uncommon but serious adverse safety outcomes, there may be differences between small phase 2 and large phase 3 trials that result in their disagreement for safety but not necessarily efficacy outcomes. Further investigation of the frequency and causes of disagreement between small and large trials for safety outcomes is warranted.

Clinical Trials, Phase II as Topic↗
PubMedDate not supplied

Obtaining medically meaningful answers from an overview of randomized clinical trials.

Answers that have medical value can often be obtained from overviews of randomized clinical trials if care is taken in formulating a biologically sensible question and unbiased and careful methods are used in collecting, extracting and analysis the results. This article discusses some of the pitfalls that are encountered during this process, outlines some solutions and emphasizes the need for a conservative interpretation of the results.

Clinical Trials as Topic↗
PubMedDate not supplied

Selection of patients for randomized controlled trials: implications of wide or narrow eligibility criteria.

This paper discusses the various philosophies that influence the selection of patients for entry into randomized controlled trials. Although a number of different and often competing issues have to be considered depending upon the trial, keeping entry criteria simple, wide and at times even flexible is usually preferable. Such a strategy can be a positive virtue by helping to attain the large numbers of patients that are usually needed to reliably detect the sorts of moderate benefits that are plausible, at a reasonable cost and by providing answers that are relevant to many different categories of patients with a particular condition.

Bias↗
PubMedDate not supplied

Beta blockade during and after myocardial infarction: an overview of the randomized trials.

Long-term beta blockade for perhaps a year or so following discharge after an MI is now of proven value, and for many such patients mortality reductions of about 25% can be achieved. No important differences are clearly apparent among the benefits of different beta blockers, although some are more convenient than others (or have slightly fewer side effects), and it appears that those with appreciable intrinsic sympathomimetic activity may confer less benefit. If monitored, the side effects of long-term therapy are not a major problem, as when they occur they are easily reversible by changing the beta blocker or by discontinuation of treatment. By contrast, although very early IV short-term beta blockade can definitely limit infarct size, more reliable information about the effects of such treatment on mortality will not be available until a large trial (ISIS) reports later this year, with data on some thousands of patients entered within less than 4 hours of the onset of pain. Our aim has been not only to review the 65-odd randomized beta blocker trials but also to demonstrate that when many randomized trials have all applied one general approach to treatment, it is often not appropriate to base inference on individual trial results. Although there will usually be important differences from one trial to another (in eligibility, treatment, end-point assessment, and so on), physicians who wish to decide whether to adopt a particular treatment policy should try to make their decision in the light of an overview of all these related randomized trials and not just a few particular trial results. Although most trials are too small to be individually reliable, this defect of size may be rectified by an overview of many trials, as long as appropriate statistical methods are used. Fortunately, robust statistical methods exist--based on direct, unweighted summation of one O-E value from each trial--that are simple for physicians to use and understand yet provide full statistical sensitivity. These methods allow combination of information from different trials while avoiding the unjustified direct comparison of patients in one trial with patients in another. (Moreover, they can be extended of such data that there is no real need for the introduction of any more complex statistical methods that might be more difficult for physicians to trust.) Their robustness, sensitivity, and avoidance of unnecessary complexity make these particular methods an important tool in trial overviews.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Blood-pressure reduction and cardiovascular risk in HOPE study.

In the Heart Outcomes Prevention Evaluation (HOPE) study, use of the angiotensin-converting-enzyme inhibitor ramipril was associated with a 22% relative risk reduction in cardiovascular death, myocardial infarction, or stroke, despite only a modest reduction in blood pressure (23.3 mm Hg systolic). To test the hypothesis that the benefits seen were not due to reduced blood pressure alone, we calculated blood-pressure-related risk estimates from the placebo group of the HOPE trial, and from earlier studies. We found that the benefits seen in HOPE were around three times greater than predicted from these calculations. In this well treated and largely normotensive population with coronary disease, but good left-ventricular function, the benefits from ramipril were additive to other proven therapies in normotensive patients and in those with higher baseline blood pressure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

Current status of safety and efficacy of calcium channel blockers in cardiovascular diseases: a critical analysis based on 100 studies.

Recently, serious concerns have been expressed about the long-term safety of the calcium channel blockers (CCBs) as a group. Safety and efficacy are, however, ultimately linked to each other; therefore both must be evaluated especially in the therapy of angina and hypertension, the main clinical indications for CCBs. The structural, functional, and pharmacokinetic heterogeneity of CCBs means that the efficacy and dangers of one subclass, such as the short-acting dihydropyridines (DHPs), in one situation, such as unstable angina, do not necessarily apply in other clinical situations. One hundred studies are reviewed according to their methods of data collection: case series, case control, cohort, randomized controlled trials (RCTs), and meta-analyses. Large, well-designed RCTs and the meta-analyses based on these trials remain the gold standard. Observational studies, though potentially less reliable sources of information because of selection bias, may nevertheless produce hypotheses that must then be tested in RCTs. Regarding safety, both observational studies and RCTs suggest that adverse effects of CCBs may be linked to short-acting agents, specifically short-acting nifedipine. Two good studies favor the safety of verapamil, even in short-acting form. Incomplete but increasing overall evidence favors the safety of longer-acting DHPs. Heart failure remains a class contraindication to the use of all CCBs, with some exceptions. Regarding efficacy, there are positive results of RCTs with CCBs in 2 specific clinical situations, namely, verapamil in postinfarct protection in the absence of pre-existing heart failure, and 2 outcome studies on hypertension with longer acting DHPs. These results cannot automatically be applied to other clinical situations and to other CCBs. For example, there is no evidence for the safety or efficacy of DHPs used without beta blockers in postinfarct patients. In diabetic hypertensives, 2 relatively large RCTs show that the blood pressure can be reduced by DHP-based therapy in diabetics, with a reduction in hard end points. To achieve current blood pressure goals, combination therapy is almost always necessary, and in diabetics there is strong evidence that 1 essential component should be an angiotensin converting enzyme inhibitor. The future aim with CCBs must be to obtain a large database gathered from RCTs, which will give the same certainty about efficacy and safety that already holds for use of the diuretics in hypertension, beta-blockers in postmyocardial infarction patients, and the angiotensin converting enzyme inhibitors in heart failure.

Angina, Unstable↗
PubMedDate not supplied

Summary of randomized trials of angiotensin converting enzyme inhibitors.

Angiotensin converting enzyme (ACE) inhibitors have been shown to reduce the risk of death, worsening heart failure and recurrent infarction in patients with left ventricular dysfunction and heart failure. They have also been shown to reduce mortality in the acute phase of myocardial infarction. They have been demonstrated to reduce major vascular events and progression of renal disease in diabetes with hypertension, compared to placebo and to calcium channel blockers. Current trials are evaluating their role in preventing major vascular events in patients with coronary artery disease, strokes and Type II diabetes who are normotensive.

Albuminuria↗