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S MacMahon

Publications and source records attributed to S MacMahon.

At least 73 records · Page 4Linked to original sources
PubMed1996

Clinical effects of anticoagulant therapy in suspected acute myocardial infarction: systematic overview of randomised trials.

OBJECTIVES: Most randomised trials of anticoagulant therapy for suspected acute myocardial infarction have been small and, in some, aspirin and fibrinolytic therapy were not used routinely. A systematic overview (meta-analysis) of their results is needed, in particular to assess the clinical effects of adding heparin to aspirin. DESIGN: Computer aided searches, scrutiny of reference lists, and inquiry of investigators and companies were used to identify potentially eligible studies. On central review, 26 studies were found to involve unconfounded randomised comparisons of anticoagulant therapy versus control in suspected acute myocardial infarction. Additional information on study design and outcome was sought by correspondence with study investigators. SUBJECTS: Patients with suspected acute myocardial infarction. INTERVENTIONS: No routine aspirin was used among about 5000 patients in 21 trials (including half of one small trial) that assessed heparin alone or heparin plus oral anticoagulants, and aspirin was used routinely among 68,000 patients in six trials (including the other half of one small trial) that assessed the addition of intravenous or high dose subcutaneous heparin. MAIN OUTCOME MEASUREMENTS: Death, reinfarction, stroke, pulmonary embolism, and major bleeds (average follow up of about 10 days). RESULTS: In the absence of aspirin, anticoagulant therapy reduced mortality by 25% (SD 8%; 95% confidence interval 10% to 38%; 2P = 0.002), representing 35 (11) fewer deaths per 1000. There were also 10 (4) fewer strokes per 1000 (2P = 0.01), 19 (5) fewer pulmonary emboli per 1000 (2P < 0.001), and non-significantly fewer reinfarctions, with about 13 (5) extra major bleeds per 1000 (2P = 0.01). Similar sized effects were seen with the different anticoagulant regimens studied. In the presence of aspirin, however, heparin reduced mortality by only 6% (SD 3%; 0% to 10%; 2P = 0.03), representing just 5 (2) fewer deaths per 1000. There were 3 (1.3) fewer reinfarctions per 1000 (2P = 0.04) and 1 (0.5) fewer pulmonary emboli per 1000 (2P = 0.01), but there was a small non-significant excess of stroke and a definite excess of 3 (1) major bleeds per 1000 (2P < 0.0001). CONCLUSIONS: The clinical evidence from randomised trials dose not justify the routine addition of either intravenous or subcutaneous heparin to aspirin in the treatment of acute myocardial infarction (irrespective of whether any type of fibrinolytic therapy is used).

Anticoagulants↗
PubMed1996

Blood pressure lowering in patients with cerebrovascular disease: results of the PROGRESS (Perindopril Protection Against Recurrent Stroke Study) pilot phase.

1. Among patients with cerebrovascular disease, there is a direct and continuous association between blood pressure and the risk of stroke, but previous trials of blood pressure lowering in this patient group have been inconclusive. 2. PROGRESS (Perindopril Protection Against Recurrent Stroke Study) is a multicentre, randomized, placebo-controlled trial that aims to determine reliably the effect of angiotensin converting enzyme (ACE) inhibitor-based blood pressure lowering on stroke risk in patients with a history of cerebrovascular disease. If a 4 week run-in period on active perindopril is well tolerated, participants are randomized to either perindopril (4 mg) +/- indapamide (2.5 mg) or matching placebo(s). The primary study outcome is stroke and follow-up is for a minimum of 4 years. 3. For the pilot study nearly 5000 medical records were screened and 60 patients with recent cerebrovascular events were approached directly in hospital or at a clinic visit. Sixty-seven patients entered the run-in phase (52 from retrospective screening and 15 by prospective approach) and 60 patients proceeded to randomization. Treatment with perindopril was well tolerated; only three patients were withdrawn due to side effects and four were withdrawn for other reasons. The mean age of randomized patients was 68 years; 70% were male and 55% were 'non-hypertensive'. The mean entry blood pressure was 142/83 mmHg and following pre-randomization treatment this was reduced by 7/4 mmHg. 4. Most patients were identified by retrospective review of medical records, but this was less efficient than prospective methods. Blood pressure lowering was well tolerated by both hypertensive and non-hypertensive patients with cerebrovascular disease. The small numbers of patients and the non-randomized nature of the data reported limit the conclusions that can be drawn, but the results confirm the feasibility of the main study.

Antihypertensive Agents↗
PubMed1996

Attitudes and practices of New Zealand anaesthetists with regard to epidural and subarachnoid anaesthesia.

A survey was conducted among 259 New Zealand specialist anaesthetists to assess attitudes and practices with regard to epidural or subarachnoid anaesthesia (ESA). Ninety-four per cent replied and virtually all of the respondents indicated that they performed ESA at some time. ESA was used by most anaesthetists for most patients undergoing major hip or knee surgery, abdomino-perineal resection, cystectomy, caesarean section or transurethral resection of the prostate, ESA was used is about half of patients undergoing abdominal aortic aneurysm repair, femoro-popliteal bypass or thoracotomy and there was marked variation between anaesthetists in the frequency of using ESA for these procedures. There was broad consensus about the importance of a number of factors that might influence the decision to employ ESA; in particular that systemic sepsis and prolonged bleeding time were important contraindications and that patient preference and chronic lung disease were important indications. However respondents were equally divided as to whether they felt that recent myocardial infarction or congestive heart failure constituted indications or contraindications to ESA.

Anesthesia, Epidural↗
PubMed1996

Blood pressure and the prevention of stroke.

RELATIONSHIP BETWEEN BLOOD PRESSURE AND STROKE: Data from prospective observational studies indicate that usual levels of blood pressure are directly and continuously related to the risk of initial stroke. A prolonged difference in usual blood pressure levels of just 9/5 mmHg is associated with approximately a one-third difference in stroke risk, with similar proportional effects in hypertensives and normotensives. Recent data from studies of individuals with a history of cerebrovascular disease indicate a similar association between blood pressure and the risk of recurrent stroke. EFFECTS OF TREATMENT ON STROKE: The results of randomized trials of blood pressure-lowering drugs in hypertensive patients suggest that much or all of the long-term potential stroke avoidance associated with prolonged blood pressure differences can be achieved within just a few years of beginning treatment. Overall, in 17 randomized trials of antihypertensive treatment a net blood pressure reduction of 10-12 mmHg systolic and 5-6 mmHg diastolic conferred a reduction in stroke incidence of 38% (SD 4), with similar reductions in fatal and non-fatal stroke. Because the proportional effects of treatment were similar in higher and lower risk patient groups, the absolute effects of treatment on stroke varied in direct proportion to the background risk of stroke. The greatest potential benefits were observed among those with a history of cerebrovascular disease; however, the results of the trials conducted in patients with a history of stroke or transient ischaemic attack, although promising, were not definitive. New trials are required to determine more reliably the effects of blood pressure lowering in patients with cerebrovascular disease.

Blood Pressure↗
PubMed1995

Blood pressure lowering for the primary and secondary prevention of coronary and cerebrovascular disease.

An overview of the 17 completed randomised trials of antihypertensive treatment demonstrates that a 5-6 mm Hg reduction in DBP reduced stroke risk by 38% (SD 4) and CHD risk by 16% (SD 4). These results indicate that a few years' treatment with diuretic- or beta-blocker-based therapy produces most or all of the long-term stroke avoidance and much of the long-term CHD avoidance that would be predicted from observational epidemiological studies, given the blood pressure reductions that were achieved in the trials. The relative risk reductions were similar in trials of older and younger patients, although the absolute reduction in events was more than twice as great in the trials in older patients. From these results it can be estimated that in fully compliant patients at similar risk of vascular disease to those included in the trials, antihypertensive treatment for 5 years would prevent one major vascular event among every 20 older patients and one major vascular event among every 60 younger patients. Obviously the benefits of treatment will be greater among those at higher risk than the patients included in the previous trials. The greatest benefits are likely to be achieved in those with a history of vascular disease since their risk of future events is particularly high. Among such patients it is possible that blood pressure reduction will confer worthwhile benefits in those without hypertension, as well as those with hypertension. It is also possible that the benefits of treatment will be determined by the size of the blood pressure reduction and by the choice of the anti-hypertensive agent. However, each of these possibilities requires confirmation in large scale randomised controlled trials.

Adult↗
PubMed1995

Fletcher Challenge-University of Auckland Heart & Health Study: design and baseline findings.

AIMS: The aims of this prospective observational study are to determine the relationship of sociodemographic factors, psychological factors and several factors measured in blood, with the risk of coronary heart disease (CHD) in a New Zealand population. METHODS: Participants were recruited from two sources: employees of the Fletcher Challenge Group and individuals listed on the general electoral roll for the Auckland region. Baseline and follow up risk factor data were obtained from a questionnaire, blood samples and a simple physical examination. Outcome data on deaths and hospitalisations due to coronary heart disease will be obtained primarily through linkage of participant identifiers to data collected nationally by the New Zealand Health Information Service. RESULTS: A total of 10,529 individuals agreed to participate (8011 from Fletcher Challenge and 2518 from the electoral roll), representing a response rate of 74%. Within the study population, there was a broad distribution of sociodemographic characteristics including ethnicity-10% of participants were Maori and 5% were of Pacific Islands origin. There was also wide heterogeneity of coronary heart disease risk as judged from the distributions of established risk factors at baseline-5% of participants had evidence of existing coronary heart disease, a quarter were current smokers, a sixth were nondrinkers, almost a half were overweight, a fifth had blood pressure > or = 150/95 mmHg or were receiving antihypertensive treatment and a sixth had cholesterol levels > or = 6.5 mmol/L. CONCLUSIONS: This is the first, large scale prospective observational study of the determinants of coronary heart disease in a New Zealand population. The study participants represent a broad cross section of society, with wide variation in sociodemographic characteristics and coronary heart disease risk. Initial results concerning the relationships of primary interest should be available within 5 years when sufficient coronary heart disease events have been documented to allow reliable analyses.

Adult↗
PubMed1995

Hospital admissions and deaths due to congestive heart failure in New Zealand, 1988-91.

AIMS: Congestive heart failure is believed to be a major public health problem in most Western countries; however, little is known about the extent of morbidity and mortality from congestive heart failure in New Zealand. This paper reports data on hospital admissions and mortality due to congestive heart failure in New Zealand during the years 1988-91. METHODS: All data were obtained from the New Zealand Health Information Service. Deaths from congestive heart failure were identified from ICD-9 codes indicating a primary diagnosis of congestive heart failure. Hospitalisations for congestive heart failure were identified both from ICD-9 codes indicating a primary diagnosis of congestive heart failure and from codes indicating a diagnosis of congestive heart failure secondary to chronic rheumatic heart disease, ischaemic heart disease or valvular heart disease (nonrheumatic). RESULTS: Each year there was an average of about 850 deaths ascribed to heart failure; two-thirds of these occurred in patients over the age of 75 years. Each year there was also an average of about 8000 hospital admissions of about 5000 patients for congestive heart failure; 75% of these admissions involved patients over 65 years old. The mean duration of hospital stay for congestive heart failure was 16 days. On this basis, it is estimated that hospital admissions for congestive heart failure are likely to cost about NZ$50 million each year, or about 1% of the total health budget. CONCLUSIONS: Congestive heart failure is clearly a major public health problem in New Zealand with high hospitalisation and mortality rates. Several strategies have been proven to reduce mortality and hospital admissions for congestive heart failure and these should be utilised widely in patients at risk.

Aged↗
PubMed1995

Blood pressure and mortality among men with prior myocardial infarction. Multiple Risk Factor Intervention Trial Research Group.

BACKGROUND: The purpose of the present study was to describe the relation between blood pressure (systolic [SBP] and diastolic [DBP]) and death from coronary heart disease (CHD) and all causes for men with a history of myocardial infarction (MI). METHODS AND RESULTS: The study cohort consisted of men aged 35 to 57 years screened for the Multiple Risk Factor Intervention Trial (MRFIT) in 1973 through 1975 and followed for survival for an average of 16 years through 1990. There were 5362 men who reported prior hospitalization for a heart attack of at least 2 weeks' duration at the initial screening of MRFIT. There was a J-shaped relation between SBP and DBP with both CHD and all-cause mortality during the first 2 years of follow-up in older (age, 45 to 57 years) men only. Risk nadirs for SBP were 152 and 145 mm Hg, respectively, for CHD death and all-cause mortality; corresponding DBP risk nadirs were 94 and 90 mm Hg. After the first 2 years, there was a positive association between SBP and death from CHD and all causes. By 15 years, cumulative CHD mortality percentages for men with screening SBP < 120, 120 to 139, 140 to 159, and > or = 160 mm Hg were 19.7%, 21.3%, 27.5%, and 32.0%, respectively. When deaths only after year 2 were considered, although the linear DBP coefficient was significant, the quadratic term for DBP was no longer significant (P > .05). However, the relation still appeared J-shaped as cumulative mortality for those with DBP < 70, 70 to 79, 80 to 89, 90 to 99, and > or = 100 mm Hg was 24.3%, 20.8%, 21.1%, 25.5%, and 29.7%, respectively. When the joint relation of SBP and DBP was considered, there were no survival differences among the four cohorts (SBP > or = 140 and DBP < 80, SBP > or = 140 and DBP > or = 80, SBP < or = 140 and DBP < 80, and SBP < or = 140 and DBP > or = 80) during the first 2 years. After 2 years, both CHD and all-cause mortality rates were approximately 40% higher for participants with SBP > or = 140 mm Hg versus < 140 mm Hg regardless of DBP level (< 80 or > or = 80 mm Hg). CONCLUSIONS: In this large cohort of men with prior MI, the association of SBP and DBP with CHD and all-cause mortality varied over the 16-year follow-up period. During early follow-up, in older men only, J- or U-shaped relations were evident. However, after 2 years, these same relations had become positive and graded. Given the substantial excess mortality risk in this cohort associated with high blood pressure, particularly SBP, efforts to gradually lower blood pressure should receive high priority among hypertensive men with prior MI.

Adult↗
PubMed1995

Association of angiotensinogen gene T235 variant with increased risk of coronary heart disease.

Several genes, including some encoding components of the renin angiotensin system, are associated with the risk of cardiovascular diseases. There have been reports linking a homozygous deletion allele of the angiotensin converting enzyme (ACE) gene (DD) with an increased risk of myocardial infarction, and some variants of the angiotensinogen gene with an increased risk of hypertension. In a case-control study of a caucasian population from New Zealand, we examined the associations with coronary heart disease (CHD) of ACE DD and of a mis-sense mutation with methionine to threonine aminoacid substitution at codon 235 in the angiotensinogen gene (T235). We studied 422 patients (mean age 62 years, 81% male) with documented CHD (50% with myocardial infarction) and 406 controls without known CHD (frequency-matched to cases by age and sex). Risk factors for CHD were assessed by standard questionnaire, physical examination, and blood tests. Genomic DNA from leucocytes was analysed for various ACE and angiotensinogen alleles. Angiotensinogen T235 homozygotes were at significantly increased risk of CHD generally (odds ratio 1.7, 2 p = 0.008) and of myocardial infarction specifically (1.8, 2 p = 0.009). Adjustment for several risk factors increased the estimate of CHD risk associated with this allele to 2.6 (2 p < 0.001) and the estimate for myocardial infarction risk to 3.4 (2 p < 0.001). By contrast, there was no evidence of a significant increase in the risk of CHD or myocardial infarction among individuals with ACE DD. We conclude that the T235 polymorphism of the angiotensinogen gene is an independent risk factor, which carries an approximately two-fold increased risk of CHD. In this study, however, ACE DD was not associated with any detectable increase in CHD risk.

Alleles↗
PubMed1995

Absence of effect of simvastatin on the progression of lens opacities in a randomised placebo controlled study. Oxford Cholesterol Study Group.

AIMS: A detailed assessment of ophthalmic effects of an HMG CoA reductase inhibitor, simvastatin, was performed. METHODS: Six hundred and twenty one individuals considered to be at increased risk of coronary heart disease were randomised, following an 8 week placebo 'run in' period, to receive 40 mg daily simvastatin, 20 mg daily simvastatin, or matching placebo. Patients with a baseline corrected visual acuity better than 6/24 and without a history of cataract were eligible for detailed ophthalmic assessment at 6 months (539 patients assessed) and at 18 months (474 patients assessed). RESULTS: No significant differences between the treatment groups were detected at the 6 month or 18 month visit in the refractive condition of the eye or in the mean intraocular pressure. Nor were there clear differences in the Oxford grading system scores for various measures of the major types of cataract (cortical spokes, posterior subcapsular cataract, nuclear brunescence, white scatter) or for other morphological features visible within the lens (fibre folds or focal dots). Scheimpflug slit image photographs and retroillumination analysis of the percentage of cataract within a defined region of the lens were also performed at each visit, with no clear differences observed between the treatment groups. CONCLUSION: This single centre double blind study found no good evidence of any adverse effects of 18 months of simvastatin treatment on lens opacity formation, using a variety of validated techniques to assess cataract development. Routine clinic follow up of visual symptoms and admission to hospital for ophthalmic procedures over 5 years of treatment was also reassuring, with no excess adverse outcomes observed with simvastatin.

Adult↗
PubMed1995

Systematic underestimation of treatment effects as a result of diagnostic test inaccuracy: implications for the interpretation and design of thromboprophylaxis trials.

Many clinical trials that have assessed strategies for the prevention of deep vein thrombosis have employed diagnostic tests that are less accurate than venography. The correct interpretation of these trials has been the subject of considerable debate. This paper attempts to quantify the likely effects of the use of inaccurate diagnostic tests (in particular fibrinogen scanning) on the validity and precision of estimates of treatment effects. It is shown that, if there is no difference in the rate of misclassification of deep vein thrombosis between study and control groups, then treatment effects will tend to be systematically underestimated in trials that only use inaccurate diagnostic tests. However, for trials in which there are no false positive diagnoses, such as those employing venography, the estimate of relative treatment effects will be unbiased. This phenomenon is demonstrated empirically by data from randomised trials of antiplatelet therapy. The implications of these findings are two-fold. First, so long as the accuracy of the test is the same in study and control groups, positive trial results cannot be ascribed to diagnostic test inaccuracy. Second, unbiased estimates of relative treatment effects can be obtained by using cheap, practicable and non-invasive screening tests that are supplemented by venographic assessment of positive test results. This would facilitate the conduct of much larger randomised trials than has generally been possible when mandatory venography was used; if future trials randomised some thousands of patients and employed confirmatory venography then they would provide both unbiased and precise estimates of relative treatment effects.

Clinical Trials as Topic↗
PubMed1995

PROGRESS (perindopril protection against recurrent stroke study): rationale and design. PROGRESS Management Committee [corrected].

RATIONALE: Patients with a history of cerebrovascular disease have a very high risk of stroke, and usual levels of both systolic and diastolic blood pressure are directly and continuously associated with this risk. Trials of blood pressure lowering in patients with transient ischaemic attacks or stroke have been too small to reliably detect the effects on stroke risk of the modest blood pressure reductions achieved. OBJECTIVES: The primary objective of PROGRESS is to determine precisely the effects of blood pressure reduction with an angiotensin converting enzyme (ACE) inhibitor-based regimen on the stroke risk in patients with a history of transient ischaemic attacks or minor stroke. DESIGN: The study is a randomized, double-blind, placebo-controlled clinical trial. Before randomization, there is a 4-week run-in phase on open-label ACE inhibitor treatment. The scheduled duration of treatment and follow-up is 4-5 years. SETTING: The study will be conducted in collaborating clinical centres in Australia, Belgium, the People's Republic of China, France, Italy, Japan, New Zealand, Sweden and the United Kingdom. PATIENTS: The study will involve 6000 patients with a history of transient ischaemic attacks or stroke (ischaemic or haemorrhagic) in the past 5 years. To be eligible patients should have no definite indication for or contra-indication to treatment with an ACE inhibitor and no disability likely to prevent regular attendance at study clinics. INTERVENTIONS: Study treatment will comprise perindopril and indapamide or matching placebos for patients without an indication for or contra-indication to treatment with a diuretic, perindopril alone or matching placebo for all other patients. STUDY OUTCOMES: The primary study outcome is total strokes and secondary outcomes include fatal or disabling strokes, total major cardiovascular events, cardiovascular deaths, cognitive function and dementia, and disability and dependency.

Angiotensin-Converting Enzyme Inhibitors↗