United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: interim results

From 1979 to 1985, 2435 patients thought to have had a transient ischaemic attack or minor ischaemic stroke were allocated at random to receive long term blind treatment with either aspirin 600 mg twice daily (n=815), aspirin 300 mg once daily (806), or placebo (814). Treatment continued with about 85% compliance until September 1986 (mean four years). The odds of suffering one or more of four categories of event—namely, non-fatal myocardial infarction, non-fatal major stroke, vascular death, or non-vascular death—were 18% less in the two groups allocated to receive aspirin than in the group allocated to receive placebo (2p=0·01). The more relevant but less frequent composite event of disabling stroke or vascular death was reduced by only 7%; this reduction was not significantly different from zero, but nor was it significantly different from a 25% reduction. There was no definite difference between responses to the 300 mg and 1200 mg daily doses, except that the lower dose was significantly less gastrotoxic.     

Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients

ObjectiveTo determine the effects of antiplatelet therapy among patients at high risk of occlusive vascular events.DesignCollaborative meta-analyses (systematic overviews).ResultsOverall, among these high risk patients, allocation to antiplatelet therapy reduced the combined outcome of any serious vascular event by about one quarter; non-fatal myocardial infarction was reduced by one third, non-fatal stroke by one quarter, and vascular mortality by one sixth (with no apparent adverse effect on other deaths). Absolute reductions in the risk of having a serious vascular event were 36 (SE 5) per 1000 treated for two years among patients with previous myocardial infarction; 38 (5) per 1000 patients treated for one month among patients with acute myocardial infarction; 36 (6) per 1000 treated for two years among those with previous stroke or transient ischaemic attack; 9 (3) per 1000 treated for three weeks among those with acute stroke; and 22 (3) per 1000 treated for two years among other high risk patients (with separately significant results for those with stable angina (P=0.0005), peripheral arterial disease (P=0.004), and atrial fibrillation (P=0.01)). In each of these high risk categories, the absolute benefits substantially outweighed the absolute risks of major extracranial bleeding. Aspirin was the most widely studied antiplatelet drug, with doses of 75-150 mg daily at least as effective as higher daily doses. The effects of doses lower than 75 mg daily were less certain. Clopidogrel reduced serious vascular events by 10% (4%) compared with aspirin, which was similar to the 12% (7%) reduction observed with its analogue ticlopidine. Addition of dipyridamole to aspirin produced no significant further reduction in vascular events compared with aspirin alone. Among patients at high risk of immediate coronary occlusion, short term addition of an intravenous glycoprotein IIb/IIIa antagonist to aspirin prevented a further 20 (4) vascular events per 1000 (P<0.0001) but caused 23 major (but rarely fatal) extracranial bleeds per 1000.ConclusionsAspirin (or another oral antiplatelet drug) is protective in most types of patient at increased risk of occlusive vascular events, including those with an acute myocardial infarction or ischaemic stroke, unstable or stable angina, previous myocardial infarction, stroke or cerebral ischaemia, peripheral arterial disease, or atrial fibrillation. Low dose aspirin (75-150 mg daily) is an effective antiplatelet regimen for long term use, but in acute settings an initial loading dose of at least 150 mg aspirin may be required. Adding a second antiplatelet drug to aspirin may produce additional benefits in some clinical circumstances, but more research into this strategy is needed.

What is already known on this topic

Antiplatelet therapy is effective for short term treatment of patients with suspected acute myocardial infarction and unstable anginaLong term treatment is beneficial for patients who have had a myocardial infarction, stroke, or transient ischaemic attackDaily aspirin doses of 75-325 mg are effective

What this study adds

Antiplatelet therapy protects against vascular events among patients with stable angina, intermittent claudication, and (if oral anticoagulants are unsuitable) atrial fibrillationAntiplatelet therapy can be started promptly during acute presumed ischaemic stroke and continued long termDaily aspirin doses of 75-150 mg seem to be as effective as higher doses for long term treatments (and clopidrogel is an appropriate alternative for patients with a contraindication to aspirin)Short term addition of a glycoprotein IIb/IIIa antagonist to aspirin prevents vascular events in patients having percutaneous coronary intervention and those with unstable angina but causes increased bleeding     

Secondary prevention of vascular disease by prolonged antiplatelet treatment

Thirty one randomised trials of antiplatelet treatment for patients with a history of transient ischaemic attack, occlusive stroke, unstable angina, or myocardial infarction were identified. Six were still in progress, and the results of the remaining 25 were reviewed. They included a total of some 29 000 patients, 3000 of whom had died. Overall, allocation to antiplatelet treatment had no apparent effect on non-vascular mortality but reduced vascular mortality by 15% (SD 4%) and non-fatal vascular events (stroke or myocardial infarction) by 30% (4%). This suggested that with good compliance these treatments might reduce vascular mortality by about one sixth, other vascular events by about a third, and total vascular events by about a quarter. There was no significant difference between the effects of the different types of antiplatelet treatment tested (300-325 mg aspirin daily, higher aspirin doses, sulphinpyrazone, or high dose aspirin with dipyridamole), nor between the effects in patients with histories of cerebral or cardiac disease. Thus antiplatelet treatment can reduce the incidence of serious vascular events by about a quarter among a wide range of patients at particular risk of occlusive vascular disease. The balance of risk and benefit, however, might be different for “primary” prevention among people at low absolute risk of occlusive disease if antiplatelet treatment produced even a small increase in the incidence of cerebral haemorrhage.     

Collaborative overview of randomised trials of antiplatelet therapy--I: Prevention of death,myocardial infarction,and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists' Collaboration.

OBJECTIVE--To determine the effects of "prolonged" antiplatelet therapy (that is, given for one month or more) on "vascular events" (non-fatal myocardial infarctions, non-fatal strokes, or vascular deaths) in various categories of patients. DESIGN--Overviews of 145 randomised trials of "prolonged" antiplatelet therapy versus control and 29 randomised comparisons between such antiplatelet regimens. SETTING--Randomised trials that could have been available by March 1990. SUBJECTS--Trials of antiplatelet therapy versus control included about 70,000 "high risk" patients (that is, with some vascular disease or other condition implying an increased risk of occlusive vascular disease) and 30,000 "low risk" subjects from the general population. Direct comparisons of different antiplatelet regimens involved about 10,000 high risk patients. RESULTS--In each of four main high risk categories of patients antiplatelet therapy was definitely protective. The percentages of patients suffering a vascular event among those allocated antiplatelet therapy versus appropriately adjusted control percentages (and mean scheduled treatment durations and net absolute benefits) were: (a) among about 20,000 patients with acute myocardial infarction, 10% antiplatelet therapy v 14% control (one month benefit about 40 vascular events avoided per 1000 patients treated (2P < 0.00001)); (b) among about 20,000 patients with a past history of myocardial infarction, 13% antiplatelet therapy v 17% control (two year benefit about 40/1000 (2P < 0.00001)); (c) among about 10,000 patients with a past history of stroke or transient ischaemic attack, 18% antiplatelet therapy v 22% control (three year benefit about 40/1000 (2P < 0.00001)); (d) among about 20,000 patients with some other relevant medical history (unstable angina, stable angina, vascular surgery, angioplasty, atrial fibrillation, valvular disease, peripheral vascular disease, etc), 9% v 14% in 4000 patients with unstable angina (six month benefit about 50/1000 (2P < 0.00001)) and 6% v 8% in 16,000 other high risk patients (one year benefit about 20/1000 (2P < 0.00001)). Reductions in vascular events were about one quarter in each of these four main categories and were separately statistically significant in middle age and old age, in men and women, in hypertensive and normotensive patients, and in diabetic and nondiabetic patients. Taking all high risk patients together showed reductions of about one third in non-fatal myocardial infarction, about one third in non-fatal stroke, and about one third in vascular death (each 2P < 0.00001). There was no evidence that non-vascular deaths were increased, so in each of the four main high risk categories overall mortality was significantly reduced. The most widely tested antiplatelet regimen was "medium dose" (75-325 mg/day) aspirin. Doses throughout this range seemed similarly effective (although in an acute emergency it might be prudent to use an initial dose of 160-325 mg rather than about 75 mg). There was no appreciable evidence that either a higher aspirin dose or any other antiplatelet regimen was more effective than medium dose aspirin in preventing vascular events. The optimal duration of treatment for patients with a past history of myocardial infarction, stroke, or transient ischaemic attack could not be determined directly because most trials lasted only one, two, or three years (average about two years). Nevertheless, there was significant (2P < 0.0001) further benefit between the end of year 1 and the end of year 3, suggesting that longer treatment might well be more effective. Among low risk recipients of "primary prevention" a significant reduction of one third in non-fatal myocardial infarction was, however, accompanied by a non-significant increase in stroke. Furthermore, the absolute reduction in vascular events was much smaller than for high risk patients despite a much longer treatment period (4.4% antiplatelet therapy v 4.8% control; five year     

Management of patients after their first myocardial infarction.

In the past 20 years there has been a steady improvement in the short term prognosis of patients with myocardial infarction, following the introduction of beta blockers, thrombolysis, and aspirin. Patients treated with thrombolytic drugs have a lower overall mortality after myocardial infarction but remain at risk of non-fatal reinfarction or death, and in one study almost half of all survivors of acute myocardial infarction died or suffered a further ischaemic event within three years. It is therefore important to have a strategy to identify patients at high risk, to reduce the subsequent development of cardiac failure and mortality, and to have effective measures for secondary prevention to reduce the incidence of reinfarction as well as to promote rehabilitation.     

Collaborative overview of randomised trials of antiplatelet therapy--II: Maintenance of vascular graft or arterial patency by antiplatelet therapy. Antiplatelet Trialists' Collaboration.

OBJECTIVE--To determine the efficacy of antiplatelet therapy in maintaining vascular patency in various categories of patients. DESIGN--Overviews of 46 randomised trials of antiplatelet therapy versus control and 14 randomised trials comparing one antiplatelet regimen with another. SETTING--Randomised trials that could have been available by March 1990 and in which vascular graft or arterial patency was to be studied systematically. SUBJECTS--About 8000 patients at varying degrees of risk of vascular occlusion (by virtue of disease or of having some vascular procedure) were in trials of antiplatelet therapy versus control and 4000 such patients were in trials directly comparing different antiplatelet regimens. RESULTS--Overall, antiplatelet therapy produced a highly significant (2P < 0.0001) reduction in vascular occlusion, with similar proportional reductions in several different types of patients. Hence the absolute reductions tended to be largest among patients at highest risk of occlusion, with smaller but still significant absolute reductions among lower risk patients. The proportions of patients with confirmed occlusion among those allocated antiplatelet therapy versus appropriately adjusted control proportions (and mean scheduled treatment durations and net absolute benefits) were: (a) among about 4000 patients with coronary artery grafts, 21% antiplatelet therapy v 30% control (seven month benefit about 90 patients protected per 1000 allocated antiplatelet therapy (2P < 0.00001)); (b) among about 800 patients after coronary angioplasty, 4% antiplatelet therapy v 8% control (six month benefit about 40/1000 (2P = 0.02)); (c) among about 3000 patients with peripheral artery procedures or disease, 16% antiplatelet therapy v 25% control (19 month benefit about 90/1000 (2P < 0.00001)); (d) among about 400 renal patients with a shunt or fistula placed for haemodialysis access, 17% antiplatelet therapy v 39% control (two month benefit about 200/1000 (2P < 0.00001)). Indirect comparisons between the effects of starting treatment before these vascular procedures and starting soon after them indicated similar sized benefits. As well as preventing subclinical occlusion, antiplatelet therapy produced a significant (2P = 0.002) reduction of about one quarter in the odds of suffering a "vascular event" (non-fatal myocardial infarction, non-fatal stroke, or vascular death). Various antiplatelet regimens (chiefly aspirin alone or aspirin plus dipyridamole) were studied but there was no significant evidence of differences between their effects on arterial occlusion or vascular events. Data on bleeding were incomplete but no large excess with antiplatelet therapy was apparent. CONCLUSION--Antiplatelet therapy (chiefly aspirin alone or aspirin plus dipyridamole) greatly reduces the risk of vascular occlusion in a wide range of patients at high risk of this complication. Further studies are required to determine exactly when treatment should start (to limit any perioperative bleeding while still preventing most early occlusion) and for how long it should be continued.     

Randomised trial of treatment of hypertension in elderly patients in primary care.

A randomised trial of the treatment of hypertension in 884 patients aged 60 to 79 years at the onset showed a reduction of 18/11 mm Hg in blood pressure over a mean follow up period of 4.4 years. The principal antihypertensive agents were atenolol and bendrofluazide. There was a reduction in the rate of fatal stroke in the treatment group to 30% of that in the control group (95% confidence interval 11-84%, p less than 0.025). The rate of all strokes (fatal and non-fatal) in the treatment group was 58% of that in the control group (95% confidence interval 35-96%, p less than 0.03). The incidence of myocardial infarction and total mortality was unaffected by treatment. Questionnaires completed by the patients and their relatives failed to identify any differences in symptoms that were likely to be due to treatment.     

Experience of coronary care in diabetes.

During 1968-1973, 94 patients with diabetes were admitted to a coronary care unit (CCU) on 99 occasions with proved myocardial infarction. Altogether 24 of them (25-5%) died, giving an overall mortality at the time of discharge of 24% for the total admissions. This was just significantly higher than the 19% mortality recorded among non-diabetics treated in the same period but was much lower than that among diabetics treated for myocardial infarction before the advent of CCUs. No definite correlation was found between the type of anti-diabetic treatment and either mortality or the incidence of primary ventricular fibrillation. Patients with "poor" control of the diabetes before admission showed a significantly higher mortality than those with "good" control, but there was no significant difference in mortality between those with previous good control and non-diabetics.     

A comparison of aspirin and anticoagulation following thrombolysis for myocardial infarction (the AFTER study): a multicentre unblinded randomised clinical trial.

OBJECTIVE: To compare aspirin with anticoagulation with regard to risk of cardiac death and reinfarction in patients who received anistreplase thrombolysis for myocardial infarction. DESIGN: A multicentre unblinded randomised clinical trial. SETTING: 38 hospitals in six countries. SUBJECTS: 1036 patients who had been treated with anistreplase for myocardial infarction were randomly assigned to either aspirin (150 mg daily) or anticoagulation (intravenous heparin followed by warfarin or other oral anticoagulant). The trial was stopped earlier than originally intended because of the slowing rate of recruitment. MAIN OUTCOME MEASURE: Cardiac death or recurrent myocardial infarction at 30 days. RESULTS: After 30 days cardiac death or reinfarction, occurred in 11.0% (57/517) of the patients treated with anticoagulation and 11.2% (58/519) of the patients treated with aspirin (odds ratio 1.02, 95% confidence interval 0.69 to 1.50, P = 0.92). Corresponding findings at three months were 13.2% (68/517) and 12.1% (63/519) (0.91, 0.63 to 1.32, P = 0.67). Patients receiving anticoagulation were more likely than patients receiving aspirin to have had severe bleeding or a stroke by three months (3.9% v 1.7% (0.44, 0.20 to 0.97, P = 0.04)). CONCLUSION: No evidence of a difference in the incidence of cardiac events was found between the two treatment groups, though the trial is too small to claim treatment equivalence confidently. A higher incidence of severe bleeding events and strokes was detected in the group receiving anticoagulation, suggesting that aspirin may be the drug of choice for most patients in this context.     

Short and long term prognosis of acute myocardial infarction since introduction of thrombolysis.

OBJECTIVE--To record prognosis and determinants of outcome in patients with acute myocardial infarction since thrombolysis was introduced. DESIGN--Observational study. SETTING--London district general hospital. PATIENTS--608 consecutive patients admitted to the coronary care unit with acute myocardial infarction between 1 January 1988 and 31 December 1991. MAIN OUTCOME MEASURE--All cause mortality, non-fatal ischaemic events (myocardial infarction, unstable angina), and revascularisation. RESULTS--Of the 608 patients, 89 (14.6%) died in hospital. 507 [corrected] patients were followed up after discharge from hospital. Mortality (95% confidence interval) at 30 days, one year, and three years was 16.0% (13.4% to 19.2%), 21.7% (18.6% to 25.2%), and 29.4% (25.3% to 33.9%) respectively. Event free survival (survival without a non-fatal ischaemic event) was 80.4% (77.0% to 83.4%) at 30 days, 66.8% (62.8% to 70.5%) at one year, and 56.1% (51.3% to 60.6%) at three years. Survival in patients treated with thrombolysis was considerably higher than in those not given thrombolysis (three year survival: 76.7% v 54.3%), although the incidence of non-fatal ischaemic events was the same in the two groups. Multivariate determinants of six month survival were left ventricular failure, treatment with thrombolysis and aspirin, smoking history, bundle branch block, and age. For patients who survived six months, age was the only factor related to long term survival. CONCLUSIONS--Although patients treated by thrombolysis had a relatively good prognosis, long term mortality and the incidence of non-fatal recurrent ischaemic events remained high. Effective strategies for the identification and treatment of high risk patients need to be reassessed.     

Reduction in mortality after myocardial infarction with long-term beta-adrenoceptor blockade. Multicentre international study: supplementary report.

In a controlled multicentre trial carried out to assess the value of long-term practolol treatment after myocardial infarction the provisional results showed a significant reduction in mortality, though some of the data were lacking. These have now been included and the results updated. The final figures for all deaths were 78 in the placebo group of 1533 patients and 48 in the practolol group of 1520 patients. The reduction in mortality (38%) was significant at the 1% level. The figures for non-fatal reinfarction (97 in the placebo group, and 75 in the practolol group) were not significantly different. Patients with pre-entry anterior infarction, and especially those with a diastolic blood pressure equal to or below the mean (78 mm Hg) at entry to the trial, were at high risk but benefited particularly well from beta-adrenoceptor blockade. After pre-entry inferior infarction the percentage reduction in deaths occurring within two hours after symptoms of a new event was similar to that after anterior infarction, but the incidence of death more than two hours after the event was greater in the practolol-treated group. Thus the difference between groups in total deaths after pretrial inferior infarction was marginal. Until the results of further trials are reported long-term beta-adrenoceptor blockade (possibly up to two years) is recommended after uncomplicated anterior myocardial infarction.     

Ischaemic Heart Disease: A Secondary Prevention Trial Using Clofibrate

A trial is reported of the effects of giving clofibrate to prevent progression of pre-existing ischaemic heart disease. There were two groups randomly distributed between clofibrate (350 patients) and placebo (367 patients) regimens. The trial lasted about six years and was conducted in 19 hospitals in Scotland. The criteria of acceptance into the trial were precise and were monitored by one observer. The standards of diagnosis of events were defined and all protocols and electrocardiograms were read blind by one observer.Three categories of patients were admissible to the trial: (1) patients with one myocardial infarction (W.H.O. E.C.G. criteria) between 8 and 16 weeks before the start of the trial; (2) patients with angina of a duration of 3 to 24 months, provided their E.C.G. showed signs of myocardial ischaemia at rest or after exercise; and (3) patients with one recent myocardial infarction and pre-existing angina as defined above.There were fewer deaths in patients with angina (categories 2 and 3 above) treated with clofibrate than in those on placebo. The mortality in the former group was reduced by 62%, and this is a statistically significant difference. Clofibrate did not have any statistically significant effect in reducing the rate of non-fatal infarction in patients with angina or in those with myocardial infarction and pre-existing angina, though a beneficial trend was evident when both subgroups were combined (a 44% reduction compared with the placebo group). There was a significant reduction in all events (fatal and non-fatal) in patients with angina (“all anginas”) in the clofibrate-treated group; the rate was reduced by 53%.Clofibrate did not alter the overall mortality or morbidity rates in patients admitted to the trial with recent myocardial infarction without preceding angina of more than three months'' duration. In one subgroup there was a statistically significant adverse effect in the clofibrate-treated group. The lack of any overall effect in patients with myocardial infarction might be related to the unexpectedly low mortality rate (2·97%) in the placebo group; it is usually in the region of 4-9% per annum after first myocardial infarction.In patients categorized as “all anginas” there was significant reduction in events whether the initial serum cholesterol level was high (greater than 260 mg/100 ml) or normal. Clofibrate seemed to have a small but not significant beneficial effect in patients with myocardial infarction with initially high serum cholesterol levels, but was of no value in those with initially normal serum cholesterol levels. There was no significant relationship between the response or lack of response of serum cholesterol to clofibrate and the incidence of events either in patients with angina or in those with infarction.The main conclusion of this trial is that clofibrate had a beneficial effect in reducing mortality and, to a lesser extent, morbidity in patients who presented with angina (“all anginas”). This effect was independent of initial serum cholesterol levels or the extent to which serum cholesterol was lowered. The drug had no significant overall effect on prognosis in patients with myocardial infarction alone.     

Risk of angina pectoris, non-fatal myocardial infarction and non-fatal stroke among hypertensives: the CroHort study

Aim of this study was to investigate association of controlled and uncontrolled hypertension with angina pectoris, non-fatal myocardial infarction and non-fatal cerebrovascular insult on a cohort from Croatian Adult Health Cohort Study (CroHort). Odds for angina pectoris, non-fatal myocardial infarction and non-fatal cerebrovascular insult were calculated for 227 respondents with controlled hypertension and 1,287 respondents with uncontrolled hypertension compared to 1,353 normotensive respondents. The results showed that among men uncontrolled hypertension was significantly associated with risk of non-fatal stroke, while among women no significant associations were recorded. Primary and secondary prevention of hypertension should be public health priority and would contribute to reducing the risk of stroke in Croatian population.     

COX-2: Where are we in 2003? - Be strong and resolute: continue to use COX-2 selective inhibitors at recommended dosages in appropriate patients

Cyclooxygenase (COX)-2 selective inhibitors have been shown to have comparable efficacy to nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Large outcome studies have shown that patients with OA and RA not taking low-dose aspirin have fewer symptomatic and complicated upper GI events when treated with COX-2 selective inhibitors than with nonselective NSAIDs. When used in recommended dosages, there is no convincing evidence that patients treated with COX-2 selective inhibitors have an increased incidence of cardiovascular thrombotic events, including non-fatal myocardial infarction, than patients treated with either placebo or nonselective NSAIDs other than naproxen. Co-therapy with low-dose aspirin is recommended in patients with OA and RA at increased risk for cardiovascular events; the need for gastroprotective therapy in such patients is controversial.     

COX-2: Where are we in 2003? - Be strong and resolute: continue to use COX-2 selective inhibitors at recommended dosages in appropriate patients

Cyclooxygenase (COX)-2 selective inhibitors have been shown to have comparable efficacy to nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Large outcome studies have shown that patients with OA and RA not taking low-dose aspirin have fewer symptomatic and complicated upper GI events when treated with COX-2 selective inhibitors than with nonselective NSAIDs. When used in recommended dosages, there is no convincing evidence that patients treated with COX-2 selective inhibitors have an increased incidence of cardiovascular thrombotic events, including non-fatal myocardial infarction, than patients treated with either placebo or nonselective NSAIDs other than naproxen. Co-therapy with low-dose aspirin is recommended in patients with OA and RA at increased risk for cardiovascular events; the need for gastroprotective therapy in such patients is controversial.     

Plasma Renin Levels and Vascular Complications in Hypertension

Plasma renin levels, measured in 39 untreated patients in 1967, under conditions of sodium loading and sodium depletion have been related to the incidence of stroke and myocardial infarction. Renin levels were not significantly different in patients with or without vascular complications. Out of 13 patients with persistently low renin levels 6 had suffered either a stroke or a myocardial infarction and 7 had not. Plasma renin levels were also measured in 116 treated hypertensive patients. There was no relation between plasma renin level and vascular complications. It is concluded that levels of plasma renin are not a reliable index of the probability of hypertensive patients suffering a stroke or myocardial infarction.     

Aspirin for Primary Prevention of Cardiovascular Events: Meta-Analysis of Randomized Controlled Trials and Subgroup Analysis by Sex and Diabetes Status

Objective

To evaluate the benefits and harms of aspirin for the primary prevention of CVD and determine whether the effects vary by sex and diabetes status.

Methods

We searched Medline, Embase, and Cochrane databases for randomized controlled trials comparing the effects of aspirin with placebo or control in people with no pre-existing CVD. Two investigators independently extracted data and assessed the study quality. Analyses were performed using Stata version 12.

Results

Fourteen trials (107,686 participants) were eligible. Aspirin was associated with reductions in major cardiovascular events (risk ratio, 0.90; 95% confidence interval, 0.85–0.95), myocardial infarction (0.86; 0.75–0.93), ischemic stroke (0.86; 0.75–0.98) and all-cause mortality (0.94; 0.89–0.99). There were also increases in hemorrhagic stroke (1.34; 1.01–1.79) and major bleeding (1.55; 1.35–1.78) with aspirin. The number needed to treat to prevent 1 major cardiovascular event over a mean follow-up of 6.8 years was 284. By comparison, the numbers needed to harm to cause 1 major bleeding is 299. In subgroup analyses, pooled results demonstrated a reduction in myocardial infarction among men (0.71; 0.59–0.85) and ischemic stroke among women (0.77; 0.63–0.93). Aspirin use was associated with a reduction (0.65; 0.51–0.82) in myocardial infarction among diabetic men. In meta-regression analyses, the results suggested that aspirin therapy might be associated with a decrease in stroke among diabetic women and a decrease in MI among diabetic men and risk reductions achieved with low doses (75 mg/day) were as large as those obtained with higher doses (650 mg/day).

Conclusions

The use of low-dose aspirin was beneficial for primary prevention of CVD and the decision regarding an aspirin regimen should be made on an individual patient basis. The effects of aspirin therapy varied by sex and diabetes status. A clear benefit of aspirin in the primary prevention of CVD in people with diabetes needs more trials.     

Regular Aspirin Intake and Acute Myocardial Infarction

The results of two large independent studies involving a combined total of 776 patients treated in hospital with a discharge diagnosis of acute myocardial infarction and 13,898 patients with other discharge diagnoses showed a negative association between regular aspirin intake and non-fatal myocardial infarction. The data are consistent with the hypothesis that aspirin protects against this disease. Clinical trials are needed to determine whether this hypothesis is correct.     

Changes in morbidity and mortality during comprehensive community programme to control cardiovascular diseases during 1972-7 in North Karelia.

A comprehensive community programme studying the control of cardiovascular diseases (CVD) was carried out in North Karelia, Finland, between 1972 and 1977. The main objective was to reduce the mortality and morbidity of CVD, particularly in middle-aged men. Changes in the mortality and incidence of CVD were monitored by community-based registers of cases of acute myocardial infarction (AMI) and stroke and data on death certificates. During the programme the total mortality in the area decreased by 5% and the mortality from CVD decreased by 13% among men and 31% among women aged 30-64 years. The incidence of AMI fell by 16% among men and 5% among women, while that of cerebral stroke fell by 38% among men and 50% among women. Changes in mortality in North Karelia were compared with those in a matched control area; the difference between the two areas was not significant. The true effect of the programme cannot be deduced from these results, but mortality from CVD and the incidence of AMI and stroke fell during the five years studied. Thus the changes in mortality and morbidity of CVD accorded with the initial objectives of the programme.     

Shock Following Myocardial Infarction: A Clinical Survey of 140 Cases

All admissions for acute myocardial infarction to a metropolitan general hospital over a 10-year period have been reviewed. One hundred and forty patients developed complications meeting the criteria for cardiogenic shock. The mortality rate in this group of patients was 83%. The mortality rate in 95 patients who received treatment with intravenous noradrenaline was no different from that in 45 patients who did not receive this type of therapy (p = >0.8). Patients dying from cardiogenic shock were younger than those dying of other complications. Autopsy study of this group of shocked patients revealed a significantly lower incidence of previous healed myocardial infarction (p = <0.01).A decline in the annual incidence of cardiogenic shock was noted over the decade surveyed. It is suggested that this may be due to the earlier and more frequent use of intravenous noradrenaline. Despite the reduction in the incidence of shock, the annual mortality rate from myocardial infarction has remained unaltered.