Lars Køber

Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients

BACKGROUND We undertook a prospective systematic overview based on data from individual patients from five long-term randomised trials that assessed inhibitors of angiotensin-converting enzyme (ACE) in patients with left-ventricular dysfunction or heart failure. METHODS Three of the trials enrolled patients within a week after acute myocardial infarction. Data were combined by use of the Peto-Yusuf method. FINDINGS Overall 12,763 patients were randomly assigned treatment or placebo and followed up for an average of 35 months. In the three post-infarction trials (n=5,966), mortality was lower with ACE inhibitors than with placebo (702/2995 [23.4%] vs 866/2971 [29.1%]; odds ratio 0.74 [95% CI 0.66-0-83]), as were the rates of readmission for heart failure (355 [11.9%] vs 460 [15.5%]; 0.73 [0.63-0.85]), reinfarction (324 [10.8%] vs 391 [13.2%]; 0.80 [0.69-0.94]), or the composite of these events (1049 [35.0%] vs 1244 [41.9%]; 0.75 [0.67-0.83]; all p<O.001). For all five trials the ACE inhibitor group had lower rates of death than the placebo group (1,467/6,391 [23.0%] vs 1,710/6,372 [26.8%]; 0.80 [0.74-0.87]) and lower rates of reinfarction (571 [8.9%] vs 703 [11.0%]; 0.79 [0.70-0.89]), readmission for heart failure (876 [13.7%] vs 1202 [18.9%]; 0.67 [0.61-0.74]), and the composite of these events (2161 [33.8%] vs 2610 [41.0%]; 0.72 [0.67-0.78]; all p<0.0001). The benefits were observed early after the start of therapy and persisted long term. The benefits of treatment on all outcomes were independent of age, sex, and baseline use of diuretics, aspirin, and beta-blockers. Although there was a trend towards greater reduction in risk of death or readmission for heart failure in patients with lower ejection fractions, benefit was apparent over the range examined.

Risk of Myocardial Infarction and Death Associated With the Use of Nonsteroidal Anti‐Inflammatory Drugs (NSAIDs) Among Healthy Individuals: A Nationwide Cohort Study

Use of some nonsteroidal anti‐inflammatory drugs (NSAIDs) is associated with increased cardiovascular risk in several patient groups, but whether this excess risk exists in apparently healthy individuals has not been clarified. Using a historical cohort design, we estimated the risk of death and myocardial infarction associated with the use of NSAIDs. Participants in the study were selected from the Danish population and were defined as healthy according to a history of no hospital admissions and no concomitant selected pharmacotherapy. The source population consisted of 4,614,807 individuals, of whom 1,028,437 were included in the study after applying selection criteria. Compared to no NSAID use, hazard ratios (95% confidence limits) for death/myocardial infarction were 1.01 (0.96–1.07) for ibuprofen, 1.63 (1.52–1.76) for diclofenac, 0.97 (0.83–1.12) for naproxen, 2.13 (1.89–2.41) for rofecoxib, and 2.01 (1.78–2.27) for celecoxib. A dose‐dependent increase in cardiovascular risk was seen for selective COX‐2 inhibitors and diclofenac. Caution should be exercised in NSAID use in all individuals, and particularly high doses should be avoided if possible.

Age-Distribution, Risk Factors and Mortality in Smokers and Non-Smokers with Acute Myocardial Infarction: A Review

Smoking is a risk factor for acute myocardial infarction; paradoxically, many studies have shown a lower post-infarct mortality among smokers. There are some important differences between smokers and non-smokers, which might explain the observed difference in mortality: smokers have less multivessel disease and atherosclerosis but are more thrombogenic; thrombolytic therapy seems to be more effective among smokers; smoking might result in an increased out-of-hospital mortality rate, by being more arrhythmogenic; and smokers are on average a decade younger than non-smokers at the time of infarction, and have less concomitant disease. Adjusting for these differences in regression analyses shows that smoking is not an independent risk factor for mortality after acute myocardial infarction. The difference in age and risk factors are responsible for the lower mortality among smokers.

Bayesian interim statistical analysis of randomised trials: the case against

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Prestroke and Poststroke Antithrombotic Therapy in Patients With Atrial Fibrillation: Results From a Nationwide Cohort

Key Points Question Is oral anticoagulation therapy used and effective for secondary stroke prophylaxis in patients with atrial fibrillation? Findings In this cohort study of 30 626 intermediate- to high-risk patients with atrial fibrillation having an ischemic stroke, 36.3% received oral anticoagulation therapy before their stroke, and 52.5% received oral anticoagulation therapy after their stroke. Oral anticoagulation therapy was associated with a statistically significant reduction in thromboembolic risk. Meaning There exists a major potential for optimization of both primary and secondary stroke prophylaxis in patients with atrial fibrillation.