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ISCHAEMIC HEART DISEASE
To use LMWH or not to use LMWH? ▸
In the UK at least, low molecular weight heparin (LMWH) rather than unfractionated heparin has become the standard of care in acute coronary syndromes (ACS). In the A phase of the A to Z trial, which involved nearly 4000 patients treated with aspirin and tirofiban, the primary end point (a seven day composite of death, myocardial infarction (MI), or refractory ischaemia) occurred in 8.4% of patients assigned to receive enoxaparin compared to 9.4% in those receiving unfractionated heparin (hazard ratio (HR) 0.88, 95% confidence interval (CI) 0.71 to 1.08). SYNERGY looked at the use of LMWH versus conventional heparin in more than 10000 patients whose ACS was also treated with an early invasive strategy. Their primary end point (30 day composite of death or MI) occurred in 14.0% of patients assigned to enoxaparin versus 14.5% receiving conventional heparin (HR 0.96, 95% CI 0.86 to 1.06). Again, the authors’ summary stated that enoxaparin was not inferior to unfractionated heparin, but neither was it superior. The meta-analysis by Peterson and colleagues included these two studies, the primary data from the ESSENCE trail, and the event frequencies derived from the TIMI 11B, ACUTE II, and INTERACT studies—thus data from over 22 000 patients were included. From these aggregate figures the authors conclude that enoxaparin is superior at preventing the 30 day occurrence of death or MI (odds ratio (OR) 0.81, or 0.91 if antithrombin treatment was given pre-randomisation).
Are statins safe to start in childhood? ▸
Atheroma begins in childhood as fatty streaks. Statins arrest, and may regress, atheroma, so why not start early? To investigate this further, Weigman and colleagues investigated the effect of 20–40 mg pravastatin in 214 children aged 8–18 years with familial hypercholesterolaemia who were treated continuously for two years. The efficacy of treatment was confirmed by lower values of low density lipoprotein (LDL) cholesterol and regression of carotid intimal–medial thickness in the treatment group compared to a group receiving placebo treatment. To determine safety, the group looked at a number of other variables including growth, muscle and liver enzymes, endocrine function, growth staging scores, maturation, onset of menses, and testicular volume between the two groups, and found no significant detriments on these variables from statin treatment.
Give Gp IIb/IIIa inhibitors before entering the cath lab for primary PCI ▸
A meta-analysis of randomised trials of the early (defined as administration before arrival in the cardiac catheterisation laboratory) versus late (given at the time of primary percutaneous coronary intervention (PCI)) administration of glycoprotein IIb/IIIa inhibitors in ST elevation myocardial infarction looked at six trials, all of which had full data on TIMI flow grades on admission and mortality. Both TIMI grade 2 or 3 (41.7% v 29.8%) and TIMI grade 3 (20.3% v 12.2%) flow were significantly more frequent in those given Gp IIb/IIIa inhibitors early. Furthermore, a 28% reduction in mortality from 4.7% to 3.4% was found. The authors conclude that further evaluation in an adequately powered clinical trial is awaited to confirm the clinical benefit of this strategy. In addition it is worth noting that abciximab is the agent with the majority of trial data.
ST segment depression carries an adverse prognosis even with early revascularisation ▸
ST segment shift is known to be an indicator of worse outcome. Is this ameliorated by early revascularisation? In this prospective cohort study, 1450 consecutive patients with unstable angina/non-ST segment elevation myocardial infarction were stratified by the presence of ST segment depression, T wave inversion, or no changes on the admission ECG. All patients underwent coronary angiography and, if appropriate, revascularisation within 24 hours after admission. During up to 59 months of follow up, the in-hospital mortality rate was 2.1% (19/895) in patients with no ECG changes, 4% (6/136) in those with ST segment depression, and 0.2% (1/419) in those with T wave inversion. The cumulative death rate at 36 months was 8.0%, 19.9%, and 5.1%, respectively (p = 0.0001 by log rank). After adjustment for potential cofounders, ST segment depression (HR 2.2, 95% CI 1.1 to 4.6) and T wave inversion (HR 0.44, 95% CI 0.20 to 0.96) were associated with long term mortality.
Are ramipril and perindopril better than other ACE inhibitors? ▸
The use of angiotensin converting enzyme (ACE) inhibitors in patients with coronary heart disease (CHD) has increased dramatically with publication of multiple trials showing benefit. However, which particular one to use is unclear. If one ignores the argument that blood pressure lowering is the important effect, and so ACE inhibitors are not special at all, then this study suggests that ramipril and perindopril are at least as good, if not better, than the others. A total of 7512 patients who filled a prescription for an ACE inhibitor within 30 days of discharge post-AMI, and who continued to receive the same drug for at least one year, were studied. Enalapril, fosinopril, captopril, quinapril, and lisinopril were associated with higher mortality than was ramipril; the adjusted hazard ratios were 1.47 (95% CI 1.14 to 1.89), 1.71 (95% CI 1.29 to 2.25), 1.56 (95% CI 1.13 to 2.15), 1.58 (95% CI 1.10 to 2.82), and 1.28 (95% CI 0.98 to 1.67), respectively. The adjusted hazard ratio associated with perindopril was 0.98 (95% CI 0.60 to 1.60).
Diabetes: more evidence of the risk of CHD ▸
Previous studies have suggested the elevated risk of acute MI in patients with diabetes mellitus. A total of 13 105 subjects from the Copenhagen city heart study were followed up prospectively for 20 years. The relative risk of first event and admission for MI was increased 1.5- to 4.5-fold in women and 1.5- to 2-fold in men, with a significant difference between sexes. The relative risk of first stroke, and admission for stroke, was increased 2- to 6.5-fold in women and 1.5- to 2-fold in men, with a significant difference between sexes. In both women and men the relative risk of death was increased 1.5–2 times.
Beware β blockers in heart failure? ▸
In patients with heart failure, doctors are often frightened to prescribe β blocker treatment. In a meta-analysis of all trials from 1966 to 2002, these agents were associated with significant absolute annual increases in risks of hypotension (11 per 1000, 95% CI 0 to 22), dizziness (57 per 1000, 95% CI 11 to 104), and bradycardia (38 per 1000, 95% CI 21 to 54). There was no significant absolute risk of fatigue associated with treatment (3 per 1000, 95% CI −2 to 9). β Blocker treatment was associated with a reduction in all cause withdrawal of medication (14 per 1000, 95% CI –2 to 29) as well as significant reductions in all cause mortality (34 per 1000, 95% CI 20 to 49), heart failure hospitalisations (40 per 1000, 95% CI 22 to 58), and worsening heart failure (52 per 1000, 95% CI 10 to 94). Thus it is time to throw out the concerns about β blockers in heart failure if there is a systolic blood pressure > 100 mm Hg and a pulse greater than 60 beats per minute.
Green tea may reduce blood pressure ▸
Habitual intake of green tea in Chinese patients was associated with a lower incidence of hypertension. Six hundred subjects (39.8%) were habitual tea drinkers, defined by tea consumption of ⩾ 120 ml/day for at least one year. Compared with non-habitual tea drinkers, the risk of developing hypertension decreased by 46% for those who drank 120–599 ml/day and was further reduced by 65% for those who drank ⩾ 600 ml/day.
Viagra improves performance up a mountain ▸
Hypoxia caused by altitude can cause pulmonary vasoconstriction and pulmonary hypertension. Sildenafil (Viagra) is a pulmonary vasodilator. Viagra and placebo were given in random order to 14 healthy mountaineers and trekkers. At low altitude, acute hypoxia reduced arterial oxygen saturation to 72.0% at rest and 60.8% at maximum exercise capacity. Systolic pulmonary artery pressure increased from 30.5 mm Hg at rest to 42.9 mmHg during exercise in participants taking placebo. Sildenafil, 50 mg, significantly increased arterial oxygen saturation during exercise (p = 0.005) and reduced systolic pulmonary artery pressure at rest (p < 0.001) and during exercise (p = 0.031). Of note, sildenafil increased maximum workload (172.5 W (95% CI 147.5 to 200.0 W) v 130.6 W (95% CI 108.8 to 150.0 W); p < 0.001) and maximum cardiac output (p < 0.001) compared with placebo. At high altitude, sildenafil had no effect on arterial oxygen saturation at rest and during exercise compared with placebo. However, sildenafil reduced systolic pulmonary artery pressure at rest (p = 0.003) and during exercise (p = 0.021), and increased maximum workload (p = 0.002) and cardiac output (p = 0.015). Could this be a treatment for some patients with mountain sickness?
Aspirin plus clopidogrel in stroke: not worth the risk ▸
The combination of aspirin plus clopidogrel has become the gold standard for the treatment of ACS. In a randomised, double blind, placebo controlled trial to compare aspirin (75 mg/day) with placebo in 7599 patients with recent ischaemic stroke or transient ischaemic attack and at least one additional vascular risk factor, who were already receiving clopidogrel 75 mg/day, the primary end point was a composite of ischaemic stroke, MI, vascular death, or rehospitalisation for acute ischaemia. At 18 months, 15.7% of patients reached the primary end point in the group receiving aspirin and clopidogrel compared with 16.7% in the clopidogrel alone group (relative risk reduction 6.4%, 95% CI −4.6% to 16.3%; absolute risk reduction 1%, 95% CI −0.6% to 2.7%). Life threatening bleedings were higher in the group receiving aspirin and clopidogrel versus clopidogrel alone (96 (2.6%) v 49 (1.3%); absolute risk increase 1.3%, 95% CI 0.6% to 1.9%). Major bleedings were also increased in the group receiving aspirin and clopidogrel but no difference was recorded in mortality.
American Journal of Medicine; American Journal of Physiology: Heart and Circulatory Physiology; Annals of Emergency Medicine; Annals of Thoracic Surgery; Archives of Internal Medicine; BMJ; Chest; European Journal of Cardiothoracic Surgery; Lancet; JAMA; Journal of Clinical Investigation; Journal of Diabetes and its Complications; Journal of Immunology; Journal of Thoracic and Cardiovascular Surgery; Nature Medicine; New England Journal of Medicine; Pharmacoeconomics; Thorax
Dr Diana Gorog, Dr Akhil Kapur, Dr Masood Khan, Dr Alistair Lindsay; Dr Andrew Sharp