Showing papers by "John G.F. Cleland published in 1997"

Effect of ramipril on morbidity and mode of death among survivors of acute myocardial infarction with clinical evidence of heart failure. A report from the AIRE Study Investigators.

Abstract: Background The importance of the effects of ACE inhibitors on sudden death, progressive heart failure and recurrent infarction to the reduction in overall mortality in heart failure and after myocardial infarction is disputed. Methods The AIRE study randomized 2006 patients with clinical or radiological evidence of heart failure within 2-9 days of a myocardial infarction to receive ramipiril 5 mg b.d. or matching placebo. Outcomes were assessed independently by members of an end-points committee blinded to treatment allocation. Results Fewer patients developed severe resistant heart failure as their first validated end-point on rampril, despite the greater number of at-risk survivors, compared to placebo (n = 143 vs 178; risk reduction 23%; CI 5 to 39%; P = 0.017). Ramipril did not alter the rate of reinfarction or stroke. Irrespective of treatment allocation 182 (46%) patients developed resistant heart failure prior to death. A validated acute or remote myocardial reinfarction occurred in 76 (19%) patients prior to death and chest pain occurred in 90 (23%) patients around the time of death suggesting an ischaemic element to these deaths Eighty deaths occurred on the index admission, 167 during re-admission and 145 out-of-hospital. Sudden death accounted for 54% of all deaths and 93% of out-of-hospital deaths. Ramipril reduced the risk of sudden death by 30% (95% CI: 8-47%; P = 0.011). However, overall, 45% of those patients who died suddenly had severe or worsening heart failure prior to their death. Only 39% of sudden deaths were considered to be due to arrhythmias. Ramipril reduced the risk of death from circulatory failure by 18%, but this did not reach statistical significance (95% CI; 41 to -14%; P = 0.237). The magnitude of the effects on sudden death and death due to circulatory failure were not significantly different. However, 38% of the reduction in overall mortality was from the subgroup with sudden death who had developed prior severe resistant heart failure (placebo n = 35, ramipril n = 15), again emphasizing the marked benefit in preventing failure. Ramipril did not selectively alter the proportion of in- to out-of-hospital deaths. Conclusion Ramipril reduces mortality and progression to resistant heart failure among patients with evidence of heart failure early after myocardial infarction. Retarding the progression of heart failure appears to be a major factor contributing to the reduction in mortality both by reducing circulatory failure and by reducing sudden death.

Is medical treatment for angina the most cost-effective option?

Abstract: A meta-analysis of the benefits of coronary artery bypass graft (CABG) surgery has been used as the basis of a model for comparing the costs and benefits of surgical and medical treatment of angina pectoris. In order to allow for the results of recent research, the economic model included the addition of aspirin and aspirin plus an HMG-CoA reductase inhibitor (statin) to medical management. The analysis indicates that in unselected patients the cost-effectiveness of CABG vs initial standard medical therapy over 5 years is towards the upper limit of what can be considered a cost-effective treatment both in terms of its effect on mortality (life-years gained) and morbidity (quality adjusted life-years). Addition of a statin to medical therapy reduced mortality and made coronary artery bypass graft surgery an expensive option in terms of improvement of quality of life. In patients with three-vessel disease or left ventricular dysfunction surgery appears fairly cost-effective in comparison with standard medical therapy but becomes relatively expensive when the benefits of aspirin or lipid-lowering therapy are added to medical treatment.

Screening For Left Ventricular Dysfunction and Chronic Heart Failure

Abstract: The definition of chronic heart failure (CHF) in clinical practice concentrates on two essential features, namely symptoms suggesting CHF and the objective demonstration of a sufficient severity of cardiac dysfunction. The cardiac dysfunction may be endocardial, myocardial, pericardial, valvular or arrhythmic in nature. Relief of symptoms, at least by the use of diuretic therapy, supports the relationship between cardiac dysfunction and symptoms. However, asymptomatic left ventricular (LV) dysfunction is also common, is associated with a high morbidity and mortality and is amenable to treatment. Therefore it is appropriate to try and identify asymptomatic LV dysfunction. Estimates of the prevalence of CHF in the adult population range from 4 to 20 per 1000 people, rising with age up to 170 per 1000 people aged 70 years and over. Previous estimates of a prevalence of CHF of about 1% (10 per 1000) are broadly supported by more recent data. Estimates of the prevalence of asymptomatic LV dysfunction range from 8 to 59 per 1000, depending on age, the echocardiographic method for measuring ventricular dysfunction and the threshold value of ejection fraction used to separate those with and without LV dysfunction. Asymptomatic LV dysfunction is at least as common and possibly twice as common as CHF. The first step in screening for CHF and LV dysfunction is the recognition of symptoms of CHF and knowledge of the past medical history, in particular a history of myocardial infarction. However, many patients with LV dysfunction will be asymptomatic and in at least 50% of patients with some of the clinical features of CHF the diagnosis cannot be sustained by more detailed investigation. Echocardiography is currently the tool of choice to investigate LV dysfunction although important problems of interpretation of many echocardiographic measurements exist. Echocardiographic examination should be performed on all patients suspected of having CHF before the diagnosis is accepted. It does not generally appear an effective use of resources to screen the general population for asymptomatic LV dysfunction echocardiographically. Screening patients who have had a myocardial infarction (recent or remote) increases the yield of LV dysfunction, with up to 40% of patients surviving hospital admission having important ventricular dysfunction. It is less clear if screening patients with longstanding hypertension or diabetes mellitus is appropriate. Access to echocardiography is restricted in some communities. In these cases, a normal ECG may identify patients at low risk of LV dysfunction. A normal chest x-ray is probably less effective than the ECG in excluding LV dysfunction. However, it should be recognised that it is probably often simpler, more accurate and less expensive to perform echocardiography as the initial investigation. More recently, the potential for natriuretic peptides to identify LV dysfunction has been investigated. Currently, there is sufficient evidence to indicate that these biochemical measures are a useful way of confirming LV dysfunction or CHF in cohorts of patients. Whether natriuretic peptides will prove sufficiently accurate to be used to exclude CHF in individuals remains to be determined. Echocardiography will still be required in those with elevated levels of natriuretic peptides to identify the cause of the cardiac dysfunction.

Carvedilol for heart failure: more than just a beta-blocker?

Abstract: Carvedilol is a non-selective beta-blocker, and the only one, in recent clinical trials, to have shown a clear reduction in mortality. It is suggested that, compared with other beta-blockers, carvedilol has additional advantageous effects in heart failure, and should be considered as part of the routine treatment of heart failure.

Is there a role for warfarin or aspirin therapy in heart failure

Abstract: Despite recent advances in pharmacologic therapy of heart failure, mortality remains high. There is growing evidence that thromboembolic events may contribute to these events. There is evidence for platelet activation, hypercoagulability and endothelial dysfunction in heart failure. The incidence of overt thromboembolism in heart failure is low. Ischemic events are a frequent prelude to heart failure. Thus, subclinical embolism and ischemic events may be contributing factors to the morbidity and mortality in heart failure patients. The role of antithrombotic therapy with warfarin or aspirin needs to be systematically investigated to determine if such therapy can reduce mortality in heart failure. Such information is particularly essential because non-randomized data have raised the possibility that aspirin may interfere with the beneficial effects of angiotensin converting enzyme inhibitors. This review summarizes available data on warfarin and aspirin therapy in heart failure.

Combination drug therapy in chronic heart failure: is treatment part of the problem in heart failure?

Abstract: Despite advances in medical treatment, the annual mortality associated with severe heart failure remains over 40%, and even in mild heart failure the associated mortality is 40% over 4 years. Once it has been demonstrated that the morbidity and mortality to heart failure can be adequately addressed by combinations of drug therapy, then it is logical to attempt to strip out redundant components of these therapeutic regimes. In the meantime, however, combination therapy is required to counter many of the pathophysiological facets of the heart failure syndrome, including fluid retention, neuroendocrine activation, progressive ventricular dysfunction, and sudden cardiac death. Diuretics and ACE inhibitors are well-established drug treatments. Digoxin appears to lessen the rate of progression of heart failure without altering survival. New evidence suggests that beta-blockers may be useful additions to the heart failure therapeutic armamentarium, although whether all beta-blockers are equally effective remains to be established.

Interactions between ACE Inhibitors and Diuretics

Abstract: Publisher Summary Diuretics and angiotensin-converting enzyme (ACE) inhibitors are commonly used in combination, both for patients with heart failure and for those with hypertension. Diuretics activate the rennin–angiotensin–aldosterone (RAAS) system that may limit the effects of diuretics on vascular tone and sodium excretion, which in turn, may limit their efficacy in reducing arterial pressure or in improving the symptoms of heart failure. ACE inhibitors can reduce plasma concentrations of angiotensin II and aldosterone, providing a theoretical rationale for use in combination with a diuretic. However, theoretical assumptions should always be tested. Clinical experiments in this field frequently have been unable to uphold theory, have sometimes contradicted it, and have occasionally revealed evidence for a more exciting interaction than predicted. Studies of hypertension confirm that ACE inhibitors enhance the antihypertensive effects of diuretics, though the interaction appears more additive than synergistic. Combining diuretics with ACE inhibitors appear to be no more effective than combining them with beta blockers. However, as diuretics may activate the sympathetic nervous system, as well as the RAAS, this cannot be taken as evidence that a neuroendocrine substrate for an ACE inhibitor/diuretic interaction does not exist.