Lege Artis Medicinae

[ACE-INHIBITORS IN THE SECONDARY PREVENTION OF CORONARY ARTERY DISEASE]

SÁRSZEGI Zsolt

JULY 14, 2007

Lege Artis Medicinae - 2007;17(06-07)

[The beneficial effects of angiotensin-converting enzyme inhibitors on biochemical and vascular markers have been proven by many experimental studies. Reduction of the angiotensin-II level has a positive effect on oxidative stress, lipid peroxidation, apoptosis, inflammatory and prothrombotic processes. Two large multicentric trials, EUROPA and HOPE, showed that perindopril and ramipril significantly reduce mortality and the risk of both fatal and non-fatal cardiovascular events in patients with atherosclerosis, thereby making them the base drugs of secondary prevention of coronary artery disease.]

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[Diuretics are an integral part of the management of chronic heart failure. Although there are no large, randomized, placebo-controlled, multicentric studies available to show that loop- and thiazid diuretics improve survival, the efficacy of these drugs in relieving heart failure symptoms and fluid retention is indisputable. The third class of diuretics used in heart failure is aldosterone antagonists, whose beneficial effects on mortality and morbidity were demonstrated in the RALES and EPHESUS trials. In this paper, the effects and side effects of the various diuretics, as well as the indications and recommendations on their use are reviewed. New options in diuretic treatment, including adenosine receptor blockers, vasopressin antagonists, atrial natriuretic peptide analogues and ultrafiltration are also presented.]

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[ANGIOTENSIN-CONVERTING ENZYME INHIBITORS AND ANGIOTENSIN-2 RECEPTOR BLOCKERS IN CHRONIC HEART FAILURE]

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[The rennin-angiotensin system plays a major role in cardiovascular diseases. In the past decade, extensive research investigated the possible clinical benefit of the use of angiotensin-converting enzyme inhibitors in various clinical conditions. Their benefits have been clearly demonstrated in many cardiovascular conditions and agreement as to their potential usefulness has been established in chronic heart failure, asymptomatic left ventricular dysfunction, acute myocardial infarction and hypertension, and in the primary prevention in patients with high risk for cardiovascular events. Numerous randomised clinical trials over the past two decades established their efficacy in reducing adverse outcomes (mortality, hospitalitazion, and physical limitation) in patients with heart failure and left ventricular systolic dysfunction. Based on these results, angiotensin-converting enzyme inhibitors are indicated in all patients with left ventricular systolic dysfunction regardless of etiology, in the absence of intolerance or a contraindication. Despite the recent improvements in the treatment of heart failure, mortality remains high, with approximately 50% patients dead at five years. Although angiotensinconverting enzyme inhibitors decrease mortality, they incompletely suppress angiotenzin-2 when used chronically. Since angiotensin receptor blockers block the biologic effects of angiotenzin-2 more completely than angiotensin-converting enzyme inhibitors, they may be beneficial in the treatment of heart failure. In comparison trials, angiotensin receptor blockers were found to have no benefit over angiotensin-converting enzyme inhibitor therapy. Thus, angiotensin-converting enzyme inhibitors should remain first-line treatment for heart failure. However, in case of intolerance, angiotensin receptor blocker therapy is a reasonable substitute and provides excellent tolerability.]

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[The beneficial effects of treatment with betablockers in patients with chronic heart failure have been demonstrated in several large, prospective, randomised, placebo-controlled clinical trials. In large trials with mortality as the endpoint, the long-term use of bisoprolol, carvedilol, nevibolol and metoprolol succinate have been associated with a reduction in total mortality, cardiovascular mortality, sudden cardiac death and death due to progression of heart failure in patients of functional classes II-IV. These favorable clinical experiences warrant a recommendation that beta-blockers should be used in all haemodynamically stable heart failure patients with reduced left ventricular systolic function who are on standard treatment, unless contraindicated. In this review, the most important data of clinical trials and practical considerations of therapy with beta-blockers in heart failure are summarized.]

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[The high world prevalence of cerebrovascular diseases, and the particularly bad morbidity rates of Hungary are well known. The physiological properties of the brain make stroke prevention outstandingly important. Effective prevention will be reflected in the reduction of the late complications that are otherwise common and expensive to treat. Because of the common simultaneous development of stroke, cardiovascular and peripheral vascular diseases, overall vascular disease prevention is preferred, even if the various vascular diseases manifest in different degrees in a patient. Hungarian data also indicate the high risk of recurrence of cerebrovascular diseases, therefore, the importance of secondary prevention is obvious. Large international studies have proven the strokepreventing effect, and, by a pleiotropic drug action, additional benefits, of the efficient treatment of blood lipid disorders. Consensus conferences in recent years defined clear and even stricter lipid-lowering target values, mostly to be reached by “double inhibition”, bile acid binding resins, fibrates and nicotinic acid derivatives, beside the most common statin treatment. Neurological and stroke departments and clinics play a pivotal role in vascular prevention.]

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[The high world prevalence of cerebrovascular diseases, and the particularly bad morbidity rates of Hungary are well known. The physiological properties of the brain make stroke prevention outstandingly important. Effective prevention will be reflected in the reduction of the late complications that are otherwise common and expensive to treat. Because of the common simultaneous development of stroke, cardiovascular and peripheral vascular diseases, overall vascular disease prevention is preferred, even if the various vascular diseases manifest in different degrees in a patient. Hungarian data also indicate the high risk of recurrence of cerebrovascular diseases, therefore, the importance of secondary prevention is obvious. Large international studies have proven the strokepreventing effect, and, by a pleiotropic drug action, additional benefits, of the efficient treatment of blood lipid disorders. Consensus conferences in recent years defined clear and even stricter lipid-lowering target values, mostly to be reached by “double inhibition”, bile acid binding resins, fibrates and nicotinic acid derivatives, beside the most common statin treatment. Neurological and stroke departments and clinics play a pivotal role in vascular prevention.]

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[Beta-blockers are among the most widely used drugs for the treatment of cardiovascular diseases. In the mid-90’s, these drugs were recommended as first-line therapies of hypertension. With the introduction of new drugs, the list of first-choice drugs has been extended. The results of recently published major hypertension trials, which compared conventional agents (beta blockers and/or diuretics) with newer agents (angiotensin converting enzyme inhibitors, Caantagonists, angiotensin receptor blockers), raised concerns regarding the role of beta blockers in cardiovascular primary prevention. Subsequently, a metaanalysis of 13 trials has shown that compared with other drug types, beta-blocker therapy is less beneficial in patients with hypertension who do not have heart disease. Nevertheless, in cardiovascular indications other than hypertension (acute myocardial infarction, heart failure and arrhythmias), betablockers retain their dominant position.]

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[If-CHANNEL INHIBITION - A NEW APPROACH IN THE TREATMENT OF ISCHAEMIC HEART DISEASE]

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[Clinical impact of acetylsalicylic acid resistance in patients with cerebrovascular disease]

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[INTRODUCTION - In the past few years, a number of studies have been published about acetylsalicylic acid resistance and its potential clinical consequences. PATIENTS AND METHODS - 281 patients with chronic cerebrovascular disease have been involved in our study. The patients were divided in two groups on the basis of their optical aggregometer results (acetylsalicylic acid responder vs. resistant). We compared the risk profiles, drug therapies, laboratory parameters and clinical outcomes of the two groups. RESULTS - Acetylsalicylic acid resistant patients were more likely to be women [23 (45.1%) vs. 92 (40%) (p<0.05)], to smoke (38% vs. 25%), have hypertension (92 vs. 78%), hypercholesterolaemia (5.69 vs. 4.85 mmol/l), and elevated LDL-levels (3.71 vs. 2.85 mmol/l), triglyceride levels (2.78 vs. 1.97 mmol/l) and hsCRP levels (17.89 vs. 7.09 mmol/l) (p<0.01). The use of statins was more frequent (56% vs. 36%) in the responder group (p<0.01). Platelet aggregation values (triggered by agonists) were significantly correlated with cholesterol, LDL, triglyceride and hsCRP levels (p<0.05). Adverse outcomes were reached in 13 (25.5%) acetylsalicylic acid nonresponders and 32 (13.9%) acetylsalicylic acid responder patients (p<0.01). In a multivariate analysis, however, only smoking (OR: 2.38, CI: 1.77-5.44) and increased LDL (OR: 3.01, CI: 2.34-5.67) and hsCRP levels (OR: 2.44, CI: 1.55-7.02) (p<0.05) were independent risk factors of adverse vascular outcomes. CONCLUSION - On the basis of our results, acetylsalicylic acid resistance was associated with a worse clinical outcome, but it was not an independent risk factor of future ischaemic events. Our results implicate that inappropriate prevention therapy might have a role in this phenomenon.]