Secondary prevention of coronary artery disease and the choice of the ACE inhibitor why EUROPA and not PEACE

ArticleinCardiovascular Drugs and Therapy 21(6):405-7 · January 2008with3 Reads
DOI: 10.1007/s10557-007-6071-x · Source: PubMed
    • "The data indicate that while there is significant variation in the use and subsequent annual costs of treating cardiovascular disease across states, participants with CerVD only and PAD only were prescribed less cardiovascular preventive medication than those with CAD only or even those with elevated risk factors and no overt atherothrombotic disease. The finding of relative undertreatment in participants with PAD only and CerVD only was not expected, as antiplatelet [18,19], antihypertensive78910111213, and lipid-lowering therapies14151617 guidelines for secondary prevention among participants with established vascular disease, given evidence of their effectiveness and cost-effectiveness [6]. Our findings were in accord with data from the global REACH reg- istry [23], as well as data specifically for Germany, Spain, United Kingdom [28], and Japan [29], where PAD was undertreated and underdiagnosed. "
    [Show abstract] [Hide abstract] ABSTRACT: Australia's Pharmaceutical Benefits Scheme supports the use of effective drugs for the prevention and control of cardiovascular risk factors. However, there are little data available describing per person costs of medication in primary prevention and secondary prevention in the community. We aim to understand annual expenditure on cardiovascular medicines according to the level and extent of cardiovascular disease, using participants enrolled in the Reduction of Atherothrombosis for Continued Health (REACH) registry. 2873 participants were recruited into the REACH registry through 273 Australian general practices. Cardiovascular medicines review was undertaken at baseline. Average weighted costs of medications were estimated using government-reimbursed prices. Annual costs were stratified by disease extent and location. The annual mean cost of pharmaceuticals per person was 1307 AU dollars. The average reported medicine use per person across all states and participants groups varied significantly. Participants with cerebrovascular or peripheral arterial disease were prescribed less cardiovascular medication than those with coronary artery disease (CAD) (mean number of drugs 3.5 vs. 4.5, P < 0.0001) and (3.6 vs. 4.5, P < 0.0001), while those with risk factor alone had the same medication use as those with CAD (mean number 4.5). Medication use was lower in Western Australia in comparison to eastern States. Participants with existing cerebrovascular disease and peripheral vascular disease receive less preventive therapy than those with CAD or even risk factors alone. This observation is consistent across all mainland states. Given the evidence of the effectiveness and cost-effectiveness of treating all types of vascular diseases, the present study suggests that there is scope to improve the treatment of these high-risk participants in Australia.
    Full-text · Article · Sep 2009
  • [Show abstract] [Hide abstract] ABSTRACT: Cardiovascular risk factors such as hypertension and diabetes are understood to trigger a sequence of pathological events starting from hypertension and atherosclerosis, which if left unmanaged can ultimately progress to end-stage cardiovascular disease. This chain of events is termed the cardiovascular continuum. The angiotensin-converting enzyme inhibitor, perindopril, has marked restorative effects on endothelial dysfunction and this translates into clinical benefits for patients at all stages of the continuum, making it a highly effective treatment in cardiovascular disease. In hypertensive patients, large-scale clinical trials have shown that perindopril-based treatments reduce morbidity and mortality and reduce the onset of stroke, renal failure, and diabetes when compared with other anti-hypertensive therapies. In patients at more advanced stages of the cardiovascular continuum, the use of perindopril on top of other standard management practices further improves long-term prognosis in coronary artery disease. Perindopril also reduces cardiac remodelling following myocardial infarction and improves patient symptoms and prognosis in diastolic heart failure. Current trial evidence confirms the clinical benefits of perindopril throughout the cardiovascular continuum, thus slowing the progression of cardiovascular disease and improving patient prognosis.
    Article · Sep 2008
  • [Show abstract] [Hide abstract] ABSTRACT: ACE inhibition is now recognized as superior to placebo on outcomes in stable coronary artery disease (CAD), including total and cardiovascular mortality, fatal and nonfatal myocardial infarction, heart failure, revascularization and stroke. This review examines clinical evidence for the mode of action of ACE inhibitors in CAD, which is dominated by the results of a single trial, EUROPA, and its substudies. The generally accepted mode of action for ACE inhibitors in CAD is blood pressure reduction. However, the EUROPA data demonstrate that endothelial protection, with the effect of arresting or reducing the processes of atherosclerosis is also important. Chronic overexpression of tissue ACE in CAD disrupts the angiotensin II/bradykinin balance with a net result of endothelial dysfunction. ACE inhibitors reduce production of angiotensin II, which prevents vasoconstriction, reduces adhesion molecules and growth factors, decreases oxidative stress and prevents apoptosis. A concomitant decrease in the degradation of bradykinin as a result of ACE inhibition raises levels of this kinin, leading to vasodilation and an antiapoptotic action, as well as opposition of the negative actions of angiotensin II. We now have clinical trial evidence of these processes in CAD patients participating in the EUROPA study by measurement of markers of endothelial function, including nitric oxide synthase (eNOS), the rate of apoptosis and levels of von Willebrand factor (vWf ). Serum from CAD patients was found to significantly downregulate eNOS protein expression and activity versus that of healthy controls (p <0.01), most probably as a result of upregulation of tissue ACE. One year of treatment with perindopril upregulated eNOS protein expression and activity (19% and 27% vs placebo; p < 0.05). Similarly, vWf was elevated at baseline and significantly reduced after 1 year of treatment with perindopril (p< 0.001). Increased endothelial apoptosis by serum of CAD patients was accompanied by excess angiotensin II and tumour necrosis factor-α and a reduction in bradykinin; all of these parameters were reversed by treatment. We therefore have clinical results showing that perindopril normalizes the angiotensin II/bradykinin balance, reduces inflammation and prevents endothelial apoptosis. Accumulating preclinical evidence for the absence of a class effect for ACE inhibitors includes differences in terms of effect on eNOS and rate of endothelial apoptosis. These differences appear to be related to tissue affinity, penetration of atherosclerotic plaque and affinity for the target enzyme. Consideration of these features is important when administering ACE inhibition as secondary prevention in CAD patients. In this context, current European guidelines for stable angina pectoris recommend prescription of agents and doses with proven efficacy in secondary prevention.
    Article · Feb 2009
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