Showing papers on "Heart Protection Study published in 2002"

The MRC/BHF Heart Protection Study: preliminary results.

Abstract: The Heart Protection Study (HPS), with over 20,500 subjects, is the largest trial of statin therapy ever conducted. It provides important and definitive new information on women, the elderly, diabetics, and people with low baseline cholesterol pre-treatment and those with prior occlusive non-coronary vascular disease. It is a prospective double blind randomised controlled trial with a 2 x 2 factorial design investigating prolonged use (>5 years) of simvastatin 40 mg and a cocktail of antioxidant vitamins (650 mg vitamin E, 250 mg vitamin C and 20 mg beta-carotene). The HPS specifically included patients with high risk for coronary heart disease (CHD) but characteristics that excluded them from participation in previous statin trials. Simvastatin 40 mg treatment showed benefit across all patient groups regardless of age, gender or baseline cholesterol value and proved safe and well tolerated. Results show a 12% reduction in total mortality, a 17% reduction in vascular mortality, a 24% reduction in CHD events, a 27% reduction in all strokes and a 16% reduction in non-coronary revascularisations. Among high-risk patients in this western population (with a minimum total cholesterol [TC] > or = 3.5 mmol/l at entry) there appears to be no threshold cholesterol value below which statin therapy is not associated with benefit; even among those with pre-treatment cholesterol levels below current national recommended targets. Over the 5.5 year study period patients and their doctors were encouraged to add an active non-study statin to the study regimen if they wished to do so. Thus the trial eventually had only two-thirds complying with the original intention-to-treat design. Nevertheless, results were highly significant for the study statin--simvastatin 40 mg once daily. Preliminary results of the HPS are negative for the antioxidant vitamin cocktail but provide reassurance that vitamins do no harm.

Management of dyslipidemia in the primary prevention of coronary heart disease.

Abstract: Coronary heart disease is a leading cause of death in industrialized nations. Hyperlipidemia with elevated serum total cholesterol, LDL cholesterol, and triglycerides is a known major cardiovascular risk factor. HDL cholesterol is considered to be protective, so low HDL cholesterol is being recognized as an independent cardiovascular risk factor that contributes to the development of atherosclerosis and related adverse cardiovascular events. The recognition of insulin resistance and metabolic syndrome is a step further in understanding these risk factors. Attempts at reducing serum cholesterol with different strategies in the past have met with limited success until the development of statins. The advent of statins has revolutionized the management of hyperlipidemia. The post-statins era has seen major clinical trials demonstrating the benefit of cholesterol reduction in the setting of both primary and secondary prevention. In general, there appears to be a 25% to 40% relative risk reduction in major adverse cardiovascular events such as death, myocardial infarction, and stroke. The recent megatrials further suggest that aggressive management of cholesterol in patients with high cardiovascular risk may be beneficial. Though the concept of the-lower-the-better may be looming, the question of "How low is good enough?" remains controversial. The results of recent megatrials such as the Heart Protection Study go a step further than the NCEP guidelines and suggest that statin therapy may benefit patients at high risk of cardiovascular disease regardless of their baseline values. We summarize the results of the available large clinical trials in our understanding of the management of dyslipidemia in a setting of primary prevention.

The future direction of cholesterol-lowering therapy.

Abstract: PURPOSE OF REVIEW Observational studies suggest a continuous positive relationship between vascular risk and cholesterol without any lower threshold level. We review recent and future clinical trials addressing the question of optimal treatment goals for cholesterol reduction and how these relate to present guidelines. With increasing focus on greater cholesterol reduction, new approaches to lipid-lowering therapy are being developed; we discuss some of these agents including the new statin, rosuvastatin and novel cholesterol transport inhibitors such as ezetimibe. RECENT FINDINGS The Heart Protection Study demonstrated that LDL cholesterol reduction to levels as low as 1.7 mmol/l was associated with significant clinical benefit in a wide range of high-risk individuals, irrespective of baseline cholesterol levels, with no apparent threshold level for LDL cholesterol with respect to cardiovascular risk. The Heart Protection Study also demonstrated that the benefits of LDL cholesterol reduction extend into peripheral vascular disease and cerebrovascular disease prevention and suggest that the most recent National Cholesterol Education Program Adult Treatment Panel III guidelines, with LDL cholesterol targets of 2.6 mmol/l, may result in undertreatment of a large number of patients. Various large end-point trials, including Treating to New Targets and Study of Effectiveness of Additional Reductions in Cholesterol and Homocysteine will attempt to further address the issue of optimal LDL cholesterol reduction. New therapies are being developed to meet the challenge of more intensive cholesterol lowering. Rosuvastatin is a potent, hydrophilic enantiomeric statin producing reductions in LDL cholesterol of 40-69% over its dose range of 5-80 mg. Ezetimibe is a selective cholesterol absorption inhibitor, with a site of action at the intestinal epithelium. Optimum reductions in LDL cholesterol of up to 25 and 60% reduction in chylomicron cholesterol content are seen with a 10-mg dose. SUMMARY Evidence is accumulating supporting the safety and benefits of aggressive cholesterol reduction, with no apparent threshold for LDL cholesterol. New therapies will aid in achieving lower cholesterol levels and the use of combination therapies targeting different aspects of cholesterol metabolism may produce additional benefits. Outcome studies are awaited to further address these issues.

Protecting the heart: a practical review of the statin studies.

Abstract: The aim of this review of the landmark HMG-CoA reductase inhibitors (statins) studies is to enable the clinician to draw practical lessons from these trials. The Scandinavian Simvastatin Survival Study (4S) established the importance of treating the hypercholesterolemic patient with established cardiovascular heart disease. The West of Scotland Coronary Prevention Study (WOSCOPS) showed the benefit of treating healthy hypercholesterolemic men who were nevertheless at high risk of developing cardiovascular heart disease in the future. The Cholesterol and Recurrent Events (CARE) study, a secondary prevention trial, proved the benefit of treating patients with myocardial ischemia and cholesterol levels within normal limits. This conclusion was confirmed by the Long-term Intervention With Pravastatin in Ischemic Disease (LIPID) study, another secondary prevention study that enrolled patients with a wide range of cholesterol levels (4-7 mmol/dL), into which the large majority of patients would belong. The importance of treating patients with established ischemic heart disease (IHD), and those at high risk of developing cardiovascular heart disease, regardless of cholesterol level, was being realized. The Air Force/Texas Coronary Artery Prevention Study (AFCAPS/TexCAPS) then showed that treatment can reduce adverse cardiovascular events even in the primary prevention of patients with normal cholesterol levels. The Myocardial Ischemia Reduction With Aggressive Cholesterol Lowering (MIRACL) trial showed that hypocholesterolemic therapy is useful in the setting of an acute coronary syndrome, while the Atorvastatin Versus Revascularisation Treatment (AVERT) study showed that aggressive statin therapy is as good as angioplasty in reducing ischemic cardiac events in patients with stable angina pectoris. Finally, the Heart Protection Study (HPS) randomized more than 20,000 patients, and the value of statins in reducing adverse cardiovascular events in the high-risk patient, including the elderly, women, and even in those with low cholesterol levels, is beyond doubt. The emphasis is now on the risk level for developing cardiovascular events, and treatment should target the high-risk group and not be dependent on the actual cholesterol level of the patient. It is interesting to compare the large amount of data on the value and safety of the statins with the much more limited and less convincing data on antioxidant vitamins.

The Heart Protection Study: implications for clinical practice. The benefits of statin therapy do not come without financial cost.

Abstract: THE AIM of the recently reported Heart Protection Study1 in the United Kingdom, with over 20000 participants aged 40–80 years, was to establish whether statin therapy is of benefit to people who are at high risk of cardiovascular disease (CVD) but have average-to-low levels of total cholesterol and LDL-cholesterol. High-risk patients (defined as those having previous coronary heart disease, diabetes, stroke, or p r pheral v scular disease) were tre ted with simvastatin (40mg daily), antioxidant vitamins (20mg betacarotene, 250 mg vitamin C and 600mg vitamin E daily) or placebo in a 2 x 2 factorial design. Among patients allocated to the antioxidant arm of the trial, there was no change in incidence of any prespecified endpoints, and there were small but significant increases in blood levels of LDL-cholesterol and triglycerides, which have the potential to increase CVD risk with long-term antioxidant use.2 High-dose antioxidant therapy is therefore not recommended.3 Reductions in cardiovascular events (including myocardial infarction, stroke and either coronary or peripheral arterial revascularisation) occurred with simvastatin therapy in women, elderly people, and people with previous cerebrovascular disease, peripheral artery disease, renal impairment or diabetes (see Box). Translating the results of the HPS into clinical practice, patients with an absolute overall CVD risk of more than 17% over five years (the lowest rate occurring in any subgroup of the HPS treated with placebo) should receive ■ high-dose statin therapy, equivalent to 40 mg/day simvastatin, independent of baseline levels of total cholesterol; and ■ other cardioprotective therapy, such as -blockers and aspirin. Overall CVD risk can be estimated with the National Prescribing Service charts,4 which refer to CVD rather than coronary heart disease risk — a strategy flowing from the HPS outcomes.1,4 These charts, based on the Framingham study, provide only an approximation of absolute risk, but serve as a useful guide. Examples of patients with five-year CVD risk above 17% include most men over 60 years who smoke and have diabetes, and a 60-year-old non-smoking, non-diabetic man with blood pressure of 160/95 mmHg and a total cholesterol/HDL-cholesterol ratio of 6:1.4 Benefits are likely to occur after 12 months of statin therapy, with greater benefits occurring the longer therapy is continued. Allowing for non-compliance, the HPS showed that about a third of major CVD events are likely to be prevented by statin therapy over five years. In the HPS, 23% of patients in the simvastatin group were smokers, 22% were being treated with antihypertensive agents, 20% with blockers, 25% with angiotensin-converting enzyme inhibitors (ACE inhibitors) and 21% with aspirin. Relative risk reductions in CVD incidence of up to 80% may be expected when statins are combined with standard cardioprotective agents (aspirin, -blockers and ACE inhibitors) and stopping smoking.3 Given that CVD reduction in the HPS was independent of baseline cholesterol levels, it has been suggested that lipid levels need not be measured before commencing statin therapy in high-risk patients. However, fasting levels of triglycerides and HDL-cholesterol should be measured after 1–2 months, as therapy may need to be modified if these lipids are inadequately controlled by statin therapy alone. For example, gemfibrozil therapy may be considered for patients with low HDL-cholesterol levels. The HPS included about 6000 individuals with diabetes — the largest number in any statin trial reported to date. The CVD event rate for placebo-treated diabetics without coronary heart disease was 18.6%, compared with 22.5% for non-diabetics with coronary heart disease. Thus, the HPS confirms diabetes as a “coronary-equivalent” risk disorder for CVD. However, risk of CVD may vary from low to very high, depending on age and other risk factors, so it is still necessary to determine the global risk of CVD for an individual with diabetes when assessing the need to treat with a statin.4 Subjects at highest risk of CVD in the HPS had slightly elevated baseline serum creatinine levels (>200 mol/L), although only results of univariate analysis have been provided. The HPS confirms the high CVD risk in patients with impaired renal function and also supports the need for treatment of their dyslipidaemia. Caution is required in giving statin therapy to patients with more severe renal impairment, as they are at increased risk of myopathy.8 In the HPS, the safety profiles for statin and placebo therapy were similar. This finding may partly be a consequence of the exclusion of patients who showed adverse The Heart Protection Study: implications for clinical practice

The heart protection study: statins for all those at risk?

Abstract: On 13 November 2001, Professor Rory Collins, Co-director of the Oxford University’s Clinical Trial Service Unit, presented the results of the Heart Protection Study (HPS) at the American Heart Association. This was noted in the British Medical Journal (BMJ) on 17 November (1) and the relevant information was made available on a website (http:/www.hpsinfo.org). A full paper will presumably be published in the not too distant future. This paper and the data already made available will have a marked impact on the assessment and management of patients at risk of dying from cardiovascular disease. The results may shift the emphasis in cardiovascular medicine away from expensive invasive procedures, such as coronary angioplasties and stents, and from the search for much more expensive and minimally more effective thrombolytic therapies towards more simple primary and secondary preventive treatments using safe, currently available drugs. The aim of the HPS was to assess the impact of simvastatin 40 mg daily and an antioxidant mixture (vitamin E – 600 mg, vitamin C – 250 mg daily and b-carotene – 20 mg daily) on the prognosis of patients considered to be at risk of dying from cardiovascular disease, but in whom their doctor did not consider that a statin or vitamins were clearly indicated or contraindicated. The patient population exceeded 20 000. They were aged 40–80 years, had a total cholesterol greater than 3Æ5 mmol/L (more than 135 mg/dL), and were considered to be at increased risk of dying from coronary heart disease (CHD) because they had: previous myocardial infarction or other evidence of CHD; occlusive disease of non-coronary arteries; diabetes mellitus; hypertension. The trial had a 2 · 2 factorial design comparing simvastatin with placebo, and vitamins with placebo. This means that about 25% of the total number of patients would be on each of the following: Simvastatin and vitamins; Simvastatin and placebo; Vitamins and placebo; Placebo and placebo. It was planned that the mean duration would be at least 5 years. Their results demonstrate that there was no interaction or association between the statin and the antioxidant vitamins (data not shown). Therefore the results are discussed separately.

Lipid lowering in hypertension and heart protection: observations from the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) and the Heart Protection Study.

Abstract: Lipid lowering in hypertension and heart protection: observations from the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) and the Heart Protection Study

Statins as the new aspirin. Conclusions from the heart protection study were premature.

Abstract: Editor—With reference to the news item by Kmietowicz, in their press release the directors of the heart protection study did not mention that their results were substantially worse than in the previous Scandinavian simvastatin survival study (4S) (table).1,2,3 The way the results were presented exaggerates the benefit for the individual patient. The most interesting figure is survival because most myocardial infarctions heal with minimal cardiac dysfunction, if any. Tell a patient that his chance not to die in five years without statin treatment is 85.4% and that simvastatin treatment can increase this to 87.1 %. With these figures in hand I doubt that anyone should accept a treatment whose long term effects are unknown. For example, it was claimed that the study presented uniquely reliable evidence that simvastatin is not carcinogenic. But the study went on for about five years only, just like other statin trials. It is not possible to say anything about the risk of cancer because it takes decades to disclose chemical carcinogenesis in human beings. Heavy smoking, for example, does not induce lung cancer in five years. All the statins and also the fibrates have proved carcinogenic in rodents, and it scares me that, if the new American guidelines for cholesterol treatment are followed strictly, half of mankind may take statins in a few years and for the rest of their lives.4 Low cholesterol concentrations have been related to depression, cognitive impairment, and suppression of the immune system. Does a reduction of 1.7 % in mortality balance these risks? As in the previous trials, the effect of simvastatin was independent of the initial cholesterol concentration; patients with low concentrations benefited just as much (or just as little) as patients with high concentrations. The best results were seen in patients older than 75 years, an age group in which the lowest quartile of cholesterol concentration had the highest total and cardiovascular mortality.5 That statin treatment works in patient and age groups in whom a high cholesterol concentration is not a risk factor for cardiovascular disease shows that the benefit is not the result of cholesterol lowering. High or low cholesterol concentrations are markers for other, more important disease factors; they are not causal factors themselves.

“Interventional lipidology”: tomographic plaque imaging and aggressive treatment of metabolic disorders

Abstract: T magnitude of the medical and financial burdens inflicted on our society by coronary artery disease (CAD) mandates a more direct approach to risk stratification, and to aggressive intervention in those at high risk, than currently employed. To meet this need, the new field of “Interventional Lipidology” has emerged. In primary prevention, treatment goals are based upon risk assessment by noninvasive measurement of subclinical atherosclerosis, followed by identification and aggressive treatment of all contributing metabolic abnormalities, as well as traditional risk factors, and reevaluation by imaging of the effects of treatment (Table 1). In secondary prevention, it is based upon aggressive therapy directed toward treatment of all identifiable metabolic disorders; imaging to assess treatment will be increasingly used. Several modalities have been considered for the noninvasive evaluation of subclinical atherosclerosis. Abnormal ankle-brachial index measurements are often associated with CAD, but are present only in advanced peripheral vascular disease and have limited reproducibility. Stress testing identifies only obstructive CAD, limiting its utility to identify patients with significant nonobstructive atherosclerosis. Carotid intima-media thickening has great epidemiologic potential, but is a surrogate for atherosclerosis, and is hampered by the difficulty of performing the procedure in an accurate, reproducible fashion, thereby restricting its use to a handful of institutions. Tomographic calcified plaque imaging currently appears to be the most suitable modality, because it directly identifies CAD in its earlier stages. Electron beam tomography (EBT) is supported by a wealth of data demonstrating its prognostic power and reproducibility; multislice computed tomography is increasingly being used. It is reasonable to assume that most clinical events in the primary prevention trials occurred in patients with subclinical CAD that placed them at higher risk, i.e., with calcified plaque on entry into the study. This is strongly supported by the very low ( 6%) incidence of zero calcium scores by EBT in patients who have acute cardiac events, and by the extremely low likelihood (0.11%/year) of clinical events in the setting of a zero score, despite the possibility of exclusively soft, noncalcified plaque. The incidence of zero or trivial scores in the West of Scotland trial (average low-density lipoprotein [LDL] cholesterol 190 mg/dl) and the Air Force/Texas Coronary Atherosclerosis Study (AFCAPS/TexCAPS) (average LDL cholesterol 150 mg/dl) is unknown. However, their inclusion is strongly suggested by the work of Hecht et al, who showed that 33% and 50% of primary prevention patients with LDL cholesterol 160 and 160 mg/dl, respectively, have zero scores. Thus, the National Cholesterol Education Program drug treatment recommendations are based upon studies involving patients with varying levels of subclinical CAD, and widely disparate risk. Therefore, there is no evidence based medicine that supports treatment in a patient with a zero calcium score, who is at low risk (0.11%/year event rate), irrespective of treatment. Similarly, there are no data supporting the withholding of drug therapy from patients with high-risk calcium scores (2.1% to 4.8%/year event rate), whose LDL cholesterol levels and Framingham risk score do not qualify them for drug treatment. Approximately 50% of asymptomatic patients with LDL cholesterol 130 mg/dl have significant calcified plaque with attendant high risk, but would not be treated by current guidelines. Moreover, the Heart Protection Study suggests that patients with LDL cholesterol 130 mg/dl, and even 100 mg/dl, benefit from statin therapy to the same degree as those with higher levels. Postmenopausal women with and without plaque have similar lipid profiles and Framingham risk scores, but vastly different EBT-determined prognoses; 50% of those with plaque would not be treated by current criteria. Logic suggests that secondary prevention treatment goals and drug therapy initiation levels be applied to patients who have significant plaque burdens, irrespective of their LDL cholesterol levels. However, in the absence of an evidence-based study demonstrating the beneficial effect on outcomes of treating patients solely on the basis of their calcium scores, this paradigm is subject to the same criticism that can be directed to the treatment of patients with zero scores with statins, solely on the basis of lipid levels and risk factors. It is clear that the required evidenced-based studies to support either viewpoint will be quite difficult to implement. Nonetheless, a solution to this problem would seem prudent to complement current clinical decision making. From the Princeton Longevity Center, Princeton, New Jersey. Manuscript received February 4, 2002; revised manuscript received and accepted April 8, 2002. Address for reprints: Harvey S. Hecht, MD, Princeton Longevity Center, 50 Vreeland Drive, Princeton, New Jersey 08858. E-mail: hhecht@aol.com.

Optimal treatment and current situation in reperfusion after thrombolysis for acute myocardial infarction.

Abstract: Acute myocardial infarction is the leading cause of death in the industrialized world and the paramount goal is establishing early, complete, and sustained reperfusion at the myocardial tissue level. For hospitals without the capacity to perform emergent percutaneous coronary intervention, fibrinolytic therapy plays a critical role although it is limited by a 67% success rate. Despite promising pilot studies, reduced-dose fibrinolytic therapy with glycoprotein IIb/IIIa therapy (GUSTO-V) and full-dose fibrinolytic therapy with enoxaparin (ASSENT-3) or bivalirudin (HERO-2) provide only marginally improved clinical outcomes. Adjunctive in-hospital and secondary preventive measures should include an aspirin, a beta-blocker, an ACE inhibitor, and a statin, based on the Heart Protection Study, unless contraindicated. Patients should be risk stratified, participate in a cardiac rehabilitation program, cease smoking tobacco, and have an intracardiac defibrillator (ICD) implanted if their LV systolic function is < or = 30% at one month based on the MADIT-2 trial.

Heart Protection Study (HPS)

Abstract: prévention cardiovasculaire pour un grand nombre de patients grâce aux études de prévention parues jusqu’alors, c’est-à-dire 4S, CARE et LIPID en prévention secondaire, WOSCOPS et AFCAPS/TexCAPS en prévention primaire. Toutefois, la place des statines, même chez le sujet à haut risque, restait à définir ou à confirmer dans un certain nombre de cas, et les principales questions en suspens concernaient le sujet âgé (audelà de 70-75 ans), la femme, le diabétique, en particulier de type 2, les sujets avec des antécédents d’accident vasculaire cérébral (AVC) ou d’accident ischémique transitoire (AIT), avec des antécédents d’artérite des membres inférieurs, etc. De plus, dans les études CARE et LIPID, réalisées avec la pravastatine 40 mg, les patients avec un LDL-cholestérol (LDL-C) inférieur à 1,30 g/l environ (1,25 g/l dans CARE, 1,35 g/l dans LIPID) n’avaient pas eu de bénéfice significatif du traitement par la pravastatine. L’intérêt d’un traitement par statine pour des patients avec un LDLC inférieur à 1,30 g/l, de même que chez les sujets avec des triglycérides franchement augmentés, n’était donc pas démontré. La nouvelle étude de prévention Heart Protection Study (HPS), dont les premiers résultats ont été présentés par R. Collins à l’AHA 2001, est particulièrement importante en termes de réponses apportées à certaines de ces questions. L’objectif général de cette étude était d’évaluer les effets sur la mortalité totale et sur la morbidité cardiovasculaire d’un traitement par simvastatine 40 mg par jour et d’une supplémentation en vitamines antioxydantes dans une large gamme de patients à haut risque cardiovasculaire. Plus de 32 000 patients recrutés dans des hôpitaux en Grande-Bretagne ont accepté d’entrer dans une phase de prérandomisation comportant deux périodes : tout d’abord une période de quatre semaines pendant laquelle tous les patients prenaient le mélange de vitamines anti-oxydantes et un placebo de simvastatine, puis une période de six semaines de double traitement actif (simvastatine 40 mg/j et vitamines actives). Cette période de pré-inclusion a surtout permis d’évaluer au préalable le niveau de cholestérol pour n’autoriser l’inclusion que des patients n’ayant pas, au moment de cette inclusion, d’indication claire pour un traitement par statine, ni de contreindication ou d’intolérance à un tel traitement. Cela a bien sûr conduit à n’inclure que des patients ayant un taux de cholestérol total proche de la normale. Tous les patients ayant un cholestérol total supérieur à 1,35 g/l pouvaient être inclus, à condition d’être âgés de 40 à 80 ans et d’être à haut risque vasculaire défini par soit des antécédents coronaires, soit des antécédents de maladie athéromateuse dans d’autres territoires artériels, soit un diabète, soit une hypertension traitée chez des hommes de plus de 65 ans. Au terme de la phase de pré-inclusion, 20 536 patients ont été randomisés entre juillet 1994 et mai 1997 pour recevoir, selon un plan factoriel deux à deux, soit l’association simvastatine et antioxydants, soit la simvastatine ou les antioxydants seuls, soit un double placebo (figure 1). L’efficacité biologique de la simvastatine 40 mg a été évaluée dans cette population au terme des six semaines de traitement de la phase de pré-inclusion, et la baisse du LDL-C était de l’ordre de 38 %. Sur le plan des paramètres biologiques, au moment de la randomisation, le taux moyen de cholestérol total était de 2,20 g/l chez les hommes et de 2,40 g/l chez les femmes, avec un LDL-cholestérol à 1,28 g/l en moyenne chez les hommes et à 1,35 g/l en moyenne chez les femmes. Dans cette étude, près de 12 000 patients avaient à l’inclusion un LDL-C < 1,35 g/l, c’està-dire pratiquement au seuil actuellement recommandé en France pour l’introduction d’un traitement par statine en prévention secondaire coronaire, et près de 7 000 patients avaient même un LDLC < 1,16 g/l, ce qui correspond au seuil des recommandations européennes. Les caractéristiques essentielles de la population randomisée sont indiquées au tableau I : près de 6 000 diabétiques ont été inclus, dont environ 4 000 sans antécédents de maladie coronaire, mais avec toutefois, pour un grand nombre d’entre eux, la notion d’antécédents de maladie cérébrovasculaire ou artérielle périphérique (au total, 17 900 patients avaient des antécédents de maladie coronaire, ou cérébrovasculaire ou artérielle périphérique). Plus de 5 000 femmes ont été incluses dans cette étude, de même que plus de 5 800 sujets âgés de plus de 70 ans.

Reassessment of national cholesterol education program adult treatment panel-III guidelines: One year later

Abstract: Since the first Adult Treatment Panel (ATP) guidelines from the National Cholesterol Education Program (NCEP), the goals have evolved from national cholesterol awareness and reduction, to the use of increasingly aggressive lipid-lowering strategies in patients at highest risk for coronary heart disease (CHD). The most recent NCEP guidelines from the ATP-III 1 appropriately suggest the most aggressive reduction in low-density lipoprotein (LDL) cholesterol in an expanded group of patients considered to be at highest risk for CHD. Since these guidelines were published approximately 1 year ago, additional clinical trial data suggest that they are already, to a certain extent, out of date. It is now clear that cholesterol reduction may not just need to target certain lipid goals, but also be broadly applied to virtually any individual at high risk for atherosclerotic disease. REDEFINING AN “OPTIMAL” LDL CHOLESTEROL LEVEL The most striking trial data since ATP-III were from the Heart Protection Study (HPS), 2 which assessed the effects of simvastatin 40 mg and/or a combination of antioxidant vitamins versus placebo in a factorial design in 20,536 patients with high risk for CHD. The study population included subjects with history of CHD, other atherosclerotic diseases, and type 2 diabetes mellitus, all consistent with ATP-III “coronary risk equivalent” status. Although the vitamins provided no cardiovascular benefits, simvastatin therapy yielded a 24% mean relative risk reduction in vascular events. Furthermore, this event reduction was maintained whether the baseline LDL cholesterol was above the traditional ATP-III drug cutpoint of 130 mg/dl, in the range for which discretional use of pharmacotherapy is advised (100 to 129 mg/dl), or even below the targeted LDL cholesterol goal of 100 mg/dl. Although the core principle of the NCEP guidelines, the reduction of LDL cholesterol to reduce CHD risk, was validated by HPS, the extent to which this principle should be applied was underestimated by ATP-III. Although LDL cholesterol concentrations 100 mg/dl are considered “optimal” by ATP-III, the findings from HPS suggest high-risk patients benefit from statin therapy even when below this level. Although providing additional guidance for the management of these patients with CHD risk-equivalent status, HPS raises further questions. Has our definition of hyperlipidemia been skewed by the effects of a Westernized diet on lipid levels? Are some nonlipid benefit(s) of statin therapy responsible for the findings of HPS? Do we even need to measure cholesterol in our high-risk patients? Can we grossly simplify the treatment algorithm for high-risk patients by applying an approach similar to HPS? The last question will likely be answered by the Treat to New Targets (TNT) and Incremental Decrease in Endpoints through Aggressive Lipid-lowering (IDEAL) trials, which are currently in progress. These studies will compare the effects of maximal versus conventional doses of simvastatin and atorvastatin in reducing coronary events in large populations. In the interim, it seems prudent to lower LDL cholesterol to 100 mg/dl or by 35% (whichever is greater) utilizing a statin in the setting of CHD risk equivalency.

Statins reduce cardiovascular risk

Abstract: Treating patients at high risk of cardiovascular events with the HMG-CoA (hydroxymethyl glutaryl coenzyme A) reductase inhibitor simvastatin reduced the risk of myocardial infarction, stroke, and revascularisation by about one third, even in patients with normal or low blood cholesterol levels, according to the latest findings from the heart protection study published this week. The study randomised 20536 adults with coronary disease, other occlusive artery disease, or diabetes to treatment with simvastatin (40 …

[Treatment with statins: further data from the Heart Protection Study].

Abstract: BACKGROUND Statins have been shown to reduce cardiovascular disease in subjects with coronary heart disease, in men with high cholesterol levels and in men and postmenopausal women with low high-density lipoprotein cholesterol levels. In meta-analysis, reduction in events is associated with reduction in serum low-density lipoprotein (LDL) cholesterol levels, however, some studies have proposed a threshold level for the effect. MATERIAL AND METHODS A clinician and a statistician reviewed the Heart Protection Study in the context of previous similar studies. RESULTS High-risk men and women (n = 20,536) aged 40-80 years with coronary heart disease, peripheral artery disease or diabetes and a cholesterol level of at least 3.5 mmol/l were randomised to simvastatin 40 mg or placebo. After 5.5 years, the incidence of nonfatal myocardial infarction or coronary death was reduced from 11.8% in the placebo group to 8.7% in the simvastatin group, and a similar reduction was seen in subjects with diabetes but no cardiovascular disease. There was no threshold of LDL cholesterol below which lowering it did not reduce risk. INTERPRETATION The study adds to the body of evidence indicating that cholesterol lowering with statins is indicated for subjects with high risk and that LDL cholesterol reduction explains the reduction in events.

Usefulness of lipid-lowering therapy in elderly patients.

Abstract: O of all acute myocardial infarcts and 60% of all acute myocardial infarction deaths occur in individuals aged 75 years. Forty-five percent of octogenarians have clinical evidence of cardiovascular disease. Coronary heart disease (CHD) is the most common problem; 58% of mortalities at 85 years of age are due to cardiovascular disease. Concomitantly, men and women aged 60 years have the highest prevalence of hypercholesterolemia. Based on Framingham Study data, although total cholesterol level loses its predictive value for CHD in men after age 70, it predicts CHD in women into the ninth decade. The total: high-density lipoprotein cholesterol ratio predicts CHD even at ages 80 years.2 Survey data demonstrate marked undertreatment of hypercholesterolemia in elderly subjects. Some of this reflects less aggressive screening in elderly populations, some is caused by the lower priority given to dyslipidemia by physicians and patients, some involves concerns about drug safety, and some is predicated by concerns about drug costs. Time trends in cholesterol-lowering therapy among 5,000 community-dwelling individuals aged 65 years in the Cardiovascular Health Study identified that 4.5% of eligible men and 5.9% of eligible women were treated with lipid-lowering agents in 1989 to 1990, increasing only to 8.1% of men and 10.0% of women in 1995 to 1996.3 In contrast, clinical trials of statin therapy show that the effectiveness of lipid lowering is similar in elderly and nonelderly populations, and that the incidence of adverse drug events and laboratory abnormalities is also similarly low in the elderly and nonelderly. Importantly, the statin-related decrease in low-density lipoprotein cholesterol levels in primary and secondary coronary prevention trials decreased the risk of CHD and of all-cause mortality. The risk reduction, about 30%, was similar in middle-aged and elderly patients treated for about 5 years (with data available to age 75 years). In patients of the Scandinavian Simvastatin Survival Study (4S), simvastatin-treated patients had a 34% decrease in all-cause mortality, due predominantly to a 43% decrease in CHD mortality. Although there was similar decrease in the relative risk for major CHD events in those older and younger than age 65, the absolute reduction was twice as great in older patients because mortality rates increase substantially with older age. Patients with myocardial infarction aged 65 to 75 years in the Cholesterol And Recurrent Events (CARE) trial showed a 32% decrease in major coronary events in the pravastatintreated group, including a 45% decrease in coronary death and a 40% decrease in stroke. Treatment of 1,000 older patients prevented 225 cardiovascular hospitalizations, in contrast to 121 hospitalizations prevented in 1,000 younger patients. Patients 65 years in the Long-term Intervention with Pravastatin and Ischemic Disease (LIPID) study, all of whom had average or below average cholesterol levels after myocardial infarction or unstable angina, had a 25% risk reduction in major coronary events when receiving pravastatin 40 mg/day, identical to the benefit of patients 65 years old.6 In the Primary Prevention AirForce/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS), there was a 32% decrease in first acute coronary event beyond age 65, compared with a 38% decrease at age 65 years. Patients 65 years of age were not included in the West Of Scotland COronary Prevention Study (WOSCOPS) primary prevention trial.8 Fewer than 20% of patients eligible for therapy based on National Cholesterol Education Program II guidelines in the Cardiovascular Health Study were untreated at baseline initiated therapy in the 6 years of follow-up, even those with a history of CHD.3 In the recently presented British Heart Protection Study (HPS), which enrolled patients 80 years of age, there was comparable benefit in the population below age 65, age 65 to 69, 70 to 74, and 75 years of age. In elderly, as in younger patients, simvastatin 40 mg/day reduced the risk of myocardial infarction, stroke, and myocardial revascularization by 1/3. There was no excess of adverse events, including abnormal blood enzyme levels, in older compared with younger patients. Current information is limited regarding patients 75 years of age. Given the comparable pathobiology of atherosclerosis at middle and elderly ages, the high attributable risk of hypercholesterolemia and high prevalence of established CHD at elderly ages, and the substantial and comparable CHD risk reduction associated with lipid-lowering at middle and elderly ages, a more aggressive screening of older individuals for lipid abnormalities is recommended, along with the institution of lipid-lowering therapy based on National Cholesterol Education Program III guidelines. From the Department of Cardiology, Emory University School of Medicine, Grady Memorial Hospital, Atlanta, Georgia. Manuscript received May 14, 2002; revised manuscript received and accepted June 4, 2002. Address for reprints: Nanette K. Wenger, MD, Emory University School of Medicine, 69 Jesse Hill Jr. Drive, SE, Atlanta, Georgia 30303. E-mail: nwenger@emory.edu.

[Broader indication for treatment with statins; the 'heart protection study'].

Abstract: The introduction of statins has been a breakthrough in the treatment of hypercholesterolaemia. Statins are safe and effective in reducing the risk of coronary heart disease in the general population. The 'Heart protection study' has provided evidence for the benefit of statin treatment in much broader populations than is presently indicated in the Dutch national guidelines, i.e. also in high-risk persons with diabetes mellitus, and irrespective of age or cholesterol level. The use and cost of statins, which have been referred to as 'lifestyle-drugs' in the lay press, have risen enormously. Recently, the Dutch College of Healthcare Insurers issued a report in which recommendations concerning the reimbursement of the costs for cholesterol-lowering drugs are based on 'generally accepted insights into the appropriate use of these drugs'. Lifestyle and/or age are not exclusion criteria for treatment with statins. The expiration of patents of some statins and modifications to the reimbursement system in 2003 could lead to cost reductions.