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Query: UMLS:C0021311 (Infection)
 38,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

While aggressive interventional therapy and anti-thrombotic therapy have revolutionized the management of acute coronary syndromes (ACS), defined as acute myocardial infarction (MI) or unstable angina (UA), long-term event rates remain high. Elevated lipids, inflammation and infection have each been implicated as additional mechanisms contributing to instability of vulnerable plaques. The new frontier in ACS management has focussed on treatment of these components of vascular disease. Preliminary trials have shown that early treatment with statins after ACS reduces coronary events but additional studies are needed to confirm this benefit. Furthermore, it is not clear what degree of low-density lipoprotein cholesterol (LDL-C) lowering is needed to stabilize the ACS patient. Chlamydia pneumoniae has been implicated in the development of coronary heart disease (CHD) but the results of preliminary trials investigating anti-chlamydial antibiotics have been inconsistent. Therefore, the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT TIMI 22) trial has been designed specifically to determine whether standard LDL-C reduction (with pravastatin 40 mg) provides a similar clinical benefit to more aggressive LDL-C reduction (with atorvastatin 80 mg). In 4162 ACS patients over a 2-year period, this trial will also evaluate the long-term effect of the quinolone antibiotic, gatifloxacin, in reducing cardiovascular events.
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PMID:The next step in cardiovascular protection. 1498 Feb 29

Statins, as compared to placebo, have proven their efficacy in reducing cardiovascular events in patients with or without cardiovascular disease and in a large range of cholesterol levels. Two new head-to-head randomised trials comparing intensive treatment with atorvastatin 80 mg/day with moderate treatment with pravastatin 40 mg/day were recently completed. The mechanistic "Reversing Atherosclerosis with Aggressive Lipid Lowering" (REVERSAL) trial randomised 502 patients with stable coronary disease. Atorvastatin 80 mg (leading to a mean LDL cholesterol of 79 mg/dl) was superior to pravastatin 40 mg (mean LDL of 110 mg/dl) in terms of limiting the progression of atheroma assessed with the use of intravascular ultrasonography after 18 months of follow up (p = 0.02). These differences may be related to the greater reduction in atherogenic lipoprotein (-46% versus -26%, p < 0.001) and C-reactive protein (-36% versus -5%, p < 0.001) in patients treated with atorvastatin as compared to pravastatin. In the clinical "Pravastatin or Atorvastatin Evaluation and Infection Therapy" (PROVE-IT) trial, 4162 patients with acute coronary syndromes were randomised to either atorvastatin 80 mg or pravastatin 40 mg and followed for a mean of 24 months. Again, atorvastatin (mean LDL of 62 mg/dl) was superior to pravastatin (mean LDL of 95 mg/dl), resulting in a 16% percent lower risk of the primary end point, a composite of major cardiovascular events (p = 0.005). Thus, both REVERSAL and PROVE-IT support the concept "the lower, the better". However, they do not allow to disentangle the independent and interdependent effects of statins on LDL cholesterol and the process of arterial inflammation. What so ever, the results suggest that the target LDL cholesterol level may be lower than recommended in the current guidelines in high-risk patient so that a sea change in the prevention and management of atherosclerotic vascular disease may occur very soon.
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PMID:[Clinical study of the month. REVERAL and PROVE-IT: confirmation of the concept " the lower, the better" for cholesterol therapy in patients with coronary heart disease]. 1513 6

Current international guidelines recommend that the goal of treatment with lipid-lowering therapy in patients with established coronary artery disease (CAD) should be a low-density lipoprotein cholesterol level of < 100 mg/dl. The question that remains to be answered is whether more aggressive lowering of low-density lipoprotein cholesterol levels below this target offers additional benefit and whether it can be tolerated. Two recently published related studies addressed this question by comparing intensive lipid lowering with atorvastatin (Lipitor, Pfizer) 80 mg/day with a moderate lipid-lowering regimen of pravastatin (Pravachol, Bristol-Myers Squibb) 40 mg/day. The first study, the Reversing Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) compared the effect of the two regimens on coronary artery atheroma burden and progression using intravascular ultrasound in patients with symptomatic CAD. The second study, the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT) was a clinical outcome trial in patients recently hospitalised with acute coronary syndromes. This article reviews the implications of these two studies in the management of patients with CAD. In addition, other ongoing trials and future directions are explored.
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PMID:Intensive lipid-lowering therapy in coronary artery disease: implications of the REVERSAL and PROVE-IT trials. 1517 57

Cardiovascular disease and its clinical sequelae remain the leading causes of morbidity and mortality in many regions of the world. Dyslipidemia is a critical risk factor to intercept in both the primary and secondary prevention of acute cardiovascular events. The prospective, placebo-controlled clinical trials conducted with statins over the course of the past 15 years have conclusively demonstrated that these drugs significantly reduce risk for fatal and nonfatal myocardial infarction, ischemic stroke, unstable angina, and frequency of myocardial ischemia, as well as cardiovascular and all-cause mortality. Of considerable interest is the fact that, even under the exquisitely controlled circumstances of a clinical trial, endpoint reductions in these trials typically occur in the range of 20% to 35%. Understandably, much attention is now being focused on deriving the pharmacologic means by which to further increase the magnitude of endpoint reduction. Epidemiologic investigation has demonstrated that the relationship between cholesterol and risk for atherosclerotic disease is a continuous one. Consequently, it is reasonable to assume that more aggressive reductions of low-density lipoprotein (LDL) cholesterol might result in even greater reductions of cardiovascular event rates and atheromatous plaque progression than heretofore observed. Two recent clinical trials, Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) and Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT), prospectively tested and confirmed the validity of more aggressive LDL cholesterol lowering in high-risk patients with established coronary artery disease.
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PMID:Low-density lipoprotein reduction in high-risk patients: how low do you go? 1529

With so many statins available for clinical use in coronary artery syndromes, there has been much discussion about which is the best. Two recent trials have compared the clinical outcomes of intensive lipid lowering with atorvastatin 80 mg/day and standard lowering with pravastatin 40 mg/day. In the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT) trial, patients with acute coronary artery syndromes were enrolled, and pravastatin lowered the low-density lipoprotein (LDL)-cholesterol to 2.46 mmol/l, whereas atorvastatin lowered it to 1.60 mmol/l. Associated with this, there was a lower rate of clinical events (myocardial infarction, revascularisation) over 2 years with atorvastatin than pravastatin (22.4 versus 26.3%, respectively). The Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial also enrolled patients requiring angiography, and pravastatin lowered the LDL-cholesterol to 2.84 mmol/l, whereas atorvastatin lowered the LDL-cholesterol to 2.04 mmol/l. In the REVERSAL trial, atheroma volume progressed with pravastatin by 2.7% whilst remaining stable in the atorvastatin group (-0.4%) over 18 months. Thus, atorvastatin 80 mg/day causes a greater reduction in LDL-cholesterol than pravastatin 40 mg/day, and this is associated with a reduced progression of atheroma and reduced clinical events. As a consequence of these findings, the National Cholesterol Education Programme and European guidelines for LDL-cholesterol levels should be lowered.
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PMID:Atorvastatin versus pravastatin: intensive versus moderate lipid lowering. 1500 10

The Pravastatin or Atorvastatin Evaluation and Infection Therapy trial (PROVE-IT/TIMI-22) showed that in patients with acute coronary syndromes, aggressive lipid-lowering using atorvastatin 80 mg/day provided greater protection against death or major cardiovascular events than did moderate lipid-lowering using pravastatin 40 mg/day. Lowering the low-density lipoprotein cholesterol level to approximately 62 mg/dL with atorvastatin resulted in a 16% reduction in cardiovascular end points.
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PMID:Lessons from the PROVE-IT trial. Higher dose of potent statin better for high-risk patients. 1544 56

Recent Canadian lipid guidelines recommend that all high-risk patients receive medication to reduce low density lipoprotein cholesterol (LDL-C) below 2.5 mmol/L. The recently published Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) and Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT) studies compared strategies of cholesterol lowering with atorvastatin 80 mg versus pravastatin 40 mg. Atorvastatin halted the progression of atherosclerosis (whereas atherosclerosis progressed in the patients receiving pravastatin), and resulted in a 16% reduction in the primary composite end point (all-cause death, myocardial infarction, unstable angina, revascularization and stroke) compared with the pravastatin-treated group. In the PROVE IT trial, LDL-C was reduced by atorvastatin to 1.6 mmol/L and by pravastatin to 2.46 mmol/L. Although lower LDL-C levels are one explanation for the improved outcomes with atorvastatin, pleiotropic differences of the two statins, such as their effects on inflammation and coagulation, cannot be excluded. Until trials are completed that compare outcomes from LDL-C lowering to different targets with the same statin, it is premature to recommend changes to the current Canadian guidelines. However, future recommendations may suggest much lower LDL-C targets than those currently recommended.
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PMID:Are Canadian guidelines for cholesterol lowering in high-risk patients optimal? 1568 8

Inflammation is pivotal in atherosclerosis, and C-reactive protein (CRP) is an inflammatory marker that predicts cardiovascular events. The Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial compared the standard lowering of low-density lipoprotein (LDL)-cholesterol with pravastatin 40 mg/day, with the intense lowering of LDL-cholesterol with atorvastatin 80 mg/day on atheroma volume in patients with coronary artery disease, and showed that the atheroma progressed by 2.7% in the pravastatin group, and remained unchanged in the atorvastatin group. At 18 months follow-up, the CRP levels were reduced from a baseline level of 2.8 mg/l to 1.8 mg/l by atorvastatin, whereas pravastatin had little effect, and there was a good correlation between both the ultrasonographic progression of disease and the reduction in CRP levels. The Pravastatin or Atorvastatin Evaluation and Infection Therapy--Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) trial compared the long-term effects of the standard lowering of LDL-cholesterol with pravastatin, with the intense lowering of LDL-cholesterol with atorvastatin in patients with an acute coronary syndrome. The primary end point was the first of death, myocardial infarction, unstable angina requiring hospitalisation, revascularisation or stroke, and, at the end of 2 years, was greater in the pravastatin than the atorvastatin group (26.3 versus 22.4%, respectively). Patients with CRP levels of 2 mg/l had lower rates of recurrent myocardial infarction or death from coronary causes than patients with higher levels. Further analysis should be undertaken to assess cardiovascular risk at different levels of CRP, including assessing cardiovascular risk at different levels in men and women. Definitive results about the importance of lowering CRP levels are not likely to be obtained until the results of the Justification for Use of Statins in Primary Prevention, an Intervention Trial in Evaluating Rosuvastatin (JUPITER) study are published.
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PMID:Relating statin therapy to C-reactive protein levels. 1608 47

Recently, two large randomised clinical trials compared the effects of standard and intensive lipid-lowering treatment (Pravastatin 40 mg vs. Atorvastatin 40 mg b.i.d.) on patient prognosis after acute coronary syndromes--the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT), and on the atherosclerosis regression--the Reversing Atherosclerosis with Aggressive Lipid Lowering (REVERSAL). Undoubtedly, the event-rate reduction and the atherosclerosis regression associated to intensive hypocholesterolemic treatment in these studies are impressive, however we would like to highlight some methodological concerns raised by both trials, more clinically oriented than planned to give rigorous answers to the scientist. The main problems of both studies are that they compare the effects of statins with different pleiotropic and pharmacokinetic properties and that the metabolic disorders that affect the studied patients have not been clearly described. Moreover, it is unclear if the cardiovascular disease history length was similar in the two treatment groups as well as the length and dosage of statin treatment of the about 25% of patients taking statins before the enrollment. Waiting for studies comparing the effects of low and high dosages of the same statin or the high dosage of two similarly potent and rapid lipid-lowering effect (as for instance atorvastatin and rosuvastatin), prudence has to be applied in the interpretation (and even more in the application) of these large and expensive study results, that have yet only confirmed the relevance of a more intensive lipid-lowering treatment in all patients affected by atherosclerosis-based coronary syndromes.
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PMID:REVERSAL and PROVE-IT: are clinically oriented trials really better than "pure" scientific studies? 1609 83

Both the American Diabetes Association (ADA) and the National Cholesterol Education Program (NCEP) consider type 2 diabetes mellitus to be a coronary artery disease (CAD) risk equivalent and thus suggest that patients with either diabetes or CAD should have their plasma levels of low-density lipoprotein (LDL) cholesterol lowered to <2.59 mmol/L (<100 mg/dL). Recently the NCEP issued a white paper suggesting an even lower plasma LDL cholesterol goal of <1.81 mmol/L (<70 mg/dL) for patients at high cardiovascular risk, including patients with diabetes. This rationale was based partly on the higher risk of future cardiovascular disease seen in patients who have diabetes with or without preexisting cardiovascular disease than in nondiabetic subjects with preexisting cardiovascular disease. Additionally, as reported in the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT) study, high-dose lipid-lowering therapy has been shown to further reduce CAD event rates compared with conventional therapy.
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PMID:Rationale for new American Diabetes Association Guidelines: are national cholesterol education program goals adequate for the patient with diabetes mellitus? 1609 41


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