Intensive lipid lowering with atorvastatin in patients with stable coronary disease.

Previous trials have demonstrated that lowering low-density lipoprotein (LDL) cholesterol levels below currently recommended levels is beneficial in patients with acute coronary syndromes. We prospectively assessed the efficacy and safety of lowering LDL cholesterol levels below 100 mg per deciliter (2.6 mmol per liter) in patients with stable coronary heart disease (CHD). A total of 10,001 patients with clinically evident CHD and LDL cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) were randomly assigned to double-blind therapy and received either 10 mg or 80 mg of atorvastatin per day. Patients were followed for a median of 4.9 years. The primary end point was the occurrence of a first major cardiovascular event, defined as death from CHD, nonfatal non-procedure-related myocardial infarction, resuscitation after cardiac arrest, or fatal or nonfatal stroke. The mean LDL cholesterol levels were 77 mg per deciliter (2.0 mmol per liter) during treatment with 80 mg of atorvastatin and 101 mg per deciliter (2.6 mmol per liter) during treatment with 10 mg of atorvastatin. The incidence of persistent elevations in liver aminotransferase levels was 0.2 percent in the group given 10 mg of atorvastatin and 1.2 percent in the group given 80 mg of atorvastatin (P<0.001). A primary event occurred in 434 patients (8.7 percent) receiving 80 mg of atorvastatin, as compared with 548 patients (10.9 percent) receiving 10 mg of atorvastatin, representing an absolute reduction in the rate of major cardiovascular events of 2.2 percent and a 22 percent relative reduction in risk (hazard ratio, 0.78; 95 percent confidence interval, 0.69 to 0.89; P<0.001). There was no difference between the two treatment groups in overall mortality. Intensive lipid-lowering therapy with 80 mg of atorvastatin per day in patients with stable CHD provides significant clinical benefit beyond that afforded by treatment with 10 mg of atorvastatin per day. This occurred with a greater incidence of elevated aminotransferase levels.

LaRosa JC ，Grundy SM ，Waters DD ，Shear C ，Barter P ，Fruchart JC ，Gotto AM ，Greten H ，Kastelein JJ ，Shepherd J ，Wenger NK ，Treating to New Targets (TNT) Investigators ... -  《-》

Effect of lowering LDL cholesterol substantially below currently recommended levels in patients with coronary heart disease and diabetes: the Treating to New Targets (TNT) study.

Shepherd J ，Barter P ，Carmena R ，Deedwania P ，Fruchart JC ，Haffner S ，Hsia J ，Breazna A ，LaRosa J ，Grundy S ，Waters D ... -  《DIABETES CARE》

Intensive versus moderate lipid lowering with statins after acute coronary syndromes.

Lipid-lowering therapy with statins reduces the risk of cardiovascular events, but the optimal level of low-density lipoprotein (LDL) cholesterol is unclear. We enrolled 4162 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and compared 40 mg of pravastatin daily (standard therapy) with 80 mg of atorvastatin daily (intensive therapy). The primary end point was a composite of death from any cause, myocardial infarction, documented unstable angina requiring rehospitalization, revascularization (performed at least 30 days after randomization), and stroke. The study was designed to establish the noninferiority of pravastatin as compared with atorvastatin with respect to the time to an end-point event. Follow-up lasted 18 to 36 months (mean, 24). The median LDL cholesterol level achieved during treatment was 95 mg per deciliter (2.46 mmol per liter) in the standard-dose pravastatin group and 62 mg per deciliter (1.60 mmol per liter) in the high-dose atorvastatin group (P<0.001). Kaplan-Meier estimates of the rates of the primary end point at two years were 26.3 percent in the pravastatin group and 22.4 percent in the atorvastatin group, reflecting a 16 percent reduction in the hazard ratio in favor of atorvastatin (P=0.005; 95 percent confidence interval, 5 to 26 percent). The study did not meet the prespecified criterion for equivalence but did identify the superiority of the more intensive regimen. Among patients who have recently had an acute coronary syndrome, an intensive lipid-lowering statin regimen provides greater protection against death or major cardiovascular events than does a standard regimen. These findings indicate that such patients benefit from early and continued lowering of LDL cholesterol to levels substantially below current target levels.

Cannon CP ，Braunwald E ，McCabe CH ，Rader DJ ，Rouleau JL ，Belder R ，Joyal SV ，Hill KA ，Pfeffer MA ，Skene AM ，Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Investigators ... -  《-》

Safety and efficacy of Atorvastatin-induced very low-density lipoprotein cholesterol levels in Patients with coronary heart disease (a post hoc analysis of the treating to new targets [TNT] study).

LaRosa JC ，Grundy SM ，Kastelein JJ ，Kostis JB ，Greten H ，Treating to New Targets (TNT) Steering Committee and Investigators ... -  《AMERICAN JOURNAL OF CARDIOLOGY》

Aggressive lipid-lowering therapy compared with angioplasty in stable coronary artery disease. Atorvastatin versus Revascularization Treatment Investigators.

BACKGROUND:Percutaneous coronary revascularization is widely used in improving symptoms and exercise performance in patients with ischemic heart disease and stable angina pectoris. In this study, we compared percutaneous coronary revascularization with lipid-lowering treatment for reducing the incidence of ischemic events. METHODS:We studied 341 patients with stable coronary artery disease, relatively normal left ventricular function, asymptomatic or mild-to-moderate angina, and a serum level of low-density lipoprotein (LDL) cholesterol of at least 115 mg per deciliter (3.0 mmol per liter) who were referred for percutaneous revascularization. We randomly assigned the patients either to receive medical treatment with atorvastatin, at 80 mg per day (164 patients), or to undergo the recommended percutaneous revascularization procedure (angioplasty) followed by usual care, which could include lipid-lowering treatment (177 patients). The follow-up period was 18 months. RESULTS:Twenty-two (13 percent) of the patients who received aggressive lipid-lowering treatment with atorvastatin (resulting in a 46 percent reduction in the mean serum LDL cholesterol level, to 77 mg per deciliter [2.0 mmol per liter]) had ischemic events, as compared with 37 (21 percent) of the patients who underwent angioplasty (who had an 18 percent reduction in the mean serum LDL cholesterol level, to 119 mg per deciliter [3.0 mmol per liter]). The incidence of ischemic events was thus 36 percent lower in the atorvastatin group over an 18-month period (P=0.048, which was not statistically significant after adjustment for interim analyses). This reduction in events was due to a smaller number of angioplasty procedures, coronary-artery bypass operations, and hospitalizations for worsening angina. As compared with the patients who were treated with angioplasty and usual care, the patients who received atorvastatin had a significantly longer time to the first ischemic event (P=0.03). CONCLUSIONS:In low-risk patients with stable coronary artery disease, aggressive lipid-lowering therapy is at least as effective as angioplasty and usual care in reducing the incidence of ischemic events.

Pitt B ，Waters D ，Brown WV ，van Boven AJ ，Schwartz L ，Title LM ，Eisenberg D ，Shurzinske L ，McCormick LS ... -  《NEW ENGLAND JOURNAL OF MEDICINE》