Clinical Investigation and Reports. Effect of Ezetimibe Coadministered With Atorvastatin in 628 Patients With Primary Hypercholesterolemia
|
|
- Arleen Green
- 5 years ago
- Views:
Transcription
1 Clinical Investigation and Reports Effect of Ezetimibe Coadministered With in 628 Patients With Primary Hypercholesterolemia A Prospective, Randomized, Double-Blind Trial Christie M. Ballantyne, MD; John Houri, MD; Alberto Notarbartolo, MD; Lorenzo Melani, MD; Leslie J. Lipka, MD, PhD; Ramachandran Suresh, PhD; Steven Sun, PhD; Alexandre P. LeBeaut, MD; Philip T. Sager, MD; Enrico P. Veltri, MD; for the Ezetimibe Study Group* Background Despite the established efficacy of statins, many patients do not achieve recommended LDL cholesterol (LDL-C) goals. Contributing factors may be inadequate dosing, increased risk for adverse effects with high-dose monotherapy, and increased potential for intolerance and adverse effects with combinations of available agents. Methods and Results In a double-blind study, 628 patients with baseline LDL-C 145 to 250 mg/dl and triglycerides 350 mg/dl were randomly assigned to receive 1 of the following for 12 weeks: ezetimibe (10 mg/d); atorvastatin (10, 20, 40, or 80 mg/d); ezetimibe (10 mg) plus atorvastatin (10, 20, 40, or 80 mg/d); or placebo. The primary efficacy end point was percentage reduction in LDL-C for pooled ezetimibe plus atorvastatin versus pooled atorvastatin treatment groups. Ezetimibe plus atorvastatin significantly improved LDL-C, HDL cholesterol (HDL-C), triglycerides, total cholesterol:hdl-c, and high-sensitivity C-reactive protein (hs-crp) compared with atorvastatin alone (P 0.01). Coadministration of ezetimibe provided a significant additional 12% LDL-C reduction, 3% HDL-C increase, 8% triglyceride reduction, and 10% hs-crp reduction versus atorvastatin alone. Ezetimibe plus atorvastatin provided LDL-C reductions of 50% to 60%, triglyceride reductions of 30% to 40%, and HDL-C increases of 5% to 9%, depending on atorvastatin dose. LDL-C reductions with ezetimibe plus 10 mg atorvastatin (50%) and 80 mg atorvastatin alone (51%) were similar. Conclusions Ezetimibe plus atorvastatin was well tolerated, with a safety profile similar to atorvastatin alone and to placebo. When coadministered with atorvastatin, ezetimibe provided significant incremental reductions in LDL-C and triglycerides and increases in HDL-C. Coadministration of ezetimibe and atorvastatin offers a well-tolerated and highly efficacious new treatment option for patients with hypercholesterolemia. (Circulation. 2003;107: ) Key Words: lipoproteins cholesterol trials drugs hypercholesterolemia HMG-CoA reductase inhibitors, or statins, are the most potent and frequently used drugs for treating hypercholesterolemia. Despite their established efficacy, however, the number of patients who attain and maintain LDL cholesterol (LDL-C) levels recommended by the US National Cholesterol Education Program Adult Treatment Panel III (ATP III) 1 is suboptimal, indicating a gap between lipid goals and clinical practice. 2 Statin doses often are not titrated to achieve goals. 2 In the Comparative Cholesterol Efficacy and Safety Study (AC- CESS), 3 only 43% of patients with coronary heart disease (CHD) receiving the initial dose of atorvastatin and even fewer patients receiving initial doses of other statins achieved ATP II goals. At maximum titration (up to 80 mg), 72% of patients with CHD receiving atorvastatin in ACCESS achieved the ATP II goal, 3 but atorvastatin at maximum dosage has been associated with increased incidence of elevated liver enzymes. 4 Hepatotoxicity and myalgias have also been reported with high doses of other statins. Concerns about safety may prevent physicians from titrating statin doses high enough to achieve recommended targets. Received December 23, 2002; revision received February 20, 2003; accepted March 5, From Baylor College of Medicine, Houston, Tex (C.M.B.); Radiant Research, Stuart, Fla (J.H.); Istituto di Medicina Interna e Geriatria, Università degli Studi, Palermo, Italy (A.N.); and Schering-Plough Research Institute, Kenilworth, NJ (L.M., L.J.L., R.S., S.S., A.P.L., P.T.S., E.P.V.). *Study organization is listed in the electronic appendix, which is available in the online-only Data Supplement at Guest editor for this article was Antonio M. Gotto, MD, Weill Medical College, NY. Dr Ballantyne has received research grants/contracts from Astra-Zeneca, Merck, Novartis, Pfizer, and Schering-Plough; has served on the Speakers Bureaus of Astra-Zeneca, Bristol Myers-Squibb, Kos, Merck, and Pfizer; has received honoraria from Astra-Zeneca, Bristol Myers-Squibb, Kos, Merck, Pfizer, Reliant, and Schering-Plough; and has served as a consultant for Astra-Zeneca, Merck, Reliant, and Schering-Plough. Drs Houri and Notarbartolo have received research grants from Schering-Plough. Drs Melani, Lipka, Suresh, Sun, and Veltri are employees and Dr LeBeaut was an employee of Schering-Plough, Inc, the sponsor of the study. Dr Sager also holds stock and stock options in Schering-Plough. Correspondence to Christie M. Ballantyne, MD, Baylor College of Medicine, 6565 Fannin Street, MS A-601, Houston, TX cmb@bcm.tmc.edu 2003 American Heart Association, Inc. Circulation is available at DOI: /01.CIR C8 2409
2 2410 Circulation May 20, 2003 Figure 1. Study design. *Q 1 first qualifying calculated LDL-C value; Q 2 second qualifying calculated LDL-C value; blood samples for Q 1 and Q 2 were collected at least 1 week apart. Random assignment to double-blind treatment occurred at visit 4. Tolerance and safety concerns may also limit the use of combination therapy. Although combining lipid-modifying agents that act through complementary pathways may provide more effective LDL-C lowering, combination therapy with available agents (bile acid sequestrants, fibric acid derivatives, statins, and nicotinic acid) may increase risk for intolerance, noncompliance, side effects, or drug interactions. 5 Ezetimibe is a novel cholesterol absorption inhibitor 6 that prevents the absorption of dietary and biliary cholesterol without affecting the absorption of triglycerides or fat-soluble vitamins. Ezetimibe inhibits cholesterol absorption in the intestine, whereas statins inhibit cholesterol production primarily in the liver. In this multicenter study, we tested the primary hypothesis that the coadministration of ezetimibe with atorvastatin would result in a significantly greater reduction in LDL-C than atorvastatin alone. Also evaluated were the change from baseline for other lipid variables and for C-reactive protein and the proportions of patients reaching ATP III LDL-C goals at final assessment. Methods Patients Men and women 18 years of age were screened for primary hypercholesterolemia, defined as calculated LDL-C 7 of 145 to 250 mg/dl, inclusive, and triglyceride levels 350 mg/dl. All patients provided written informed consent. Exclusion criteria included congestive heart failure (defined as New York Heart Association class III or IV heart failure 8 ); uncontrolled cardiac arrhythmias; myocardial infarction, coronary bypass surgery, or angioplasty within 6 months of study entry; history of unstable or severe peripheral artery disease within 3 months of study entry; unstable angina pectoris; uncontrolled or newly diagnosed (within 1 month of study entry) diabetes mellitus; unstable endocrine or metabolic diseases known to influence serum lipids and lipoproteins; known impairment of renal function; active or chronic hepatic or hepatobiliary disease; and known coagulopathy. Design This randomized, double-blind, placebo-controlled, balanced parallel group trial was conducted in conformance with good clinical practices and consisted of 3 phases (Figure 1). The protocol was reviewed and approved by each institution s independent ethics committee or institutional review board. The 2- to 12-week screening phase included washout of previous lipid-modifying drug therapy (12 weeks for fibrates, 1 year for probucol, and 6 weeks for statins, bile acid sequestrants, nicotinic acid, garlic, fish oil, and other lipid-altering agents) and instruction to follow a Step I 9 (or stricter) diet throughout the trial. During the 4-week, single-blind, placebo lead-in phase, blood samples were collected at weeks 4 and 2 to assess for qualifying mean calculated LDL-C, with no single value 145 mg/dl or 250 mg/dl. At week 0, qualifying patients were randomly assigned to 1 of 10 treatments: placebo, ezetimibe (10 mg), atorvastatin (10 mg), ezetimibe (10 mg) plus atorvastatin (10 mg), atorvastatin (20 mg), ezetimibe (10 mg) plus atorvastatin (20 mg), atorvastatin (40 mg), ezetimibe (10 mg) plus atorvastatin (40 mg), atorvastatin (80 mg), or ezetimibe (10 mg) plus atorvastatin (80 mg). Blood samples were collected at baseline and weeks 2, 4, 8, and 12, and lipid measurements were performed in plasma; HDL cholesterol (HDL-C) subfractions, apolipoproteins, and lipoprotein(a) were measured at baseline and week 12. LDL-C was measured directly by ultracentrifugation ( -quantification; direct LDL-C) and also calculated by the Friedewald equation. 7 Total cholesterol and triglyceride levels were quantified enzymatically with the Hitachi 747 analyzer (Roche Diagnostics Corporation). Total HDL-C was determined enzymatically after selective removal of LDL-C and VLDL-C by heparin and manganese chloride precipitation. The HDL 3 -C subfraction was quantified enzymatically after separation by ultracentrifugation, 10 and the HDL 2 -C subfraction was calculated by subtracting HDL 3 -C from total HDL-C. Non HDL-C was calculated by subtracting HDL-C from total cholesterol. Apolipoprotein (apo) A-I and apo B were determined by fixed-rate nephelometry. Lipoprotein(a) was quantified by competitive enzyme-linked immunosorbent assay. Samples collected at baseline and week 12 were quantified for C-reactive protein (CRP) by means of high-sensitivity immunonephelometry 11 (hs-crp; Dade Behring, Inc). All clinical laboratory analyses were conducted at the central laboratory (Medical Research Laboratories). All qualifying lipid determinations, as well as lipid profiles after visit 1, were blinded to the investigators and study sponsor. Safety was evaluated through patient reports, investigator observations, laboratory tests, ECGs, physical examinations, and vital signs. Alanine transaminase (ALT) or aspartate transaminase (AST) levels 3 the upper limit of normal (ULN) on 2 consecutive visits were considered elevated. Patients were also considered to have 2 consecutive elevations if a single elevation 3 ULN occurred during the study and no follow-up measurement was made 2 days after discontinuation of study drug. Myopathy was defined as
3 Ballantyne et al Combination Therapy of Ezetimibe Plus 2411 creatine phosphokinase (CPK) 10 ULN with associated muscle symptoms. Statistical Analysis The primary efficacy end point was the percentage reduction in direct LDL-C from baseline to final assessment (last available postbaseline direct LDL-C value for each patient) for the intent-totreat population. The primary efficacy analysis was performed with the use of a 2-way ANOVA model that extracted effects due to atorvastatin dose (0, 10, 20, 40, or 80 mg), treatment (ezetimibe 10 mg or placebo coadministration), and dose-by-treatment interaction for the percentage change in direct LDL-C from baseline to final assessment. The comparisons (pooled ezetimibe [10 mg] plus atorvastatin [10, 20, 40, 80 mg] group versus pooled atorvastatin [10, 20, 40, 80 mg] group and pooled ezetimibe [10 mg] plus atorvastatin [10, 20, 40, 80 mg] group versus ezetimibe [10 mg] group) were performed by using contrast statements under the model to evaluate the primary hypothesis. Consistency of the effect across subgroups (sex, age [ 65 years, 65 years], and race [white, nonwhite]) and treatment-by-subgroup interactions were evaluated for the primary variable in the intent-to-treat population by using ANOVA models, including factors for treatment, dose, treatment-by-dose interaction, subgroup, and treatment-by-subgroup interaction. With the planned sample size of 650 patients (65 patients per treatment group), a difference between percentage reduction of direct LDL-C of any 2 treatment groups 5 percentage points could be detected with 80% power and a significance level of 0.05 (2-tailed), assuming a standard deviation of 10. Secondary efficacy end points included change from baseline to final assessment for calculated LDL-C, total cholesterol, triglyceride, HDL-C, HDL 2 -C, HDL 3 -C, non HDL-C, lipoprotein(a), apo A-I, apo B, and total cholesterol:hdl-c and direct LDL-C:HDL-C ratios. The proportion of subjects achieving ATP III goals for direct LDL-C at final assessment was summarized. For hs-crp, percent change from baseline to final median values was compared for the pooled and individual treatment groups by using the Wilcoxon Rank Sum procedure. All statistical analyses were conducted with the use of SAS software (version 8). Results Of 1703 individuals screened, 628 met the eligibility criteria and were randomly assigned. The treatment groups were well balanced regarding demographics and baseline characteristics (Table 1). Mean baseline direct LDL-C ranged from 175 to 184 mg/dl across treatment groups. Study treatment was discontinued early in 52 (8%) patients because of adverse events (34 patients), patient request (10 patients), noncompliance with protocol (5 patients), and loss to follow-up (3 patients). There was no trend across treatment groups in the distribution of patients who discontinued or in the reasons for discontinuation. Coadministration of ezetimibe plus atorvastatin (pooled treatment groups) resulted in significantly greater mean reductions of direct LDL-C from baseline to final assessment ( 54.5%) than either atorvastatin alone ( 42.4% for pooled treatment groups; P 0.01 for difference between pools) or ezetimibe alone ( 18.4%; P 0.01 for difference between pools) (Table 2). Across individual treatment groups, mean changes in direct LDL-C from baseline to final assessment ranged from 50% to 60% for coadministration versus 35% to 51% for atorvastatin monotherapy (Figure 2A). The incremental mean percentage change with coadministration was statistically significant (P 0.01) compared with each corresponding dose of atorvastatin monotherapy, with effects observed as early as week 2 and maintained throughout the treatment period. Subgroup analysis indicated that the incremental LDL-C reductions with coadministration (all doses) was generally consistent across all subgroups, regardless of sex, age, race, or baseline lipids. Coadministration of ezetimibe with atorvastatin also significantly reduced the more commonly used calculated LDL-C across all atorvastatin doses (P 0.01; Figure 2B). Although increased doses of atorvastatin were associated with greater reductions in total cholesterol, LDL-C, and triglycerides (Figure 2D), a favorable dose response was not observed for changes in HDL-C (6% increase for 10 mg, 3% increase for 80 mg; Figure 2C), as has been observed in other studies with atorvastatin. 4,12 Combination therapy improved the total cholesterol:hdl-c ratio at all atorvastatin doses (P 0.01; Figure 2E). Coadministration of ezetimibe with the starting dose of atorvastatin (10 mg) provided similar reductions to those achieved with the maximal dose of atorvastatin (80 mg) alone for LDL-C (50% and 51%), total cholesterol:hdl-c ratio (43% and 41%), and triglycerides (both 31%) but significantly greater increase in HDL-C (9% versus 3%). Coadministration (pooled groups) also provided greater median reduction in hs-crp than atorvastatin alone ( 41% versus 31%, P 0.01); median reductions across combination therapy groups ranged from 25% to 62% and were generally larger than those observed with statin monotherapy (Figure 3). LDL-C was above ATP III target at baseline and below target at final assessment in 85% (215/252) of patients receiving coadministration therapy compared with 73% (180/ 245) of patients receiving atorvastatin monotherapy. The difference between the 2 pooled treatment groups in the proportion of patients achieving ATP III LDL-C targets was statistically significant (P 0.01). Coadministration of ezetimibe and atorvastatin was well tolerated. Treatment-related adverse events were reported for 17% (42/248) of patients receiving atorvastatin monotherapy and 23% (58/255) of patients receiving combination therapy (Table 3). Most ( 90%) adverse events were mild or moderate, and 66% were considered unlikely to be related to study treatment. In general, the types of adverse events resulting in treatment discontinuation (34/628, 5% of patients) or interruption (31/628, 5% of patients) were no more common or severe in any treatment group. No patient died during the study. All elevations in hepatic enzymes after random assignment were asymptomatic, and no cases of hepatitis, jaundice, or other clinical signs of liver dysfunction were reported. Consecutive and presumed consecutive elevations in ALT or AST level 3 ULN occurred in only 5 patients and did not differ significantly between atorvastatin monotherapy ( 1%) and combination therapy (2%) (see Table 3). Of these patients, 1 receiving atorvastatin (80 mg) monotherapy and 2 receiving ezetimibe plus atorvastatin (40 mg) were discontinued from the study; the other 2, receiving ezetimibe plus atorvastatin (10 mg) and ezetimibe plus atorvastatin (20 mg), completed the study. One patient had CPK elevations 10 ULN with associated muscle symptoms. This patient, who received ezetimibe plus atorvastatin (40 mg), reported moderate diffuse myalgias
4 2412 Circulation May 20, 2003 TABLE 1. Baseline Characteristics Placebo Characteristic (n 60) Demographic Age, mean SD, y Male/female 29 (48)/31 (52) 29 (45)/36 (55) 95 (38)/153 (62) 107 (42)/148 (58) White 49 (82) 57 (88) 205 (83) 222 (87) Clinical Previous coronary intervention Coronary angioplasty 3 (5) 1 (2) 7 (3) 8 (3) CABG 2 (3) 0 6 (2) 6 (2) Family history of CHD 21 (35) 31 (48) 104 (42) 101 (40) Current smoker 9 (15) 11 (17) 33 (13) 35 (14) Physically active 33 (55) 32 (49) 118 (48) 128 (50) History of hypertension 23 (38) 24 (37) 80 (32) 85 (33) History of diabetes mellitus 1 (2) 2 (3) 11 (4) 17 (7) History of CHD 5 (8) 6 (9) 23 (9) 23 (9) No CHD 55 (92) 59 (91) 225 (91) 232 (91) 1 risk factor* 0 1 (2) 9 (4) 4 (2) 0 risk factors 16 (27) 12 (18) 55 (22) 37 (5) 1 risk factor 18 (30) 26 (40) 99 (40) 103 (40) 2 risk factors 14 (23) 15 (23) 44 (18) 62 (24) 2 risk factors 7 (12) 5 (8) 18 (7) 26 (10) Laboratory Direct LDL-C, mean SEM, mmol/l Calculated LDL-C, mean SEM, mmol/l Total cholesterol, mean SEM, mmol/l Triglycerides, median, mmol/l HDL-C, mean SEM, mmol/l hs-crp, median, mg/l Washout information Statin 24 (40) 19 (29) 79 (32) 83 (33) Fibrate 0 1 (2) 6 (2) 4 (2) Bile acid sequestrant (1) 3 (1) Nicotinic acid 0 1 (2) 6 (2) 6 (2) Other 3 (5) 2 (3) 14 (6) 17 (7) and moderate weakness, coincident with CPK of 403 U/L. Follow-up at a local laboratory indicated values as high as 5379 U/L with ongoing symptoms. After treatment was discontinued, symptoms resolved and CPK level returned to normal (96 U/L). Other measurements of safety (other laboratory tests, vital signs, ECGs, and cardiopulmonary examinations) did not suggest any clinically meaningful differences between the safety profiles of combination therapy and atorvastatin monotherapy in the study overall or in subgroups defined by sex, age, or race. There was no evidence that ezetimibe worsened statin intolerance or statin-related toxicity. Ezetimibe (10 mg) (n 65) All (n 248) All Ezetimibe (n 255) Data are presented as n (% of pooled treatment group) except as indicated. All atorvastatin pool of all doses of atorvastatin; all ezetimibe atorvastatin pool of all combinations of ezetimibe and atorvastatin. *In the Adult Treatment Panel III guidelines, HDL-C 1.55 mmol/l is defined as a negative risk factor, decreasing the total No. of risk factors by 1. Discussion Coadministration of ezetimibe plus atorvastatin was significantly (P 0.01) more effective at reducing LDL-C concentrations than atorvastatin or ezetimibe alone for both the pooled treatment groups and each atorvastatin dose. Reductions in apo B, total cholesterol, and triglycerides, as well as increases in HDL-C, were all significantly greater with combination therapy than atorvastatin alone (P 0.01) or ezetimibe alone (P 0.05). Total cholesterol:hdl-c and LDL-C:HDL-C ratios and non HDL-C concentration also showed significant improvement with coadministration compared with atorvastatin or ezetimibe alone (P 0.01).
5 Ballantyne et al Combination Therapy of Ezetimibe Plus 2413 TABLE 2. Least-Squares Mean Percentage Changes From Baseline to Final Assessment in Lipid-Related Variables Mean Percent Change SEM Difference Variable, mmol/l Placebo (n 60) Ezetimibe (10 mg) (n 65) All (pooled) (n 248) All Ezetimibe (pooled) (n 255) P* P Direct LDL-C Calculated LDL-C Total cholesterol Triglycerides HDL-C Apo B, g/l Non HDL-C HDL 2 -C HDL 3 -C Apo A-I, g/l Lipoprotein(a), mg/l Direct LDL-C:HDL-C TC:HDL-C Not every patient had a postbaseline measurement for every variable; n ranged from 56 to 60 for the placebo group, 61 to 65 for the ezetimibe group, 244 to 248 for the pooled atorvastatin groups, and 249 to 253 for the pooled combination therapy groups. *All ezetimibe atorvastatin (pooled) vs atorvastatin (pooled). All ezetimibe atorvastatin (pooled) vs ezetimibe. Median percent change. Ezetimibe plus the starting dose of atorvastatin (10 mg) lowered direct LDL-C as effectively as the maximum dose of atorvastatin (80 mg) alone (50% and 51%, respectively), reduced median triglycerides by a similar amount (both 31%), but provided significantly greater increases in HDL-C (9% versus 3%). The difference in incremental LDL-C reduction observed in this trial versus the 21% incremental reduction reported with the addition of ezetimibe in subjects already receiving statin therapy 13 can be attributed to how incremental change is calculated: change in LDL-C/baseline LDL-C level on no therapy versus change in LDL-C/LDL-C level on statin therapy. In the present study, the incremental LDL-C reduction achieved by coadministration of ezetimibe plus statin compared with the LDL-C level achieved by statin monotherapy was on average 22% (20%, 28%, 21%, and 17% for ezetimibe plus atorvastatin [10, 20, 40, and 80 mg], respectively), which is the same benefit reported when ezetimibe was added to statin therapy in the other study (21%). 13 The apparent attenuation in incremental LDL-C lowering observed at the highest dose (80 mg) in the present study may be related to the method of calculation. Although high-dose statin can reduce cholesterol excretion into bile, 14 which may theoretically lessen the effect of ezetimibe, this has not been observed with simvastatin (80 mg), 15 and further reductions in LDL-C were observed with ezetimibe plus atorvastatin (80 mg) in the present study. The combination of ezetimibe plus atorvastatin was well tolerated, with an overall safety profile similar to that of atorvastatin alone. All elevations in hepatic enzymes were asymptomatic, and no hepatitis, jaundice, or other clinical signs of liver dysfunction were reported. These findings are consistent with the asymptomatic increases in transaminases that have been observed with all lipid-lowering drugs, including bile acid binding resins and niacin, which act by different mechanisms, 16 and may represent a pharmacodynamic effect due to cholesterol reduction or changes in hepatic metabolism. No cases of rhabdomyolysis were reported in this study, and the low occurrence of reversible increases in CPK level suggests no increased risk of myopathy with the coadministration of ezetimibe and atorvastatin compared with atorvastatin alone. Increases in CPK level have been observed with lipid-lowering therapies, particularly high doses of statins or upward dosage titration. 17 Coadministration of ezetimibe with low-dose atorvastatin was a well-tolerated option to high-dose atorvastatin monotherapy. Study limitations include short duration (12 weeks), which precludes analysis of long-term efficacy and safety, and exclusion criteria that prevent extrapolation of the results to other populations. Because of the low incidence of transaminase elevations in all groups, the sample size was too small to examine whether ezetimibe plus low-dose atorvastatin differs from high-dose atorvastatin monotherapy in liver function test abnormalities. Coadministration of ezetimibe with the starting dose (10 mg) of atorvastatin provided a 50% reduction in LDL-C, comparable to the 51% reduction obtained with high-dose (80 mg) atorvastatin. Because each doubling of a statin dose provides only 5% to 6% additional LDL-C reduction, 16 the need for multiple dosage adjustments may limit the routine use of optimum statin doses in clinical practice. Statin doses are often not titrated to achieve recommended LDL-C goals, 2 and at starting doses of statin therapy, most patients do not receive sufficient LDL-C reductions to reach target. In
6 2414 Circulation May 20, 2003 Figure 3. Change in hs-crp from baseline to final assessment. *P 0.01, P 0.07 for combination therapy vs corresponding dose of atorvastatin alone. Figure 2. Change in direct LDL-C (A), calculated LDL-C (B), HDL-C (C), and triglyceride (D) concentrations and total cholesterol:hdl-c ratio (E) from baseline to final assessment. Atorva indicates atorvastatin; EZE, ezetimibe. P 0.01 for combination therapy vs *corresponding dose of atorvastatin alone, atorvastatin (20 mg or 40 mg) alone, and atorvastatin (40 mg) alone; P 0.05 for combination therapy vs corresponding dose of atorvastatin alone. ACCESS overall, at initial doses, LDL-C goals were met in 53% of patients receiving atorvastatin, 38% of patients receiving simvastatin, 28% of patients receiving lovastatin, and 15% of patients receiving pravastatin or fluvastatin. 3 Even fewer patients in the highest-risk category of CHD can achieve the ATP goal of LDL-C 100 mg/dl: 6% to 43% of patients with CHD in ACCESS, 3 and 1% to 32% of patients with documented atherosclerosis receiving starting doses of atorvastatin, fluvastatin, lovastatin, or simvastatin. 18 In ATP III, this highest-risk category has been expanded to include individuals with noncoronary atherosclerosis, diabetes mellitus, and multiple risk factors conferring 10-year CHD risk 20%, doubling the number of individuals with this difficultto-attain LDL-C goal. The importance of aggressive LDL-C lowering in high-risk patients has been supported by the results of the Heart Protection Study, 19 which showed that high-risk individuals with LDL-C lower than the drug initiation threshold also benefited from statin therapy, suggesting that the optimal LDL-C for high-risk patients may be below the goals recommended by the guidelines. The significant reductions in hs-crp observed when ezetimibe was added to atorvastatin suggest an added antiinflammatory effect of the combination, possibly resulting from the overall complex effect of ezetimibe on the lipid profile. Similar reductions in hs-crp were observed when ezetimibe was added to a variety of statins. 13 In clinical practice, ezetimibe coadministered with a statin may enable more patients to achieve recommended target LDL-C levels by offering greater LDL-C lowering with fewer dose titrations as well as a well-tolerated alternative for patients in whom maximal dose statin monotherapy is inadequate. Ezetimibe has also been shown to be efficacious when coadministered with simvastatin. In a similarly designed study, 15 the combination of ezetimibe (10 mg/d) and simvastatin (pooled doses of 10, 20, 40, and 80 mg/d) provided significantly greater reductions in LDL-C (13.8%) and triglyceride (7.5%) and increases in HDL-C (2.4%) than simvastatin alone (P 0.01). Combining the different mechanisms of action of these agents (inhibition of cholesterol synthesis by the statin and inhibition of cholesterol absorption across the intestinal wall by ezetimibe) appears to provide substantial incremental reductions in LDL-C, with additional favorable changes in total cholesterol, triglycerides, apo B, and HDL-C.
7 Ballantyne et al Combination Therapy of Ezetimibe Plus 2415 TABLE 3. Safety Placebo (n 60) Ezetimibe (10 mg) (n 65) All (n 248) All Ezetimibe (n 255) All adverse events 34 (57) 41 (63) 146 (59) 148 (58) Treatment-related adverse events 12 (20) 12 (18) 42 (17) 58 (23) Gastrointestinal adverse events 6 (10) 4 (6) 13 (5) 20 (8) Musculoskeletal disorders 3 (5) 3 (5) 14 (6) 20 (8) Discontinuations due to adverse events 3 (5) 3 (5) 13 (5) 15 (6) Liver function tests 3 ULN, 2 consecutive times Alanine aminotransferase ( 1) 4 (2) Aspartate aminotransferase ( 1) 2 ( 1) Creatine phosphokinase 10 ULN ( 1) Acknowledgments This study was funded by Schering-Plough Research Institute, Kenilworth, NJ, and Merck/Schering-Plough Pharmaceuticals, North Wales, Pa. We thank Arlene Reiss and Kerrie Jara for their assistance in the preparation of this manuscript. This study was conducted by Schering-Plough Research Institute, Kenilworth, NJ, on behalf of Merck/Schering-Plough Pharmaceuticals, North Wales, Pa. References 1. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285: Pearson TA, Laurora I, Chu H, et al. The Lipid Treatment Assessment Project (L-TAP): a multicenter survey to evaluate the percentages of dyslipidemic patients receiving lipid-lowering therapy and achieving lowdensity lipoprotein cholesterol goals. Arch Intern Med. 2000;160: Andrews TC, Ballantyne CM, Hsia JA, et al. Achieving and maintaining National Cholesterol Education Program low-density lipoprotein cholesterol goals with five statins. Am J Med. 2001;111: Illingworth DR, Crouse JR III, Hunninghake DB, et al. A comparison of simvastatin and atorvastatin up to maximal recommended doses in a large multicenter randomized clinical trial. Curr Med Res Opin. 2001;17: Farmer JA, Gotto AM Jr. Antihyperlipidaemic agents: drug interactions of clinical significance. Drug Saf. 1994;11: van Heek M, France CF, Compton DS, et al. In vivo metabolism-based discovery of a potent cholesterol absorption inhibitor, SCH58235, in the rat and rhesus monkey through the identification of the active metabolites of SCH J Pharmacol Exp Ther. 1997;283: Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18: New York Heart Association. Diseases of the Heart and Blood Vessels: Nomenclature and Criteria for Diagnosis. 6th ed. Boston, Mass: Little, Brown; 1964: Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). JAMA. 1993;269: Rifai N, Warnick GR, Dominiczak MH, eds. Handbook of Lipoprotein Testing. 2nd ed. Washington, DC: AACC Press; 2000: Rifai N, Tracy RP, Ridker PM. Clinical efficacy of an automated highsensitivity C-reactive protein assay. Clin Chem. 1999;45: Crouse JR III, Frohlich J, Ose L, et al. Effects of high doses of simvastatin and atorvastatin on high-density lipoprotein cholesterol and apolipoprotein A-I. Am J Cardiol. 1999;83: Gagné C, Bays HE, Weiss SR, et al. Efficacy and safety of ezetimibe added to ongoing statin therapy for treatment of patients with primary hypercholesterolemia. Am J Cardiol. 2002;90: Mitchell JC, Logan GM, Stone BG, et al. Effects of lovastatin on biliary lipid secretion and bile acid metabolism in humans. J Lipid Res. 1991; 32: Davidson M, McGarry T, Bettis R, et al, for the Ezetimibe Study Group. Ezetimibe co-administered with simvastatin in patients with primary hypercholesterolemia. J Am Coll Cardiol. 2002;40: Knopp RH. Drug treatment of lipid disorders. N Engl J Med. 1999;341: Ucar M, Mjörndal T, Dahlqvist R. HMG-CoA reductase inhibitors and myotoxicity. Drug Saf 2000;22: Brown AS, Bakker-Arkema RG, Yellen L, et al. Treating patients with documented atherosclerosis to National Cholesterol Education Programrecommended low-density-lipoprotein cholesterol goals with atorvastatin, fluvastatin, lovastatin and simvastatin. J Am Coll Cardiol. 1998;32: Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7 22.
Prevention and Rehabilitation
Prevention and Rehabilitation Dose-comparison study of the combination of ezetimibe and simvastatin (Vytorin) versus atorvastatin in patients with hypercholesterolemia: The Vytorin Versus statin (VYVA)
More informationCoronary heart disease is the leading cause of death in
PHARMACOLOGY NOTES Ezetimibe (Zetia): a new type of lipid-lowering agent JIGNA PATEL, PHARMD CANDIDATE, VALERIE SHEEHAN, PHARMD, AND CHERYLE GURK-TURNER, RPH Coronary heart disease is the leading cause
More informationSTATIN UTILIZATION MANAGEMENT CRITERIA
STATIN UTILIZATION MANAGEMENT CRITERIA DRUG CLASS: HMG Co-A Reductase Inhibitors & Combinations Agents which require prior review: Advicor (niacin extended-release/lovastatin) Crestor (rosuvastatin)(5mg,10mg,
More informationATP IV: Predicting Guideline Updates
Disclosures ATP IV: Predicting Guideline Updates Daniel M. Riche, Pharm.D., BCPS, CDE Speaker s Bureau Merck Janssen Boehringer-Ingelheim Learning Objectives Describe at least two evidence-based recommendations
More informationSafety profile of atorvastatin-treated patients with low LDL-cholesterol levels
Atherosclerosis 149 (2000) 123 129 www.elsevier.com/locate/atherosclerosis Safety profile of atorvastatin-treated patients with low LDL-cholesterol levels Rebecca G. Bakker-Arkema *, James W. Nawrocki,
More information2013 ACC AHA LIPID GUIDELINE JAY S. FONTE, MD
2013 ACC AHA LIPID GUIDELINE JAY S. FONTE, MD How do you interpret my blood test results? What are our targets for these tests? Before the ACC/AHA Lipid Guidelines A1c:
More informationAndrew Cohen, MD and Neil S. Skolnik, MD INTRODUCTION
2 Hyperlipidemia Andrew Cohen, MD and Neil S. Skolnik, MD CONTENTS INTRODUCTION RISK CATEGORIES AND TARGET LDL-CHOLESTEROL TREATMENT OF LDL-CHOLESTEROL SPECIAL CONSIDERATIONS OLDER AND YOUNGER ADULTS ADDITIONAL
More informationThe clinical trial information provided in this public disclosure synopsis is supplied for informational purposes only.
The clinical trial information provided in this public disclosure synopsis is supplied for informational purposes only. Please note that the results reported in any single trial may not reflect the overall
More informationDrug Class Review HMG-CoA Reductase Inhibitors (Statins) and Fixed-dose Combination Products Containing a Statin
Drug Class Review HMG-CoA Reductase Inhibitors (Statins) and Fixed-dose Combination Products Containing a Statin Final Report Update 5 November 2009 This report reviews information about the comparative
More informationChanging lipid-lowering guidelines: whom to treat and how low to go
European Heart Journal Supplements (2005) 7 (Supplement A), A12 A19 doi:10.1093/eurheartj/sui003 Changing lipid-lowering guidelines: whom to treat and how low to go C.M. Ballantyne Section of Atherosclerosis,
More informationSimvastatin With or Without Ezetimibe in Familial Hypercholesterolemia
Simvastatin With or Without Ezetimibe in Familial Hypercholesterolemia The trial ClinicalTrials.gov number: NCT00552097 John J.P. Kastelein, MD, PhD* Department of Vascular Medicine Academic Medical Center
More informationReducing low-density lipoprotein cholesterol treating to target and meeting new European goals
European Heart Journal Supplements (2004) 6 (Supplement A), A12 A18 Reducing low-density lipoprotein cholesterol treating to target and meeting new European goals University of Sydney, Sydney, NSW, Australia
More informationIntroduction. KEYWORDS Ezetimibe; Pravastatin; Hypercholesterolemia; Cholesterol absorption inhibitor; Coadministration; LDL-cholesterol
European Heart Journal (2003) 24, 717 728 Efficacy and safety of ezetimibe coadministered with pravastatin in patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial Lorenzo
More information2.0 Synopsis. Choline fenofibrate capsules (ABT-335) M Clinical Study Report R&D/06/772. (For National Authority Use Only) Name of Study Drug:
2.0 Synopsis Abbott Laboratories Individual Study Table Referring to Part of Dossier: (For National Authority Use Only) Name of Study Drug: Volume: Choline Fenofibrate (335) Name of Active Ingredient:
More informationCoronary heart disease (CHD) has. Clearfield The National Cholesterol Education Program Adult Treatment Panel III guidelines
the osteopathic physician. The treatment approach involves therapeutic lifestyle changes with diet, exercise, and weight loss. It requires regular, careful monitoring of serum cholesterol levels. The new
More informationEzetimibe: The First Cholesterol Absorption Inhibitor
PHARMACEUTICAL SPOTLIGHT Ezetimibe: The First Cholesterol Absorption Inhibitor Beata M. Domagala, PharmD, Michelle Leady, PharmD, and Daniel S. Streetman, PharmD OVERVIEW Ezetimibe (Zetia TM, Merck/Schering-Plough)
More informationAntihyperlipidemic Drugs
Antihyperlipidemic Drugs Hyperlipidemias. Hyperlipoproteinemias. Hyperlipemia. Hypercholestrolemia. Direct relationship with acute pancreatitis and atherosclerosis Structure Lipoprotein Particles Types
More informationEvan A. Stein 1, David Sullivan 2, Anders G. Olsson 3, Rob Scott 4, Jae B. Kim 4, Allen Xue 4, Thomas Liu 4, Scott M. Wasserman 4
Goal Achievement after Utilizing an Anti-PCSK9 Antibody in Statin-Intolerant Subjects (GAUSS): Results from a Randomized, Double-blind, Placebo and Ezetimibe Controlled Study Evan A. Stein 1, David Sullivan
More informationRosuvastatin: An Effective Lipid Lowering Drug against Hypercholesterolemia
ISPUB.COM The Internet Journal of Cardiovascular Research Volume 3 Number 1 Rosuvastatin: An Effective Lipid Lowering Drug against Hypercholesterolemia V Save, N Patil, G Rajadhyaksha Citation V Save,
More informationComparison of Original and Generic Atorvastatin for the Treatment of Moderate Dyslipidemic Patients
Comparison of Original and Generic Atorvastatin for the Treatment of Moderate Dyslipidemic Patients Cardiology Department, Bangkok Metropolitan Medical College and Vajira Hospital, Bangkok, Thailand Abstract
More informationANTIHYPERLIPIDEMIA. Darmawan,dr.,M.Kes,Sp.PD
ANTIHYPERLIPIDEMIA Darmawan,dr.,M.Kes,Sp.PD Plasma lipids consist mostly of lipoproteins Spherical complexes of lipids and specific proteins (apolipoproteins). The clinically important lipoproteins, listed
More informationEzetimibe: a selective inhibitor of cholesterol absorption
European Heart Journal Supplements (2001) 3 (Supplement E), E6 E10 Ezetimibe: a selective inhibitor of cholesterol absorption Dipartimento di Scienze Farmacologiche, Universita degli Studi di Milano, Milano,
More informationEzetimibe: a selective inhibitor of cholesterol absorption
European Heart Journal Supplements (2001) 3 (Supplement E), E6 E10 Ezetimibe: a selective inhibitor of cholesterol absorption Dipartimento di Scienze Farmacologiche, Universita degli Studi di Milano, Milano,
More informationGoal Achievement after Utilizing an Anti-PCSK9 Antibody in Statin-Intolerant Subjects (GAUSS): Results from a
Goal Achievement after Utilizing an Anti-PCSK9 Antibody in Statin-Intolerant Subjects (GAUSS): Results from a Randomized, d Double-blind, bli Placebo- Controlled Study Evan A. Stein 1, David Sullivan 2,
More informationDyslipedemia New Guidelines
Dyslipedemia New Guidelines New ACC/AHA Prevention Guidelines on Blood Cholesterol November 12, 2013 Mohammed M Abd El Ghany Professor of Cardiology Cairo Universlty 1 1 0 Cholesterol Management Pharmacotherapy
More informationSupplement Table 2. Categorization of Statin Intensity Based on Potential Low-Density Lipoprotein Cholesterol Reduction
Supplement: Tables Supplement Table 1. Study Eligibility Criteria Supplement Table 2. Categorization of Statin Intensity Based on Potential Low-Density Lipoprotein Cholesterol Reduction Supplement Table
More informationSafety of Anacetrapib in Patients with or
Safety of Anacetrapib in Patients with or at Risk for Coronary Heart Disease Christopher P. Cannon, MD, Sukrut Shah, PhD, RPh, Hayes M. Dansky, MD, Michael Davidson, MD, Eliot A. Brinton, MD, Antonio M.
More informationInfluence of Previous Statin Therapy on Cholesterol-Lowering Effect of Ezetimibe
Original Article Print ISSN 1738-5520 On-line ISSN 1738-5555 Korean Circulation Journal Influence of Previous Statin Therapy on Cholesterol-Lowering Effect of Ezetimibe Young Hwan Choi, MD, Young Kim,
More informationEzetimibe and SimvastatiN in Hypercholesterolemia EnhANces AtherosClerosis REgression (ENHANCE)
Ezetimibe and SimvastatiN in Hypercholesterolemia EnhANces AtherosClerosis REgression (ENHANCE) Thomas Dayspring, MD, FACP Clinical Assistant Professor of Medicine University of Medicine and Dentistry
More informationReview of guidelines for management of dyslipidemia in diabetic patients
2012 international Conference on Diabetes and metabolism (ICDM) Review of guidelines for management of dyslipidemia in diabetic patients Nan Hee Kim, MD, PhD Department of Internal Medicine, Korea University
More informationMipomersen (ISIS ) Page 2 of 1979 Clinical Study Report ISIS CS3
(ISIS 301012) Page 2 of 1979 2 SYNOPSIS ISIS 301012-CS3 synopsis Page 1 Title of Study: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability, Pharmacokinetics,
More informationManagement of Post-transplant hyperlipidemia
Management of Post-transplant hyperlipidemia B. Gisella Carranza Leon, MD Assistant Professor of Medicine Lipid Clinic - Vanderbilt Heart and Vascular Institute Division of Diabetes, Endocrinology and
More information(For National Authority Use Only) Name of Study Drug: to Part of Dossier:
2.0 Synopsis Abbott Laboratories Individual Study Table Referring to Part of Dossier: (For National Authority Use Only) Name of Study Drug: Volume: ABT-335 Name of Active Ingredient: Page: ABT-335, A-7770335.115
More informationAnne Carol Goldberg, MD, FACP, FAHA, FNLA Washington University, St. Louis, MO USA
Efficacy and Safety of Bempedoic Acid Added to Maximally Tolerated Statins in Patients with Hypercholesterolemia and High Cardiovascular Risk: The CLEAR Wisdom Trial Anne Carol Goldberg, MD, FACP, FAHA,
More informationThe new guidelines issued in PRESENTATIONS... Future Outlook: Changing Perspectives on Best Practice
... PRESENTATIONS... Future Outlook: Changing Perspectives on Best Practice Based on a presentation by Daniel J. Rader, MD Presentation Summary The guidelines recently released by the National Cholesterol
More informationVascular Medicine. Lapaquistat Acetate Development of a Squalene Synthase Inhibitor for the Treatment of Hypercholesterolemia
Vascular Medicine Acetate Development of a Squalene Synthase Inhibitor for the Treatment of Hypercholesterolemia Evan A. Stein, MD, PhD; Harold Bays, MD; Dennis O Brien, MD, MBA; Jim Pedicano, MS, MBA;
More information( Diabetes mellitus, DM ) ( Hyperlipidemia ) ( Cardiovascular disease, CVD )
005 6 69-74 40 mg/dl > 50 mg/dl) (00 mg/dl < 00 mg/dl(.6 mmol/l) 30-40% < 70 mg/dl 40 mg/dl 00 9 mg/dl fibric acid derivative niacin statin fibrate statin niacin ( ) ( Diabetes mellitus,
More informationEffects of Ezetimibe Added to Ongoing Statin Therapy on C-Reactive Protein Levels in Hypercholesterolemic Patients
ORIGINAL ARTICLE DOI 10.4070/kcj.2011.41.5.253 Print ISSN 1738-5520 / On-line ISSN 1738-5555 Copyright 2011 The Korean Society of Cardiology Open Access Effects of Ezetimibe Added to Ongoing Statin Therapy
More informationWhat do the guidelines say about combination therapy?
What do the guidelines say about combination therapy? Christie M. Ballantyne, MD Center for Cardiovascular Disease Prevention Methodist DeBakey Heart & Vascular Center Baylor College of Medicine Houston,
More informationNovel HDL Targeted Therapies: The Search Continues Assoc. Prof. K.Kostner,, Univ. of Qld, Brisbane
Novel HDL Targeted Therapies: The Search Continues Assoc. Prof. K.Kostner,, Univ. of Qld, Brisbane Kostner, 2007 2008 LDL Target depends on your level of Risk Acute Plaque Rupture ACS (UA/NSTEMI/STEMI)
More information2013 Cholesterol Guidelines. Anna Broz MSN, RN, CNP, AACC Adult Certified Nurse Practitioner North Ohio Heart, Inc.
2013 Cholesterol Guidelines Anna Broz MSN, RN, CNP, AACC Adult Certified Nurse Practitioner North Ohio Heart, Inc. Disclosures Speaker Gilead Sciences NHLBI Charge to the Expert Panel Evaluate higher quality
More informationHow would you manage Ms. Gold
How would you manage Ms. Gold 32 yo Asian woman with dyslipidemia Current medications: Simvastatin 20mg QD Most recent lipid profile: TC = 246, TG = 100, LDL = 176, HDL = 50 What about Mr. Williams? 56
More informationThe JUPITER trial: What does it tell us? Alice Y.Y. Cheng, MD, FRCPC January 24, 2009
The JUPITER trial: What does it tell us? Alice Y.Y. Cheng, MD, FRCPC January 24, 2009 Learning Objectives 1. Understand the role of statin therapy in the primary and secondary prevention of stroke 2. Explain
More informationUpdate on Dyslipidemia and Recent Data on Treating the Statin Intolerant Patient
Update on Dyslipidemia and Recent Data on Treating the Statin Intolerant Patient Steven E. Nissen MD Chairman, Department of Cardiovascular Medicine Cleveland Clinic Disclosure Consulting: Many pharmaceutical
More informationLearning Objectives. Patient Case
Joseph Saseen, Pharm.D., FASHP, FCCP, BCPS Professor and Vice Chair, Department of Clinical Pharmacy University of Colorado Anschutz Medical Campus Learning Objectives Identify the 4 patient populations
More informationPIEDMONT ACCESS TO HEALTH SERVICES, INC. Guidelines for Screening and Management of Dyslipidemia
PIEDMONT ACCESS TO HEALTH SERVICES, INC. Policy Number: 01-09-021 SUBJECT: Guidelines for Screening and Management of Dyslipidemia EFFECTIVE DATE: 04/2008 REVIEWED/REVISED: 04/12/10, 03/17/2011, 4/10/2012,
More informationOriginal paper. Abstract. Abdullah S. Asia 1*, Al-Mahdi A. Modar 2, Hadi M. Ali 3
Original paper Frequency Of Potential Adverse Effects Of A Semisynthetic Statin (Simvastatin) Compared To A Synthetic Statin (Atorvastatin) Used To Reduce Cardiovascular Risk For Patients In Basra 1*,
More informationLipid Panel Management Refresher Course for the Family Physician
Lipid Panel Management Refresher Course for the Family Physician Objectives Understand the evidence that was evaluated to develop the 2013 ACC/AHA guidelines Discuss the utility and accuracy of the new
More informationMaking War on Cholesterol with New Weapons: How Low Can We/Should We Go? Shaun Goodman
Making War on Cholesterol with New Weapons: How Low Can We/Should We Go? Shaun Goodman Disclosures Research grant support, speaker/consulting honoraria: Sanofi and Regeneron Including ODYSSEY Outcomes
More informationAlirocumab Treatment Effect Did Not Differ Between Patients With and Without Low HDL-C or High Triglyceride Levels in Phase 3 trials
Alirocumab Treatment Effect Did Not Differ Between Patients With and Without Low HDL-C or High Triglyceride Levels in Phase 3 trials G. Kees Hovingh, 1 Richard Ceska, 2 Michael Louie, 3 Pascal Minini,
More informationDrug Class Monograph
Drug Class Monograph Class: Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitor Drugs: Praluent (alirocumab), Repatha (evolocumab) Line of Business: Medi-Cal Effective Date: February 17, 2016
More informationDrug Class Review on HMG-CoA Reductase Inhibitors (Statins)
Drug Class Review on HMG-CoA Reductase Inhibitors () Final Report June 2004 Mark Helfand, MD, MPH Susan Carson, MPH Cathy Kelley, PharmD Oregon Evidence-based Practice Center Oregon Health & Science University
More informationThe TNT Trial Is It Time to Shift Our Goals in Clinical
The TNT Trial Is It Time to Shift Our Goals in Clinical Angioplasty Summit Luncheon Symposium Korea Assoc Prof David Colquhoun 29 April 2005 University of Queensland, Wesley Hospital, Brisbane, Australia
More informationCholesterol Management Roy Gandolfi, MD
Cholesterol Management 2017 Roy Gandolfi, MD Goals Interpreting cholesterol guidelines Cholesterol treatment in diabetics Statin use and side effects therapy Reporting- Comparison data among physicians
More informationMedical evidence suggests that
COMBINATION THERAPY TO ACHIEVE LIPID GOALS David G. Robertson, MD* ABSTRACT Coronary heart disease (CHD) remains the leading cause of death in the United States despite recent advances in treatment and
More informationPHARMACOKINETICS ABSORPTION
Ezetrol adalah obat baru yang terdaftar tahun 2003. Informasi di bawah ini merupakan informasi update tahun 2007. EZETROL Tablet Ezetimibe COMPOSITION Each tablet of EZETROL for oral administration contains
More informationAchieving Lipid Goals: 2008 Update. Laura Hansen, Pharm.D. Associate Professor, University of Colorado School of Pharmacy
Achieving Lipid Goals: 2008 Update Laura Hansen, Pharm.D. Associate Professor, University of Colorado School of Pharmacy Discuss relationship between lipid values and coronary events Evaluate clinical
More informationMOLINA HEALTHCARE OF CALIFORNIA
MOLINA HEALTHCARE OF CALIFORNIA HIGH BLOOD CHOLESTEROL IN ADULTS GUIDELINE Molina Healthcare of California has adopted the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel
More informationDyslipidemia in the light of Current Guidelines - Do we change our Practice?
Dyslipidemia in the light of Current Guidelines - Do we change our Practice? Dato Dr. David Chew Soon Ping Senior Consultant Cardiologist Institut Jantung Negara Atherosclerotic Cardiovascular Disease
More informationIntroduction. Objective. Critical Questions Addressed
Introduction Objective To provide a strong evidence-based foundation for the treatment of cholesterol for the primary and secondary prevention of ASCVD in women and men Critical Questions Addressed CQ1:
More information2013 ACC/AHA Cholesterol Guidelines JULIE HAMMOND, D.O. PGY-2 MATTHEW PAOLI, D.O. PGY-2
2013 ACC/AHA Cholesterol Guidelines JULIE HAMMOND, D.O. PGY-2 MATTHEW PAOLI, D.O. PGY-2 GOALS ACC/AHA as publisher of guidelines Determining which patients are appropriate for statin therapy The treatment
More informationDYSLIPIDEMIA PHARMACOLOGY. University of Hawai i Hilo Pre- Nursing Program NURS 203 General Pharmacology Danita Narciso Pharm D
DYSLIPIDEMIA PHARMACOLOGY University of Hawai i Hilo Pre- Nursing Program NURS 203 General Pharmacology Danita Narciso Pharm D 1 LEARNING OBJECTIVES Know normal cholesterol levels Understand what the role
More informationPCSK9 Agents Drug Class Prior Authorization Protocol
PCSK9 Agents Drug Class Prior Authorization Protocol Line of Business: Medicaid P & T Approval Date: February 21, 2018 Effective Date: April 1, 2018 This policy has been developed through review of medical
More informationAntihyperlipidemic Drugs
Antihyperlipidemic Drugs Lipid disorders: Disorders of lipid metabolism are manifest by elevation of the plasma concentrations of the various lipid and lipoprotein fractions (total and LDL cholesterol,
More informationnicotinic acid 375mg, 500mg, 750mg, 1000mg modified release tablet (Niaspan ) No. (93/04) Merck
Scottish Medicines Consortium Resubmission nicotinic acid 375mg, 500mg, 750mg, 1000mg modified release tablet (Niaspan ) No. (93/04) Merck New formulation 6 January 2006 The Scottish Medicines Consortium
More informationAchievement of target plasma cholesterol levels in hypercholesterolaemic patients being treated in general practice
Atherosclerosis 149 (2000) 199 205 www.elsevier.com/locate/atherosclerosis Achievement of target plasma cholesterol levels in hypercholesterolaemic patients being treated in general practice P.J. Barter
More informationDrug Class Review on HMG-CoA Reductase Inhibitors (Statins)
Drug Class Review on HMG-CoA Reductase Inhibitors (Statins) August 2006 Original Report Date: April 2002 Update 1 Report Date: July 2003 Update 2 Report Date: June 2004 Update 3 Report Date: September
More informationEffective Treatment Options With Add-on or Combination Therapy. Christie Ballantyne (USA)
Effective Treatment Options With Add-on or Combination Therapy Christie Ballantyne (USA) Effective treatment options with add-on or combination therapy Christie M. Ballantyne, MD Center for Cardiovascular
More informationPRODUCT INFORMATION. EZETROL (ezetimibe)
PRODUCT INFORMATION EZETROL (ezetimibe) NAME OF THE MEDICINE EZETROL, ezetimibe is described chemically as 1-(4-fluorophenyl)-3(R)-[3-(4- fluorophenyl)-3(s)-hydroxypropyl]-4(s)-(4-hydroxyphenyl)-2-azetidinone.
More informationSponsor Novartis. Generic Drug Name Fluvastatin. Therapeutic Area of Trial Dyslipidemia
Page 1 Sponsor Novartis Generic Drug Name Fluvastatin Therapeutic Area of Trial Dyslipidemia Approved Indication Therapeutic area and approved indications in Germany: Hypercholesterolemia (HC), combined
More informationManagement of LDL as a Risk Factor. Raul D. Santos MD, PhD Heart Institute-InCor University of Sao Paulo Brazil
Management of LDL as a Risk Factor Raul D. Santos MD, PhD Heart Institute-InCor University of Sao Paulo Brazil Disclosure Consulting for: Merck, Astra Zeneca, ISIS- Genzyme, Novo-Nordisk, BMS, Pfizer,
More informationAccumulating evidence suggests that intensive lipid lowering produces
Combination Therapy versus Monotherapy for Dyslipidemia: Are 2 Pills Better than 1? Accumulating clinical trial evidence and recently updated national guidelines support more aggressive efforts to reduce
More informationInternational Journal of Research and Development in Pharmacy and Life Sciences. Research Article
International Journal of Research and Development in Pharmacy and Life Sciences Available online at http//www.ijrdpl.com February - March, 214, Vol. 3, No.2, pp 943-948 ISSN: 2278-238 Research Article
More informationNCEP Report. Implications of Recent Clinical Trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines
NCEP Report Implications of Recent Clinical Trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines Scott M. Grundy; James I. Cleeman; C. Noel Bairey Merz; H. Bryan Brewer,
More informationIn-Ho Chae. Seoul National University College of Medicine
The Earlier, The Better: Quantum Progress in ACS In-Ho Chae Seoul National University College of Medicine Quantum Leap in Statin Landmark Trials in ACS patients Randomized Controlled Studies of Lipid-Lowering
More informationT REV 21. See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling. Revised: 07/2009
HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use ZETIA safely and effectively. See full prescribing information for ZETIA. ZETIA (ezetimibe) Tablets
More informationIn May 2001, the National Cholesterol. Effective Management of Patients With Dyslipidemia REPORT. Robert J. Lipsy, PharmD
REPORT Effective Management of Patients With Dyslipidemia Robert J. Lipsy, PharmD Abstract Coronary heart disease (CHD) is the leading cause of morbidity and mortality in the United States. A direct relationship
More informationThe Framingham Coronary Heart Disease Risk Score
Plasma Concentration of C-Reactive Protein and the Calculated Framingham Coronary Heart Disease Risk Score Michelle A. Albert, MD, MPH; Robert J. Glynn, PhD; Paul M Ridker, MD, MPH Background Although
More information(For National Authority Use Only) Name of Study Drug: to Part of Dossier:
2.0 Synopsis Abbott Laboratories Individual Study Table Referring to Part of Dossier: (For National Authority Use Only) Name of Study Drug: Volume: Niaspan Name of Active Ingredient: Page: Niacin extended-release
More informationZetia (Ezetimibe) Drug Monograph. Clinical clerkship Students (Week 1)
Zetia (Ezetimibe) Drug Monograph Clinical clerkship Students (Week 1) Fan Sheung Yin Chan Wai Lok Lau Man Pong Li Kwan Lam Chau Chung Yan Wong Yi Man Law Wing Yan Tsang Chun Man Li Wing Suen Cynthia Ho
More informationRaising high-density lipoprotein cholesterol: where are we now?
European Heart Journal Supplements (23) 5 (Supplement D), D17 D25 Raising high-density lipoprotein cholesterol: where are we now? Baylor College of Medicine, Houston, Texas, U.S.A. KEYWORDS Apolipoprotein;
More information4/24/15. AHA/ACC 2013 Guideline Key Points
Review of the ACC/AHA 2013 Guidelines Anita Ralstin, MS, CNS, CNP Next Step Health Consultant, LLC 1! Discuss the rationale for the change in lipid guidelines and how that affects the decision to implement
More informationAn update on lipidology and cardiovascular risk management. Lipids, Metabolism & Vascular Risk Section - Royal Society of Medicine
An update on lipidology and cardiovascular risk management Lipids, Metabolism & Vascular Risk Section - Royal Society of Medicine National and international lipid modification guidelines: A critical appraisal
More information2013 Cholesterol Guidelines. Anna Broz MSN, RN, CNP, AACC Cer=fied Adult Nurse Prac==oner North Ohio Heart, Inc.
2013 Cholesterol Guidelines Anna Broz MSN, RN, CNP, AACC Cer=fied Adult Nurse Prac==oner North Ohio Heart, Inc. Disclosures Speaker Gilead Sciences NHLBI Charge to the Expert Panel Evaluate higher quality
More informationRandomized Comparison of the Safety, Tolerability, and Efficacy of Long-term Administration of AMG 145: 52-Week Results From the OSLER Study
Randomized Comparison of the Safety, Tolerability, and Efficacy of Long-term Administration of AMG 145: 52-Week Results From the OSLER Study Michael J Koren 1, Robert P Giugliano 2, Frederick Raal 3, David
More informationNATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE. Overview
NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE Overview Ezetimibe for the treatment of primary (heterozygous familial and non-familial) hypercholesterolaemia The overview is written by members of
More informationAUSTRALIAN PI BLOOMS THE CHEMISTS-EZETIMIBE TABLETS (EZETIMIBE) 2 AND 3 QUALITATIVE AND QUANTITATIVE COMPOSITION AND PHARMACEUTICAL FORM
AUSTRALIAN PI BLOOMS THE CHEMISTS-EZETIMIBE TABLETS (EZETIMIBE) 1 NAME OF THE MEDICINE Ezetimibe. 2 AND 3 QUALITATIVE AND QUANTITATIVE COMPOSITION AND PHARMACEUTICAL FORM Each tablet of ezetimibe for oral
More informationDisclosure. This study was sponsored by Pfizer, Inc. All authors are employees of Pfizer, Inc. with ownership of stock in Pfizer, Inc.
Disclosure This study was sponsored by Pfizer, Inc. All authors are employees of Pfizer, Inc. with ownership of stock in Pfizer, Inc. Effects of 12 Weeks of Treatment with RN316 (PF-04950615), a Humanized
More informationEmerging data suggest that the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase
REVIEW ARTICLE Risk for Myopathy With Statin Therapy in High-Risk Patients Christie M. Ballantyne, MD; Alberto Corsini, PhD; Michael H. Davidson, MD; Hallvard Holdaas, MD; Terry A. Jacobson, MD; Eran Leitersdorf,
More informationLipids & Hypertension Update
Lipids & Hypertension Update No financial disclosures Michael W. Cullen, MD, FACC Senior Associate Consultant, Assistant Professor of Medicine Mayo Clinic Department of Cardiovascular Diseases 34 th Annual
More informationNICE QIPP about Lipitor. Robert Trotter. Clinical Effectiveness Consultant
NICE QIPP about Lipitor Robert Trotter Clinical Effectiveness Consultant LIP2894c Date of preparation: April 2009 Prescribing information for atorvastatin is available on the last slide Roadmap Background
More informationJournal of the American College of Cardiology Vol. 54, No. 25, by the American College of Cardiology Foundation ISSN /09/$36.
Journal of the American College of Cardiology Vol. 54, No. 25, 2009 2009 by the American College of Cardiology Foundation ISSN 0735-1097/09/$36.00 Published by Elsevier Inc. doi:10.1016/j.jacc.2009.10.005
More informationAMR101, a Pure-EPA Omega-3 Fatty Acid, Lowers Triglycerides in Patients with Very High Triglycerides Without Raising LDL- C: The MARINE Study
AMR101, a Pure-EPA Omega-3 Fatty Acid, Lowers Triglycerides in Patients with Very High Triglycerides Without Raising LDL- C: The MARINE Study HE Bays, 1 CM Ballantyne, 2 JJ Kastelein, 3 E Stein, 4 JL Isaacsohn,
More informationCombined lipid lowering drug therapy for the effective treatment of hypercholesterolaemia
European Heart Journal (2003) 24, 685 689 Editorial Combined lipid lowering drug therapy for the effective treatment of hypercholesterolaemia James Shepherd * Institute of Biochemistry, Royal Infirmary,
More informationHighlights of the new blood pressure and cholesterol guidelines: A whole new philosophy. Jeremy L. Johnson, PharmD, BCACP, CDE, BC-ADM
Highlights of the new blood pressure and cholesterol guidelines: A whole new philosophy Jeremy L. Johnson, PharmD, BCACP, CDE, BC-ADM OSHP 2014 Annual Meeting Oklahoma City, OK April 4, 2014 1 Objectives
More informationJACC Vol. 32, No. 3 September 1998:665 72
JACC Vol. 32, No. 3 September 1998:665 72 665 Treating Patients With Documented Atherosclerosis to National Cholesterol Education Program-Recommended Low-Density-Lipoprotein Cholesterol Goals With Atorvastatin,
More informationDyslipidemia is a strong risk factor for myocardial infarction, 1
Safety of Simvastatin and Goal Attainment for Low-Density Lipoprotein Cholesterol in Sultan Qaboos University Hospital Khalid Al-Siyabi, 1 Hatem Farhan, 2 Khalid Al-Rasadi, 3 Amaal Al-Salhi, 4 Ali T. Al-Hinai,
More informationMetabolism, Atherogenic Properties and Agents to reduce Triglyceride-Rich Lipoproteins Manfredi Rizzo, MD, PhD
Metabolism, Atherogenic Properties and Agents to reduce Triglyceride-Rich Lipoproteins Manfredi Rizzo, MD, PhD Associate Professor of Internal Medicine Faculty of Medicine, University of Palermo, Italy
More informationNovel Therapeutic Strategies in Lipid Management: Lowering LDL C to Improve Patient Outcomes
Novel Therapeutic Strategies in Lipid Management: Lowering LDL C to Improve Patient Outcomes Rajat Deo, MD, MTR Assistant Professor of Medicine Division of Cardiology University of Pennsylvania April 25,
More informationEzetimibe: A First-in-Class, Novel Cholesterol Absorption Inhibitor
Cardiovascular Drug Reviews Vol. 21, No. 4, pp. 293 312 2003 Neva Press, Branford, Connecticut Ezetimibe: A First-in-Class, Novel Cholesterol Absorption Inhibitor Leslie J. Lipka Schering-Plough Research
More information