Limited impact of IL28B genotype on response rates in telaprevir-treated patients with prior treatment failure.

Background & Aims: Nucleotide polymorphisms upstream of the interleukin 28B (IL28B) gene are strongly associated with hepatitis C virus (HCV) clearance in treatment-naïve patients treated with peginterferon/ribavirin (PegIFN/RBV). This subanalysis of the REALIZE study evaluated the impact of IL28B polymorphisms on sustained virologic response (SVR) in telaprevir-treated, HCV genotype 1-infected patients with prior PegIFN/RBV treatment failure.

Methods: Treatment-experienced patients were randomized to 12 weeks of telaprevir (750 mg every 8h) with/without a 4-week PegIFN/RBV lead-in, or placebo, each with PegIFN-α-2a (180 μg/week) and ribavirin (1000-1200 mg/day) for 48 weeks overall.

Sustained virologic response rates with telaprevir by response after 4 weeks of lead-in therapy in patients with prior treatment failure.

Background & Aims: For hepatitis C virus (HCV)-infected patients who have not responded to previous PegIFN/ribavirin treatment, it is unclear whether subsequent direct-acting antiviral therapy outcomes are better predicted by prior treatment response or by on-treatment response to a PegIFN/ribavirin lead-in.

Methods: In REALIZE, treatment-experienced patients randomized to the lead-in telaprevir arm received 4 weeks of PegIFN-α-2a (180 μg/week) and ribavirin (1000-1200 mg/day), then 12 weeks of telaprevir (750 mg every 8h) plus PegIFN-α-2a/ribavirin, followed by 32 weeks of PegIFN-α-2a/ribavirin. This subanalysis only included patients in the lead-in telaprevir arm with available week 4 on-treatment response data (n=240).

Futility rules for telaprevir combination treatment for patients with hepatitis C virus infection.

For patients treated with telaprevir, peginterferon, and ribavirin, futility rules have been developed to prevent needless drug exposure and minimize development of drug-resistant variants for patients who have little or no chance of achieving a sustained virologic response. We performed retrospective analyses of data from phase 3 trials and validated the current futility rule. All therapy should be stopped for treatment-naive and treatment-experienced patients if hepatitis C virus RNA levels are greater than 1000 IU/mL at weeks 4 or 12, or if hepatitis C virus RNA is detectable at week 24.

Telaprevir for retreatment of HCV infection.

Background: Up to 60% of patients with hepatitis C virus (HCV) genotype 1 infection do not have a sustained virologic response to therapy with peginterferon alfa plus ribavirin.

Methods: In this randomized, phase 3 trial, we evaluated the addition of telaprevir to peginterferon alfa-2a plus ribavirin in patients with HCV genotype 1 infection who had no response or a partial response to previous therapy or who had a relapse after an initial response. A total of 663 patients were assigned to one of three groups: the T12PR48 group, which received telaprevir for 12 weeks and peginterferon plus ribavirin for a total of 48 weeks; the lead-in T12PR48 group, which received 4 weeks of peginterferon plus ribavirin followed by 12 weeks of telaprevir and peginterferon plus ribavirin for a total of 48 weeks; and the control group (PR48), which received peginterferon plus ribavirin for 48 weeks.

Effects of increasing doses of atorvastatin on the atherogenic lipid subclasses commonly associated with hypertriglyceridemia.

The increased cardiovascular risk associated with hypertriglyceridemia is thought to be due in part to high levels of triglyceride (TG)-rich lipoproteins and small dense low-density lipoprotein (LDL). In this post hoc analysis, effects of increasing doses of atorvastatin (10, 20, 40, and 80 mg) on atherogenic lipid subclasses commonly associated with hypertriglyceridemia were evaluated in 191 men and women who were candidates for lipid-lowering therapy and had baseline TG levels >200 mg/dl (2.3 mmol/L).

Effects of high-dose atorvastatin in patients > or =65 years of age with acute coronary syndrome (from the myocardial ischemia reduction with aggressive cholesterol lowering [MIRACL] study).

After acute coronary syndromes (ACSs), older patients are particularly susceptible to early complications, including death and recurrent ACS. Lipid management guidelines do not differentiate elderly from younger patients, and lack of evidence for statin benefits in older patients has led to underutilization of statins in the elderly. The MIRACL study randomized 3,086 patients to 16 weeks of 80 mg/day of atorvastatin or placebo 24 to 96 hours after ACS and demonstrated significant decreases in the combined primary end point (nonfatal acute myocardial infarction, resuscitated cardiac arrest, recurrent symptomatic myocardial ischemia).

Effects of intensive versus moderate lipid-lowering therapy on myocardial ischemia in older patients with coronary heart disease: results of the Study Assessing Goals in the Elderly (SAGE).

Background: Clinical trials have demonstrated that, compared with placebo, intensive statin therapy reduces ischemia in patients with acute coronary syndromes and in patients with stable coronary artery disease. However, no studies to date have assessed intensive versus moderate statin therapy in older patients with stable coronary syndromes.

Methods And Results: A total of 893 ambulatory coronary artery disease patients (30% women) 65 to 85 years of age with > or = 1 episode of myocardial ischemia that lasted > or = 3 minutes during 48-hour ambulatory ECG at screening were randomized to atorvastatin 80 mg/d or pravastatin 40 mg/d and followed up for 12 months.

Analysis of efficacy and safety in patients aged 65-75 years at randomization: Collaborative Atorvastatin Diabetes Study (CARDS).

Objective: Rates of cardiovascular disease are highest in the elderly. Lipid-lowering statin therapy reduces the proportional risk as effectively in older patients as in younger individuals; however, limited data are available for elderly patients with type 2 diabetes. We conducted a post hoc analysis to compare the efficacy and safety of atorvastatin among 1,129 patients aged 65-75 years at randomization with 1,709 younger patients in the Collaborative Atorvastatin Diabetes Study (CARDS).

Tolerability of atorvastatin in a population aged > or =65 years: a retrospective pooled analysis of results from fifty randomized clinical trials.

Objective: The aim of this study was to compare the safety profile of atorvastatin calcium at 4 doses with that of placebo in elderly patients (age, > or =65 years).

Methods: A single pooled database (Pfizer Atorvastatin Clinical Program Database) of 50 published and unpublished completed clinical trials was analyzed retrospectively. Tolerability data from male and female study participants aged > or =65 years at the time of study enrollment were extracted from this database and grouped based on treatment: atorvastatin 10, 20, 40, or 80 mg/d, or placebo.

Comparative safety of atorvastatin 80 mg versus 10 mg derived from analysis of 49 completed trials in 14,236 patients.

Atorvastatin has been shown to reduce coronary events and revascularization procedures in patients with multiple risk factors for coronary heart disease. Recent studies with atorvastatin 80 mg support the overall safety of this dose during long-term treatment. However, physicians appear reluctant to use high doses of statins.