Vladimir A. Kryzhanovski

Comparison of the Lipid-Lowering Effects of Pitavastatin 4 mg Versus Pravastatin 40 mg in Adults With Primary Hyperlipidemia or Mixed (Combined) Dyslipidemia: A Phase IV, Prospective, US, Multicenter, Randomized, Double-blind, Superiority Trial

PURPOSE Results from a Phase III, European, non-inferiority trial in elderly (age ≥65 years) patients with primary hyperlipidemia or mixed (combined) dyslipidemia demonstrated significantly greater reductions in LDL-C for pitavastatin versus pravastatin across 3 pair-wise dose comparisons (1 mg vs 10 mg, 2 mg vs 20 mg, and 4 mg vs 40 mg, respectively). The present study investigated whether pitavastatin 4 mg is superior to pravastatin 40 mg in LDL-C reduction in adults (18-80 years old) with primary hyperlipidemia or mixed (combined) dyslipidemia. METHODS This was a Phase IV, multicenter, randomized, double-blind, double-dummy, active-control superiority study conducted in the United States. Patients with baseline LDL-C levels of 130 to 220 mg/dL (inclusive) and triglyceride levels ≤400 mg/dL after a 6-week washout/dietary stabilization period were randomized to 12 weeks of once-daily treatment with either pitavastatin 4 mg or pravastatin 40 mg. FINDINGS A total of 328 subjects (164 per treatment arm) were randomized (mean age, 57.9 years [76% were aged <65 years]; 49.4% women; mean body mass index, 30.2 kg/m(2)) to treatment. The median percent change in LDL-C from baseline to the week 12 endpoint was -38.1% for pitavastatin 4 mg and -26.4% for pravastatin 40 mg; the difference in median percent change between treatments was -12.5% (P < 0.001). Differences between treatments in median percent reductions from baseline for apolipoprotein B, total cholesterol, and non-HDL-C were also significant in favor of pitavastatin (P < 0.001). Both treatments significantly (P < 0.001) increased HDL-C and decreased triglycerides, but the differences between treatments were not statistically significant. The overall rate of treatment-emergent adverse events was 47.6% (78 of 164) for pitavastatin and 44.5% (73 of 164) for pravastatin. Myalgia was reported by 3 patients (1.8%) in the pitavastatin group and by 4 patients (2.4%) in the pravastatin group. There were no reports of myositis or rhabdomyolysis. IMPLICATIONS Pitavastatin 4 mg demonstrated superior LDL-C reductions compared with pravastatin 40 mg after 12 weeks of therapy in adults with primary hyperlipidemia or mixed (combined) dyslipidemia. There were no new safety findings in the trial. Clinical Trials.gov identifier: NCT01256476.

Pitavastatin versus pravastatin in adults with HIV-1 infection and dyslipidaemia (INTREPID): 12 week and 52 week results of a phase 4, multicentre, randomised, double-blind, superiority trial

BACKGROUND People living with HIV-1 infection are at greater risk for cardiovascular disease than seronegative adults. Treatment of dyslipidaemia with statins has been challenging in people with HIV because of an increased potential for drug interactions due to competing cytochrome P450 metabolism between statins and commonly used antiretroviral agents. Neither pitavastatin nor pravastatin depend on cytochrome P450 for primary metabolism. We aimed to assess the safety and efficacy of pitavastatin versus pravastatin in adults with HIV and dyslipidaemia. METHODS In the INTREPID (HIV-infected patieNts and TREatment with PItavastatin vs pravastatin for Dyslipidemia) randomised, double-blind, active-controlled, phase 4 trial (INTREPID, we recruited adults aged 18-70 years with controlled HIV (with CD4 counts >200 cells per μL and HIV-1 RNA <200 copies per mL) on antiretroviral therapy for at least 6 months and dyslipidaemia (LDL cholesterol 3·4-5·7 mmol/L and triglycerides ≤4·5 mmol/L) from 45 sites in the USA and Puerto Rico. Patients being treated with darunavir, or who had homozygous familial hypercholesterolaemia or any condition causing secondary dyslipidaemia, or a history of statin intolerance, diabetes, or coronary artery disease were not eligible. We randomly assigned patients (1:1) to pitavastatin 4 mg or pravastatin 40 mg with matching placebos once daily orally for 12 weeks, followed by a 40 week safety extension. Randomisation was stratified by viral hepatitis B or C coinfection and computer-generated. Investigators, patients, study staff, and those assessing outcomes were masked to treatment group. The primary endpoint was percentage change in fasting serum LDL cholesterol from baseline to week 12 and the primary efficacy analysis was done in the modified intention-to-treat population. The safety analysis included all patients who took at least one dose of study medication. This study is registered with ClinicalTrials.gov, number NCT01301066. FINDINGS Between Feb 23, 2011, and March 29, 2013, we randomly assigned 252 patients to the pitavastatin (n=126) or pravastatin group (n=126). LDL cholesterol reduction was 31·1% with pitavastatin and 20·9% with pravastatin (least squares mean difference -9·8%, 95% CI -13·8 to -5·9; p<0·0001) at 12 weeks. At week 52, four patients (3%) in the pitavastatin group and six (5%) in the pravastatin group had virological failure, with no significant difference between treatments. Both treatments had neutral effects on glucose metabolism parameters. 85 patients treated with pitavastatin (68%) and 88 patients treated with pravastatin (70%) reported treatment-emergent adverse events, and these caused study discontinuation in six patients (5%) versus five patients (4%). No serious adverse event occurred in more than one participant and none were treatment-related according to investigator assessment. The most common treatment-emergent adverse events were diarrhoea in the pitavastatin group (n=12, 10%) and upper respiratory tract infection in the pravastatin group (n=14, 11%). 11 treatment-emergent serious adverse events were noted in seven patients (6%) in the pitavastatin group (atrial septal defect, chronic obstructive pulmonary disease, chest pain, diverticulitis, enterovesical fistula, gastroenteritis, viral gastroenteritis, herpes dermatitis, multiple fractures, respiratory failure, and transient ischaemic attack) and four events in three patients (2%) in the pravastatin group (cerebrovascular accident, arteriosclerosis coronary artery, myocardial infraction, and muscle haemorrhage). In the pravastatin treatment group, one additional patient discontinued due to an adverse event (prostate cancer that was diagnosed during the screening period, 42 days before first dose of study treatment, and therefore was not a treatment-emergent adverse event). INTERPRETATION The INTREPID results support guideline recommendations for pitavastatin as a preferred drug in the treatment of dyslipidaemia in people with HIV. FUNDING Kowa Pharmaceuticals America and Eli Lilly and Company.

PITAVASTATIN 4 MG PROVIDES SIGNIFICANTLY GREATER REDUCTION IN LDL-C COMPARED TO PRAVASTATIN 40 MG WITH NEUTRAL EFFECTS ON GLUCOSE METABOLISM: PRESPECIFIED SAFETY ANALYSIS FROM THE SHORT-TERM PHASE 4 PREVAIL US TRIAL IN PATIENTS WITH PRIMARY HYPERLIPIDEMIA OR MIXED DYSLIPIDEMIA

Recent studies showed that some statins may impair glucose metabolism. In a reanalysis of WOSCOPS, individual risk of diabetes with pravastatin was reported as null. Limited information is available on the glycemic effect of a recently approved statin, pitavastatin. The objective of this

SHORT-TERM AND LONG-TERM EFFECTS OF PITAVASTATIN AND SIMVASTATIN ON FASTING PLASMA GLUCOSE IN PATIENTS WITH PRIMARY HYPERLIPIDEMIA OR MIXED DYSLIPIDEMIA AND ≥2 RISK FACTORS FOR CORONARY HEART DISEASE

Recent meta-analyses showed deterioration of glucose metabolism following administration of statins. Limited information is available on the glycemic effect of a recently approved statin, pitavastatin (PTA). In Phase 3 non-inferiority trials, LDL-C reductions with PTA 2 mg and 4 mg were comparable

Factors associated with statin selection among privately insured commercial and Medicare patients.

Abstract Objectives: Given the availability of several statins in the United States, it is important to understand patient characteristics associated with their initiation. We analyzed demographic and clinical factors associated with statin selection among new statin users. Methods: This retrospective cohort study examined factors associated with statin selection among patients newly initiated on therapy between 1/1/2007 and 12/31/2007. Commercial and Medicare patient cohorts were evaluated separately and comparisons were made between pravastatin (PS) and other statins including simvastatin (SS), atorvastatin (AS), or rosuvastatin (RS). Multiple logistic regression models were employed to assess factors associated with PS initiation versus other statins. Results: In commercially insured patients, patients initiating PS were more likely to be older, female, and have diabetes mellitus, liver dysfunction, human immunodeficiency virus (HIV) infection, or hypertension and use calcium channel blockers, protease inhibitors, or additional lipid-modifying agents (p < 0.01 for each comparison). In Medicare-age patients, a higher percentage of PS initiators were aged 75–85, female, had atrial fibrillation, and were prescribed warfarin or triazole antifungals (p < 0.01 for each comparison). Presence of atrial fibrillation or HIV infection, or use of calcium channel blockers or additional lipid-modifying agents was associated with PS initiation compared with AS and SS. Use of warfarin was significantly associated with initiating PS compared with SS, AS, and RS in Medicare-age patients. Conclusion: Older age and female gender were associated with PS initiation. In addition, selected comorbidities and use of certain medications including warfarin or protease inhibitors were associated with PS initiation, which may reflect the tolerability of PS and its reduced risk of significant drug–drug interactions for certain patients. Because this study is a retrospective analysis of US healthcare claims, the findings are limited to only those factors captured within claims data and may not be generalizable to all patient populations in which statin therapy is initiated.

Pitavastatin 4 mg Superior to Pravastatin 40 mg on LDL-C Reduction in HIV-Positive Patients with Dyslipidemia with and without Ritonavir-based Therapy†

Poster presented at the 2015 National Lipid Association Scientific Sessions, June 11-14, 2015, Chicago, IL (Encore poster, previously presented at the 20th International AIDS Conference (AIDS 2014), 20–25 July 2014, Melbourne, Australia.) Research sponsored by Kowa Pharmaceuticals America, Inc. and Eli Lilly and Company. Craig Sponseller, MD, Stuart Campbell, BBA, Vladimir Kryzhanovski, MD, Judith Aberg, MD Kow Ph rmaceuticals America, Inc., Montgomery AL, USA; Kowa Research Institute, Inc., Morrisville NC, USA; Lilly USA, LLC, I dianapolis, IN, USA; Icahn School f Medicine at Mount Sinai, New York, NY USA