Pitavastatin Shows Greater Lipid-Lowering, Article Critique Example

The objective of the study was to compare the safety and efficacy of pitavastatin and determine if the drug meets the required long-term criteria in elderly patients compared to the drug named pravastatin. The study was designed as a randomized double-blind study double-dummy, parallel-group, active-comparator-controlled study. The study was interventional in nature. The patients were randomized into six treatment groups (1, 2, or 4 mg pitavastatin vs. 10, 20, or 40 mg pravastatin) over the course of a 18-20 week multicenter double blind, double-dummy, parallel-group, active-comparator-controlled study.  An interactive voice response system randomized the patient in regard to receiving either the pitavastatin or pravastatin. Participants received either pitavastatin or pravastatin at a ratio of 2:1 for each of the doses.

The patient population consisted of sample size of 942 men elderly patients from 65 years of age or older (mean age 70, range 65-89) from one of the study sites conducted in Denmark, Germany, Israel, the Netherlands, and the UK, with a confirmed diagnosis of primary hypercholesterolemia or combined (mixed) dyslipidemia at two consecutive assessment.  In addition, criteria levels, such as LDL-C plasma levels between 3.4 mmol/l and 5.7 mmmol/l and moderately elevated triglyceride levels (<4.6 mmol/l) at two consecutive evaltions were also indicative of patient participation. NCEP ATP III LCL-C targets were measured on a patient-by patient basis depending on cardiovascular risk factors.  Exclusion criteria from this study included homozygous familial hypercholesterolemia or conditions that could lead to secondary dyslipidemia, uncontrolled medical, uncontrolled hypothyroidism, uncontrolled hypertension, and impaired liver, renal or heart conditions.

The patients underwent 6-8 week washout/dietary period before the start of the treatment.  The patients were randomized into six treatment groups.  Pitavastatin served as the intervention and pravastatin, a previously used drug served as the control in this study. The dosages for the study consisted of either(1, 2, or 4 mg of pitavastatin vs. 10, 20, or 40 mg pravastatin. The patient received the treatment once daily for a total of 12 weeks. The patient who received higher dosages of the drugs began the study at lower doses of 2 mg for pitavastatin or 20 mg for pravastatin for 4 weeks before reaching the higher dosage for the remaining 8 weeks.  The patients had to fast for at least 12 hours prior to each visit. During each visit, blood samples were obtained to measure for total cholesterol, LDL-C, HDL-C, non-HDL-C, triglycerides, and ratios of these measurements. Analyses of measurements were conducted at 0, 4, 8, and 12 weeks.  Safety assessments conducted for adverse events. Regular blood measurements, chemistry, urinalysis, vital sizes, electrocardiograms and physical examinations were conducted for the patients.

The control in the study was used as the regular prescribing drug pravastatin at 10, 20, or 40 mg.

The mean LDL-C concentrations feel below the baseline to endpoint from a dose-dependent perspective.  The mean percentage changes indicated that pitavastatin met the primary endpoint of non-inferiority in the LDL-C reduction compared to pravastatin at approximately 10%. The pitvastatin 1mg vs. pravastatin 10mg comparison analysis showed a mean difference at 8.79%. The secondary outcomes showed that the plasma concentrations, non-HDL-C, oxidized LDL-C, the non-HDL-C:HDL-C ratio, the TC:HDL-C ratio, Apo-B and the Apo-V:Apo-A1 ratios had a significant different in pitavastatin samples than pravastatin.  The proportion of patients that met the NCEP ATAIII target were at 83.1 and 65.0% for low dosages, 88.8 and 81.3% for moderate doses, and 91.0 and 88.2% for high dosages.  Some patients also reported at least one adverse event and were comparable between the groups at 49,0 and 55.3%.  In addition, the percentage of treatment-related adverse events ranges from 12,9 to 23.3%.  Furthermore, there was isolated increase in liver enzymes observed in two of the patients.

There were a few strengths notable in the study.  For one, the study had a large sample size of 942 people.  A large sample size is necessary for analyzing and comparing data. Secondly, the study based exclusion data in order to reduce the amount of underlying diseases that could alter test results. Lastly, the study used three variable dosages for both of the drugs in order to obtain a comparison between groups and within groups.

There were a few limitations notable in the study. For one, the study had a larger percentage of Caucasian subjects, at 44.3%, which could cause some bias on populations that the drug can support. Secondly, patients that received the higher dosages started out at lower dosages for 4 weeks; therefore, it is possible that the full effects of higher dosages could not be determined within 8 weeks. Lastly, the age range was from 65-89 years of age, which could have some differences in the health of the patients, which in turn is difficult to compare a 65 year old to an 85 year old.

The results of the study offer another form of treatment for patients with vascular diseases. The results of the study did not address the impact of pitavstatin on mortality rates; however, pitavastatincan help decrease LDL-C after statin treatment for primary and secondary prevention of cardiovascular events, which in turn can decrease mortality in patients.

I would prescribe this drug since pitavastatin 1-4 mg reduced LDL-C in elderly patients with primary hypercholesterolemia or combined dyslipidemia significantly more than the pravastatin drug at 10-40 mg.  This is important because the lower dose of pravastatin had greater effects than a higher dosage of pravastatin.

In order to help manage pitavastatin, the number and types of adverse events should be monitored and reported, the medication-error prevention management should be implemented, and the development of a care and plan guideline should be written.   The adverse events were noted in some of the patients during the study; therefore, it is important that each adverse event is monitored closely and reported properly.  Medication-error management is important as different dosages can be provided to patients; therefore, clear descriptions on dosages should be provided to the staff.  In addition, a specific care and plan of action should be implemented as well, in order to provide a timeline for the daily dosage and the length of time between doctor visits and measurements of vitals and other analyses.