EAL

H/A: Hyperlipidemia (2009)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To compare dietary advice alone with dietary advice plus pravastatin in a group of HIV-positive men taking a protease inhibitor drug.

Inclusion Criteria:

Patients established on protease inhibitor-based regimens for greater than 12 weeks
Viral load less than 500 copies per ml
Cholesterol more than 6.5mmol per L.

Exclusion Criteria:

None specifically mentioned.

Description of Study Protocol:

Recruitment

Methods not described.

Design

Randomized clinical trial. Group assignment carried out by generating two sequences with equal numbers in each group and sealed opaque envelopes.

Intervention

24-week trial of dietary advice alone (based on lowering cholesterol and triglyceride) or with pravastatin (20mg per day for first two weeks, then 40mg per day thereafter).

Statistical Analysis

No power calculations were made. Statistical analysis was not described.

Data Collection Summary:

Timing of Measurements

Blood samples taken within one month of commencement for cholesterol measurements. All patients received dietary advice on day zero and week 12. Blood sampling performed fasting at day zero and weeks 12 and 24.

Dependent Variables

Total, HDL and LDL cholesterol, triglycerides
Glucose
Viral load
CD4 cells
Clinical and laboratory adverse effects.

Independent Variables

24-week trial of dietary advice alone (based on lowering cholesterol and triglyceride) or with pravastatin (20mg per day for the first two weeks, and then 40mg per day thereafter)
Intake of energy, fat, fiber and sugars assessed with three-day food diaries.

Description of Actual Data Sample:

Initial N: 37 screened, 31 male patients randomized. Six did not meet inclusion criteria.
Attrition (final N): Five withdrawals for personal reasons. 26 completed the study, 12 in the dietary advice alone, 14 in the dietary advice and pravastatin group.
Anthropometrics: Baseline demographics were well matched and there were no significant differences between groups
Location: United Kingdom.

Summary of Results:

Total cholesterol (mmol per L)	Dietary Advice Alone	Dietary Advice Plus Pravastatin	P-value
Baseline	7.4 (6.8 to 7.9)	7.5 (6.7 to 8.3)	0.782
12 weeks	6.9 (6.1 to 7.7)	6.2 (5.7 to 6.7)	0.156
24 weeks	7.1 (6.6 to 7.5)	6.3 (5.5 to 7.1)	0.069
Change from baseline to 12 weeks	-0.49 (-1.12 to 0.13)	-1.25 (-0.88 to -0.63)	0.075
Change from baseline to 24 weeks	-0.34 (-1.10 to 0.41)	-1.23 (-1.8 to -0.7)	0.051

Other Findings

There were no significant clinical or laboratory events and no patient discontinuation secondary to adverse effects.

Viral rebound did not occur.

Relative to baseline, total cholesterol at week 24 fell significantly in the pravastatin (1.2mmol per L, 17.3%, P<0.05) but not in the dietary advice (0.3mmol per L, 4%) group.

The difference between the two groups approached significance at week 24 (P=0.051).

This fall was entirely accounted for by a reduction in LDL (calculated change 1.24mmol per L, 19% and 0.07mmol, 5.5% in pravastatin and dietary advice groups, respectively) as HDL rose non-significantly by 0.6mmol per L in both groups.

Weight, basal metabolic rate, fasting glucose and triglycerides did not change significantly in either group.

Author Conclusion:

In conclusion, pravastatin may be safely and effectively given to protease inhibitor treated HIV-positive persons with hypercholesterolemia. The changes in cholesterol observed with pravastatin are comparable to those seen in studies in endogenous hyperlipidemia.

Funding Source:

Reviewer Comments:

Cholesterol levels taken within one month of study commencement but not at commencement. Statistical analysis were not described, power calculations were not done. Subjects were not well described. Small sample sizes.

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		???
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	???
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
3.	Were study groups comparable?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	Yes
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	N/A
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	Yes
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	N/A
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	Yes
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	Yes
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		???
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	???
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	???
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		???
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	No
	8.2.	Were correct statistical tests used and assumptions of test not violated?	???
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	???
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	???
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
9.	Are conclusions supported by results with biases and limitations taken into consideration?		???
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	No
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes