# Presentation: 525405

## ? OTC LOVASTATIN

- Jesse M. Polansky M.D., M.P.H.
- 	jmpqz@yahoo.com
- Representing self

## ? EFFICACY PRIMARY PREVENTION

- FDA Statistical Review:
- Uncertainty in post-hoc AFSCAPs analysis (low HDL population vs OTC population)
- Absolute vs. Relative Risk Reduction
- ? “Lower is Better” in moderate and low risk populations

## ? EMERGING SAFETY CONCERNS STATINS

- Hemorrhagic Stroke - FDA label change atorvastatin based on post-hoc analysis SPARCL (4D/atorvastatin in diabetics on dialysis had a reported stroke finding also)
- GI and Prostate Cancer Clinical Trial Findings (pravastatin and rosuvastatin respectively)
- Cognitive, Behavioral (including suicide, sleep disturbances), and Gross Underreporting of Statin Side Effects (UCSD Statin Study)
- ALS   (WHO)

## Balancing Risks & Benefits: NCEP ATP-III

- 2003 NCEP Update : drug therapy _only_ for Moderate Risk patients with LDL>160
- Moderate Risk = 2 RF (includes Family Hx) and <10% Framingham Risk Score
- The NCEP Moderate Risk category includes approx 13 million Americans who according to the guidelines _only require Total Lifestyle Change (TLC)_ (?impact of self-rx)

##        NCEP Risk Categories

-        _**NCEP Risk Categories**_

## Balancing Risks & Benefits: The UK Experience

- 11/2003 simvastatin approved for Behind the Counter use for “Moderate Risk” patients
- In the UK “Moderate Risk” = 10%-15% 10 year risk of a first major coronary event
- 	(note NCEP Moderate Risk is defined as <10%)
- Controversy Continues
- ? Update

## ? Balancing Risks & Benefits: The Underserved

- Under treatment for patients with favorable risk/benefit profiles
- Marginalizing the Total Lifestyle Change Imperative

## Customer Use Study

- Although the investigators collected data necessary to evaluate self-rx decision vs. NCEP guidelines the data was not presented and could not be extracted from publically available data.
- In addition, the Mrk presentations to the OTC Committee inappropriately collapsed the NCEP Moderate and Moderately High Risk categories they renamed the “Moderate Risk Group”.

## ? Thoughts

- The lovastatin OTC request should be denied
- The risks of lovastatin OTC are not insignificant and magnified in an unmanaged OTC population
- The benefits of lovastatin OTC are uncertain and limited at best
- OTC lovastatin is an uncontrolled and ill-begotten  public health experiment of unprecedented scale
- Approval would be a substantial failure of FDA’s obligation to be an advocate for patient safety

## Background

**I Statin Safety**
- FDA Atorvastatin label change: Addition of Precaution for patients with recent stroke or TIA
- NEJM:  Atorvastatin in Patients with Type 2 Diabetes Mellitus Undergoing Hemodialysis
- Drug Safety: Physician Response to Patient Reports of Adverse Drug Effects: Implications For Patient-Targeted Adverse Effect Surveillance. <note: Statin Case Study>
- Drug Safety:  Statins, Neuromuscular Degenerative Disease and an Amyotrophic Lateral Sclerosis-Like Syndrome An Analysis of Individual Case Safety Reports from Vigibase
- JACC: Effect of the Magnitude of Lipid Lowering on Risk of Elevated Liver Enzymes, Rhabdomyolysis, and Cancer
- Journal of Clinical Oncology: Statins and Cancer Risk: A Literature-Based Meta-Analysis and Meta-Regression Analysis of 35 Randomized Controlled Trials
- NEJM: Use of Statins and Outcome of BCG Treatment for Bladder Cancer
- NEJM Statins for Atherosclerosis — As Good as It Gets? <Note: Immunologic considerations>
- Clinical P&T: Benefit/Risk Ratio of Statins in Primary Prevention
- AJCard: Effect of Atorvastatin on Left Ventricular Diastolic Function and Ability of Coenzyme Q10 to Reverse That Dysfunction
- BMJ: Controversy: Should we lower cholesterol as much as possible?

## Background

**II Eficacy Considerations**
- JACC: Low and Lowered Cholesterol and Total Mortality
- Annals IM: Narrative Review: Lack of Evidence for Recommended Low-Density
-             Lipoprotein Treatment Targets: A Solvable Problem
- PLOS: Factors Associated with Findings of Published Trials of Drug–Drug Comparisons: Why Some Statins Appear More Efficacious than Others
- FDA Memos; Statistical Review AFCAPS/TEXCAPS and Clinical Review Excerpt
- Center for Science in the Public Interest: Petition to the National Institutes of Health Seeking an Independent Review Panel to Re-Evaluate the NCEP Guidelines
**III  OTC Statins**
** **
- NEJM: Statins and Over-the-Counter Availability
**IV NCEP Data**
- Distribution of Patients by NCEP Risk Category