Vytorin, as most familiar with the file are aware, is a combination of two drugs: Zetia (ezetimibe), a drug that works to prevent cholesterol absorption, and Zocor (simvastatin), an older statin. Statin drugs - and there are several on the market - are popularly used to lower the so-called “bad” LDL cholesterol in an individual’s bloodstream. LDL cholesterol is thought to be the demon that promotes buildup of arterial plaques that can lead to heart attacks and other cardiovascular events. It was thought that teaming a statin like Zocor with Zetia would do an even better job of preventing heart attacks and strokes in patients with serious cholesterol issues.
While Vytorin has been found to successfully reduce LDL cholesterol levels, the jury is still out on whether or not Vytorin does anything to prevent Vytorin heart attack over and above the employment of a single statin alone.
It was approved in 2004 - but even then, cardiologists were skeptical over the capacity for Vytorin to significantly lower the incidence of heart disease and cardiovascular events. When a study determined several years ago that Vytorin was no better than Zocor alone for the lowering of bad cholesterol, it was no surprise to noted cardiologist Dr. Steven E. Nissen, chair of cardiovascular medicine at the Cleveland Clinic, and a past president of the American College of Cardiology. He characterized the results as “a stunning reversal for Zetia and Vytorin,” he said in comments to WebMD at the time (1/15/2008).
While other cardiologists were satisfied with cutting Vytorin some slack, Nissen was adamant. “Zetia works only by blocking the absorption of cholesterol, but it has not been shown to produce any health benefits,” he said at the time. “I have been skeptical of these drugs from the beginning because I wasn’t sure that Zetia’s mechanism of cholesterol lowering would produce the same benefits that we see with statins.”
The efficacy of Vytorin continues to be questioned for heart disease
Now, there are reports that the US Food and Drug Administration (FDA) has admitted there is little to no effectiveness on the part of Vytorin within the context of preventing heart disease and a Vytorin heart attack. Meanwhile, the potential for cancer associated with the combination of Zetia and Zocor remains a concern.
The so-called SEAS study (Simvastatin and Ezetimibe in Aortic Stenosis, or SEAS) compared simvastatin (Zocor) and ezetimibe (Zetia) with a sugar pill to determine whether intensive lipid-lowering improved clinical outcomes in 1,873 patients with mild to moderate asymptomatic aortic stenosis. Patients were followed up for an average of 4.35 years.
The results, according to the Medicines and Healthcare Products Regulatory Agency in the United Kingdom found no changes in the overall mortality rate amongst the Vytorin group and the control group. However, an unexpected increase in cancer incidence and mortality was observed in the active treatment arm. Study authors noted there is no good evidence to suggest that statins alone increase the risk of cancer, so the cloud of increased cancer risk casts a shadow over ezetimibe (Zetia).
Actual numbers from the SEAS trial stacked up this way, according to WebMD (8/22/08). There were 39 cancer deaths in the Vytorin group against 23 similar deaths in the control group using placebo. WebMD reported that study leader Dr. Terje R. Pederson of Ulleval University Hospital of Oslo, Norway, and colleagues then enlisted the help of Richard Peto, FRCP, professor of medical statistics and epidemiology at Oxford University in England.
Peto looked at the unblinded data from two other, ongoing trials: IMPROVE-IT, and SHARP, the latter study Peto was actually leading. While there was about the same number of incidents of cancers amongst the Vytorin group v. the Zocor control group (313 v. 326 respectively), there were more deaths from cancer amongst the Vytorin group v. the control group taking the statin Zocor alone: 97 deaths in the Vytorin group and 72 cancer deaths in the Zocor control group out of a total of 20,000 combined study participants.
Researchers admit the numbers are small and the cancer risk remote, but a risk nonetheless with further study needed. What irks advocates is the apparent reality that Vytorin carries no more benefit in the prevention of heart disease and a Vytorin heart attack than Zocor alone. Thus, the increased cancer risk is a needless risk.
Is the FDA listening?
Meanwhile, the FDA has been continuing to approve new combination drugs. Five years after the SEAS trial concluded there was no real benefit to reduced heart disease (although there was a realized cut in cholesterol) with Vytorin, the federal drug regulator in 2013 approved Liptruzet, the combination of Zetia with the generic version of Lipitor.
According to the New York Times (5/3/13), critic Dr. Steven E. Nissen was once again displeased. “This is extremely surprising and disturbing,” he said at the time in comments to the New York Times.
And this year the FDA approved Zontivity (vorapaxar), a drug indicated for the prevention of myocardial infarction (MI), stroke and cardiovascular death in high-risk patients. According to reports, this first protease-activated receptor (PAR-1) to be endorsed by the FDA has had a rocky road to approval. In 2011, the TRA2-TIMI 50 phase III trial had to be changed. On top of that the TRACER trial was stopped early. With both trials there was concern over an interim analysis that found an increase in the rate of intracranial hemorrhage (ICH). When, in early 2012, full trial results revealed a significant reduction in ischemic events in the overall trial population (including patients with a history of stroke, MI or established peripheral arterial disease), results also showed an increased rate of moderate or severe bleeding and ICH.
Reviewers with the FDA nonetheless recommended in January 2013 that vorapaxar should be approved anyway. And this spring, the FDA did just that.
The health care industry is bullish on statin drugs and their capacity to effectively lower the so-called “bad” LDL cholesterol toward the prevention of heart disease. To that end, recent changes to treatment and cholesterol management guidelines suggest statins should be used not just for patients at risk for heart disease and stroke, but as preventative therapy for all Americans in a certain age group. While various critics claim there are better and more natural ways of controlling cholesterol, the guidelines suggest a widespread faith in statins amongst health care providers.
But combination drugs like Vytorin, or the relationship of Zetia and Vytorin? That’s another story. Zocor, the statin part of Vytorin, works akin to other statin drugs by blocking an enzyme required for the production of cholesterol. Zetia, on the other hand, works by preventing the gut from absorbing cholesterol.
READ MORE VYTORIN LEGAL NEWS
Vytorin liver damage is one adverse reaction that concerns some amidst the basket of Vytorin side effects. But it is the potential for cancer that remains a cause of increasing angst and concern.
Questionable efficacy for heart disease and the potential for cancer and other side effects appears to be behind a renewed advancement of Vytorin lawsuits.