Merck's Long-Acting Niacin Drug Has Serious Side EffectsMain Category: Cardiovascular / Cardiology
Also Included In: Cholesterol | Vascular
Article Date: 11 Mar 2013
Tredaptive, Merck & Co's long-acting niacin medication aimed at elevating HDL cholesterol (good cholesterol) has unexpected serious side effects, researchers announced on Saturday. This is more evidence against using niacin therapy for heart patients.
A major study (HPS2-THRIVE) found that Tredaptive, which consist of the vitamin niacin combined with anti-flushing agent laropiprant, provides no benefit and may even be hazardous for patients with vascular disease.
The HPS2-THRIVE study involving 25,673 patients, which lasted four years, tested a combination of ER (extended-release) niacin with laropiprant on patients with heart disease, stroke and other cardiovascular problems - 14,741 patients were from Europe (United Kingdom and Scandinavia) and 10,932 were from China. They were randomly selected to receive either ER niacin/laropiprant 2g/40mg or a placebo. They were all on simvastatin (with or without ezetimibe) - simvastatin is a widely prescribed cholesterol-lowering drug.
HPS2-THRIVE did not meet the primary endpoint of reducing the risk of a major vascular event, defined as the composite of nonfatal heart attack or heart-related death, a need for angioplasty or bypass surgery, or stroke.
Those in the ER niacin/laropiprant group had approximately the same rates of major vascular events as participants in the placebo group (13.2% vs. 13.7%).
Tredaptive sales stoppedTradaptive was already being abandoned by Merck earlier on this year. In January 2013, doctors were being told that Tredaptive does not work and can cause serious and sometimes fatal side effects. Physicians were told by Merck to stop prescribing the drug.
Tredaptive combines extended-release niacin with laropiprant, an experimental medication designed to prevent facial flushing (linked to niacin).
When Merck announced that Tredaptive did not prevent strokes, heart attacks, death and other complications in heart patients, it abandoned any thoughts of seeking approval from the US FDA (Food and Drug Administration). The company added that sales in several countries where it was available would stop. The company had hoped to market this combination under the trade names Tredaptive in Europe and Cordaptive in the USA.
Several adverse effects linked to TredaptiveA study reported last week found that Tredaptive can cause muscle weakness, especially among Asians. However, findings presented at the American College of Cardiology Scientific Meeting, San Francisco, revealed even more alarming data on the medication.
The researchers in the HPS2-THRIVE study found that patients in the Tredaptive group, compared to those in the placebo group:
"We are disappointed that these results did not show benefits for our patients. Still, finding out a drug is not helping people is just as important as finding that it has benefits - the net result is that people are healthier. Niacin has been used for many years in the belief that it would help patients and prevent heart attacks and stroke, but we now know that its adverse side effects outweigh the benefits when used with current treatments."
Niacin, also called nicotinic acid, vitamin PP or Vitamin B3, has drawn significant attention from patients and doctors because it is said to raise HDL cholesterol (high-density lipoprotein "good" cholesterol), while at the same time reducing "bad" LDL cholesterol (LDL=low-density lipoprotein). Niacin blocks the availability of LDL building blocks by preventing the breakdown of fat.
Uncomfortable facial flushing prevents many patients from taking niacin. The flushing occurs because of PGD2 (prostaglandin2) release. Niacin flush occurs when the blood vessels expand and relax.
A high LDL cholesterol level is a risk factor for stroke and heart disease. At-risk patients are typically put on special diets and encouraged to adopt healthy lifestyles; they are also prescribed medications, such as cholesterol absorption inhibitors, resins and statins. However, even when they have well controlled cholesterol - when their LDL cholesterol has reached 30-80mg/dL, known as 'therapeutic levels' as a result of statin therapy - stroke and heart disease remain major causes of death and disability, Dr. Armitage explained. It was hoped that by adding niacin to standard therapy, these patients outcomes would improve.
In 2011, a clinical trial (AIM-HIGH) was stopped early when the researchers found that niacin did not reduce the risk of cardiovascular events.
Some experts said that AIM-HIGH had too few participants (3,414) to make any conclusion. Dr Armitage says that the latest trial (HPS2-THRIVE), with over twenty-five thousand participants, confirms the findings in the previous study, as well as revealing other harms, with reliable data (because of the size of the trial).
Dr. Armitage and team say that patients currently on niacin preparations to prevent heart disease "should consider talking with their health care providers to determine whether the therapy is appropriate to continue."
Tredaptive (ER niacin/laropiprant) was/is being sold in 40 countries - it has been approved in 70 nations. The FDA had been waiting for data from the HPS2-THRIVE before deciding on whether or not to approve the drug.
Merck & Co funded the HPS2-THRIVE study, which was carried out by Oxford University. Merck provided all of the study drugs. Dr. Armitage indicated no conflict of interest.
Regarding the latest clinical trial, Michael Mendelsohn, M.D., senior vice president, cardiovascular medicine, Merck Research Laboratories, said:
"Merck has a long and proud history of supporting major outcomes studies to investigate challenging scientific questions and advance our collective understanding of cardiovascular medicine. The results of HPS2-THRIVE add substantially to the body of scientific knowledge in this important therapeutic area."
Tredaptive (USA: Cordaptive), short history
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