Statin

In 1951, evidence showed that 75% of 300 corpses from men with an average age of 22 had lesions in their arteries during the Korean War.

In August 1973, Dr. Akira Endo discovered compactin (Mevastatin), an HMG-CoA reductase inhibitor, in the fermentation broth of the fungus Penicillium citrinum. This discovery led to the development of statins for lowering cholesterol levels.

In 1976, Akira Endo discovered Compactin (ML-236B) from Penicillinium citrinum, which showed a reduction in cholesterol synthesis in rats. Compactin was a potent inhibitor of HMG-CoA reductase.

In 1978, Alfred Alberts and his colleagues at Merck Research Laboratories discovered a potent inhibitor of HMG-CoA reductase in a fermentation broth of Aspergillus terreus. The compound was named lovastatin, mevinolin, or monacolin K.

In 1979, Merck isolated mevinolin from Aspergillus terreus, which was later discovered to be the same as monacolin K found by Endo from Monascus ruber. Lovastatin, later renamed Mevacor, was developed and clinical trials were initiated.

In April of 1980, Merck started clinical trials of lovastatin after animal safety studies showed no adverse effects.

In September of 1980, Sankyo Company halted trials with structurally similar compactin due to serious animal toxicity issues.

Mabuchi H. and colleagues investigated the effect of an inhibitor of 3-hydroxy-3-methyglutaryl coenzyme A reductase on serum lipoproteins and ubiquinone-10 levels in patients with familial hypercholesterolemia in 1981.

Tobert JA, Bell GD, Birtwell J, and others studied the cholesterol-lowering effect of Mevinolin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, in healthy volunteers in 1982.

In 1983, Merck decided to resume the clinical development program for lovastatin, focusing initially on patients at very high risk of myocardial infarction.

In 1985, Drs. Brown and Goldstein were awarded the Nobel Prize in Medicine for their groundbreaking work on the cell-surface LDL receptor and its role in cholesterol regulation.

Brown MS and Goldstein JL proposed a receptor-mediated pathway for cholesterol homeostasis in a study published in Science in 1986.

Lovastatin, the first statin, was approved for commercial use in the United States on September 1, 1987. This marked a significant milestone in the treatment of cardiovascular diseases.

Simvastatin, an analog of lovastatin, was approved for marketing in Sweden in 1988, leading to worldwide distribution.

In 1989, Sankyo developed and launched pravastatin, another statin drug, following the success of lovastatin in clinical trials.

In 1991, two semi-synthetic statins, simvastatin (Zocor) by Merck and pravastatin (Pravachol) by BMS, were introduced to the market, expanding the options for cholesterol management.

In April 1994, the results of the Scandinavian Simvastatin Survival Study were published, showing a 30% reduction in all-cause mortality with simvastatin treatment in patients with coronary heart disease. This study played a key role in changing the perception of statins in medical practice.

In 1995, Zocor and Mevacor, both statins developed by Merck, generated over US$1 billion in revenue.

In 1996, atorvastatin (Lipitor) by Parke-Davis was introduced to the market, becoming a widely used synthetic statin for lowering cholesterol.

Bayer marketed cerivastatin, a pure synthetic statin that was 100 times more powerful than Mevacor. However, it was later withdrawn from the market in 2001 due to severe side effects, including a significant increase in rhabdomyolysis cases and reported deaths.

Cerivastatin was approved in 1998 as a statin medication for reducing cholesterol levels.

The book chapter 'Discovery and development of the statins' by Endo A. discusses the history and evolution of statins, the HMG CoA reductase inhibitors, providing insights into their significance in medicine.

Cerivastatin, introduced in 1998, was withdrawn from the market in August 2001 due to reports of fatal rhabdomyolysis.

Ezetimibe, an intestinal cholesterol absorption inhibitor, was introduced by Schering-Plough in 2002. It offered a new approach to lowering cholesterol levels.

In 2003, atorvastatin, also known as Lipitor, became the best-selling pharmaceutical in history, marking a significant milestone in the pharmaceutical industry.

In 2005, statins were included in the World Health Organization's List of Essential Medicines, with simvastatin being the listed medicine.

A scientist named Peter Landers discovered the first statin while studying molds. This discovery was reported in the Wall Street Journal on January 9, 2006.

The JUPITER trial in 2008 demonstrated that statins provided benefits for individuals with elevated high-sensitivity C-reactive protein levels, indicating inflammation, even if they had no history of high cholesterol or heart disease.

A study was published in a journal in May 2010, focusing on the use of statin, an HMG-CoA reductase inhibitor, as a cholesterol-lowering agent to combat atherosclerosis and coronary heart disease.

In 2012, the FDA updated safety information on statin labels, mentioning a slight risk of higher blood sugar levels and potential cognitive effects like confusion and memory loss.

The guideline focused on identifying individuals with very high blood cholesterol levels or high calculated clinical risk to reduce cardiac risk. It emphasized the importance of considering risk rather than solely focusing on blood cholesterol levels, with a strong recommendation for statin therapy.

Both Alirocumab and Evolocumab, fully human anti-PCSK-9 antibodies, received FDA approval in 2015. These medications offered a new treatment option for individuals with high cholesterol levels.

A study discussing the analysis of evidence regarding the effectiveness and safety of statin therapy, published in Lancet.

Research highlighting the changes in statin usage and costs in the US adult population over a decade, published in JAMA Cardiology.

An article in The New York Times discussed the pros and cons of statins.

Clinical studies have been conducted to investigate the use of statins in dementia, lung cancer, nuclear cataracts, hypertension, prostate cancer, and breast cancer.

The U.S. Food and Drug Administration (FDA) requested the removal of the strongest warning against using cholesterol-lowering statins during pregnancy, advising most pregnant patients to stop taking statins.

Recent crystallography studies revealed the structures of the catalytic portion of human HMGR enzyme complexed with six different statins, leading to the discovery of new possibilities for designing even better HMGR inhibitors. A new study utilizing comparative molecular field analysis (CoMFA) and three-dimensional quantitative structure-activity relationship (3D QSAR) identified novel active pharmacophores as potent HMGR inhibitors.

The article 'Statin History' by Tomislav Meštrović was retrieved from News-Medical on April 17, 2024, for citation purposes.