1987: Lovastatin: First Approved Statin (1987)

Hypercholesterolaemia was recognised as a major cardiovascular risk factor by the mid-20th century,
but effective, tolerable drugs to lower LDL cholesterol were lacking. The statin class emerged from
the convergence of biochemical understanding of cholesterol synthesis and a natural product screening
programme.

Akira Endo, a researcher at Sankyo in Japan, isolated compactin (mevastatin) from Penicillium
citrinum in 1973 after a systematic screen of fungal metabolites for HMG-CoA reductase inhibitors—
the rate-limiting enzyme in hepatic cholesterol synthesis. Compactin's potency was extraordinary,
and Endo's 1976 papers describing it launched global interest in the class. Independently, Merck
chemist Carl Hoffman isolated a related compound, mevinolin (later lovastatin), from Aspergillus
terreus.

Merck's clinical development of lovastatin moved rapidly. The drug reduced LDL cholesterol by
30–40% with a favourable safety profile. FDA approved lovastatin (Mevacor) on 31 August 1987,
making it the first statin approved in the United States.

The clinical significance of statins was confirmed by a series of landmark trials beginning with
the Scandinavian Simvastatin Survival Study (4S, 1994), which demonstrated 30% mortality reduction
in post-MI patients treated with simvastatin. Subsequent trials established statins as the most
evidence-based class in cardiovascular prevention. Atorvastatin (Lipitor) became the best-selling
drug of any class in pharmaceutical history. As of 2023, statins are taken daily by over 200 million
people worldwide.