[A 50-year history of new drugs in Japan: the developments and trends of antihyperlipidemic drugs].
The developments and trends of antihyperlipidemic drugs and their effects on the mortality of coronary heart disease in Japan were investigated. The developed drugs available for hyperlipidemia were recorded with their approval dates by the Ministry of Health and Welfare (Table 1). 1. Antihyperlipidemic drugs have been developed since the late 1950s. Useful drugs among them include the fibrate series and the statin (HMG-CoA reductase inhibitor) series. Clofibrate, developed in 1965, was the first fibrate drug, and pravastatin sodium (Mevalotin(R) Sankyo Co.), developed in 1989, was the first statin drug. They have sure effectiveness for lowering serum cholesterol and triglyceride. But they induce an unfavorable side-effect, rhabdomyolisis, especially after the continuous or simultaneous use of both. The other drug classes using hyperlipidemia include various different types, e.g., probucol, nicotinates, anion exchange resins, ethyl icosapentate, and dextran sodium sulfate. Despite their mild activities, the low incidence of adverse effects make them suitable for supplementary use with fibrates or statins. 2. "Guideline for Diagnosis and Treatment of Hyperlipidemia in Adult" was presented by the Japan Atherosclersis Society in 1997. The standard criteria of serum cholesterol and triglyceride levels in Japanese adults were proposed. The hypercholesterolemia is the state of more than a 220 mg/dl level of serum cholesterol, and hypertriglyceridemia is of more than a 150 mg/dl level of serum triglyceride. The pharmacotherapy should be applied for a high serum level of cholesterol exceeding 240 mg/dl. But the standard routine formula of drug therapy were not indicated in the present guideline. 3. Epidemiological surveys show that hyperlipidemia induces coronary heart diseases in the United States, European countries, and Japan. The mortality of all heart disease patients in Japan increased rapidly from the late 1960s, but the mortality resulting from coronary heart disease was suppressed from 1968. This suppression continued throughout 1994 when artificial statistical changes occurred. It may be due to the newly developed antihyperlipidemic drugs, e.g., the clofibrate group, the statin series, and others (Fig.2).