Secondary prevention trials using clofibrate: a joint commentary on the Newcastle and Scottish trials.

Dewar, H. A.; Oliver, M.F.

doi:10.1136/bmj.4.5790.784

Cited by 73 publications

(16 citation statements)

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“…Clofibrate was quite effective, decreasing blood cholesterol by z20%, and it had already been reported to significantly reduce cardiac end points in high-risk men (14). However, it was more effective in decreasing VLDL than LDL, and its use had been associated with significant increases in gallstones (15) and other diseases of the gastrointestinal tract.…”

Section: How Did the Candidate Drugs Look?mentioning

confidence: 99%

Thematic review series: The Pathogenesis of Atherosclerosis. An interpretive history of the cholesterol controversy, part IV: The 1984 Coronary Primary Prevention Trial ends it—almost

Steinberg

2006

Journal of Lipid Research

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Section: How Did the Candidate Drugs Look?mentioning

confidence: 99%

Thematic review series: The Pathogenesis of Atherosclerosis. An interpretive history of the cholesterol controversy, part IV: The 1984 Coronary Primary Prevention Trial ends it—almost

Steinberg

2006

Journal of Lipid Research

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“…In the Newcastle trial, there was a statistically significant reduction in mortality in the clofibrate group when compared with the placebo group, but this was not evident in the Scottish trial. 26 However, in both trials, there was benefit of clofibrate when examining the subgroups of patients with angina and excluding patients with myocardial infarction only. In retrospect, it is clear that the trials were statistically underpowered to allow for such overinterpretation of the details.…”

Section: Early Drug Trialsmentioning

confidence: 99%

The Success Story of LDL Cholesterol Lowering

Pedersen

2016

Circulation Research

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Abstract:We can look back at >100 years of cholesterol research that has brought medicine to a stage where people at risk of severe or fatal coronary heart disease have a much better prognosis than before. This progress has not come about without resistance. Perhaps one of the most debated topics in medicine, the cholesterol controversy, could only be brought to rest through the development of new clinical research methods that were capable of taking advantage of the amazing achievements in basic and pharmacological science after the second World War. It was only after understanding the biochemistry and physiology of cholesterol synthesis, transport and clearance from the blood that medicine could take advantage of drugs and diets to reduce the risk of atherosclerotic diseases. This review points to the highlights of the history of low-density lipoprotein-cholesterol lowering, with the discovery of the low-density lipoprotein receptor and its physiology and not only the development of statins as the stellar moments but also the development of clinical trial methodology as an effective tool to provide scientifically convincing evidence. (Circ Res. 2016;118:721-731.

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“…Both had positive results. In the Newcastle trial, there was a significant reduction in sudden deaths and total CHD mortality and in the rate of first nonfatal infarct [13]. In the Scottish trial, clofibrate had a beneficial but not statistically significant effect in reducing morbidity and mortality from CHD, particularly in patients with pre-existing angina [14].…”

Section: Secondary Prevention Trialsmentioning

confidence: 99%

The clofibrate saga: a retrospective commentary

Oliver¹

2012

Brit J Clinical Pharma

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IntroductionAfter many years of study clofibrate, the first of the fibrates, seemed in the 1960s, to be an effective means of lowering raised plasma cholesterol. It provided an opportunity for examining the key question of whether reduction of plasma cholesterol might lead to reduction in the incidence of coronary heart disease (CHD). While small secondary prevention trials looked promising, a large primary prevention trial (the WHO trial) carried out over 5.3 years on 15 745 men aged 30-59 years provided contradictory results with reduction in nonfatal myocardial infarction, less hypertension, no change in coronary mortality but an increase in non-cardiovascular mortality. Clofibrate also increased gall stone formation and the need for cholecystectomies. Clofibrate was not an appropriate drug to recommend for population control of CHD. It did, however, usher in other fibrates and foreshadowed successful statin trials.

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Secondary prevention trials using clofibrate: a joint commentary on the Newcastle and Scottish trials.

Cited by 73 publications

References 1 publication

Thematic review series: The Pathogenesis of Atherosclerosis. An interpretive history of the cholesterol controversy, part IV: The 1984 Coronary Primary Prevention Trial ends it—almost

Thematic review series: The Pathogenesis of Atherosclerosis. An interpretive history of the cholesterol controversy, part IV: The 1984 Coronary Primary Prevention Trial ends it—almost

The Success Story of LDL Cholesterol Lowering

The clofibrate saga: a retrospective commentary

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