Correspondence
Pravastatin and Coronary Heart Disease
N Engl J Med 1999; 340:1115-1117April 8, 1999
- Article
To the Editor:
The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) trial (Nov. 5 issue)1 is the third study, after the Scandinavian Simvastatin Survival Study2 and the Cholesterol and Recurrent Events study,3 on the use of 3-hydroxy-3-methylglutaryl–coenzyme A reductase inhibitors for secondary prevention of coronary disease. The positive results of this trial are as marginal as those of the studies that preceded it.
The authors calculated relatively high values for risk reduction with pravastatin as compared with placebo, those being between 11 and 23 percent, which might tempt the inexperienced physician to use statins universally. The relevant values with respect to the reduction of events are, however, much lower and demonstrate a small treatment effect. However, the data on the “number needed to treat” are the most informative for the expert. It can be deduced, for example, that 316 patients have to be treated in order for one coronary event to be averted in 1 patient. Yet, 315 patients would be burdened with a medication, the dangers of which cannot be foreseen in the case of treatment over a period of 20 to 30 years. Pravastatin has no particular advantage over placebo, even for certain subgroups at higher risk (those ≥70 years of age and those with hypertension, diabetes, or total cholesterol levels ≥251 mg per deciliter).
The optimistic conclusion of the authors that “the current low rate of use of cholesterol-lowering therapy among patients with CHD [coronary heart disease] can no longer be accepted” is not defensible when the appropriate measures (reduction of events and number needed to treat) are considered. Incidentally, Krumholz et al.4 already called for patients over 70 years of age not to be burdened with lipid-lowering agents, and Weverling-Rijnsburger et al.5 demonstrated that, in the case of the very elderly, life expectancy shows a positive correlation with cholesterol values.
Healthful living, a varied diet, physical activity, not smoking, and adequate social integration are of greater use than statins for increasing life expectancy. Statins are rather fragile props.
5 ReferencesFrank P. Meyer, M.D.
Otto von Guericke University, D-39120 Magdeburg, Germany1
The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group
Full Text | Web of Science | Medline2
Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S) 3
Sacks FM ,Pfeffer MA ,Moye LA , et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 1996;335:1001-1009
Full Text | Web of Science | Medline4
Krumholz HM ,Seeman TE ,Merrill SS , et al. Lack of association between cholesterol and coronary heart disease mortality and morbidity and all-cause mortality in persons older than 70 years. JAMA 1994;272:1335-1340
CrossRef | Web of Science | Medline5
Weverling-Rijnsburger AW ,Blauw GJ ,Lagaay AM ,Knook DL ,Meinders AE ,Westendorp RG . Total cholesterol and risk of mortality in the oldest old. Lancet 1997;350:1119-1123[Erratum, Lancet 1998;351:70.]
CrossRef | Web of Science | Medline
To the Editor:
The LIPID Study Group concludes, “The current low rate of use of cholesterol-lowering therapy among patients with CHD can no longer be accepted”; however, less than 50 percent of the patients in their study received β-adrenergic blockers. No comment was made about this fact. Beta-blocker therapy effectively reduces the incidence of myocardial infarction in patients with coronary artery disease,1 yet many patients for whom beta-blocker therapy would be ideal are not prescribed these drugs at the time of their discharge from the hospital after acute myocardial infarction.2
Given that pravastatin is much more expensive than beta-blockers and aspirin and that cost constraints are a concern, we ought to try aspirin and beta-blockers before we prescribe a 3-hydroxy-3-methylglutaryl–coenzyme A reductase inhibitor.
2 ReferencesJeffrey M. Bloom, M.D.
Central Coast Primary Care, San Luis Obispo, CA 934011
Gottlieb SS ,McCarter RJ ,Vogel RA . Effect of beta-blockade on mortality among high-risk and low-risk patients after myocardial infarction. N Engl J Med 1998;339:489-497
Full Text | Web of Science | Medline2
Krumholz HM ,Radford MJ ,Wang Y ,Chen J ,Heiat A ,Marciniak TA . National use and effectiveness of β-blockers for the treatment of elderly patients after acute myocardial infarction. JAMA 1998;280:623-629
CrossRef | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: In the LIPID trial of patients with CHD, we studied the effects of pravastatin used with dietary advice and usual care, including myocardial revascularization and drugs such as beta-blockers and aspirin. Similar benefits of pravastatin treatment were seen in those who received beta-blockers and those who did not. Among the 4229 patients receiving beta-blockers at the time of study entry, pravastatin therapy resulted in a 19 percent reduction in coronary events (P=0.01), a 29 percent reduction in mortality from CHD (P=0.004), and a 30 percent reduction in total mortality (P<0.001) as compared with placebo. Consequently, the benefits of pravastatin should be regarded as additional to any benefits of beta-blocker therapy.
The cost effectiveness of pravastatin is the subject of a separate report, but a preliminary analysis has shown this treatment to be cost effective, as compared with other accepted medical interventions. The cost is less than $6,300 ($10,000 Australian) for each year of life gained.
In response to the comments of Meyer: the LIPID trial extends the results of the Scandinavian Simvastatin Survival Study and the Cholesterol and Recurrent Events study in important ways. The results of the LIPID trial provide convincing evidence of a treatment effect on total mortality in patients with CHD and typical cholesterol levels. Although the size of the treatment effect is moderate, with an absolute reduction in mortality of 3.1 percent over 6.1 years, this rate means that 32 patients need to be treated over this period in order for one death to be prevented. If serious nonfatal events (myocardial infarction or stroke) are also considered, only 15 patients need to be treated over 6.1 years in order for one serious fatal or nonfatal event to be prevented. For a treatment with no demonstrated serious side effects and a long-term record of safety, this represents substantial clinical benefit.
The LIPID trial did not have the power to demonstrate reliable separate treatment effects for women, the elderly, or patients with diabetes. However, the results were consistent, with a similar relative reduction in CHD events for each of the prespecified subgroups. Assuming the same relative reduction, a larger absolute benefit will result for those in groups at higher risk. This is particularly so when the patients in the LIPID trial are compared with populations without CHD and those with1 or without2 elevated cholesterol levels. In fact, larger benefits can be expected from the treatment of patients with CHD and average cholesterol levels than from the treatment of those without CHD but with elevated cholesterol levels.
We accept that the LIPID study has not ruled out the possibility of long-term complications associated with treatment over the course of decades. We continue to follow the entire LIPID cohort, with approximately 85 percent of the patients continuing to receive pravastatin therapy. We plan to analyze results after a further two years of follow-up and again after five years.
2 ReferencesAndrew Tonkin, M.D.
National Heart Foundation of Australia, Melbourne, Victoria 3003, AustraliaDavid Hunt, M.D.
Royal Melbourne Hospital, Parkville, Victoria 3050, AustraliaR. John Simes, M.D.
University of Sydney, Sydney, NSW 2006, Australiafor the LIPID Study Group
1
Shepherd J ,Cobbe SM ,Ford I , et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995;333:1301-1307
Full Text | Web of Science | Medline2
Downs JR ,Clearfield M ,Weis S , et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. JAMA 1998;279:1615-1622
CrossRef | Web of Science | Medline
- Citing Articles (3)
Citing Articles
1
WJE Bemelmans. (2003) Voedingsadvies is effectief preventief. Huisarts en Wetenschap 46:6, 573-577
CrossRef2
Joe Flower, Leonard S. Dreifus, Alfred A. Bové, William S. Weintraub. (2000) Technological advances and the next 50 years of cardiology: Glossary. Journal of the American College of Cardiology 35:5, 88B-90B
CrossRef3
Joe Flower, Leonard S Dreifus, Alfred A Bové, William S Weintraub. (2000) Technological advances and the next 50 years of cardiology. Journal of the American College of Cardiology 35:4, 1082-1091
CrossRef
