Prevention of Coronary Heart Disease with Pravastatin in Men with Hypercholesterolemia
James Shepherd, M.D., Stuart M. Cobbe, M.D., Ian Ford, Ph.D., Christopher G. Isles, M.D., A. Ross Lorimer, M.D., Peter W. Macfarlane, Ph.D., James H. McKillop, M.D., Christopher J. Packard, D.Sc., for The West of Scotland Coronary Prevention Study Group
Background Lowering the blood cholesterol level may reduce therisk of coronary heart disease. This double-blind study wasdesigned to determine whether the administration of pravastatinto men with hypercholesterolemia and no history of myocardialinfarction reduced the combined incidence of nonfatal myocardialinfarction and death from coronary heart disease.
Methods We randomly assigned 6595 men, 45 to 64 years of age,with a mean (±SD) plasma cholesterol level of 272±23mg per deciliter (7.0±0.6 mmol per liter) to receivepravastatin (40 mg each evening) or placebo. The average follow-upperiod was 4.9 years. Medical records, electrocardiographicrecordings, and the national death registry were used to determinethe clinical end points.
Results Pravastatin lowered plasma cholesterol levels by 20percent and low-density lipoprotein cholesterol levels by 26percent, whereas there was no change with placebo. There were248 definite coronary events (specified as nonfatal myocardialinfarction or death from coronary heart disease) in the placebogroup, and 174 in the pravastatin group (relative reductionin risk with pravastatin, 31 percent; 95 percent confidenceinterval, 17 to 43 percent; P<0.001). There were similarreductions in the risk of definite nonfatal myocardial infarctions(31 percent reduction, P<0.001), death from coronary heartdisease (definite cases alone: 28 percent reduction, P = 0.13;definite plus suspected cases: 33 percent reduction, P = 0.042),and death from all cardiovascular causes (32 percent reduction,P = 0.033). There was no excess of deaths from noncardiovascularcauses in the pravastatin group. We observed a 22 percent reductionin the risk of death from any cause in the pravastatin group(95 percent confidence interval, 0 to 40 percent; P = 0.051).
Conclusions Treatment with pravastatin significantly reducedthe incidence of myocardial infarction and death from cardiovascularcauses without adversely affecting the risk of death from noncardiovascularcauses in men with moderate hypercholesterolemia and no historyof myocardial infarction.
Earlier trials of lipid-lowering drugs in the primary preventionof coronary heart disease have demonstrated that lowering cholesterollevels in middle-aged men with hypercholesterolemia reducesthe incidence of myocardial infarction.1,2,3,4 However, thesestudies, because of their design and low rates of observed events,were unable to show a clear effect of therapy on the risk ofdeath from coronary heart disease or death from any cause. Ameta-analysis of the trials provided support for the likelihoodthat therapy lowered the risk of death from coronary heart disease,but it also aroused concern that the risk of death from noncardiovascularcauses might be increased by treatment.5,6,7,8 Whether thislatter association was due to chance, to the reduction in cholesterolitself, or to an adverse effect of the drugs is not clear.
Recently, a new class of lipid-lowering drug, the 3-hydroxy-3-methylglutaryl–coenzymeA reductase inhibitors, has been introduced into clinical practice.These drugs block endogenous synthesis of cholesterol and reducethe levels of low-density lipoprotein (LDL) cholesterol. Theyslow the progression of coronary disease and reduce the incidenceof death from coronary causes and death from any cause in menwith manifest coronary heart disease.9,10,11,12,13,14,15 Thepresent study was designed to evaluate the effectiveness ofa reductase inhibitor, pravastatin (Pravachol), in preventingcoronary events in men with moderate hypercholesterolemia andno history of myocardial infarction.
Methods
Design
The objective was to enroll approximately 6000 middle-aged men,randomly assigned in a double-blind fashion to receive eitherpravastatin (40 mg each evening) or placebo and to record theirclinical progress over a period of five years. The details ofthe study design, including the definitions of the end points,have been described previously.16 Briefly, the primary end pointof the study was the occurrence of nonfatal myocardial infarctionor death from coronary heart disease as a first event; thesetwo categories were combined. Other principal end points werethe occurrence of death from coronary heart disease and nonfatalmyocardial infarction. In all categories, the events were classifiedas either definite or suspected. In addition to the main endpoints, the effect of treatment on death from cardiovascularcauses, death from any cause, and the frequency of coronaryrevascularization procedures was analyzed.
All subjects provided written informed consent. The study wasapproved by the ethics committees of the University of Glasgowand all participating health boards.
Recruitment and Follow-Up
Coronary screening clinics were established in primary medicalcare facilities throughout the West of Scotland district. Approximately160,000 men ranging in age from 45 to 64 years were invitedto attend the clinics to assess their coronary risk factors.A total of 81,161 appeared for the first visit, and those whosenonfasting plasma cholesterol level was at least 252 mg perdeciliter (6.5 mmol per liter) but who had no history of myocardialinfarction were given lipid-lowering dietary advice17 and askedto return four weeks later. A total of 20,914 men returned forthe second visit, at which time a lipoprotein profile was obtainedthat measured plasma cholesterol, the cholesterol content ofLDL and high-density lipoprotein (HDL), and plasma triglycerideswhile the subjects were fasting. If on this occasion the LDLcholesterol level was at least 155 mg per deciliter (4.0 mmolper liter) and the subject had no exclusion criteria,16 he wasadvised to stay on the lipid-lowering diet for a further fourweeks and then to return for a third visit (13,654 attended),at which time a second lipoprotein profile and a 12-lead electrocardiogram(ECG) were obtained. On the fourth visit the patients underwentrandomization if they met the following criteria: fasting LDLcholesterol level of at least 155 mg per deciliter during thesecond and third visits, with at least one value of 174 mg perdeciliter or above (4.5 mmol per liter) and one value of 232mg per deciliter or below (6.0 mmol per liter); no serious ECGabnormalities according to Minnesota code18 1 (pathologic Qwaves), 4-1, 5-1, or 7-1-1 or arrhythmia such as atrial fibrillation;and no history of myocardial infarction or other serious illness,although men with stable angina who had not been hospitalizedwithin the previous 12 months were eligible. Further detailsof the inclusion and exclusion criteria were described previously.16
The subjects were seen at three-month intervals, and dietaryadvice was reinforced on each occasion. A fasting lipoproteinprofile was obtained every six months, and an ECG was recordedannually or as required clinically. The subjects received afull medical examination by a physician each year.
Laboratory Analyses
The cholesterol measurement during the first visit was performedon a Reflotron bench-top analyzer (Boehringer–Mannheim,Lewes, Kent, United Kingdom). All subsequent laboratory analyses,including biochemical, hematologic, and lipoprotein profiles,were conducted at the central laboratory at the Glasgow RoyalInfirmary. Lipoprotein profiles were determined according tothe Lipid Research Clinics protocol19 with enzymatic cholesteroland triglyceride assays. The laboratory was certified throughthe Lipid Standardization Program of the Centers for DiseaseControl and Prevention in Atlanta. Abnormalities in the resultsof blood tests were identified with the use of published referenceranges.16
Siemens Sicard 440 electrocardiographs were used to record the12-lead ECGs, and the data were transmitted by telephone tothe ECG core laboratory at the Glasgow Royal Infirmary for storageon a central Mingocare data base (Siemens Elema, Stockholm,Sweden) and subsequent automated classification according tothe Minnesota code, including serial comparisons.18,20,21,22All ECG results were verified by visual inspection.
Identification and Classification of End Points
At each follow-up visit, adverse events were documented on thebasis of the subjects' recall, and if appropriate, further informationwas obtained from hospital records. All data on randomized subjectswere flagged electronically on national computer data basesso that the numbers of deaths, incident cancers, hospitalizations,and cardiac surgeries could be monitored according to previouslydescribed methods.23 Potential end points were reviewed andclassified according to predefined criteria16 by the End-PointsCommittee, whereas non–coronary heart disease events werereviewed and classified by the Adverse-Events Committee. Theprogress and conduct of the study were monitored regularly bythe independent, unblinded Data and Safety Monitoring Committee.Except for the trial statistician and his assistant, all trialpersonnel remained unaware of the subjects' treatment assignmentsthroughout the study.
Statistical Analysis
All data were analyzed according to the intention-to-treat principle.The results of the two fasting lipoprotein profiles obtainedduring visits 2 and 3 were averaged to produce base-line values.The LDL cholesterol results were analyzed according to boththe treatment actually received and the intention-to-treat principle.The analysis based on actual treatment used only the measuredlipid levels in subjects who had attended the previous scheduledvisit and who had been issued with trial medication at thatvisit. For the intention-to-treat analysis, all recorded levelswere included, without reference to the subjects' degree ofcompliance at previous visits. In addition, in cases in whichno lipid value was available for a scheduled visit and no medicationhad been issued at the previous visit, the subject's base-linelevel was used. For each end-point category, the lengths oftime to a first event were compared with use of the log-ranktest, and the relative reduction in risk resulting from pravastatintreatment, with 95 percent confidence intervals, was calculatedwith the Cox proportional-hazards model.24 In addition, Kaplan–Meiertime-to-event curves were used to estimate the absolute riskof each event at five years for each treatment group. When asilent myocardial infarction was detected on the basis of serialcomparison of ECGs, the event was considered to have occurredmidway between the first diagnostic ECG and the previous ECG.Two-tailed P values were used throughout.
For the primary end point, an analysis was performed for predefinedsubgroups16 characterized at base line according to age (<55years or >55 years), smoking status (smoker or nonsmokerof cigarettes, cigars, or pipes), and whether at least two ofthe following risk factors were present: smoking, hypertension,a history of chest pain or intermittent claudication (as indicatedby positive responses on the Rose questionnaire), diabetes,and a minor ECG abnormality associated with coronary heart disease(Minnesota code 4-2, 4-3, 5-2, or 5-3).
In addition, the effect of treatment was examined in a subgroupwith and a subgroup without vascular disease at base line. Vasculardisease was considered to be present if there was evidence ofangina, intermittent claudication, stroke, transient ischemicattack, and ECG abnormalities according to the Minnesota code.Finally, the influence of base-line lipid levels on the effectof treatment was assessed by dividing the randomized populationaccording to the median plasma cholesterol, LDL or HDL cholesterol,or plasma triglyceride concentration.
The Data and Safety Monitoring Committee conducted annual reviewsof the main end points according to the O'Brien and Flemingcriteria for stopping the trial prematurely.25 The overall Pvalue indicating statistical significance was set at 0.01.
Results
A total of 6595 subjects underwent randomization. The clinicalcharacteristics of the subjects who were screened and thosewho were randomized have been described previously.26 The firstpatient was enrolled on February 1, 1989, and recruitment wascompleted by September 30, 1991. The final visits were madebetween February and May 1995, by which time the study populationhad accrued 32,216 subject-years of follow-up (an average of4.9 years per subject). At the end of the study, the vital andclinical status of all randomized subjects was ascertained.The base-line characteristics of the pravastatin and placebogroups are summarized in Table 1. As expected in a trial ofthis size, the groups were well balanced. For the study populationas a whole, the average (±SD) plasma cholesterol levelwas 272±23 mg per deciliter (7.0±0.6 mmol perliter), the LDL cholesterol level was 192±17 mg per deciliter(5.0±0.5 mmol per liter), and the HDL cholesterol levelwas 44±9 mg per deciliter (1.14±0.26 mmol perliter). On the basis of positive responses on the Rose questionnaire,evidence of angina was present in 5 percent of the men, whereas8 percent had ECG ST-T wave changes (Minnesota codes 4-2, 4-3,5-2, and 5-3). The prevalence of self-reported diabetes mellituswas 1 percent, and that of hypertension was 16 percent; 44 percentof the subjects were current smokers.
Table 1. Base-Line Characteristics of the Randomized Subjects, According to Treatment Group.
Withdrawals
The cumulative rates of withdrawal from treatment in the placeboand pravastatin groups were 14.9 percent and 15.5 percent, respectively,at year 1, 19.1 percent and 19.4 percent at year 2, 22.5 percentand 22.7 percent at year 3, 25.2 percent and 24.7 percent atyear 4, and 30.8 percent and 29.6 percent at year 5. There wasno significant difference in the withdrawal rates between thetwo groups at any time. The disproportionate increase from year4 to year 5 can be attributed to the withdrawal from the studyof some subjects who had completed the five years of follow-upand who could have proceeded further but did not wish to doso.
Reduction in Lipid Levels
When the data were analyzed according to the treatment actuallyreceived, pravastatin was found to have lowered plasma levelsof cholesterol by 20 percent, LDL cholesterol by 26 percent(Figure 1), and triglycerides by 12 percent, whereas HDL cholesterolwas increased by 5 percent. There were no such changes withplacebo. When the data were analyzed according to the intention-to-treatprinciple, because such analysis includes subjects who withdrewand noncompliant subjects, there was an apparent reduction inthe observed difference in LDL cholesterol levels between treatmentgroups over time. This result is in contrast to that based onactual treatment, which showed that the differnce was maintained.
Figure 1. Effects of Pravastatin Therapy on Plasma LDL Cholesterol Levels.
To convert values for cholesterol to millimoles per liter, multiply by 0.026.
End Points
As compared with placebo, pravastatin produced a significantreduction in the risk of the combined primary end point of definitenonfatal myocardial infarction and death from coronary heartdisease (reduction, 31 percent; 95 percent confidence interval,17 to 43 percent; P<0.001; absolute difference in the riskat five years, 2.4 percentage points) (Table 2 and Figure 2).The effects of pravastatin on other principal end points aregiven in Table 2, Figure 3A, Figure 3B, Figure 3C, Figure 3D,and Figure 3E. The reduction in the risk of nonfatal myocardialinfarction was significant (P<0.001) whether the definitecases of myocardial infarction were considered alone or in combinationwith suspected cases. Excluding silent myocardial infarctionsfrom the analysis of the primary end point did not affect theoutcome (Table 2). For the end point of death from coronaryheart disease, there was a significant treatment effect in theanalysis of both definite and suspected cases (risk reduction,33 percent; 95 percent confidence interval, 1 to 55 percent;P = 0.042), but not in the analysis of definite cases alone,probably because of the smaller number of events in this group.However, there was a similar reduction in risk (28 percent).When the effect of treatment with pravastatin on death fromall cardiovascular causes was analyzed, a 32 percent reductionin risk (95 percent confidence interval, 3 to 53 percent; P= 0.033) was observed. Treatment with pravastatin was associatedwith similar reductions in the frequency of coronary angiography(31 percent; 95 percent confidence interval, 10 to 47 percent;P = 0.007) and revascularization procedures (37 percent; 95percent confidence interval, 11 to 56 percent; P = 0.009).
Figure 2. Kaplan–Meier Analysis of the Time to a Definite Nonfatal Myocardial Infarction or Death from Coronary Heart Disease, According to Treatment Group.
Figure 3. Kaplan–Meier Analysis of the Time to a Definite Nonfatal Myocardial Infarction (Panel A), Death Definitely from Coronary Heart Disease (Panel B), Death from All Cardiovascular Causes (Panel C), Death from Noncardiovascular Causes (Panel D), and Death from Any Cause (Panel E), According to Treatment Group.
There were 56 deaths from noncardiovascular causes in the pravastatingroup and 62 in the placebo group (P = 0.54). There was no significantdifference between treatment groups in the numbers of deathsfrom cancer, suicide, or trauma. There were 46 strokes (6 ofwhich were fatal) in the pravastatin group and 51 (4 fatal)in the placebo group. In the pravastatin group, the reductionin the number of deaths from cardiovascular causes in the absenceof any increase in the number of deaths from noncardiovascularcauses resulted in a 22 percent reduction in the overall riskof death (95 percent confidence interval, 0 to 40 percent; P= 0.051).
The beneficial effects of pravastatin therapy were evident inall subgroups (Table 3). The numbers of subjects in the subgroupswith either multiple risk factors at base line or vascular diseaseat base line were too small to show a statistically significanteffect.
Table 3. Incidence of the Primary End Point, According to Subgroup.
Other Adverse Events
In the pravastatin group 116 subjects had incident (fatal ornonfatal) cancers, as compared with 106 in the placebo group(P = 0.55). These figures include cases of malignant melanomabut not minor skin cancers. For the placebo and pravastatingroups, respectively, there were 30 and 31 gastrointestinalcancers, 26 and 32 genitourinary cancers, 28 and 27 respiratorytract cancers, and 22 and 26 other cancers. Twenty subjectsin the pravastatin group reported myalgia, and 97 muscle aches.The corresponding numbers in the placebo group were 19 and 102(P not significant). Four subjects (three in the pravastatingroup and one in the placebo group) had asymptomatic episodesof elevated creatine kinase concentrations (>10 times theupper reference limit). Elevations in aspartate aminotransferaseand alanine aminotransferase values (>3 times the upper referencelimits) were recorded for 26 and 16 subjects, respectively,in the pravastatin group, as compared with 20 and 12 subjectsin the placebo group (P not significant).
Discussion
As compared with placebo, pravastatin reduced the risk of fatalor nonfatal coronary events in middle-aged men with hypercholesterolemiaand no history of myocardial infarction by approximately 30percent. The beneficial effects of treatment were remarkablyconsistent across a variety of coronary end points. In contrastto the results of studies using resins, fibrates, or other 3-hydroxy-3-methylglutaryl–coenzymeA reductase inhibitors,1,2,3,4,9 the time-to-event curves beganto diverge within six months of the initiation of treatmentand continued to do so at the same rate throughout the trial.The frequency of the need for coronary angiography and revascularizationprocedures was significantly lower in the pravastatin groupthan in the placebo group.
The subjects in this study were representative of the generalpopulation in terms of socioeconomic status and risk factors(Table 1). Their plasma cholesterol levels were in the highestquartile of the range found in the British population.27 A numberhad evidence of minor vascular disease, and in order to makethe findings of the trial applicable to typical middle-agedmen with hypercholesterolemia, they were not excluded.
In line with accepted guidelines,28 the LDL cholesterol levelwas used as a criterion for entry into the study. As comparedwith placebo, pravastatin produced a major reduction in thislipoprotein fraction (Figure 1) and moderate decreases in plasmatriglycerides, as well as an increase in HDL cholesterol. Thesechanges are in line with the expected response to pravastatin,29and all could potentially result in clinical benefit. The changesin the LDL cholesterol level are more substantial than thoseobserved in earlier primary prevention studies.1,2,3,4
When the subjects were divided into two groups according totheir lipid levels at base line, we found that coronary riskwas related to higher plasma LDL cholesterol and triglyceridelevels (i.e., levels above the median values) and lower HDLcholesterol levels (i.e., levels below the median value) (Table 3).The plasma cholesterol level was not a significant factor,principally because of the narrow range of cholesterol valuesused as a criterion for entry into the study. The relative reductionin risk with pravastatin therapy was statistically significantand of a similar magnitude in subjects with lipid values aboveand below the median.
The relative reductions in risk attributable to pravastatintherapy were not affected by age (<55 years vs. >55 years)or smoking status. Furthermore, a significant treatment effectwas seen in the subgroup without multiple risk factors and thesubgroup without preexisting vascular disease. Thus, it is possibleto conclude that in the subjects who might be considered tofall strictly into the primary-prevention category, pravastatintherapy produced a significant reduction in the relative riskof a coronary event.
Pravastatin therapy was well tolerated and resulted in no morestudy withdrawals than placebo. In particular, as in an earlierstudy,15 there was no evidence that pravastatin adversely affectedliver function or caused myopathy. Our results support thoseof a recent secondary-prevention trial9 that found that lipidlowering with a 3-hydroxy-3-methylglutaryl–coenzyme Areductase inhibitor is not associated with an increased riskof death from noncardiovascular causes. As in that earlier trial,9a comparison of the treatment and placebo groups showed no significantincrease in the incidence of fatal or incident cancers or deathsdue to suicide or trauma. More data on the adverse-event profileof this class of drugs will become available as the resultsof other prevention trials are published. In the current study,the benefit of pravastatin therapy with respect to fatal coronaryevents and the absence of any increase in the number of deathsfrom other causes led to a 22 percent reduction in the relativerisk of death from any cause (P = 0.051).
From the data in Table 2, it can be estimated that treating1000 middle-aged men with hypercholesterolemia and no evidenceof a previous myocardial infarction with pravastatin for fiveyears will result in 14 fewer coronary angiograms, 8 fewer revascularizationprocedures, 20 fewer nonfatal myocardial infarctions, 7 fewerdeaths from cardiovascular causes, and 2 fewer deaths from othercauses than would be expected in the absence of treatment. Sincethese figures are based on an intention-to-treat analysis, themagnitude of the benefit in fully compliant subjects is likelyto be greater. These findings can be compared favorably withthe results of the Medical Research Council trial30,31 of thetreatment of mild hypertension in middle-aged subjects. In thatstudy, it was estimated that five years of active treatmentof 1000 men ranging in age from 35 to 64 years would resultin six fewer strokes and two fewer cardiovascular events thanwould be expected. Thus, our results indicate that reducingcholesterol levels with pravastatin reduces the risk of coronaryevents in asymptomatic subjects with hypercholesterolemia.
Supported by a research grant from the Bristol-Myers SquibbPharmaceutical Research Institute, Princeton, N.J.
* The members of the West of Scotland Coronary Prevention StudyGroup are listed in the Appendix.
Source Information
From the Departments of Pathological Biochemistry (J.S., C.J.P.), Medical Cardiology (S.M.C., A.R.L., P.W.M.), and Medicine (J.H.M.), University of Glasgow and Royal Infirmary, Glasgow; Robertson Centre for Biostatistics, University of Glasgow, Glasgow (I.F.); and the Department of Medicine, Dumfries and Galloway District General Hospital, Dumfries (C.G.I.) — all in Scotland.
Address reprint requests to Dr. Ford at the Robertson Centre for Biostatistics, Boyd Orr Bldg., University of Glasgow, Glasgow G12 8QQ, Scotland.
References
A co-operative trial in the primary prevention of ischaemic heart disease using clofibrate: report from the Committee of Principal Investigators. Br Heart J 1978;40:1069-1118. [Free Full Text]
The Lipid Research Clinics Coronary Primary Prevention Trial results. I. Reduction in incidence of coronary heart disease. JAMA 1984;251:351-364. [Free Full Text]
The Lipid Research Clinics Coronary Primary Prevention Trial results. II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. JAMA 1984;251:365-374. [Free Full Text]
Frick MH, Elo O, Haapa K, et al. Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia: safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med 1987;317:1237-1245. [Abstract]
Oliver MF. Might treatment of hypercholesterolaemia increase non-cardiac mortality? Lancet 1991;337:1529-1531. [CrossRef][Medline]
Hulley SB, Walsh JMB, Newman TB. Health policy on blood cholesterol: time to change directions. Circulation 1992;86:1026-1029. [Free Full Text]
Davey Smith G, Pekkanen J. Should there be a moratorium on the use of cholesterol lowering drugs? BMJ 1992;304:431-434.
LaRosa JC, Hunninghake D, Bush D, et al. The cholesterol facts: a summary of the evidence relating dietary fats, serum cholesterol, and coronary heart disease: a joint statement by the American Heart Association and the National Heart, Lung, and Blood Institute. Circulation 1990;81:1721-1733. [Free Full Text]
The Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344:1383-1389. [CrossRef][Medline]
MAAS Investigators. Effect of simvastatin on coronary atheroma: the Multicentre Anti-Atheroma Study (MAAS). Lancet 1994;344:633-638. [Erratum, Lancet 1994;344:762.] [CrossRef][Medline]
Furberg CD, Adams HP Jr, Applegate WB, et al. Effect of lovastatin on early carotid atherosclerosis and cardiovascular events. Circulation 1994;90:1679-1687. [Free Full Text]
Jukema JW, Bruschke AVG, van Boven AJ, et al. Effects of lipid lowering by pravastatin on progression and regression of coronary artery disease in symptomatic men with normal to moderately elevated serum cholesterol levels: the Regression Growth Evaluation Statin Study (REGRESS). Circulation 1995;91:2528-2540. [Free Full Text]
Crouse JR III, Byington RP, Bond MG, et al. Pravastatin, Lipids, and Atherosclerosis in the Carotid Arteries (PLAC-II). Am J Cardiol 1995;75:455-459. [Erratum, J Cardiol 1995;75:862.] [CrossRef][Medline]
Pitt B, Mancini GBJ, Ellis SG, Rosman HS, Park J-SP, McGovern ME. Pravastatin Limitation of Atherosclerosis in the Coronary Arteries (PLAC I): reduction in atherosclerosis progression and clinical events. J Am Coll Cardiol (in press).
The Pravastatin Multinational Study Group for Cardiac Risk Patients. Effects of pravastatin in patients with serum total cholesterol levels from 5.2 to 7.8 mmol/liter (200 to 300 mg/dl) plus two additional atherosclerotic risk factors. Am J Cardiol 1993;72:1031-1037. [CrossRef][Medline]
West of Scotland Coronary Prevention Study Group. A coronary primary prevention study of Scottish men age 45-64 years: trial design. J Clin Epidemiol 1992;45:849-860. [CrossRef][Medline]
EAS Task Force for Prevention of Coronary Heart Disease. Prevention of coronary heart disease: scientific background and new clinical guidelines. Nutr Metab Cardiovasc Dis 1992;2:113-156.
Prineas RJ, Crow RS, Blackburn H. The Minnesota code manual of electrocardiographic findings: standards and procedures for measurement and classification. Boston: John Wright, PSG, 1982.
Lipid Research Clinics manual of laboratory operations, 1975. Washington, D.C.: Government Printing Office, 1975. (DHEW publication no. (NIH) 85-268.)
Crow RS, Prineas RJ, Jacobs DR Jr, Blackburn H. A new epidemiologic classification system for interim myocardial infarction from serial electrocardiographic changes. Am J Cardiol 1989;64:454-461. [CrossRef][Medline]
Macfarlane PW, Devine B, Latif S, McLaughlin S, Shoat DB, Watts MP. Methodology of ECG interpretation in the Glasgow program. Methods Inf Med 1990;29:354-361. [Medline]
Macfarlane PW, Latif S, Shoat DS, Cobbe SM. Automated serial ECG comparison using the Minnesota Code. Eur Heart J 1990;11:Suppl:411-411.abstract
West of Scotland Coronary Prevention Study Group. Computerised record linkage: compared with traditional follow-up methods in clinical trials and illustrated in a prospective epidemiologic study. J Clin Epidemiol (in press).
Collett D. Modelling survival data in medical research. London: Chapman & Hall, 1994.
O'Brien PC, Fleming TR. A multiple testing procedure for clinical trials. Biometrics 1979;35:549-556. [CrossRef][Medline]
West of Scotland Coronary Prevention Study Group. Screening experience and baseline characteristics in the West of Scotland Coronary Prevention Study. Am J Cardiol 1995;76:485-491. [CrossRef][Medline]
Mann JI, Lewis B, Shepherd J, et al. Blood lipid concentrations and other cardiovascular risk factors: distribution, prevalence, and detection in Britain. BMJ 1988;296:1702-1706.
Summary of the second report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel II). JAMA 1993;269:3015-3023. [Free Full Text]
Jones PH, Farmer JA, Cressman MD, et al. Once-daily pravastatin in patients with primary hypercholesterolemia: a dose-response study. Clin Cardiol 1991;14:146-151. [Medline]
Medical Research Council Working Party. MRC trial of treatment of mild hypertension: principal results. BMJ 1985;291:97-104.
Miall WE, Greenberg G. Mild hypertension: is there pressure to treat? An account of the MRC trial. Cambridge, United Kingdom: Cambridge University Press, 1987.
Appendix
The members of the West of Scotland Coronary Prevention Studyare as follows: Executive Committee (Voting Members) —J. Shepherd (chairman), S.M. Cobbe, A.R. Lorimer, J.H. McKillop,I. Ford, C.J. Packard, P.W. Macfarlane, and G.C. Isles; Dataand Safety Monitoring Committee — M.F. Oliver (chairman),A.F. Lever, B.W. Brown, J.G.G. Ledingham, S.J. Pocock, and B.M.Rifkind; End-Points Committee — S.M. Cobbe, B.D. Vallance,P.W. Macfarlane; Adverse-Events Committee — A.R. Lorimer,J.H. McKillop, and D. Ballantyne; Data-Center Staff —L. Anderson, D. Duncan, J. McGrath, S. Kean, A. Lawrence, V.Montgomery, and J. Norrie; Population Screening — M. Percy;Clinical Coordination, Monitoring, and Administration —E. Pomphrey, A. Whitehouse, P. Cameron, P. Parker, F. Porteous,L. Fletcher, and C. Kilday; Computerized ECG Analysis —D. Shoat (deceased), S. Latif, and J. Kennedy; Laboratory Operations— M.A. Bell and R. Birrell; and Company Liaison and GeneralSupport — M. Mellies, J. Meyer, and W. Campbell.
Prevention of Coronary Heart Disease with Pravastatin
Rogers S., Samani N. J., de Bono D. P., Davis D. R., Shepherd J., Cobbe S. M., Ford I., The West of Scotland Coronary Prevention Study Group , Pedersen T. R.
Extract |
Full Text
N Engl J Med 1996;
334:1333-1335, May 16, 1996.
Correspondence
Drugs in Cardiac Transplantation
Ballantyne C. M., von Moltke L. L., Greenblatt D. J., Kobashigawa J., Keogh A. M., Spratt P., Valantine H. A.
Extract |
Full Text
N Engl J Med 1996;
334:400-402, Feb 8, 1996.
Correspondence
Melander, O., Newton-Cheh, C., Almgren, P., Hedblad, B., Berglund, G., Engstrom, G., Persson, M., Smith, J. G., Magnusson, M., Christensson, A., Struck, J., Morgenthaler, N. G., Bergmann, A., Pencina, M. J., Wang, T. J.
(2009). Novel and Conventional Biomarkers for Prediction of Incident Cardiovascular Events in the Community. JAMA
302: 49-57
[Abstract][Full Text]
Meaney, A., Ceballos, G., Asbun, J., Solache, G., Mendoza, E., Vela, A., Meaney, E.
(2009). The Vytorin on Carotid Intima-Media Thickness and Overall Arterial Rigidity (VYCTOR) Study. J Clin Pharmacol
49: 838-847
[Abstract][Full Text]
Thanassoulis, G., O'Donnell, C. J.
(2009). Mendelian Randomization: Nature's Randomized Trial in the Post-Genome Era. JAMA
301: 2386-2388
[Full Text]
Than, M. P, Flaws, D. F
(2009). Communicating diagnostic uncertainties to patients: The problems of explaining unclear diagnosis and risk. Evid. Based Med.
14: 66-67
[Full Text]
Grimes, D. S.
(2009). History of the cholesterol hypothesis in Britain. QJM
102: 436-438
[Full Text]
Kokudai, M., Inui, N., Takeuchi, K., Sakaeda, T., Kagawa, Y., Watanabe, H.
(2009). Effects of Statins on the Pharmacokinetics of Midazolam in Healthy Volunteers. J Clin Pharmacol
49: 568-573
[Abstract][Full Text]
Wilson, S. R., Scirica, B. M., Braunwald, E., Murphy, S. A., Karwatowska-Prokopczuk, E., Buros, J. L., Chaitman, B. R., Morrow, D. A.
(2009). Efficacy of ranolazine in patients with chronic angina observations from the randomized, double-blind, placebo-controlled MERLIN-TIMI (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Segment Elevation Acute Coronary Syndromes) 36 Trial.. J Am Coll Cardiol
53: 1510-1516
[Abstract][Full Text]
Dormuth, C. R., Patrick, A. R., Shrank, W. H., Wright, J. M., Glynn, R. J., Sutherland, J., Brookhart, M. A.
(2009). Statin Adherence and Risk of Accidents: A Cautionary Tale. Circulation
119: 2051-2057
[Abstract][Full Text]
Hassan, C., Pickhardt, P. J., Laghi, A., Zullo, A., Kim, D. H., Iafrate, F., Di Giulio, L., Morini, S.
(2009). Impact of Whole-Body CT Screening on the Cost-effectiveness of CT Colonography. Radiology
251: 156-165
[Abstract][Full Text]
Karalis, D. G.
(2009). Intensive Lowering of Low-Density Lipoprotein Cholesterol Levels for Primary Prevention of Coronary Artery Disease. Mayo Clin Proc.
84: 345-352
[Abstract][Full Text]
Jick, S S, Choi, H, Li, L, McInnes, I B, Sattar, N
(2009). Hyperlipidaemia, statin use and the risk of developing rheumatoid arthritis. Ann Rheum Dis
68: 546-551
[Abstract][Full Text]
Chhatriwalla, A. K., Nicholls, S. J., Wang, T. H., Wolski, K., Sipahi, I., Crowe, T., Schoenhagen, P., Kapadia, S., Tuzcu, E. M., Nissen, S. E.
(2009). Low levels of low-density lipoprotein cholesterol and blood pressure and progression of coronary atherosclerosis.. J Am Coll Cardiol
53: 1110-1115
[Abstract][Full Text]
Alexander, K. P., Blazing, M. A., Rosenson, R. S., Hazard, E., Aronow, W. S., Smith, S. C. Jr, Ohman, E. M.
(2009). Management of Hyperlipidemia in Older Adults. J CARDIOVASC PHARMACOL THER
14: 49-58
[Abstract]
Lester, S. J., Eleid, M. F., Khandheria, B. K., Hurst, R. T.
(2009). Carotid Intima-Media Thickness and Coronary Artery Calcium Score as Indications of Subclinical Atherosclerosis. Mayo Clin Proc.
84: 229-233
[Abstract][Full Text]
Pletcher, M. J., Lazar, L., Bibbins-Domingo, K., Moran, A., Rodondi, N., Coxson, P., Lightwood, J., Williams, L., Goldman, L.
(2009). Comparing Impact and Cost-Effectiveness of Primary Prevention Strategies for Lipid-Lowering. ANN INTERN MED
150: 243-254
[Abstract][Full Text]
Weingartner, O., Bohm, M., Laufs, U.
(2009). Controversial role of plant sterol esters in the management of hypercholesterolaemia. Eur Heart J
30: 404-409
[Full Text]
Silbernagel, G., Fauler, G., Renner, W., Landl, E. M., Hoffmann, M. M., Winkelmann, B. R., Boehm, B. O., Marz, W.
(2009). The relationships of cholesterol metabolism and plasma plant sterols with the severity of coronary artery disease. J. Lipid Res.
50: 334-341
[Abstract][Full Text]
Thompson, G. R.
(2009). History of the cholesterol controversy in Britain. QJM
102: 81-86
[Abstract][Full Text]
Whayne, T. F. Jr
(2009). Response to Letter of Mascitelli L, Ravnskov U, Pezzetta F, and Goldstein M. ANGIOLOGY
60: 129-130
Kushiro, T., Mizuno, K., Nakaya, N., Ohashi, Y., Tajima, N., Teramoto, T., Uchiyama, S., Nakamura, H., for the Management of Elevated Cholesterol in the,
(2009). Pravastatin for Cardiovascular Event Primary Prevention in Patients With Mild-to-Moderate Hypertension in the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) Study. Hypertension
53: 135-141
[Abstract][Full Text]
Robinson, J. G., Wang, S., Smith, B. J., Jacobson, T. A.
(2009). Meta-analysis of the relationship between non-high-density lipoprotein cholesterol reduction and coronary heart disease risk.. J Am Coll Cardiol
53: 316-322
[Abstract][Full Text]
Liu, P.-Y., Liu, Y.-W., Lin, L.-J., Chen, J.-H., Liao, J. K.
(2009). Evidence for Statin Pleiotropy in Humans: Differential Effects of Statins and Ezetimibe on Rho-Associated Coiled-Coil Containing Protein Kinase Activity, Endothelial Function, and Inflammation. Circulation
119: 131-138
[Abstract][Full Text]
Sakamoto, N., Hayashi, S., Mukae, H., Vincent, R., Hogg, J. C., van Eeden, S. F.
(2009). Effect of Atorvastatin on PM10-induced Cytokine Production by Human Alveolar Macrophages and Bronchial Epithelial Cells. International Journal of Toxicology
28: 17-23
[Abstract][Full Text]
Trivedi, H., Xiang, Q., Klein, J. P.
(2009). Risk factors for non-fatal myocardial infarction and cardiac death in incident dialysis patients. Nephrol Dial Transplant
24: 258-266
[Abstract][Full Text]
Spatz, E. S., Canavan, M. E., Desai, M. M.
(2009). From Here to JUPITER: Identifying New Patients for Statin Therapy Using Data From the 1999-2004 National Health and Nutrition Examination Survey. Circ Cardiovasc Qual Outcomes
2: 41-48
[Abstract][Full Text]
Jukema, J W., Bergheanu, S. C
(2008). Statins: established indications and controversial subgroups. Heart
94: 1656-1662
[Full Text]
Bhindi, R., Ormerod, O., Newton, J., Banning, A.P., Testa, L.
(2008). Interaction between statins and clopidogrel: is there anything clinically relevant?. QJM
101: 915-925
[Abstract][Full Text]
Krasuski, R. A.
(2008). Primary Prevention and Statins: Is It Just About Going to Class?. Mayo Clin Proc.
83: 1313-1315
[Full Text]
Jacobson, T. A., Wertz, D. A., Hoy, T., Kuznik, A., Grochulski, D., Cziraky, M.
(2008). Comparison of Cardiovascular Event Rates in Patients Without Cardiovascular Disease in Whom Atorvastatin or Simvastatin Was Newly Initiated. Mayo Clin Proc.
83: 1316-1325
[Abstract][Full Text]
Hothersall, E J, Chaudhuri, R, McSharry, C, Donnelly, I, Lafferty, J, McMahon, A D, Weir, C J, Meiklejohn, J, Sattar, N, McInnes, I, Wood, S, Thomson, N C
(2008). Effects of atorvastatin added to inhaled corticosteroids on lung function and sputum cell counts in atopic asthma. Thorax
63: 1070-1075
[Abstract][Full Text]
Mills, E. J., Rachlis, B., Wu, P., Devereaux, P. J., Arora, P., Perri, D.
(2008). Primary Prevention of Cardiovascular Mortality and Events With Statin Treatments A Network Meta-Analysis Involving More Than 65,000 Patients.. J Am Coll Cardiol
52: 1769-1781
[Abstract][Full Text]
Ridker, P. M, Danielson, E., Fonseca, F. A.H., Genest, J., Gotto, A. M. Jr., Kastelein, J. J.P., Koenig, W., Libby, P., Lorenzatti, A. J., MacFadyen, J. G., Nordestgaard, B. G., Shepherd, J., Willerson, J. T., Glynn, R. J., the JUPITER Study Group,
(2008). Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein. NEJM
359: 2195-2207
[Abstract][Full Text]
Belch, J.
(2008). Author's reply. BMJ
337: a2582-a2582
[Full Text]
Forst, T., Wilhelm, B., Pfutzner, A., Fuchs, W., Lehmann, U., Schaper, F., Weber, M., Muller, J., Konrad, T., Hanefeld, M.
(2008). Investigation of the vascular and pleiotropic effects of atorvastatin and pioglitazone in a population at high cardiovascular risk. Diabetes and Vascular Disease Research
5: 298-303
[Abstract]
Wiesbauer, F., Heinze, G., Mitterbauer, C., Harnoncourt, F., Horl, W. H., Oberbauer, R.
(2008). Statin Use Is Associated with Prolonged Survival of Renal Transplant Recipients. J. Am. Soc. Nephrol.
19: 2211-2218
[Abstract][Full Text]
Prakash, C., Chen, W., Rossulek, M., Johnson, K., Zhang, C., O'Connell, T., Potchoiba, M., Dalvie, D.
(2008). Metabolism, Pharmacokinetics, and Excretion of a Cholesteryl Ester Transfer Protein Inhibitor, Torcetrapib, in Rats, Monkeys, and Mice: Characterization of Unusual and Novel Metabolites by High-Resolution Liquid Chromatography-Tandem Mass Spectrometry and 1H Nuclear Magnetic Resonance. Drug Metab. Dispos.
36: 2064-2079
[Abstract][Full Text]
Rosenzweig, J. L., Ferrannini, E., Grundy, S. M., Haffner, S. M., Heine, R. J., Horton, E. S., Kawamori, R.
(2008). Primary Prevention of Cardiovascular Disease and Type 2 Diabetes in Patients at Metabolic Risk: An Endocrine Society Clinical Practice Guideline. J. Clin. Endocrinol. Metab.
93: 3671-3689
[Abstract][Full Text]
Steiner, M. J., Brown, W. D., Liles, E.
(2008). An Assessment of the New Lipid Screening Guidelines. Pediatrics
122: 904-905
[Full Text]
Alsheikh-Ali, A. A., Trikalinos, T. A., Kent, D. M., Karas, R. H.
(2008). Statins, Low-Density Lipoprotein Cholesterol, and Risk of Cancer. J Am Coll Cardiol
52: 1141-1147
[Abstract][Full Text]
Antonicelli, R., Testarmata, P., Spazzafumo, L., Gagliardi, C., Bilo, G., Valentini, M., Olivieri, F., Parati, G.
(2008). Impact of telemonitoring at home on the management of elderly patients with congestive heart failure. J Telemed Telecare
14: 300-305
[Abstract][Full Text]
Reynolds, T. M., Mardani, A., Twomey, P. J., Wierzbicki, A. S.
(2008). Targeted versus global approaches to the management of hypercholesterolaemia. The Journal of the Royal Society for the Promotion of Health
128: 248-254
[Abstract]
Lopez, J., Mendoza, R., Cleva Villanueva, G., Martinez, G., Castillo, E. F., Castillo, C.
(2008). Participation of K+ Channels in the Endothelium-Dependent and Endothelium-Independent Components of the Relaxant Effect of Rosuvastatin in Rat Aortic Rings. J CARDIOVASC PHARMACOL THER
13: 207-213
[Abstract]
Herrler, T., Bohm, M., Heeschen, C.
(2008). More good reasons for adherence to statin therapy during acute coronary syndromes. Eur Heart J
29: 2061-2063
[Full Text]
Steinberg, D., Glass, C. K., Witztum, J. L.
(2008). Evidence Mandating Earlier and More Aggressive Treatment of Hypercholesterolemia. Circulation
118: 672-677
[Full Text]
Sakamoto, S., Kusuhara, H., Horie, K., Takahashi, K., Baba, T., Ishizaki, J., Sugiyama, Y.
(2008). Identification of the Transporters Involved in the Hepatobiliary Transport and Intestinal Efflux of Methyl 1-(3,4-Dimethoxyphenyl)-3-(3-ethylvaleryl)-4-hydroxy-6,7,8-trimethoxy-2-naphthoate (S-8921) Glucuronide, a Pharmacologically Active Metabolite of S-8921. Drug Metab. Dispos.
36: 1553-1561
[Abstract][Full Text]
Foster, C., Porcari, J. P., Battista, R. A., Udermann, B., Wright, G., Lucia, A.
(2008). The Risk in Exercise Training. AMERICAN JOURNAL OF LIFESTYLE MEDICINE
2: 279-284
[Abstract]
Triplitt, C., Alvarez, C. A.
(2008). Best Practices for Lowering the Risk of Cardiovascular Disease in Diabetes. Diabetes Spectr.
21: 177-189
[Abstract][Full Text]
Ishigaki, Y., Katagiri, H., Gao, J., Yamada, T., Imai, J., Uno, K., Hasegawa, Y., Kaneko, K., Ogihara, T., Ishihara, H., Sato, Y., Takikawa, K., Nishimichi, N., Matsuda, H., Sawamura, T., Oka, Y.
(2008). Impact of Plasma Oxidized Low-Density Lipoprotein Removal on Atherosclerosis. Circulation
118: 75-83
[Abstract][Full Text]
Robinson, R. G., Jorge, R. E., Moser, D. J., Acion, L., Solodkin, A., Small, S. L., Fonzetti, P., Hegel, M., Arndt, S.
(2008). Escitalopram and Problem-Solving Therapy for Prevention of Poststroke Depression: A Randomized Controlled Trial. JAMA
299: 2391-2400
[Abstract][Full Text]
Abe, M., Matsuda, M., Kobayashi, H., Miyata, Y., Nakayama, Y., Komuro, R., Fukuhara, A., Shimomura, I.
(2008). Effects of Statins on Adipose Tissue Inflammation: Their Inhibitory Effect on MyD88-Independent IRF3/IFN-{beta} Pathway in Macrophages. Arterioscler. Thromb. Vasc. Bio.
28: 871-877
[Abstract][Full Text]
Taylor, G L, Murphy, N F, Berry, C, Christie, J, Finlayson, A, MacIntyre, K, Morrison, C, McMurray, J
(2008). Long-term outcome of low-risk patients attending a rapid-assessment chest pain clinic. Heart
94: 628-632
[Abstract][Full Text]
Mamdani, M., Ching, A., Golden, B., Melo, M., Menzefricke, U.
(2008). Challenges to Evidence-Based Prescribing in Clinical Practice. The Annals of Pharmacotherapy
42: 704-707
[Abstract][Full Text]
Lai, C.-L., Yuen, M.-F.
(2008). What Is the Best End Point for Hepatitis B Treatment?. ANN INTERN MED
148: 560-560
[Full Text]
Chiba, Y., Arima, J., Sakai, H., Misawa, M.
(2008). Lovastatin inhibits bronchial hyperresponsiveness by reducing RhoA signaling in rat allergic asthma. Am. J. Physiol. Lung Cell. Mol. Physiol.
294: L705-L713
[Abstract][Full Text]
Ferns, G., Keti, V.
(2008). HDL-cholesterol modulation and its impact on the management of cardiovascular risk. Ann Clin Biochem
45: 122-128
[Abstract][Full Text]
Sabatine, M. S., Ploughman, L., Simonsen, K. L., Iakoubova, O. A., Kirchgessner, T. G., Ranade, K., Tsuchihashi, Z., Zerba, K. E., Long, D. U., Tong, C. H., Packard, C. J., Pfeffer, M. A., Devlin, J. J., Shepherd, J., Campos, H., Sacks, F. M., Braunwald, E.
(2008). Association Between ADAMTS1 Matrix Metalloproteinase Gene Variation, Coronary Heart Disease, and Benefit of Statin Therapy. Arterioscler. Thromb. Vasc. Bio.
28: 562-567
[Abstract][Full Text]
Vamvakopoulos, J. E, Kountouri, M., Marshall, T., Greenfield, S. M
(2008). Lifestyle or Life-Saving Medicines? A Primary Healthcare Professional and Consumer Opinion Survey on Over-the-Counter Statins. The Annals of Pharmacotherapy
42: 413-420
[Abstract][Full Text]
Nassief, A., Marsh, J. D.
(2008). Statin Therapy for Stroke Prevention. Stroke
39: 1042-1048
[Abstract][Full Text]
Bolland, M. J, Barber, P A., Doughty, R. N, Mason, B., Horne, A., Ames, R., Gamble, G. D, Grey, A., Reid, I. R
(2008). Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial. BMJ
336: 262-266
[Abstract][Full Text]
Glaros, E. N., Kim, W. S., Quinn, C. M., Jessup, W., Rye, K.-A., Garner, B.
(2008). Myriocin slows the progression of established atherosclerotic lesions in apolipoprotein E gene knockout mice. J. Lipid Res.
49: 324-331
[Abstract][Full Text]
Tomkin, G. H.
(2008). Targets for Intervention in Dyslipidemia in Diabetes. Diabetes Care
31: S241-S248
[Abstract][Full Text]
Iakoubova, O. A., Tong, C. H., Rowland, C. M., Kirchgessner, T. G., Young, B. A., Arellano, A. R., Shiffman, D., Sabatine, M. S., Campos, H., Packard, C. J., Pfeffer, M. A., White, T. J., Braunwald, E., Shepherd, J., Devlin, J. J., Sacks, F. M.
(2008). Association of the Trp719Arg polymorphism in kinesin-like protein 6 with myocardial infarction and coronary heart disease in 2 prospective trials: the CARE and WOSCOPS trials.. J Am Coll Cardiol
51: 435-443
[Abstract][Full Text]
Shiffman, D., Chasman, D. I., Zee, R. Y.L., Iakoubova, O. A., Louie, J. Z., Devlin, J. J., Ridker, P. M.
(2008). A kinesin family member 6 variant is associated with coronary heart disease in the Women's Health Study.. J Am Coll Cardiol
51: 444-448
[Abstract][Full Text]
Superko, H. R., King, S. III
(2008). Lipid Management to Reduce Cardiovascular Risk: A New Strategy Is Required. Circulation
117: 560-568
[Full Text]
Mizuno, K., Nakaya, N., Ohashi, Y., Tajima, N., Kushiro, T., Teramoto, T., Uchiyama, S., Nakamura, H., for the MEGA Study Group,
(2008). Usefulness of Pravastatin in Primary Prevention of Cardiovascular Events in Women: Analysis of the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA Study). Circulation
117: 494-502
[Abstract][Full Text]
Jenkins, D. J.A. MD PhD, Josse, A. R. MSc, Beyene, J. PhD, Dorian, P. MD MSc, Burr, M. L. MD DSc (Me, LaBelle, R. BSc, Kendall, C. W.C. PhD, Cunnane, S. C. PhD
(2008). Fish-oil supplementation in patients with implantable cardioverter defibrillators: a meta-analysis. CMAJ
178: 157-164
[Abstract][Full Text]
Bibbins-Domingo, K., Coxson, P., Pletcher, M. J., Lightwood, J., Goldman, L.
(2007). Adolescent Overweight and Future Adult Coronary Heart Disease. NEJM
357: 2371-2379
[Abstract][Full Text]
Natarajan, N., Putnam, R. W., Yip, A. M., Frail, D.
(2007). Family practice patients' adherence to statin medications. cfp
53: 2144-2145
[Abstract][Full Text]
Tavridou, A., Kaklamanis, L., Papalois, A., Kourounakis, A. P., Rekka, E. A., Kourounakis, P. N., Charalambous, A., Manolopoulos, V. G.
(2007). EP2306 [2-(4-Biphenyl)-4-methyl-octahydro-1,4-benzoxazin-2-ol, hydrobromide], A Novel Squalene Synthase Inhibitor, Reduces Atherosclerosis in the Cholesterol-Fed Rabbit. J. Pharmacol. Exp. Ther.
323: 794-804
[Abstract][Full Text]
Keddissi, J. I., Younis, W. G., Chbeir, E. A., Daher, N. N., Dernaika, T. A., Kinasewitz, G. T.
(2007). The Use of Statins and Lung Function in Current and Former Smokers. Chest
132: 1764-1771
[Abstract][Full Text]
Rosengarten, B., Auch, D., Kaps, M.
(2007). Effects of Initiation and Acute Withdrawal of Statins on the Neurovascular Coupling Mechanism in Healthy, Normocholesterolemic Humans. Stroke
38: 3193-3197
[Abstract][Full Text]
Henyan, N. N, Riche, D. M, East, H. E, Gann, P. N
(2007). Impact of Statins on Risk of Stroke: A Meta-Analysis. The Annals of Pharmacotherapy
41: 1937-1945
[Abstract][Full Text]
Goodson, J. D.
(2007). Unintended Consequences of Resource-Based Relative Value Scale Reimbursement. JAMA
298: 2308-2310
[Full Text]
Thielmann, M., Neuhauser, M., Marr, A., Jaeger, B. R., Wendt, D., Schuetze, B., Kamler, M., Massoudy, P., Erbel, R., Jakob, H.
(2007). Lipid-lowering effect of preoperative statin therapy on postoperative major adverse cardiac events after coronary artery bypass surgery.. J. Thorac. Cardiovasc. Surg.
134: 1143-1149
[Abstract][Full Text]
Agarwal, R.
(2007). Effects of Statins on Renal Function. Mayo Clin Proc.
82: 1381-1390
[Abstract][Full Text]
Feringa, H. H.H., Schouten, O., Karagiannis, S. E., Brugts, J., Elhendy, A., Boersma, E., Vidakovic, R., van Sambeek, M. R.H.M., Noordzij, P. G., Bax, J. J., Poldermans, D.
(2007). Intensity of Statin Therapy in Relation to Myocardial Ischemia, Troponin T Release, and Clinical Cardiac Outcome in Patients Undergoing Major Vascular Surgery. J Am Coll Cardiol
50: 1649-1656
[Abstract][Full Text]
Ford, I., Murray, H., Packard, C. J., Shepherd, J., Macfarlane, P. W., Cobbe, S. M., the West of Scotland Coronary Prevention Study Gro,
(2007). Long-Term Follow-up of the West of Scotland Coronary Prevention Study. NEJM
357: 1477-1486
[Abstract][Full Text]
Domanski, M. J.
(2007). Primary Prevention of Coronary Artery Disease. NEJM
357: 1543-1545
[Full Text]
Authors/Task Force Members, , Graham, I., Atar, D., Borch-Johnsen, K., Boysen, G., Burell, G., Cifkova, R., Dallongeville, J., De Backer, G., Ebrahim, S., Gjelsvik, B., Herrmann-Lingen, C., Hoes, A., Humphries, S., Knapton, M., Perk, J., Priori, S. G., Pyorala, K., Reiner, Z., Ruilope, L., Sans-Menendez, S., Scholte op Reimer, W., Weissberg, P., Wood, D., Yarnell, J., Zamorano, J. L., Other experts who contributed to parts of the guid, , Walma, E., Fitzgerald, T., Cooney, M. T., Dudina, A., European Society of Cardiology (ESC) Committee for, , Vahanian, A., Camm, J., De Caterina, R., Dean, V., Dickstein, K., Funck-Brentano, C., Filippatos, G., Hellemans, I., Kristensen, S. D., McGregor, K., Sechtem, U., Silber, S., Tendera, M., Widimsky, P., Zamorano, J. L., Document reviewers:, , Hellemans, I., Altiner, A., Bonora, E., Durrington, P. N., Fagard, R., Giampaoli, S., Hemingway, H., Hakansson, J., Kjeldsen, S. E., Larsen, M. L., Mancia, G., Manolis, A. J., Orth-Gomer, K., Pedersen, T., Rayner, M., Ryden, L., Sammut, M., Schneiderman, N., Stalenhoef, A. F., Tokgozoglu, L., Wiklund, O., Zampelas, A.
(2007). European guidelines on cardiovascular disease prevention in clinical practice: executive summary: Fourth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (Constituted by representatives of nine societies and by invited experts). Eur Heart J
28: 2375-2414
[Full Text]
Cahoon, W. D Jr, Crouch, M. A
(2007). Preprocedural Statin Therapy in Percutaneous Coronary Intervention. The Annals of Pharmacotherapy
41: 1687-1693
[Abstract][Full Text]
Colivicchi, F., Bassi, A., Santini, M., Caltagirone, C.
(2007). Discontinuation of Statin Therapy and Clinical Outcome After Ischemic Stroke. Stroke
38: 2652-2657
[Abstract][Full Text]
Barter, P., Gotto, A. M., LaRosa, J. C., Maroni, J., Szarek, M., Grundy, S. M., Kastelein, J. J.P., Bittner, V., Fruchart, J.-C., the Treating to New Targets Investigators,
(2007). HDL Cholesterol, Very Low Levels of LDL Cholesterol, and Cardiovascular Events. NEJM
357: 1301-1310
[Abstract][Full Text]
Lipson, A. H., Fallis, W. M., Wang, X., Yi, Y.
(2007). Are patients with hyperlipidemia undertreated?: Study of patients admitted to hospital with coronary events. cfp
53: 1502-1507
[Abstract][Full Text]
Perler, B. A.
(2007). Should Statins Be Given Routinely Before Carotid Endarterectomy?. PERSPECT VASC SURG ENDOVASC THER
19: 240-245
[Abstract]
La Rovere, M. T., Pinna, G. D., Maestri, R., Robbi, E., Mortara, A., Fanfulla, F., Febo, O., Sleight, P.
(2007). Clinical relevance of short-term day-time breathing disorders in chronic heart failure patients. Eur J Heart Fail
9: 949-954
[Abstract][Full Text]
Mozayan, M., Lee, T. J. F.
(2007). Statins prevent cholinesterase inhibitor blockade of sympathetic {alpha}7-nAChR-mediated currents in rat superior cervical ganglion neurons. Am. J. Physiol. Heart Circ. Physiol.
293: H1737-H1744
[Abstract][Full Text]
