Background In patients with coronary heart disease and a broadrange of cholesterol levels, cholesterol-lowering therapy reducesthe risk of coronary events, but the effects on mortality fromcoronary heart disease and overall mortality have remained uncertain.
Methods In a double-blind, randomized trial, we compared theeffects of pravastatin (40 mg daily) with those of a placeboover a mean follow-up period of 6.1 years in 9014 patients whowere 31 to 75 years of age. The patients had a history of myocardialinfarction or hospitalization for unstable angina and initialplasma total cholesterol levels of 155 to 271 mg per deciliter.Both groups received advice on following a cholesterol-loweringdiet. The primary study outcome was mortality from coronaryheart disease.
Results Death from coronary heart disease occurred in 8.3 percentof the patients in the placebo group and 6.4 percent of thosein the pravastatin group, a relative reduction in risk of 24percent (95 percent confidence interval, 12 to 35 percent; P<0.001). Overall mortality was 14.1 percent in the placebo groupand 11.0 percent in the pravastatin group (relative reductionin risk, 22 percent; 95 percent confidence interval, 13 to 31percent; P<0.001). The incidence of all cardiovascular outcomeswas consistently lower among patients assigned to receive pravastatin;these outcomes included myocardial infarction (reduction inrisk, 29 percent; P<0.001), death from coronary heart diseaseor nonfatal myocardial infarction (a 24 percent reduction inrisk, P<0.001), stroke (a 19 percent reduction in risk, P=0.048),and coronary revascularization (a 20 percent reduction in risk,P<0.001). The effects of treatment were similar for all predefinedsubgroups. There were no clinically significant adverse effectsof treatment with pravastatin.
Conclusions Pravastatin therapy reduced mortality from coronaryheart disease and overall mortality, as compared with the ratesin the placebo group, as well as the incidence of all prespecifiedcardiovascular events in patients with a history of myocardialinfarction or unstable angina who had a broad range of initialcholesterol levels.
By the end of the 1980s, there was strong epidemiologic evidenceof a continuous association between plasma cholesterol levelsand the risk of coronary heart disease (CHD).1,2,3 Most patientswith CHD have cholesterol levels that are not markedly elevated.4However, most randomized, controlled trials of cholesterol-loweringtherapy have involved patients with at least moderate hypercholesterolemia,and the treatments used have had limited efficacy in loweringcholesterol. Taken together, those trials have demonstrateda clear reduction in the incidence of coronary events, bothamong persons with a history of CHD5 and among those withoutsuch a history.6 However, the reduction in coronary mortalityassociated with cholesterol-lowering therapy has been small(about 10 percent) and may be partially counterbalanced by anonsignificant excess of deaths from noncoronary causes.7 Therehas therefore been considerable uncertainty about the effectsof cholesterol-lowering therapy on overall mortality among patientswith high cholesterol levels8 and about its effects on the riskof coronary events among patients with lower cholesterol levels.
The Long-Term Intervention with Pravastatin in Ischaemic Disease(LIPID) trial was initiated in 1989 to investigate the effectsof substantial lowering of cholesterol levels with the 3-hydroxy-3-methylglutaryl–coenzymeA (HMG-CoA) reductase inhibitor pravastatin on death from CHDamong patients with a history of myocardial infarction or unstableangina and a broad range of initial cholesterol levels (155to 271 mg per deciliter [4.0 to 7.0 mmol per liter]). Sinceour study began, two other large-scale trials of HMG-CoA reductaseinhibitors in patients with CHD have been completed.9,10 TheScandinavian Simvastatin Survival Study9 demonstrated a significantreduction in overall mortality with simvastatin therapy amongpatients with higher initial cholesterol levels than those ofour patients (213 to 309 mg per deciliter [5.5 to 8.0 mmol perliter]). The Cholesterol and Recurrent Events (CARE) trial10studied patients who had had myocardial infarction and who hadcholesterol levels below 240 mg per deciliter (6.2 mmol perliter); it demonstrated a significant reduction in the incidenceof the composite outcome of coronary death and nonfatal myocardialinfarction with pravastatin therapy. However, the study wasnot designed to detect a significant effect on overall mortalityor mortality from CHD alone. Consequently, the effect of cholesterol-loweringtherapy on these outcomes in patients with average cholesterollevels remained uncertain.
Methods
Study Design and Patients
The design of the study is described in detail elsewhere.11We recruited a total of 9014 patients, 31 to 75 years of age,at 87 centers — 67 in Australia and 20 in New Zealand.Patients were eligible if they had had an acute myocardial infarctionor had a hospital-discharge diagnosis of unstable angina between3 and 36 months before study entry. Patients entered an eight-week-longsingle-blind placebo run-in phase during which they receiveddietary advice aimed at reducing their fat intake to less than30 percent of total energy intake. For patients to qualify forthe study, the plasma total cholesterol level measured fourweeks before randomization was required to be 155 to 271 mgper deciliter and the fasting triglyceride level less than 445mg per deciliter (5.0 mmol per liter). Exclusion criteria includeda clinically significant medical or surgical event within threemonths before study entry, cardiac failure, renal or hepaticdisease, and the current use of any cholesterol-lowering agents.
After stratification according to the qualifying event (myocardialinfarction or unstable angina) and clinical center, patientswere randomly assigned to receive either 40 mg of pravastatin(Pravachol, Bristol-Myers Squibb) or matching placebo once daily.Both groups continued to receive dietary advice. Plasma cholesterollevels were measured by the core laboratory at randomization,six months later, each year after randomization, and at theend of the study. High-density lipoprotein (HDL) cholesteroland triglyceride levels were measured in blood samples obtainedwhile patients were fasting, at base line, one, three, and fiveyears after randomizaton, and at the end of the study. Low-densitylipoprotein (LDL) cholesterol was estimated indirectly, withuse of the formula of Friedewald et al.12 Study personnel andpatients remained blinded to the results of the central analysesof lipid levels. The patients' usual care, including the institutionof other cholesterol-lowering treatment, continued to be underthe direction of their own doctors. The results of the otherlarge-scale trials of HMG-CoA reductase inhibitors9,10,13 werecommunicated to both patients and their treating doctors, withthe further explanation that if it was considered indicated,open-label cholesterol-lowering therapy could be commenced.Routine visits to the clinic were scheduled every six monthsafter randomization to monitor compliance with the study treatmentand to obtain data on hospital admissions, serious adverse events,and study outcomes.
Classification and Review of Outcomes
The primary study outcome was death from CHD. Deaths from CHDwere further classified as death due to fatal myocardial infarction,sudden death, death in the hospital after possible myocardialinfarction, or death due to heart failure or another coronarycause. Secondary outcomes were death from any cause; death fromcardiovascular causes; death from CHD or nonfatal myocardialinfarction; myocardial infarction; stroke; nonhemorrhagic stroke;coronary revascularization (coronary angioplasty, coronary-arterybypass surgery, or both); number of days in the hospital; serumlipid levels; and the relation of changes in lipid levels tothe occurrence of cardiovascular end points. Each of these analyseswas prespecified in the original protocol or in subsequent amendmentsmade without knowledge of the results of any analysis accordingto treatment assignment.
All deaths, myocardial infarctions, and strokes were reviewedby an outcomes-assessment committee or stroke-adjudication committeewhose members had no knowledge of the patient's treatment assignment.Myocardial infarction was diagnosed on the basis of the presenceof at least two new pathologic Q waves on the electrocardiogram11or two of the following three criteria: at least 15 minutesof ischemic chest pain, evolutionary ST-T wave changes (as previouslydefined11), or elevation of the serum level of creatine kinaseor its MB isoenzyme to at least twice the upper limit of normal.A stroke was defined as an acute new disturbance of focal neurologicfunction resulting in death or lasting more than 24 hours.
An independent data and safety monitoring committee regularlymonitored the progress of the study; five formal interim analyseswere planned to examine differences in overall mortality orthe incidence of serious adverse events associated with pravastatintreatment. Guidelines for stopping the trial early were basedon a difference of at least 3 SD (P<0.003) between the groupsin either of these outcomes.14 The trial was conceived, managed,and analyzed independently of Bristol-Myers Squibb. All patientsgave written informed consent, and the trial was approved bythe ethics committee at each participating center.
Statistical Analysis
The study was designed to have 80 percent power to detect areduction of 18.3 percent in the risk of death due to CHD atfive years, with a two-sided P value of <0.05. The trialwas planned to continue until 700 deaths from CHD had occurredunless it was stopped early. All analyses were performed onan intention-to-treat basis.
Time-to-event analyses were performed with the log-rank test,with stratification according to the qualifying event.15 Estimatesof the relative reduction in risk associated with pravastatintherapy and 95 percent confidence intervals were derived withuse of the Cox proportional-hazards model.16 Prespecified subgroupanalyses evaluated variation in the effect of treatment on thecomposite outcome of death due to CHD and nonfatal myocardialinfarction, on the basis of tests for interaction in the Coxmodel16 and with use of continuous variables for age and base-linelipid values. P values were not adjusted for multiple comparisons.
Results
Between June 12, 1990, and December 18, 1992, 9014 patientswere randomly assigned to study treatment: 4512 to pravastatinand 4502 to placebo. Of these, 91 patients (1 percent) weresubsequently found not to meet all the eligibility criteria(31 did not meet the criteria for myocardial infarction or unstableangina within 3 to 36 months before study entry; 46 underwentcoronary revascularization or had unstable angina within 3 monthsbefore study entry; 8 were taking cholesterol-lowering drugs;and 6 met other exclusion criteria); these patients were includedin all analyses. The two groups were very well balanced in termsof base-line characteristics (Table 1). Twelve percent had bothqualifying events and were included in the stratum with myocardialinfarction. A total of 42 percent of patients had a qualifyingplasma total cholesterol level of less than 213 mg per deciliter(5.5 mmol per liter).
Table 1. Base-Line Characteristics of Patients Randomly Assigned to Receive Pravastatin or Placebo.
Status at the End of the Study
In May 1997, after the data and safety monitoring committeedetermined that the prespecified boundary for a difference inoverall mortality had been crossed, all patients were advisedthat the study would end. Patients' final follow-up visits tookplace between July 1 and September 30, 1997, when the mean durationof the study was 6.1 years and vital status was ascertainedin all but one patient. After one year, after three years, andat the end of the study, 6 percent, 11 percent, and 19 percent,respectively, of the patients randomly assigned to treatmentwith pravastatin had permanently stopped taking the study drug,whereas 3 percent, 9 percent, and 24 percent of those assignedto placebo had begun open-label therapy with a cholesterol-loweringdrug.
Effects of Treatment on Lipid Levels
Lipid levels, averaged over the first five years of follow-up,were analyzed on an intention-to-treat basis. In the pravastatingroup, the plasma total cholesterol level fell by 39 mg perdeciliter (1.0 mmol per liter) from the initial level of 218mg per deciliter (5.6 mmol per liter); the reduction in totalcholesterol was 18 percentage points greater than in the placebogroup (P<0.001). Similarly, the LDL cholesterol level inthe pravastatin group, initially 150 mg per deciliter (3.9 mmolper liter), was reduced by 25 percentage points more than inthe placebo group; the plasma triglyceride level, initially142 mg per deciliter (1.6 mmol per liter), was reduced by 11percentage points more than in the placebo group; and the HDLcholesterol level, initially 36 mg per deciliter (0.9 mmol perliter), increased by 5 percentage points more than in the placebogroup (P<0.001 for all comparisons). At six months, the totalcholesterol level in the pravastatin group was an average of21 percent lower than that in the placebo group. This differencedeclined to 13 percent at six years because of the discontinuationof treatment by patients assigned to pravastatin and the commencementof open-label cholesterol-lowering treatment by patients assignedto placebo.
Effects on Outcomes
The effects of treatment on cardiovascular outcomes are shownin Table 2. Among patients assigned to pravastatin, the incidenceof the primary study end point of death from CHD was 6.4 percentin the pravastatin group, as compared with 8.3 percent in theplacebo group (relative reduction in risk with pravastatin therapy,24 percent; 95 percent confidence interval, 12 to 35 percent;P<0.001) (Figure 1). Overall mortality was 22 percent lower(95 percent confidence interval, 13 to 31 percent) in the pravastatingroup (11.0 percent) than in the placebo group (14.1 percent,P<0.001) (Figure 2A, Figure 2B, and Figure 2C). Mortalityfrom cardiovascular causes was 25 percent lower (7.3 percentvs. 9.6 percent, P<0.001). There were fewer deaths from cancerand trauma or suicide among patients assigned to pravastatin,but these differences were not significant (Table 3).
Figure 1. Kaplan–Meier Estimates of Mortality Due to Coronary Heart Disease (CHD), the Primary Outcome, in the Pravastatin and Placebo Groups.
The relative reduction in risk with pravastatin therapy was derived from the Cox proportional-hazards model. The P value was based on the log-rank test with stratification according to the qualifying event. On the basis of the differences in the proportions of patients who died of CHD during the entire study period, for every 1000 patients assigned to pravastatin, death from CHD was avoided in 19 patients.
Figure 2. Kaplan–Meier Estimates of the Incidence of Major Secondary Outcomes in the Pravastatin and Placebo Groups.
Panel A shows mortality from all causes, Panel B death due to coronary heart disease (CHD) or nonfatal myocardial infarction (MI), and Panel C stroke of any type. The relative reductions in risk with pravastatin therapy were derived from the Cox proportional-hazards model. The P values were based on the log-rank test, with stratification according to the qualifying event. On the basis of the differences in the proportions of patients with an event during the entire study period, for every 1000 patients assigned to pravastatin, death from any cause was avoided in 30 patients, death due to CHD or nonfatal MI was avoided in 35 patients, and stroke was avoided in 8 patients.
Table 3. Causes of Death According to Treatment Group.
There were also significant reductions in mortality from CHDand overall mortality among patients assigned to pravastatinin each of the two groups defined by qualifying event. In thesubgroup with previous myocardial infarction, mortality fromCHD was 23 percent lower among those assigned to pravastatinthan among those assigned to placebo (P= 0.004), and overallmortality was 21 percent lower (P=0.002). In the subgroup ofpatients who had been hospitalized for unstable angina beforerandomization, mortality from CHD was 26 percent lower withpravastatin (P=0.036), and overall mortality was 26 percentlower (P=0.004).
With respect to other secondary end points, the incidence ofmyocardial infarction was 7.4 percent among those assigned topravastatin, as compared with 10.3 percent in the placebo group(relative reduction in risk, 29 percent; P<0.001), the incidenceof stroke was 3.7 percent as compared with 4.5 percent (reductionin risk, 19 percent; P=0.048), the rate of coronary-artery bypasssurgery was 9.2 percent as compared with 11.6 percent (reductionin risk, 22 percent; P<0.001), the rate of coronary angioplastywas 4.7 percent as compared with 5.6 percent (reduction in risk,19 percent; P=0.024), and the rate of hospitalization for unstableangina was 22.3 percent as compared with 24.6 percent (reductionin risk, 12 percent; P=0.005).
Patients in the pravastatin group also spent significantly lesstime in the hospital (2.9 days less per patient, P<0.001),had fewer hospital admissions, and spent less time in the hospitalper admission (0.6 day, or 10 percent, less time per admission;P=0.002).
Prespecified Subgroup Analyses
Table 4 shows the analyses of subgroups with respect to thecombined end point of death from CHD and nonfatal myocardialinfarction. There was no evidence of significant heterogeneityof the treatment effect in any of these subgroup analyses. Thereduction in risk with pravastatin treatment in each subgroupwas consistent with the overall 24 percent reduction in riskfor the entire cohort. Significant reductions in the risk ofcoronary events among patients treated with pravastatin wereobserved both among patients with previous myocardial infarctionand among those who had been hospitalized for unstable anginapectoris and also in other large subgroups, such as patientswith initial plasma total cholesterol levels below 213 mg perdeciliter.
Table 4. Effects of Pravastatin Treatment on Death Due to Coronary Heart Disease and Nonfatal Myocardial Infarction within Subgroups Defined in the Protocol.
Safety
A total of 403 newly diagnosed primary cancers occurred in 379patients assigned to receive pravastatin, as compared with 417cancers in 399 patients assigned to receive placebo (P=0.43).Organ-specific analysis of cancers, including breast cancer(10 invasive cancers in the placebo group, as compared with9 invasive cancers and 1 carcinoma in situ in the pravastatingroup), showed no significant differences. There was also nodifference in the incidence of accidents, violence, or attemptedsuicide (213 patients in the pravastatin group died or werehospitalized for one of these reasons, as compared with 221in the placebo group). There was no significant increase inthe incidence of adverse events that were ultimately attributedto the study medication (3.2 percent vs. 2.7 percent, P=0.16)or of serious adverse events. Among laboratory variables, 2.1percent of the pravastatin group had a serum alanine aminotransferaselevel greater than three times the upper limit of normal, ascompared with 1.9 percent of the placebo group (P=0.41). Therewere no significant differences in the proportions of patientswith elevated serum creatine kinase levels, myopathy (8 vs.10 cases), or serious adverse events due to hepatic disease.
Discussion
Our results provide strong evidence that lowering cholesterollevels with pravastatin in patients with a broad range of initialcholesterol levels and a history of myocardial infarction orunstable angina reduces the risk of death from CHD, cardiovasculardisease, and all causes combined. In addition, the risk of myocardialinfarction or stroke is significantly reduced. Over a periodof 6.1 years, we estimate that 30 deaths, 28 nonfatal myocardialinfarctions, and 9 nonfatal strokes were avoided (with allowancefor multiple events in each patient) in 48 patients for every1000 randomly assigned to treatment with pravastatin. Twenty-threeepisodes of coronary-artery bypass surgery, 20 of coronary angioplasty,and 82 hospital admissions for unstable angina were also avoided.These benefits were not offset by adverse effects. Our resultsdemonstrate that pravastatin reduced the risk of all major cardiovascularevents in a large group of patients who were representativeof those seen in current practice. Indeed, the mean total cholesterollevel in our study approximates that in recent epidemiologicstudies of patients with CHD.17,18
These results extend the findings of the Scandinavian SimvastatinSurvival Study,9 which showed that treatment had benefit interms of mortality from CHD and overall mortality among patientswith CHD who had a mean cholesterol level of 261 mg per deciliter(6.7 mmol per liter) at study entry. Our results demonstratesimilar benefits in patients with a mean cholesterol level about44 mg per deciliter (1.1 mmol per liter) lower than in thatstudy. Our study sample also had a wider range of initial triglyceridelevels (some patients had mixed hyperlipidemia), and a muchlarger proportion of our patients had undergone coronary revascularization(41 percent, as compared with 8 percent in the Scandinavianstudy) and were receiving aspirin at entry (82 percent vs. 37percent). Our results also extend the findings of the CARE study,10which showed a reduction in the composite outcome of death dueto CHD and nonfatal myocardial infarction in patients with CHDand had a similar mean cholesterol level at entry (209 mg perdeciliter [5.4 mmol per liter]), by providing clear evidenceof benefit in terms of both mortality from CHD and overall mortality.
Our study also extends the evidence of benefit to patients withunstable angina, who were not specifically included in the ScandinavianSimvastatin Survival Study and the CARE trial. Since this conditionis now a more frequent cause of hospital admission than myocardialinfarction,19 the demonstration of significant reductions bothin major coronary events and in mortality among patients withunstable angina represents an important new finding. Furthermore,the effects of treatment with pravastatin on the incidence ofstroke are important, particularly because stroke is now thechief cause of functional impairment in many countries. Ourfindings with respect to stroke are consistent with those ofthe other studies.9,10
We examined the effects of treatment on coronary events in prespecifiedsubgroups defined by sex, age, initial lipid levels, and thepresence or absence of other risk factors. No evidence of significantheterogeneity of treatment effect was detected. Specifically,we found no evidence of a greater relative effect of treatmentin women than in men, as had been suggested by the results ofthe CARE study.10 However, although the effects of treatmentwere not significant in some subgroups, such as patients withdiabetes and women, the power of our study to determine theeffects of treatment reliably in these relatively small subgroupswas inadequate. The estimate of the effect of treatment in thestudy group as a whole nonetheless provides a reasonable indicationof the probable relative benefits of treatment in these andother subgroups. Hence, the absolute benefits of treatment arelikely to be greater in groups of patients who are at higherabsolute risk for a major coronary event, such as those witha lower HDL cholesterol level, a higher LDL cholesterol level,older age, or a history of diabetes or smoking.
Although the relative and absolute effects we observed are clinicallyimportant, it is necessary to consider possible biases thatmay have modified the observed effects. The large number ofpatients who were assigned to pravastatin but discontinued treatmentor who were assigned to placebo but ultimately received cholesterol-loweringtherapy outside the study is likely to have reduced the differencein the incidence of events between the treatment groups. Sincethe rate of crossover from the allocated treatment at the midpointof the trial was 20 percent (9 percent of the placebo groupbegan nonstudy treatment and 11 percent of the pravastatin groupdiscontinued active treatment), it is possible that the effectsof treatment on both the average difference in the cholesterollevels and the relative difference in the incidence of majorevents were reduced by a similar proportion.
It is also possible that the patients we studied were at lowerrisk than the general population of patients with myocardialinfarction or unstable angina. The rate of death from CHD amongthe patients assigned to receive placebo was only 1.4 percentper year, as compared with the rate of 2 percent per year thatwas expected initially.11 In general, if the rate of eventsis higher in patients who elect not to enroll in trials, thena greater absolute benefit would be expected, assuming a similarrelative effect of treatment. Consequently, the absolute effectsof treatment in our study may significantly underestimate theeffects of such therapy in broader clinical practice. Conversely,the likely effect of a policy of cholesterol-lowering treatmentmay be less in a community, where there is poorer adherenceto long-term treatment regimens.20
Finally, in our study, as in the Scandinavian Simvastatin SurvivalStudy9 and the CARE trial,10 at least three months elapsed afterthe qualifying event before patients were enrolled. Consequently,our data do not clarify the effects of pravastatin early afteran acute coronary event but, rather, approximate event ratesamong patients with stable CHD, to whom it would be reasonableto extrapolate these results.
Treatment with pravastatin was safe and well tolerated. Theresults of this study confirm those of other large-scale trials9,10,13in showing no association between cholesterol-lowering therapyand cancer, deaths due to trauma or suicide, or other seriousadverse events. In particular, there was no increase in thenumber of newly diagnosed breast cancers among the women assignedto receive pravastatin, suggesting that the excess rate of breastcancer in the CARE study was a chance finding.10 Further dataon long-term safety and outcomes will be obtained from ongoingfollow-up of our study cohort.
Because of our results, cholesterol-lowering therapy shouldnow be considered for virtually all patients presenting withCHD. Whether individual patients are treated will also dependon cost-effectiveness analyses, other factors defining individualrisk, and coexisting conditions. With respect to other aspectsof treatment, our study does not indicate whether a dose ofpravastatin lower than that we used (40 mg once daily) wouldbe sufficient, whether treatment should target a particularcholesterol level or aim for a specific reduction, or whetherthe duration of treatment should be lifelong.
The current low rate of use of cholesterol-lowering therapyamong patients with CHD can no longer be accepted. A recentNorth American study found that only 30 percent of patientswho had survived a myocardial infarction were prescribed lipid-loweringdrugs.21 The situation is similar in many European countries18and in the Asian–Pacific region,22 whereas in the UnitedKingdom only about 10 percent of such patients are receivingtreatment.23 On the basis of the findings reported here, currentrecommendations for treatment after acute myocardial infarctionor hospitalization for unstable angina should be reviewed.
Supported by a grant from the Bristol-Myers Squibb PharmaceuticalResearch Institute and conducted under the auspices of the NationalHeart Foundation of Australia.
This article is dedicated to the late Dr. John Shaw, the firstchairman of the LIPID study management committee. We are indebtedto the patients for their commitment to the study; to John Varigos,Maynard MacAskill, Margot Mellies, Ray Turner, Mike Ablett,and Robert Wolf for their support; and to the principal investigatorsand study coordinators at the participating centers for theirdedication and enthusiasm.
* The members of the LIPID Study Group are listed in the Appendix.
Source Information
Address reprint requests to the National Health and Medical Research Council Clinical Trials Centre, Mallett St. Campus, University of Sydney, NSW 2006, Australia. Drs. Andrew Tonkin and R. John Simes assume responsibility for the overall content of the manuscript.
References
Stamler J, Wentworth D, Neaton JD. Is the relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? Findings in 356,222 primary screenees of the Multiple Risk Factor Intervention Trial (MRFIT). JAMA 1986;256:2823-2828. [Free Full Text]
Law MR, Wald NJ, Wu T, Hackshaw A, Bailey A. Systematic underestimation of association between serum cholesterol concentration and ischaemic heart disease in observational studies: data from the BUPA study. BMJ 1994;308:363-366. [Free Full Text]
Chen Z, Peto R, Collins R, MacMahon S, Lu J, Li W. Serum cholesterol concentration and coronary heart disease in populations with low cholesterol concentrations. BMJ 1991;303:276-282.
Kannel WB. Range of serum cholesterol values in the population developing coronary artery disease. Am J Cardiol 1995;76:69C-77C. [CrossRef][Medline]
Rossouw JE, Lewis B, Rifkind BM. The value of lowering cholesterol after myocardial infarction. N Engl J Med 1990;323:1112-1119. [Medline]
Muldoon MF, Manuck SB, Mathews KA. Lowering cholesterol concentrations and mortality: a quantitative review of primary prevention trials. BMJ 1990;301:309-314.
Peto R, Yusuf S, Collins R. Cholesterol lowering trial results in their epidemiological context. Circulation 1985;72:Suppl III:451-451.abstract
Keech A. Does cholesterol lowering reduce total mortality? Postgrad Med J 1992;68:870-871.
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]
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. [Free Full Text]
The LIPID Study Group. Design features and baseline characteristics of the LIPID (Long-Term Intervention with Pravastatin in Ischaemic Disease) Study: a randomized trial in patients with previous acute myocar-dial infarction and/or unstable angina pectoris. Am J Cardiol 1995;76:474-479. [CrossRef][Medline]
Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499-502. [Abstract]
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. [Free Full Text]
Peto R, Pike MC, Armitage P, et al. Design and analysis of randomised clinical trials requiring prolonged observation of each patient. I. Introduction and design. Br J Cancer 1976;34:585-612. [Medline]
Lee ET. Statistical methods for survival data analysis. 2nd ed. New York: John Wiley, 1992.
Cox DR. Regression models and life-tables. J R Stat Soc [B] 1972;34:187-220.
Rubins HB, Robins SJ, Collins D, et al. Distribution of lipids in 8,500 men with coronary artery disease. Am J Cardiol 1995;75:1196-1201. [CrossRef][Medline]
The EUROASPIRE Study Group. A European Society of Cardiology survey of secondary prevention of coronary heart disease: principal results. Eur Heart J 1997;18:1569-1582. [Erratum, Eur Heart J 1998;19:356-7.] [Free Full Text]
Simons LA, Levis G, Simons J. Apparent discontinuation rates in patients prescribed lipid-lowering drugs. Med J Aust 1996;164:208-211. [Medline]
Pearson TA, McBride PE, Miller NH, Smith SC. Task Force 8: organization of preventive cardiology service. J Am Coll Cardiol 1996;27:1039-1047. [CrossRef][Medline]
Keech A. Risk factor management in CHD patients in Asia: current status. Atherosclerosis 1998;136:Suppl:S31-S31.abstract
Bowker TJ, Clayton TC, Ingham J, et al. A British Cardiac Society survey of the potential for secondary prevention of coronary disease: ASPIRE (Action on Secondary Prevention through Intervention to Reduce Events). Heart 1996;75:334-342. [Free Full Text]
Appendix
The participants in the LIPID study were as follows: ManagementCommittee — A. Tonkin (chair), P. Aylward, D. Colquhoun,P. Glasziou, P. Harris, D. Hunt, A. Keech, S. MacMahon, P. Magnus,D. Newel, P. Nestel, N. Sharpe, J. Shaw, R.J. Simes, P. Thompson,A. Thomson, M. West, H. White; Audit Committee — A. Thomson(chair), S. Simes, D. Colquhoun, W. Hague, S. MacMahon, R.J.Simes; Cost-Effectiveness Committee — R.J. Simes (chair),P. Glasziou, S. Caleo, J. Hall, A. Martin, S. Mulray; Data andSafety Monitoring Committee — P. Barter (chair), L. Beilin,R. Collins, J. McNeil, P. Meier, H. Willimott; Finance Committee— P. Harris (chair), W. Hague, D. Smithers, A. Tonkin,P. Wallace, H. Willimott; Outcomes-Assessment Committee —D. Hunt (chair), J. Baker, P. Aylward, P. Harris, M. Hobbs,P. Thompson; Publications Committee — N. Sharpe (chair),D. Hunt, M. West, P. Thompson, H. White; Quality-Assurance Committee— P. Aylward (chair), D. Colquhoun, D. Sullivan, A. Keech;Related-Studies Committee — P. Thompson (chair), S. MacMahon,A. Tonkin, M. West; Stroke-Adjudication Committee — H.White (chair), N. Anderson, G. Hankey, R.J. Simes, S. Simes,J. Watson; Writing-Allocation Committee — R.J. Simes (chair),N. Sharpe, A. Thomson, A. Tonkin, H. White; National Healthand Medical Research Council Clinical Trials Centre, Universityof Sydney — W. Hague (study manager), J. Baker, M. Arulchelvam(biostatisticians), S. Chup, J. Daly, J. Hanna, A. Leach, M.Lee, J. Loughhead, H. Lundie-Jenkin, J. Morrison, A. Martin,S. Mulray, S. Netting, A. Nguyen, H. Pater, R. Philip, G. Pinna,D. Rattos, S. Ryerson, V. Sazhin, S. Simes, R. Walsh, A. Keech(deputy director), R.J. Simes (director); Clinical Trials ResearchUnit, Auckland — A. Clague, M. Mackie, J. Yallop, K. Boss,S. MacMahon (director); Central Lipid Laboratory, Flinders MedicalCentre — M. Whiting, M. Shepard, J. Leach; Bristol-MyersSquibb Pharmaceuticals — M. Gandy, J. Joughin, J. Seabrook;LIPID investigators (numbers of patients enrolled are shownin parentheses) — Australia (5958): New South Wales (1616)— R. Abraham, J. Allen, F. Bates, I. Beinart, E. Breed,D. Brown, N. Bunyan, D. Calvert, T. Campbell, D. Condon-Paoloni,B. Conway, L. Coupland, J. Crowe, N. Cunio, B. Cuthbert, N.Cuthbert, S. D'Arcy, P. Davidson, B. Dwyer, J. England, C. Friend,G. Fulcher, S. Grant, K. Hellestrand, M. Kava, L. Kritharides,D. McGill, H. McKee, A. McLean, M. Neaverson, G. Nelson, M.O'Neill, C. Onuma, F. O'Reilly, A. Owensby, D. Owensby, J. Padley,G. Parnell, S. Paterson, C. Pawsey, R. Portley, K. Quinn, D.Ramsay, M. Russell, J. Ryan, B. Sambrook, L. Shields, J. Silberberg,S. Sinclair, D. Sullivan, P. Taverner, D. Taylor, M. Taylor,M. Threlfall, J. Turner, A. Viles, J. Waites, R. Walker, W.Walsh, K. Wee, P. West, R. Wikramanayake, D. Wilcken, J. Woods,R. Wyndham; Victoria (1374) — K. Barnett, Z. Bogetic,H. Briggs, A. Broughton, L. Brown, A. Buncle, P. Calafiore,L. Carrick, Y. Cavenett, L. Champness, R. Clark, H. Connor,J. Counsell, J. Deague, G. Derwent-Smith, A. Driscoll, B. Feldtmann,L. Fisher, B. Forge, A. Hamer, H. Harrap, S. Hodgens, M. Hooten,J. Hurley, B. Jackson, J. Johns, J. Krafchek, H. Larwill, I.Lyall, S. Marks, M. Martin, B. Mason, J. McCabe, C. Medley,L. Morgan, L. Mullan, D. Ogilvy, G. Phelps, P. Phillips, H.Prendergast, D. Rose, G. Rudge, W. Ryan, M. Sallaberger, G.Savige, B. Sia, A. Soward, C. Steinfort, K. Tankard, J. Tippett,B. Tyack, J. Voukelatis, M. Wahlqvist, N. Walker, S. Whitten,R. Yee, M. Zanoni, R. Ziffer; Queensland (1431) — K. Anderson,G. Aroney, C. Atkinson, K. Boyd, R. Bradfield, G. Cameron, D.Careless, A. Carle, P. Carroll, T. Carruthers, D. Chaseling,B. Cooke, S. Coverdale, B. Currie, M. d'Emden, F. Ekin, R. Elder,T. Elsley, L. Ferry, C. Gnanaharan, K. Graham, K. Gunawardane,C. Hadfield, C. Halliday, R. Halliday, A. Heyworth, B. Hicks,P. Hicks, T. Htut, L. Hughes, J. Humphries, H. LeGood, J. Nye,D. O'Brien, G. Real, K. Roberts, L. Ross-Lee, J. Sampson, I.Scott, H. Smith, V. Smith-Orr, Y. Tan, B. Wicks, J. Wicks, S.Woodhouse; South Australia (512) — J. Bradley, L. Callaway,A. Calvert, J. Crettenden, A. Dufek, B. Dunn, C. Dunphy, D.Gow, I. Hamilton-Craig, K. Herewane, S. Keynes, L. McLeay, R.McLeay, L. Ng, C. Thomas, P. Tideman, L. Wilson, R. Yeend, C.Zhang, Y. Zhang; Western Australia (623) — P. Bradshaw,M. Brooks, R. Burton, J. Garrett, K. Gotch-Martin, J. Hargan,B. Hockings, G. Lane, S. Ross; Tasmania (402) — R. Cutforth,D. D'Silva, W. Hitchener, V. Kimber, G. Kirkland, P. Neid, R.Parkes, B. Singh, C. Singh, M. Smith, S. Smith, M. Templer,N. Whitehouse; New Zealand (3056) — R. Allen-Narker, R.Anandaraja, S. Anandaraja, P. Barclay, S. Baskaranathan, P.Bridgman, J. Brown, J. Bruning, J. Calton, A. Clague, M. Clark,D. Clarke, T. Cook, R. Coxon, M. Denton, A. Doone, R. Easthope,J. Elliott, C. Ellis, P. Foster-Pratt, C. Frenneux, M. Frenneux,D. Friedlander, D. Fry, L. Gibson, M. Gluyas, A. Hall, K. Hall,A. Hamer, H. Hart, P. Healy, J. Hedley, P. Heuser, H. Ikram,D. Jardine, J. Kenyon, H. King, T. Kirk, T. Lawson, P. Leslie,G. Lewis, E. Low, R. Luke, S. Mann, D. McClean, D. McHaffie,L. Nairn, H. Patel, L. Pearce, K. Ramanathan, R. Rankin, J.Reddy, S. Reuben, R. Ronaldson, D. Roy, H. Roy, P. Scobie, D.Scott, J. Scott, K. Skjellerup, R. Stewart, D. Walters, T. Wilkins,A. Vitanachy, P. Wright, A. Zambanini.
Unstable Angina Pectoris
Colwell N. S., Buckley B. M., Murphy M. B., Shavelle D. M., Wuthrich D. A., Srivathsan K., Showalter J. C., Dieter R. S., Yeghiazarians Y., Stone P. H.
Extract |
Full Text
N Engl J Med 2000;
342:1676-1678, Jun 1, 2000.
Correspondence
This article has been cited by other articles:
Zhang, Y., Donohue, J. M., Lave, J. R., O'Donnell, G., Newhouse, J. P.
(2009). The Effect of Medicare Part D on Drug and Medical Spending. NEJM
361: 52-61
[Abstract][Full Text]
Moschovitis, A., Meier, B.
(2009). Are adapted guidelines required for patients with prior bypass surgeries and heart failure in acute myocardial infarction?. Eur Heart J
30: 1429-1430
[Full Text]
Leon, M. B., Allocco, D. J., Dawkins, K. D., Baim, D. S.
(2009). Late Clinical Events After Drug-Eluting Stents: The Interplay Between Stent-Related and Natural History-Driven Events. J Am Coll Cardiol Intv
2: 504-512
[Abstract][Full Text]
McWilliams, J. M., Meara, E., Zaslavsky, A. M., Ayanian, J. Z.
(2009). Differences in Control of Cardiovascular Disease and Diabetes by Race, Ethnicity, and Education: U.S. Trends From 1999 to 2006 and Effects of Medicare Coverage. ANN INTERN MED
150: 505-515
[Abstract][Full Text]
Hunt, S. A., Abraham, W. T., Chin, M. H., Feldman, A. M., Francis, G. S., Ganiats, T. G., Jessup, M., Konstam, M. A., Mancini, D. M., Michl, K., Oates, J. A., Rahko, P. S., Silver, M. A., Stevenson, L. W., Yancy, C. W.
(2009). 2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation. J Am Coll Cardiol
53: e1-e90
[Full Text]
2005 WRITING COMMITTEE MEMBERS, , Hunt, S. A., Abraham, W. T., Chin, M. H., Feldman, A. M., Francis, G. S., Ganiats, T. G., Jessup, M., Konstam, M. A., Mancini, D. M., Michl, K., Oates, J. A., Rahko, P. S., Silver, M. A., Stevenson, L. W., Yancy, C. W.
(2009). 2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: Developed in Collaboration With the International Society for Heart and Lung Transplantation. Circulation
119: e391-e479
[Full Text]
Khavandi, A, Khavandi, K, Greenstein, A, Karsch, K, Heagerty, A M
(2009). n-3 Polyunsaturated fatty acids are still underappreciated and underused post myocardial infarction. Heart
95: 540-541
[Full Text]
Tonkin, A M, Forbes, A, Haas, S J
(2009). The evidence on trial: cholesterol lowering and cancer. Heart Asia
2009: 6-10
[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]
Redfern, J, Briffa, T, Ellis, E, Freedman, S B
(2009). Choice of secondary prevention improves risk factors after acute coronary syndrome: 1-year follow-up of the CHOICE (Choice of Health Options In prevention of Cardiovascular Events) randomised controlled trial. Heart
95: 468-475
[Abstract][Full Text]
Sassano, A., Lo Iacono, M., Antico, G., Jordan, A., Uddin, S., Calogero, R. A., Platanias, L. C.
(2009). Regulation of leukemic cell differentiation and retinoid-induced gene expression by statins. Molecular Cancer Therapeutics
8: 615-625
[Abstract][Full Text]
Briel, M., Ferreira-Gonzalez, I., You, J. J, Karanicolas, P. J, Akl, E. A, Wu, P., Blechacz, B., Bassler, D., Wei, X., Sharman, A., Whitt, I., Alves da Silva, S., Khalid, Z., Nordmann, A. J, Zhou, Q., Walter, S. D, Vale, N., Bhatnagar, N., O'Regan, C., Mills, E. J, Bucher, H. C, Montori, V. M, Guyatt, G. H
(2009). Association between change in high density lipoprotein cholesterol and cardiovascular disease morbidity and mortality: systematic review and meta-regression analysis. BMJ
338: b92-b92
[Abstract][Full Text]
Shalev, V., Chodick, G., Silber, H., Kokia, E., Jan, J., Heymann, A. D.
(2009). Continuation of Statin Treatment and All-Cause Mortality: A Population-Based Cohort Study. Arch Intern Med
169: 260-268
[Abstract][Full Text]
Rafnsson, S. B, Deary, I. J, Fowkes, F.
(2009). Peripheral arterial disease and cognitive function. Vasc Med
14: 51-61
[Abstract]
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]
Maher, B. M., Dhonnchu, T. N., Burke, J. P., Soo, A., Wood, A. E., Watson, R. W. G.
(2009). Statins alter neutrophil migration by modulating cellular Rho activity--a potential mechanism for statins-mediated pleotropic effects?. J. Leukoc. Biol.
85: 186-193
[Abstract][Full Text]
Adams, H. P. Jr
(2009). Secondary Prevention of Atherothrombotic Events After Ischemic Stroke. Mayo Clin Proc.
84: 43-51
[Abstract][Full Text]
Krumholz, H. M., Anderson, J. L., Bachelder, B. L., Fesmire, F. M., Fihn, S. D., Foody, J. M., Ho, P. M., Kosiborod, M. N., Masoudi, F. A., Nallamothu, B. K.
(2008). ACC/AHA 2008 Performance Measures for Adults With ST-Elevation and Non-ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology/American Heart Association Task Force on Performance Measures (Writing Committee to Develop Performance Measures for ST-Elevation and Non-ST-Elevation Myocardial Infarction) Developed in Collaboration With the American Academy of Family Physicians and American College of Emergency Physicians Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation, Society for Cardiovascular Angiography and Interventions, and Society of Hospital Medicine. J Am Coll Cardiol
52: 2046-2099
[Full Text]
Krumholz, H. M., Anderson, J. L., Bachelder, B. L., Fesmire, F. M., Fihn, S. D., Foody, J. M., Ho, P. M., Kosiborod, M. N., Masoudi, F. A., Nallamothu, B. K.
(2008). ACC/AHA 2008 Performance Measures for Adults With ST-Elevation and Non-ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology/American Heart Association Task Force on Performance Measures (Writing Committee to Develop Performance Measures for ST-Elevation and Non-ST-Elevation Myocardial Infarction): Developed in Collaboration With the American Academy of Family Physicians and the American College of Emergency Physicians: Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation, Society for Cardiovascular Angiography and Interventions, and Society of Hospital Medicine. Circulation
118: 2596-2648
[Full Text]
Jisheng Cui, , Forbes, A., Kirby, A., Marschner, I., Simes, J., West, M., Tonkin, A.
(2008). Parametric conditional frailty models for recurrent cardiovascular events in the lipid study. Clin Trials
5: 565-574
[Abstract]
Tabata, M., Khalpey, Z., Cohn, L. H., Chen, F. Y., Bolman, R. M. III, Rawn, J. D.
(2008). Effect of preoperative statins in patients without coronary artery disease who undergo cardiac surgery.. J. Thorac. Cardiovasc. Surg.
136: 1510-1513
[Abstract][Full Text]
Mukherjee, R., Locke, K. T., Miao, B., Meyers, D., Monshizadegan, H., Zhang, R., Search, D., Grimm, D., Flynn, M., O'Malley, K. M., Zhang, L., Li, J., Shi, Y., Kennedy, L. J., Blanar, M., Cheng, P. T., Tino, J., Srivastava, R. A.
(2008). Novel Peroxisome Proliferator-Activated Receptor {alpha} Agonists Lower Low-Density Lipoprotein and Triglycerides, Raise High-Density Lipoprotein, and Synergistically Increase Cholesterol Excretion with a Liver X Receptor Agonist. J. Pharmacol. Exp. Ther.
327: 716-726
[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]
Coletta, A. P., Cullington, D., Clark, A. L., Cleland, J. G.F.
(2008). Clinical trials update from European Society of Cardiology meeting 2008: TIME-CHF, BACH, BEAUTIFUL, GISSI-HF, and HOME-HF. Eur J Heart Fail
10: 1264-1267
[Abstract][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]
Sillesen, H., Amarenco, P., Hennerici, M. G., Callahan, A., Goldstein, L. B., Zivin, J., Messig, M., Welch, K. M., on Behalf of the SPARCL Investigators,
(2008). Atorvastatin Reduces the Risk of Cardiovascular Events in Patients With Carotid Atherosclerosis: A Secondary Analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Trial. Stroke
39: 3297-3302
[Abstract][Full Text]
Young, M. J., McCardle, J. E., Randall, L. E., Barclay, J. I.
(2008). Improved Survival of Diabetic Foot Ulcer Patients 1995-2008: Possible impact of aggressive cardiovascular risk management. Diabetes Care
31: 2143-2147
[Abstract][Full Text]
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]
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]
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]
Nichol, G., Thomas, E., Callaway, C. W., Hedges, J., Powell, J. L., Aufderheide, T. P., Rea, T., Lowe, R., Brown, T., Dreyer, J., Davis, D., Idris, A., Stiell, I.
(2008). Regional Variation in Out-of-Hospital Cardiac Arrest Incidence and Outcome. JAMA
300: 1423-1431
[Abstract][Full Text]
Cayley, W. E.
(2008). Monitoring Cholesterol Levels: Understanding Variance and Finding the Most Useful Data. ANN INTERN MED
149: 436-437
[Full Text]
Giraldez, R. R., Giugliano, R. P., Mohanavelu, S., Murphy, S. A., McCabe, C. H., Cannon, C. P., Braunwald, E.
(2008). Baseline Low-Density Lipoprotein Cholesterol Is an Important Predictor of the Benefit of Intensive Lipid-Lowering Therapy: A PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22) Analysis. J Am Coll Cardiol
52: 914-920
[Abstract][Full Text]
Bruschke, A. V.G., Jukema, J. W.
(2008). Aggressive Therapy Is Not Always the Best Therapy. J Am Coll Cardiol
52: 921-923
[Full Text]
Steg, P. G., Kerner, A., Van de Werf, F., Lopez-Sendon, J., Gore, J. M., FitzGerald, G., Feldman, L. J., Anderson, F. A., Avezum, A., for the Global Registry of Acute Coronary Events (,
(2008). Impact of In-Hospital Revascularization on Survival in Patients With Non-ST-Elevation Acute Coronary Syndrome and Congestive Heart Failure. Circulation
118: 1163-1171
[Abstract][Full Text]
Wei, L, Lang, C C, Sullivan, F M, Boyle, P, Wang, J, Pringle, S D, MacDonald, T M
(2008). Impact on mortality following first acute myocardial infarction of distance between home and hospital: cohort study. Heart
94: 1141-1146
[Abstract][Full Text]
Goldstein, L. B., Amarenco, P., LaMonte, M., Gilbert, S., Messig, M., Callahan, A., Hennerici, M., Sillesen, H., Welch, K. M. A., on behalf of the SPARCL Investigators,
(2008). Relative Effects of Statin Therapy on Stroke and Cardiovascular Events in Men and Women: Secondary Analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Study. Stroke
39: 2444-2448
[Abstract][Full Text]
Fonseca, V. A., Rosenstock, J., Wang, A. C., Truitt, K. E., Jones, M. R.
(2008). Colesevelam HCl Improves Glycemic Control and Reduces LDL Cholesterol in Patients With Inadequately Controlled Type 2 Diabetes on Sulfonylurea-Based Therapy. Diabetes Care
31: 1479-1484
[Abstract][Full Text]
Kataoka, H.
(2008). Response to Letter by Paraskevas. Stroke
39: e135-e135
[Full Text]
Filippatos, T. D., Mikhailidis, D. P.
(2008). Statins and Heart Failure. ANGIOLOGY
59: 58S-61S
[Abstract]
Woodard, J., Sassano, A., Hay, N., Platanias, L. C.
(2008). Statin-Dependent Suppression of the Akt/Mammalian Target of Rapamycin Signaling Cascade and Programmed Cell Death 4 Up-Regulation in Renal Cell Carcinoma. Clin. Cancer Res.
14: 4640-4649
[Abstract][Full Text]
Zhou, M.-S., Schuman, I. H., Jaimes, E. A., Raij, L.
(2008). Renoprotection by statins is linked to a decrease in renal oxidative stress, TGF-{beta}, and fibronectin with concomitant increase in nitric oxide bioavailability. Am. J. Physiol. Renal Physiol.
295: F53-F59
[Abstract][Full Text]
Reaume, K. T, Erickson, S. R, Dorsch, M. P, Dunham, N. L., Hiniker, S. M, Prabhakar, N., Kline-Rogers, E. M, Eagle, K. A
(2008). Effects of Cerivastatin Withdrawal on Statin Persistence. The Annals of Pharmacotherapy
42: 956-961
[Abstract][Full Text]
Tanaka, K., Ishikawa, Y., Yokoyama, M., Origasa, H., Matsuzaki, M., Saito, Y., Matsuzawa, Y., Sasaki, J., Oikawa, S., Hishida, H., Itakura, H., Kita, T., Kitabatake, A., Nakaya, N., Sakata, T., Shimada, K., Shirato, K., for the JELIS Investigators, Japan,
(2008). Reduction in the Recurrence of Stroke by Eicosapentaenoic Acid for Hypercholesterolemic Patients: Subanalysis of the JELIS Trial. Stroke
39: 2052-2058
[Abstract][Full Text]
U.S. Preventive Services Task Force,
(2008). Screening for Type 2 Diabetes Mellitus in Adults: U.S. Preventive Services Task Force Recommendation Statement. ANN INTERN MED
148: 846-854
[Abstract][Full Text]
Jacobson, T. A.
(2008). Toward 'Pain-Free' Statin Prescribing: Clinical Algorithm for Diagnosis and Management of Myalgia. Mayo Clin Proc.
83: 687-700
[Abstract][Full Text]
Glasziou, P. P., Irwig, L., Heritier, S., Simes, R. J., Tonkin, A., for the LIPID Study Investigators,
(2008). Monitoring Cholesterol Levels: Measurement Error or True Change?. ANN INTERN MED
148: 656-661
[Abstract][Full Text]
Caymaz, H. O., Yuksel, G.
(2008). Fate of Incidental, Asymptomatic Lesions Discovered During Percutaneous Coronary Intervention. ANGIOLOGY
59: 193-197
[Abstract]
Brunzell, J. D., Davidson, M., Furberg, C. D., Goldberg, R. B., Howard, B. V., Stein, J. H., Witztum, J. L.
(2008). Lipoprotein Management in Patients With Cardiometabolic Risk: Consensus Conference Report From the American Diabetes Association and the American College of Cardiology Foundation. J Am Coll Cardiol
51: 1512-1524
[Full Text]
Betteridge, D. J., DeFronzo, R. A., Chilton, R. J.
(2008). PROactive: time for a critical appraisal. Eur Heart J
29: 969-983
[Abstract][Full Text]
Nusca, A., Melfi, R., Di Sciascio, G.
(2008). Review: Percutaneous coronary interventions and statins therapy. Ther Adv Cardiovasc Dis
2: 101-107
[Abstract]
West, M. J., Nestel, P. J., Kirby, A. C., Schnabel, R., Sullivan, D., Simes, R. J., Pollicino, C., Lubos, E., Munzel, T. F., White, H. D., Tonkin, A. M., Bickel, C., Tiret, L., Blankenberg, S., for the LIPID Study Investigators,
(2008). The value of N-terminal fragment of brain natriuretic peptide and tissue inhibitor of metalloproteinase-1 levels as predictors of cardiovascular outcome in the LIPID study. Eur Heart J
29: 923-931
[Abstract][Full Text]
MacFadyen, R. J., Ng Kam Chuen, M. J.
(2008). Developing the utility of blood biomarker associations beyond population sample linkage to events in cardiovascular patients. Eur Heart J
29: 837-839
[Full Text]
Brunzell, J. D., Davidson, M., Furberg, C. D., Goldberg, R. B., Howard, B. V., Stein, J. H., Witztum, J. L.
(2008). Lipoprotein Management in Patients With Cardiometabolic Risk: Consensus statement from the American Diabetes Association and the American College of Cardiology Foundation. Diabetes Care
31: 811-822
[Full Text]
Griel, A. E., Cao, Y., Bagshaw, D. D., Cifelli, A. M., Holub, B., Kris-Etherton, P. M.
(2008). A Macadamia Nut-Rich Diet Reduces Total and LDL-Cholesterol in Mildly Hypercholesterolemic Men and Women. J. Nutr.
138: 761-767
[Abstract][Full Text]
Wenger, N K, Lewis, S J, Welty, F K, Herrington, D M, Bittner, V, on behalf of the TNT Steering Committee and Invest,
(2008). Beneficial effects of aggressive low-density lipoprotein cholesterol lowering in women with stable coronary heart disease in the Treating to New Targets (TNT) study. Heart
94: 434-439
[Abstract][Full Text]
Athyros, V. G., Kakafika, A. I., Tziomalos, K., Karagiannis, A., Mikhailidis, D. P.
(2008). CORONA, Statins, and Heart Failure: Who Lost the Crown?. ANGIOLOGY
59: 5-8
Badger, S. A., Soong, C. V., Lee, B., Swain, G. R., McGuigan, K. E.
(2008). Prescribing Practice of General Practitioners in Northern Ireland for Peripheral Arterial Disease. ANGIOLOGY
59: 57-63
[Abstract]
Nassief, A., Marsh, J. D.
(2008). Statin Therapy for Stroke Prevention. Stroke
39: 1042-1048
[Abstract][Full Text]
Bell, K. J L, Irwig, L., Craig, J. C, Macaskill, P.
(2008). Use of randomised trials to decide when to monitor response to new treatment. BMJ
336: 361-365
[Full Text]
Vergouwen, M. D.I., de Haan, R. J., Vermeulen, M., Roos, Y. B.W.E.M.
(2008). Statin Treatment and the Occurrence of Hemorrhagic Stroke in Patients With a History of Cerebrovascular Disease. Stroke
39: 497-502
[Abstract][Full Text]
Wienbergen, H., Senges, J., Gitt, A. K.
(2008). Should We Prescribe Statin and Aspirin for Every Diabetic Patient?: Is it time for a polypill?. Diabetes Care
31: S222-S225
[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]
Afilalo, J., Duque, G., Steele, R., Jukema, J. W., de Craen, A. J.M., Eisenberg, M. J.
(2008). Statins for secondary prevention in elderly patients: a hierarchical bayesian meta-analysis.. J Am Coll Cardiol
51: 37-45
[Abstract][Full Text]
Cleland, J. G.F., Coletta, A. P., Abdellah, A. T., Cullington, D., Clark, A. L., Rigby, A. S.
(2008). Clinical trials update from the American Heart Association 2007: CORONA, RethinQ, MASCOT, AF-CHF, HART, MASTER, POISE and stem cell therapy. Eur J Heart Fail
10: 102-108
[Abstract][Full Text]
McWilliams, J. M., Meara, E., Zaslavsky, A. M., Ayanian, J. Z.
(2007). Health of Previously Uninsured Adults After Acquiring Medicare Coverage. JAMA
298: 2886-2894
[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]
Holman, J. R.
(2007). Some Docs in Denial About Statin Side Effects. DOC News
4: 1-12
[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]
Kjekshus, J., Apetrei, E., Barrios, V., Bohm, M., Cleland, J. G.F., Cornel, J. H., Dunselman, P., Fonseca, C., Goudev, A., Grande, P., Gullestad, L., Hjalmarson, A., Hradec, J., Janosi, A., Kamensky, G., Komajda, M., Korewicki, J., Kuusi, T., Mach, F., Mareev, V., McMurray, J. J.V., Ranjith, N., Schaufelberger, M., Vanhaecke, J., van Veldhuisen, D. J., Waagstein, F., Wedel, H., Wikstrand, J., the CORONA Group,
(2007). Rosuvastatin in Older Patients with Systolic Heart Failure. NEJM
357: 2248-2261
[Abstract][Full Text]
Grover, S. A., Lowensteyn, I., Joseph, L., Kaouache, M., Marchand, S., Coupal, L., Boudreau, G., for the Cardiovascular Health Evaluation to Improv,
(2007). Patient Knowledge of Coronary Risk Profile Improves the Effectiveness of Dyslipidemia Therapy: The CHECK-UP Study: A Randomized Controlled Trial. Arch Intern Med
167: 2296-2303
[Abstract][Full Text]
Arsenault, B. J., Lemieux, I., Despres, J.-P., Wareham, N. J., Luben, R., Kastelein, J. J.P., Khaw, K.-T., Boekholdt, S. M.
(2007). Cholesterol levels in small LDL particles predict the risk of coronary heart disease in the EPIC-Norfolk prospective population study. Eur Heart J
28: 2770-2777
[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]
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]
Gnavi, R., Migliardi, A., Demaria, M., Petrelli, A., Caprioglio, A., Costa, G.
(2007). Statins prescribing for the secondary prevention of ischaemic heart disease in Torino, Italy. A case of ageism and social inequalities. Eur J Public Health
17: 492-496
[Abstract][Full Text]
Cleland, J. G.F., Abdellah, A. T., Khaleva, O., Coletta, A. P., Clark, A. L.
(2007). Clinical trials update from the European Society of Cardiology Congress 2007: 3CPO, ALOFT, PROSPECT and statins for heart failure. Eur J Heart Fail
9: 1070-1073
[Abstract][Full Text]
Marschner, I. C., Simes, R. J., Keech, A.
(2007). Biases in the Identification of Risk Factor Thresholds and J-Curves. Am J Epidemiol
166: 824-831
[Abstract][Full Text]
Hippisley-Cox, J., Parker, C., Coupland, C., Vinogradova, Y.
(2007). Inequalities in the primary care of patients with coronary heart disease and serious mental health problems: a cross-sectional study. Heart
93: 1256-1262
[Abstract][Full Text]
Previous
