Skip Navigation


European Heart Journal Advance Access originally published online on August 3, 2006
European Heart Journal 2006 27(19):2310-2316; doi:10.1093/eurheartj/ehl180
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
27/19/2310    most recent
ehl180v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (11)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Ray, K. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ray, K. K.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The European Society of Cardiology 2006. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Benefits of achieving the NCEP optional LDL-C goal among elderly patients with ACS

Kausik K. Ray1,*, Richard G. Bach2, Christopher P. Cannon1, Richard Cairns3, Ajay J. Kirtane4, Stephen D. Wiviott1, Carolyn H. McCabe1, Eugene Braunwald1, C. Michael Gibson4 for the PROVE IT-TIMI 22 Investigators

1 The TIMI Study Group and Cardiovascular Division, Department of Medicine, Brigham & Women's Hospital/Harvard Medical School, Boston, MA 02115, USA
2 Cardiovascular Division, Washington University School of Medicine, St Louis, MO 63110, USA
3 Nottingham Clinical Research Ltd, Isaac Newton Centre, Nottingham Science & Technology Park, Nottingham, N67 2RH, UK
4 Cardiovascular Division, Beth Israel Deaconness Medical Centre, Harvard Medical School, Boston, MA 02215, USA

Received 2 March 2006; revised 7 July 2006; accepted 14 July 2006; online publish-ahead-of-print 3 August 2006.

* Corresponding author: TIMI Study Group, 350 Longwood Avenue, First Floor, Boston, MA 02115, USA. Tel: +1 617 278 0145; fax: +1 617 734 7329. E-mail address: koshray{at}gmail.com


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 Conclusions
 Acknowledgements
 References
 
Aims To assess the efficacy and safety of the achievement of the NCEP goal of LDL-C <1.8 mmol/L in elderly patients with ACS.

Methods and results The relationship between LDL-C at 30 days after ACS and subsequent clinical outcomes were compared among elderly patients (aged ≥70 years) vs. younger counterparts in the PROVE IT-TIMI 22 trial, using the composite endpoint of death, myocardial infarction, or unstable angina. Among 634 elderly patients, the achievement of the NCEP goal was associated with an 8% absolute and a 40% relative lower risk of events [Hazard ratio (HR) 0.60, 95% confidence interval (CI) 0.41–0.87, P=0.008] vs. corresponding benefits of 2.3 and 26% in 3150 younger patients (HR 0.74, 95% CI 0.59–0.94, P=0.013). The estimated number of events preventable among the elderly by the achievement of these goals was 80 events at 2 years for every 1000 patients at goal vs. those not at goal, compared with 23 events potentially prevented in younger patients. The incidence of major side effects among the elderly was similar to that in younger patients and did not differ with the intensity of the statin regimen.

Conclusion Among elderly ACS patients, achieving the new NCEP LDL-C optional goal as part of a secondary prevention strategy can be both as safe and effective as in younger patients.

Key Words: Elderly • NCEP • LDL-C • Clinical events • Statins


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 Conclusions
 Acknowledgements
 References
 
Lipid lowering with standard doses of statin therapy has been associated with clinical benefits among elderly patients with a prior history of vascular disease or major risk factors for atherosclerosis in the Pravastatin in Elderly Individuals at Risk of Vascular Disease (PROSPER) trial.1 Compared with stable disease, patients with acute coronary syndromes (ACS) are at higher risk of recurrent events and the elderly are a particularly high-risk subgroup.2 Registry data however suggest that despite their higher risk of recurrent events, elderly patients are paradoxically treated with fewer evidence-based therapies such as revascularization or cardioprotective drugs including statins.3 In addition, the elderly frequently do not achieve guideline-based treatment goals.4,5 The recent National Cholesterol Expert Panel (NCEP) consensus statement recommended a low-density lipoprotein (LDL) cholesterol (LDL-C) <1.8 mmol/L as an optional goal for patients at very high risk of cardiovascular events.6 Although data on the safety and efficacy of lowering an LDL-C to ~2.5 mmol/L with statins are available in stable elderly patients,1 it is unclear whether achieving an LDL-C <1.8 mmol/L would be both safe and effective in elderly patients with ACS. We assessed the benefit of achieving the new NCEP LDL-C optional goal of <1.8 mmol/L among ACS patients ≥70 years age in the Pravastatin or Atorvastatin Evaluation and Infection Therapy Thrombolysis in Myocardial Infarction (PROVE IT-TIMI) 22 trial to evaluate whether the new NCEP recommendations were applicable to high-risk elderly patients.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 Conclusions
 Acknowledgements
 References
 
Study population and intervention
The design of the PROVE IT-TIMI 22 protocol has been described previously.7 Briefly, 4162 patients with a total cholesterol level of ≤6.2 mmol/L, who had been hospitalized for an ACS within the previous 10 days, and who were stable were enrolled. ACS included patients with ST-elevation MI (STEMI), non-STEMI, or high-risk unstable angina (UA). Eligible patients were randomly assigned in a 1:1 ratio to pravastatin 40 mg or atorvastatin 80 mg daily, and gatifloxacin vs. placebo, administered in a double-blind fashion with an average follow-up of 24 months.

Lipid measurements
Core laboratory total cholesterol, HDL, triglyceride (TG), and high-sensitivity CRP (hS-CRP) were measured at enrolment, 30 days, 4 months, and end of study (average 2 years) in fasting samples. Lipid components were measured by Labcorp (Raritan, NJ) and CRP was measured at the Children's Hospital, Boston, MA. Total cholesterol, HDL, and TGs were measured by an enzymatic colorimetric method (Roche Modular system) using standardized assays8 and LDL-C was obtained by the calculation [total cholesterol–(TG/5+HDL)].9 CRP was measured using the validated Denka-Seiken method for hS-CRP.10

Clinical endpoints
The clinical endpoint for this analysis focused on the acute cardiac clinical events of death, myocardial infarction (MI), or UA requiring rehospitalization. In addition, we also assessed the relationship between achieving optional NCEP goals and subsequent risk of the primary endpoint of the PROVE IT-TIMI 22 trial, which included the acute cardiovascular endpoints of death, MI, UA or stroke, as well as the non-acute endpoint of revascularization after 30 days, as previously described.7 All acute endpoints were adjudicated by the clinical events committee.7

Safety
Discontinuation of study drug was assessed for any reports of myalgia or creatinine kinase (CK) rise, for any side effect (elevated liver enzymes, elevated CK, myalgia or arthralgia, or any other side effect felt to the drug related), or for patient preference (patient withdrawing consent to treatment or follow-up). Abnormal liver function tests are defined as alanine aminotransferase (ALT) >3x the upper limit of normal (ULN) among patients with normal ALT at enrolment. Elevated CK was defined as any rise in CK >3x ULN during follow-up.

Statistical analysis
Categorical variables were compared using a {chi}2 test, whereas continuous variables were compared using a two-sample t-test where the data were normally distributed, otherwise a Wilcoxon test. The earliest time point that was available to assess the relationship between achieved LDL-C and subsequent outcomes was 30 days after study entry. Patients who experienced one of the clinical endpoints in question prior to day 30 were not included, because such an event could have an effect on both their lipid profile and the likelihood of experiencing subsequent events. In total, 378 patients (83 of whom had an endpoint before 30 days) were excluded, constituting 13% of the elderly and 8% of the younger original PROVE IT-TIMI 22 cohort. The incidence of clinical events is reported as the Kaplan–Meier event rate at 2 years, and hazard ratio (HR) estimates with associated 95% CIs were obtained from a Cox proportional hazards model, with age and LDL-C stratum as covariates. The proportional hazards assumption was tested using the method of Grambsch and Thernau.11 Additionally we performed multivariable adjustment for traditional risk factors and variables that were different between groups. These included gender, diabetes, smoking, prior history of MI, hypertension, BMI, revascularization for index event, extent of angiographic disease, use of medications at 30 days, 30-day HDL, TG, CRP, and systolic blood pressure. The number of events potentially prevented within each age group was estimated from Kaplan–Meier rates for each outcome at 2 years and multiplied by 1000 to obtain estimates of treatment benefit for 1000 patients treated for 2 years. Analyses were performed using SAS v9 (SAS Institute Inc., Cary, NC) and S-Plus v6.2 (Insightful Corp., Seattle, WA); the statistical analyses were performed by the TIMI Data Coordinating Center and the Nottingham Clinical Research Group.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 Conclusions
 Acknowledgements
 References
 
Clinical characteristics
In PROVE IT-TIMI 22, there were 730 patients ≥70 years of age and 3432 patients <70 years of age at enrolment. Elderly patients were more likely to have a history of hypertension (P<0.0001), diabetes (P=0.02), a prior MI (P<0.0001), and more extensive coronary artery disease (CAD) (two or more vessels with>50% stenosis, P<0.0001), but were less likely to be male (P<0.001) or smokers (P<0.001) when compared with younger patients. The use of percutaneous coronary intervention (PCI) during the index hospitalization was lower in the elderly (46) vs. 59% in the younger patients (P<0.0001). The elderly had lower baseline LDL-C and TG levels but higher HDL levels (P<0.0001 for each) and a higher rate of prior statin use (P<0.0001). At the 30-day follow-up, the use of cardioprotective drugs was similar among elderly and younger patients, but fewer elderly patients were receiving aspirin (92.5 vs. 95%, P=0.01). Within each age stratum, there were no differences in the clinical characteristics of patients between the two randomized statin regimens. The clinical characteristics of patients within each age and LDL-C stratum are shown in Table 1.


View this table:
[in this window]
[in a new window]

  		Table 1 Clinical characteristics of elderly and younger counterparts stratified by day 30 LDL-C

 
LDL-C levels during follow-up
Overall in the study, LDL-C levels were significantly lower among the elderly at 30 days, 4 months, and end of study compared with younger counterparts (Figure 1). As expected, a greater proportion of patients in both age groups achieved the NCEP goals at 30 days on atorvastatin 80 mg vs. those allocated pravastatin 40 mg (74.6 vs. 27.7% among the elderly, P<0.001, and 72.1 vs. 20.5% among younger subjects, P<0.001).


Figure 1801
View larger version (9K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Figure 1 LDL-C levels among elderly and younger patients in the PROVE IT-TIMI 22 trial. Data shown reflect mean (SD).

 
Relationship between age and clinical events
Overall in the trial the risk of acute events individually or in combination was significantly higher among the elderly (Table 2). In contrast, the risk of revascularization after 30 days (a non-acute endpoint) tended to be lower (Table 2). The composite triple endpoint of death/MI or UA occurred more frequently with increasing decade of age, and among the elderly, this triple acute endpoint occurred in 20.1% of subjects compared with 11.0% in younger patients [HR 1.93, 95% confidence interval (CI) 1.59–2.33, P<0.0001].


View this table:
[in this window]
[in a new window]

  		Table 2 Summary of clinical endpoint components: young vs. older patients (unadjusted) throughout entire study

 
Relationship between LDL-C at day 30 and subsequent risk
Among stable subjects free from clinical events at day 30, the absolute benefit of achieving the optional goal and subsequent risk of death, MI, or UA was lowest in those <50 years of age and rose with increasing decade of age (Figure 2). There were 634 elderly patients (≥70 years age) and 3150 patients <70 years who remained free of events at 30 days (87 and 92% of each original group, respectively). Among older patients, the achievement of the LDL-C goal of <1.8 mmol/L was associated with a 40% lower risk of the composite endpoint vs. older patients who did not reach goal (13.5 vs. 21.5% absolute rates, respectively; HR 0.60, 95% CI 0.41–0.87; P=0.008) (Figure 3). Among younger patients, the achievement of the LDL-C optional goal was associated with a 26% lower risk vs. younger patients who did not reach goal (8.1 vs. 10.4% absolute rates, respectively; HR 0.74, 95% CI 0.59–0.94; P=0.013). The test for interaction between achieving the NCEP goal and age<70 years or age≥70 years was not significant (P=0.34). The absolute reduction in death, MI, or UA was 8% in elderly vs. 2.3% in younger patients. An analysis using the primary endpoint (death, MI, UA, stroke, or revascularization after 30 days) produced qualitatively similar results.


Figure 1802
View larger version (15K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Figure 2 Risk of death, MI, or UA requiring rehospitalization after 30 days stratified by day 30 LDL-C and decades of age.

 

Figure 1803
View larger version (23K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Figure 3 Relationship between achievement or failure to reach NCEP LDL-C goal (<1.8 mmol/L) at 30 days and subsequent risk of clinical events (death, MI, or UA requiring rehospitalization) in elderly and younger subjects.

 
Multivariable adjustment
Compared with the reference group (age<70 years, LDL-C<1.8 mmol/L), the hazard of death, MI, or UA after day 30 was 29% higher among younger patients with an LDL-C≥1.8 mmol/L (HR 1.29, 95% CI 1.0–1.65, P=0.047). As expected, the overall hazard in the elderly was higher, with a hazard of death, MI, or UA of 1.73 (95% CI 1.19–2.51, P=0.004) even among those with an LDL-C<1.8 mmol/L, which increased to 2.90 (95% CI 2.08–4.04, P<0.0001), among those with an LDL-C≥1.8 mol/L. The unadjusted and adjusted hazards of death, MI, or UA are shown in Figure 4. Using the same model, compared with younger patients with an LDL-C < 1.8 mmol/L (reference group), the hazard of the primary endpoint after 30 days was higher among younger patients with an LDL-C≥1.8 mmol/L (HR 1.12, 95% CI 0.95–1.13, P=0.18). Among the elderly, the hazard was 1.12 (95% CI, 0.86–1.46, P=0.38) among patients with a 30-day LDL-C<1.8 mmol/L and 1.44 (95% CI, 1.12–1.85, P=0.004) among patients with an LDL-C ≥ 1.8 mmol/L.


Figure 1804
View larger version (13K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Figure 4 (A) Unadjusted and (B) adjusted risk of death, MI, or UA after 30 days showing the risk among younger and elderly patients achieving or failing to achieve the NCEP optional LDL-C goal at day 30. All groups compared with younger patients with LDL-C < 1.8 mmol/L (reference group). The multivariable model was adjusted for gender, diabetes, smoking, prior history of MI, hypertension, BMI, revascularization for index event, extent of angiographic disease, use of medications at 30 days, 30 day HDL, TG, CRP, and systolic blood pressure.

 
Number of potentially preventable events
Among 1000 elderly ACS patients treated for 2 years, the achievement of an LDL-C < 1.8 mmol/L would be expected to prevent 43 deaths, 58 MIs, 14 rehospitalizations for UA, 43 fewer revascularizations after 30 days, and one less stroke (Table 3). This reflects nearly a four-fold reduction in the number of composite events (death, MI, or UA) prevented among the elderly (80 events) when compared with younger patients who achieve the same level of LDL-C reduction (23 events).


View this table:
[in this window]
[in a new window]

  		Table 3 Expected number of cardiovascular events preventablea at 2 years by achieving an LDL-C < 1.8 mmol/Lb at 30 days for every 1000 patients treated with statins in different age groups

 
Safety
Overall, the incidence of elevated liver enzymes (ALT rise > 3x ULN) was similar between the elderly and younger patients (2.3 vs. 2.2%, respectively, P=0.8) as were the rates of CK rise > 3x ULN (1.1 vs. 1.3% P=0.6). There were no significant differences in the rates of discontinuation of study drug for myalgia or CK rise or for any other side effect among the elderly. As with younger patients, the elderly were more likely to experience transient elevations in liver enzymes (ALT > 3x ULN) with atorvastatin 80 mg compared with pravastatin 40 mg (4.8 vs. 0%, P<0.0001), but the rates of CK rise (>3x ULN) between statin regimens were identical in the elderly (1.1%, P=0.9). There were no cases of rhabdomyolysis in either age group.


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
Conclusions
 Acknowledgements
 References
 
In this analysis from PROVE IT-TIMI 22, the achievement of the new NCEP LDL-C therapeutic option of <1.8 mmol/L among elderly ACS patients appeared safe and was also associated with a significant 8% absolute lower rate of clinical events compared with those not achieving this low target. We estimated that the achievement of the NCEP optional goals could possibly prevent 80 acute events (death, MI, or UA) over 2 years for every 1000 elderly ACS patients treated. Because high-risk elderly patients constitute an increasing proportion of the ACS population, these results provide supportive evidence that aggressive lipid lowering to achieve the NCEP LDL-C optional goal of <1.8 mmol/L after ACS may be both safe and effective as a secondary prevention strategy among elderly patients.

Achievement of the NCEP optional goal appeared to be as beneficial in the elderly as in younger counterparts. However, because the risk of death, MI, or UA after ACS was much higher in the elderly, the achievement of the same LDL-C goal of <1.8 mmol/L was translated into a numerically greater absolute difference in death, MI, or UA among the elderly (8.0 vs. 2.3%). From a public health perspective, this is a potentially important observation, as achieving the NCEP optional goal could potentially prevent nearly four times as many acute events among the elderly vs. younger counterparts (80 vs. 23 events prevented for every 1000 patients at goal over 2 years).

Even after adjustment for co-morbidity, achieved lipid and CRP levels at 30 days, and medical care received, elderly patients who achieved the optional LDL-C goal were at higher risk than younger counterparts who achieved the same goal (HR 1.73, 95% CI 1.19–2.51). This risk was even greater among elderly patients whose LDL-C level was ≥ 1.8 mmol/L (HR 2.90, 95% CI 2.08–4.04). The unadjusted and adjusted risk of adverse events were similar (Figure 4), suggesting that the observed clinical benefit of reaching the optional LDL-C goals among the elderly was largely independent of the associated co-morbidity in this group.

In contrast to the benefits observed in this trial, data from the National Registry of Myocardial Infarction 35 and the Global Registry of Acute Coronary Events (GRACE)12 suggest that elderly patients are less likely than younger patients to receive lipid-lowering medication at hospital discharge. Similarly, in ACS trials, patients who did not receive lipid-lowering therapy at hospital discharge are significantly older.13 The discrepancies in prescribing practices in different age groups are further highlighted in a recent community-based study of nearly 400 000 patients in Canada, aged > 66 years, in whom only 19% of potentially eligible patients received statin therapy.3

Data from secondary prevention statin trials suggest that statin therapy is as beneficial to those >65 years of age as it is to younger patients.14–16 Among patients >65 years of age in the Scandanavian Simvastatin Survival Study (4S), lowering LDL-C to an average of 2.95 mmol/L was associated with a 36% reduction in coronary heart disease (CHD)-related events.14 Likewise in the Cholesterol and Recurrent Events (CARE) and the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) trials, lowering LDL-C on average to 2.64 and 2.82 mmol/L, respectively, was associated with a 32% reduction in major CHD events (CARE)15 and a 24% reduction in CHD deaths (LIPID) among patients >65 years.16 In the Heart Protection Study (HPS), patients ≥70 years of age allocated to simvastatin 40 mg had a 5.1% absolute reduction in the risk of coronary death, non-fatal MI, stroke, or revascularization, which was of similar magnitude to the absolute benefit observed in patients 65–69 years and those <65 years.17 These recent data have led the American Heart Association (AHA) to recommend that statin therapy should not be withheld in older patients as secondary prevention for CHD.18

Following the release of this AHA position statement, the PROSPER study demonstrated the benefit of statins among stable elderly patients (70–82 years) with pre-existing vascular disease or cardiovascular risk factors.1 In the PROSPER study, reducing LDL-C from 3.81 mmol/L at baseline to 2.54 mmol/L at 3 months was associated with a 19% relative reduction in the risk of CHD death or non-fatal MI at 3 years.1 More recently, the benefits of lowering LDL-C among those >65 years have also been observed in the Treat to New Targets Trial, where reducing LDL-C from ~2.51 to 1.86 mmol/L after 3 months was associated with a 2.3% absolute lower risk of cardiovascular events.19 The results of the present analysis from PROVE IT-TIMI 22 are consistent with observations from the prior statin trials in stable disease and add to the existing data by demonstrating that the elderly ACS population as a group can derive as much, if not greater absolute benefit from intensive lipid lowering, as younger counterparts.

In PROVE IT-TIMI 22, aggressive lipid lowering with statins in the elderly was also found to be safe. The rates of study drug discontinuation due to myalgia or a CK rise were low and were not higher among elderly patients treated with the more potent lipid-lowering regimen (atorvastatin 80 mg). There were also no cases of rhabdomyolysis in PROVE IT-TIMI 22. Although 4.8% of the elderly developed a rise in liver enzymes with atorvastatin 80 mg, these were all reversible with a dose reduction or discontinuation of study drug.

Limitations
These analyses are post hoc and therefore should be considered exploratory. In addition, PROVE IT-TIMI 22 assessed two different fixed doses of lipid-lowering therapy rather than dose titration to an achieved LDL-C. Also, for this analysis, we used the earliest time point available for LDL-C measurement, which was 30 days, and a cut-point of 1.8 mmol/L rather than a later time point or another LDL-C cut-point in order to assess the correlation of the achievement of the new NCEP optional goals at a specific time with subsequent risk of clinical events. The magnitude of benefit could therefore differ using another LDL-C cut-point or censoring events at a later time point. Additionally, patients without available data or those who experienced an endpoint prior to day 30 were excluded. Although the demographic characteristics of those excluded were not significantly different from the study cohort, there were more patients excluded among the elderly than younger counterparts (13 vs. 8%), which may have reduced the difference between groups, if those patients omitted had on average higher LDL-C levels. While exploratory, these findings build upon and are consistent with findings from other statin trials and add further supportive data to the hypothesis that achieving a low LDL-C among elderly patients with coronary disease is safe and can be at least as beneficial as in younger counterparts.


   Conclusions
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusions
Acknowledgements
 References
 
Among ACS patients ≥70 years of age prescribed statin therapy at hospital discharge, achieving the NCEP LDL-C optional goal of <1.8 mmol/l appears to be safe, and was as beneficial in the elderly as in younger patients. However as the elderly are at higher risk, achieving the NCEP optional goal may prevent four times as many events among the elderly compared with younger counterparts. Routine use of statin therapy at hospital discharge after ACS and achieving the NCEP LDL-C optional goal could be a simple and effective secondary prevention strategy among the elderly.


   Acknowledgements
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusions
 Acknowledgements
References
 
The PROVE IT-TIMI 22 trial was funded by Bristol–Myers Squibb and Sankyo. K.K.R. is funded by a British Heart Foundation international fellowship.

Conflict of interest: A.J.K., C.M.C., R.C., and C.M.G. have no conflicts of interest. K.K.R. has received research grant support from Bristol-Myers Squibb and Pfizer, honoraria for lectures and consulting fees from Pfizer. R.B. has received research support from sanofi-aventis. S.D.W. has received research support from Lilly and Sankyo, and honoraria for lectures from Pfizer. C.P.C. has received research grant support from Bristol-Myers Squibb, Sanofi, and Merck and consulting fees from AstraZeneca, GlaxoSmithKline, and Pfizer. E.B. has received research support from Bristol-Myers Squibb, Merck, and AstraZeneca, and honoraria for lectures from Bristol-Myers Squibb, Sanofi, and Pfizer.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusions
 Acknowledgements
 References
 

  1. Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM, Cobbe SM, Ford I, Gaw A, Hyland M, Jukema JW, Kamper AM, Macfarlane PW, Meinders AE, Norrie J, Packard CJ, Perry IJ, Stott DJ, Sweeney BJ, Twomey C, Westendorp RG. (2002) Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 360:1623–1630.[CrossRef][Web of Science][Medline]
  2. Collinson J, Bakhai A, Flather MD, Fox KA. (2005) The management and investigation of elderly patients with acute coronary syndromes without ST elevation: an evidence-based approach? Results of the Prospective Registry of Acute Ischaemic Syndromes in the United Kingdom (PRAIS-UK). Age Ageing 34:61–66.[Abstract/Free Full Text]
  3. Koth DT, Mamdani M, Alter DA. (2004) Lipid-lowering therapy with statins in high-risk elderly patients: the treatment-risk paradox. Jama 291:1864–1870.[Abstract/Free Full Text]
  4. Jenni D, Osterwalder R, Osswald S, Buser P, Pfisterer M. (2001) Evidence for age-based rationing in a Swiss university hospital. Swiss Med Wkly 131:630–634.[Medline]
  5. Fonarow GC, French WJ, Parsons LS, Sun H, Malmgren JA. (2001) Use of lipid-lowering medications at discharge in patients with acute myocardial infarction: data from the National Registry of Myocardial Infarction 3. Circulation 103:38–44.[Abstract/Free Full Text]
  6. Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr, Clark LT, Hunninghake DB, Pasternak RC, Smith SC Jr, Stone NJ. (2004) Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 110:227–239.[Abstract/Free Full Text]
  7. Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, Joyal SV, Hill KA, Pfeffer MA, Skene AM. (2004) Intensive vs moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 350:1495–1504.[Abstract/Free Full Text]
  8. Myers GL, Cooper GR, Winn CL, Smith SJ. (1989) The Centers for Disease Control–National Heart, Lung and Blood Institute Lipid Standardization Program. An approach to accurate and precise lipid measurements. Clin Lab Med 9:105–135.[Web of Science][Medline]
  9. Friedewald WT, Levy RI, Fredrickson DS. (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502.[Abstract]
  10. Ridker PM, Cannon CP, Morrow D, Rifai N, Rose LM, McCabe CH, Pfeffer MA, Braunwald E. (2005) the Pravastatin or Atorvastatin Evaluation Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) Investigators C-reactive protein levels and outcomes after statin therapy. N Engl J Med 352:20–28.[Abstract/Free Full Text]
  11. Gambsch P and Thernau T. (1994) Proportional hazards tests and diagnostics based on weighted residuals. Biometrica 81:515.[CrossRef]
  12. Avezum A, Makdisse M, Spencer F, Gore JM, Fox KA, Montalescot G, Eagle KA, White K, Mehta RH, Knobel E, Collet JP. (2005) Impact of age on management and outcome of acute coronary syndrome: observations from the Global Registry of Acute Coronary Events (GRACE). Am Heart J 149:67–73.[CrossRef][Web of Science][Medline]
  13. Smith CS, Cannon CP, McCabe C, Murphy SA, Bentley J. (2005) Early initiation of lipid lowering therapy for acute coronary syndromes improves compliance with guideline recomendations: observations from the Orbofiban in patients with unstable coronary syndromes (OPUS-TIMI 16) trial. Am Heart J 149:444–450.[CrossRef][Web of Science][Medline]
  14. Miettinen TA, Pyorala K, Olsson AG, Musliner TA, Cook TJ, Faergeman O, Berg K, Pedersen T, Kjekshus J f.t.S.S.S. (1997) Group. Cholesterol-lowering therapy in women and elderly patients with myocardial infarction or angina pectoris: findings from the Scandinavian Simvastatin Survival Study (4S). Circulation 96:4211–4218.[Abstract/Free Full Text]
  15. Lewis SJ, Moye LA, Sacks FM, Johnstone DE, Timmis G, Mitchell J, Limacher M, Kell S, Glasser SP, Grant J, Davis BR, Pfeffer MA, Braunwald E. (1998) Effect of pravastatin on cardiovascular events in older patients with myocardial infarction and cholesterol levels in the average range: results of the Cholesterol and Recurrent Events (CARE) trial. Ann Intern Med 129:681–689.[Abstract/Free Full Text]
  16. Hunt D, Young P, Simes J, Hague W, Mann S, Owensby D, Lane G, Tonkin A. (2001) Benefits of pravastatin on cardiovascular events and mortality in older patients with coronary heart disease are equal to or exceed those seen in younger patients: results from the LIPID trial. Ann Intern Med 134:931–940.[Abstract/Free Full Text]
  17. . (2002) MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebo-controlled trial. Lancet 360:7–22.[CrossRef][Web of Science][Medline]
  18. Williams MA, Fleg JL, Ades PA, Chaitman BR, Miller NH, Mohiuddin SM, Ockene IS, Taylor CB, Wenger NK. (2002) Secondary prevention of coronary heart disease in the elderly (with emphasis on patients >=75 years of age): an American Heart Association scientific statement from the Council on Clinical Cardiology Subcommittee on Exercise, Cardiac Rehabilitation, and Prevention. Circulation 105:1735–1743.[Free Full Text]
  19. LaRosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart JC, Gotto AM, Greten H, Kastelein JJ, Shepherd J, Wenger NK. (2005) Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 352:1425–1435.[Abstract/Free Full Text]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J CARDIOVASC PHARMACOL THERHome page
K. P. Alexander, M. A. Blazing, R. S. Rosenson, E. Hazard, W. S. Aronow, S. C. Smith Jr, and E. M. Ohman
Management of Hyperlipidemia in Older Adults
Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2009; 14(1): 49 - 58.
[Abstract] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
K. K. Ray, C. P. Cannon, R. Cairns, D. A. Morrow, P. M Ridker, and E. Braunwald
Prognostic Utility of ApoB/AI, Total Cholesterol/HDL, Non-HDL Cholesterol, or hs-CRP as Predictors of Clinical Risk in Patients Receiving Statin Therapy After Acute Coronary Syndromes: Results From PROVE IT-TIMI 22
Arterioscler Thromb Vasc Biol, March 1, 2009; 29(3): 424 - 430.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
M. Miller, C. P. Cannon, S. A. Murphy, J. Qin, K. K. Ray, E. Braunwald, and for the PROVE IT-TIMI 22 Investigators
Impact of Triglyceride Levels Beyond Low-Density Lipoprotein Cholesterol After Acute Coronary Syndrome in the PROVE IT-TIMI 22 Trial.
J. Am. Coll. Cardiol., February 19, 2008; 51(7): 724 - 730.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
R. P. Giugliano and E. Braunwald
The Year in Non ST-Segment Elevation Acute Coronary Syndrome
J. Am. Coll. Cardiol., October 2, 2007; 50(14): 1386 - 1395.
[Full Text] [PDF]

Home page
 CirculationHome page
K. P. Alexander, L. K. Newby, P. W. Armstrong, C. P. Cannon, W. B. Gibler, M. W. Rich, F. Van de Werf, H. D. White, W. D. Weaver, M. D. Naylor, et al.
Acute Coronary Care in the Elderly, Part II: ST-Segment-Elevation Myocardial Infarction: A Scientific Statement for Healthcare Professionals From the American Heart Association Council on Clinical Cardiology: In Collaboration With the Society of Geriatric Cardiology
Circulation, May 15, 2007; 115(19): 2570 - 2589.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
27/19/2310    most recent
ehl180v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (11)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Ray, K. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ray, K. K.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?