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Original Contribution |

Lipid-Lowering Therapy With Statins in High-Risk Elderly Patients:  The Treatment-Risk Paradox FREE

Dennis T. Ko, MD; Muhammad Mamdani, PharmD, MPH; David A. Alter, MD, PhD
[+] Author Affiliations

Author Affiliations: Division of Cardiology, Schulich Heart Centre, and Department of Medicine, Sunnybrook and Women's College Health Sciences Centre (Drs Ko and Alter), and Institute for Clinical Evaluative Sciences (Drs Ko, Mamdani, and Alter), Toronto, Ontario.


JAMA. 2004;291(15):1864-1870. doi:10.1001/jama.291.15.1864.
Text Size: A A A
Published online

Context The benefits of cardiovascular therapies such as statins for secondary prevention have been well documented, although they may not be optimally used in patients most likely to benefit. Ideally, aggressiveness in the use of these beneficial therapies should correlate with baseline cardiovascular risk.

Objective To examine the association between physicians' treatment aggressiveness and baseline cardiovascular risk.

Design, Setting, and Patients Retrospective cohort study incorporating the use of multiple linked health care administrative databases covering more than 1.4 million elderly residents of Ontario. We included 396 077 patients aged 66 years or older who had a history of cardiovascular disease or diabetes while undergoing medical treatment and who were alive on April 1, 1998. Baseline cardiovascular risk was derived using a risk-adjustment index in which we modeled probability of death after 3 years of follow-up.

Main Outcome Measure Likelihood of statin use, stratified by baseline cardiovascular risk, after adjusting for age, sex, socioeconomic status, and rural or urban residence.

Results Only 75 617 patients (19.1%) in this secondary prevention cohort were prescribed statins. In patients 66 to 74 years old, the adjusted probabilities of statin prescription were 37.7%, 26.7%, and 23.4% in the categories of low, intermediate, and high baseline risk, respectively. The likelihood of statin prescription was 6.4% lower (adjusted odds ratio, 0.94; 95% confidence interval, 0.93-0.95) for each year of increase in age and each 1% increase in predicted 3-year mortality risk. The influence of age also interacted synergistically with baseline risk on the prescription of statins (P<.001).

Conclusions We found that prescription of statins diminished progressively as baseline cardiovascular risk and future probability of death increased. Since the benefits of a therapy are dependent on the baseline risk, the maximum benefits of statins may not be fully realized until implementation of therapy includes patients at highest risk.

Figures in this Article

Available evidence has demonstrated that the impact of cardiovascular evidence-based therapies is predominantly dependent on patients' baseline risk of future adverse cardiovascular events.1 If physicians are appropriately attuned to the risk profiles of their patients, one might reasonably assume that patients who are at highest baseline risk should be treated most aggressively. Yet, for many cardiovascular therapies, this is not the case.26 For example, studies have consistently demonstrated an inverse relationship between treatment propensity and age.2,7 Moreover, patients with multiple chronic conditions are less likely to receive evidence-based therapies than healthier patients with lower illness severity,8 an observation that may relate to high baseline risk and/or concerns about treatment complications. Nonetheless, the extent to which the discordant relationship between baseline risk and treatment propensity is a phenomenon driven by age alone, arguably the most important determinant of baseline risk in the population, is unknown. Furthermore, the extent to which the treatment-risk paradox applies only to extremes of illness severity or, conversely, applies incrementally throughout the entire spectrum of risk is also unclear.

Statins for secondary prevention provide a useful test case for several reasons. First, statins are among the most efficacious therapies in reducing future cardiac events and mortality.915 Initially shown to be beneficial in patients with substantially elevated cholesterol,9,10 the benefits of statin therapy have currently extended to previously "normal" cholesterol levels.1114 Second, clinical trials have demonstrated consistent treatment effects across multiple subgroups, including elderly persons.15 Third, clinical guideline recommendations advocate the use of statins according to individual baseline risk of future cardiovascular events.16 Accordingly, the primary objective of this study was to examine the association between physician aggressiveness in the prescription of statins among a secondary prevention cohort of elderly patients and baseline risk throughout the entire risk-severity spectrum.

System Context

The Canadian health insurance system provides free universal coverage for most hospitals and ambulatory medical services. The Ontario Drug Benefit (ODB) program is a government-funded drug benefit program that covers outpatient drug costs for all Ontario residents aged 65 years or older. Patients are responsible for a dispensing fee of approximately Can $6, but this fee is waived for patients whose annual income falls below a threshold of Can $15 500 (US $1 = Can $1.34 on March 17, 2004).

Data Source

The Geriatric Ontario Longitudinal Database (GOLD) was created by linking several major health care administrative databases with follow-up tracking of mortality over time, regardless of location of death. Briefly, GOLD includes 1.44 million residents aged 66 years or older who were alive in Ontario on April 1, 1998. Unique encrypted patient identifiers were used for linkage in the multiple databases to protect patient confidentiality. We identified previous hospitalizations using the Canadian Institute of Health Information hospital discharge abstracts and identified physician visits and previous cardiac interventions using physician claims data obtained by the Ontario Health Insurance Plan. We used the ODB to obtain information on medication prescriptions within 1 year before cohort inception. Demographic and geographic information was identified using the Registered Persons Database and data from the official 1996 Census. We excluded all non-Ontario residents and those who did not have a valid health card number. The research ethics board of Sunnybrook and Women's College Health Science Center, University of Toronto, approved the study and waived a requirement for informed consent.

Study Cohort

We selected patients at high risk of future cardiovascular events and included patients older than 66 years with a history of cardiovascular disease or diabetes mellitus while undergoing medical therapy. We defined a statin prescription as one in which a patient had been dispensed any prescription for statin medication within the year before the inception of the cohort. Statins covered in the ODB at the time of the study included atorvastatin, cerivastatin, fluvastatin, lovastatin, pravastatin, and simvastatin. We defined cardiovascular disease in the study sample as 1 or more of the following: cardiovascular hospitalization within 5 years, coronary intervention (cardiac catheterization, percutaneous coronary intervention, or coronary artery bypass graft surgery) within 5 years, or angina (defined as concurrent use of nitrates within the year of cohort inception). Using hospital discharge abstracts, a previous cardiovascular hospitalization was defined as an admission with any of the following: unstable angina, myocardial infarction, congestive heart failure, stroke or transient ischemic attack, or peripheral vascular disease (abdominal aortic aneurysm, peripheral vascular surgery, or carotid endarterectomy). A diagnosis of drug-treated diabetes mellitus required receipt of insulin or oral hypoglycemic agents within 1 year before cohort inception. The definitions and codes that were used to identify eligible patients focused on maximizing specificity rather than sensitivity to ensure the construction of a valid secondary prevention cohort. The coding accuracy of acute myocardial infarction, heart failure, and diabetes had positive predictive values of more than 90%.1719 Although individual cholesterol profiles were unavailable, we assumed that most of these patients would be eligible for statin therapy based on the fact that they were all secondary prevention patients.16 We excluded patients with a history of cancer within 5 years because of competing risks. Our final cohort included 396 077 patients after applying inclusion and exclusion criteria.

Comorbidity, Socioeconomic, and Geographic Characteristics

The total number of medications dispensed within the previous year was used as a marker of comorbidity. The use of such measures has been validated as a comorbidity index and is described elsewhere.20 Socioeconomic status was defined as a binary variable (impoverished: yes or no). Any patient whose annual individual income was Can $15 500 or less (or who had a household income of Can $22 000 or less) and who applied for full subsidization for prescription drug dispensing fees was classified as impoverished. Patient residence was categorized as a binary term (urban vs rural) based on residential postal codes.

Derivation of the Baseline Risk Index

To disentangle baseline risk for future adverse events from the effects of other factors on mortality, we derived a baseline risk index using multiple logistic regression models that adjusted for various clinical characteristics but excluded age, sex, socioeconomic status, and location of residence. We modeled likelihood of death after 3 years of follow-up as a function of the following clinical variables: previous cardiovascular hospitalizations (stratified according to diagnosis), total number of previous cardiovascular hospitalizations, number of dispensed cardiovascular medications (excluding statins), and the comorbidity index. Similar risk-adjustment indexes have been previously used to characterize illness severity and validated in disease-specific cohorts (eg, acute myocardial infarction).21 The area under the receiver operating characteristic curve (AUROC) of our baseline risk index was 0.71. When age and sex were added into the risk index, the AUROC increased to 0.79, suggesting good discriminating characteristics.

Statistical Analysis

We first compared demographic and clinical characteristics in patients with and without statin prescriptions. In univariate fashion, categorical variables were compared using χ2 tests, and continuous variables were compared using either a t test or another nonparametric test as appropriate.

We examined the relationship among baseline risk index, age, and statin prescription using multiple logistic regression techniques, while adjusting for sex, socioeconomic status, and rural vs urban status. We tested for multiple statistical interactions, including the interaction between age and baseline risk, in each of our models. Adjusted probability curves (ie, the probability of receiving vs not receiving statins) were constructed according to age and the baseline risk index by imputing average covariate patterns for sex, income, and geographic residence. When examining the probability of statin prescription by age, we stratified the baseline risk index into 3 groups (25th, 50th, and 75th percentiles of death). Similarly, when examining the probability of statin prescription by baseline risk index, we categorized age into 3 subgroups (a typical 71-year-old, a typical 75-year-old, and a typical 81-year-old).

A series of sensitivity analyses was performed to examine the robustness of our results. First, analyses were repeated by evaluating the prescription of all lipid-lowering therapies (eg, fibric acid derivatives) rather than the prescription of statins alone. Second, all data were reanalyzed when confining the cohort to patients with a history of preexisting cardiovascular disease (ie, excluding those with diabetes alone). Third, due to potential concerns arising from the confounding "protective" survival effects of statins themselves, baseline risk was derived with and without the inclusion of statins in our risk-adjustment models. Fourth, we undertook additional modifications to the derivation of our risk-adjustment index in which baseline risk was modeled as a function of the composite of death or myocardial infarction rather than as a function of death alone. Fifth, because of concerns that we might have included patients with substantial comorbid conditions for which statins might not be appropriate, we repeated the analysis using 2 different cohorts. One cohort excluded patients in the 75th percentile of the comorbidity index, and the other excluded patients who died within 1 year of cohort inception. Finally, we examined a different risk index that excluded the comorbidity index and adjusted only for cardiovascular risks in both our original cohort and lower risk cohorts. In all of these sensitivity analyses, our overall results did not materially change. All statistical analyses were performed using SAS statistical software, version 8.2 (SAS Institute Inc, Cary, NC). P<.05 was considered statistically significant for all analyses.

Baseline Characteristics

In our study sample, 271 504 patients (68.6%) had a history of cardiovascular disease alone, 70 535 (17.8%) had diabetes mellitus alone, and 54 038 (13.6%) had both preexisting cardiovascular disease and diabetes mellitus. The median age of the overall cohort was 75 years; 216 089 (54.6%) were women, 143 790 (36.3%) had low socioeconomic status, and 69 210 (17.5%) lived in rural areas (Table 1). The correlation between age and the baseline risk index was modest (r = 0.31). In this cohort, 75 617 patients (19.1%) were prescribed statin therapy. Patients prescribed statins were younger; were more likely to be men; had a history of angina, acute myocardial infarction, or prior cardiac invasive procedures; and had more visits to a cardiologist within the past year. Conversely, patients not prescribed statins were more likely to have diabetes, congestive heart failure, or stroke; to have lower socioeconomic status; and to live in rural areas (P<.001 for all) (Table 1). Table 2 illustrates the observed rates of death and the expected probabilities of death at 3 years according to different categories of age and different categories of the baseline risk index.

Table Graphic Jump LocationTable 1. Baseline Participant Characteristics*
Table Graphic Jump LocationTable 2. Observed and Expected Probability of 3-Year Mortality in Ontario According to Age and Baseline Risk*
Relationship Between Baseline Risk and Statin Prescription

Table 3 illustrates the independent determinants of statin prescription according to multivariable analysis. Both age and baseline risk inversely correlated with the likelihood of receiving statins, after adjusting for sex, socioeconomic status, and rural vs urban residence. Moreover, age interacted with baseline risk in determining statin prescription (P<.001 for the interaction term). For each year of increase in age and each 1% increase in the baseline risk index, there was a 6.4% lower odds of statin prescription (adjusted odds ratio, 0.94; 95% confidence interval, 0.93-0.95; P<.001) after adjusting for all other factors.

Table Graphic Jump LocationTable 3. Adjusted Probability of Statin Prescription in Ontario According to Age and Baseline Risk*

Progressively lower use of statins in patients with higher cardiovascular risk existed across the full spectrum of cardiovascular risk (Figure 1, A). Similarly, we also observed lower use of statins in elderly patients across the entire spectrum of age (Figure 1, B). The 95% confidence intervals were very small in the probability estimations of statin use across the whole spectrum of baseline risk and age (data not shown).

Figure. Relationship of Adjusted Probability of Receiving Statins With Baseline Risk According to Age and Age According to Baseline Risk
Graphic Jump Location
The 95% confidence intervals were very small in the probability estimations of statin use across the whole spectrum of baseline risk and age (data not shown). A, Younger age is 71 years, median age is 75 years, and older age is 81 years. Baseline risk refers to the expected probability of death in 3 years as derived at inception. P<.001 for the probability of statin prescription for variations in age, risk, and age-risk interaction. B, Low risk is the 25th percentile for the expected probability of death in 3 years as derived at inception, median risk is the 50th percentile, and high risk is the 75th percentile. P<.001 for the probability of statin prescription for variations in age, risk, and age-risk interaction.

Despite convincing evidence demonstrating substantial mortality reductions from the use of statins in secondary prevention, we found that only a small proportion of elderly patients with preexisting cardiovascular disease were prescribed statin therapy in Ontario. Moreover, the likelihood that physicians prescribed statin therapy was inversely correlated with baseline risk and did so across the entire spectrum of illness severity, independent of age. Finally, the effects of age and baseline risk had a synergistic effect on the prescribing behaviors of physicians.

Our observed low prescription rate of statin therapy adds to a growing body of literature demonstrating that statin therapy is substantially underused.2225 This is concordant with recent data collected by the National Registry of Myocardial Infarction, in which only 31.7% of all patients discharged from the hospital with acute myocardial infarction were prescribed lipid-lowering therapy.22 Furthermore, when examining treatment targets, a recent survey demonstrated that only 5.4% of patients known to have hyperlipidemia had achieved a target total cholesterol level in the United States,26 representing a substantial opportunity for improvement.

Although the overall prescription of statins in the population was low, we found that the decision to withhold therapy was not only observed at the extremes of illness severity but increased progressively and incrementally in patients with advancing age and advancing baseline risk. Furthermore, we observed a significant interaction effect between age and risk in the prescription of statin therapy. Thus, age and risk acted in concert to further reduce the propensity of physicians to prescribe statins in secondary prevention.

We do not believe that our findings are explainable by variations in affordability and/or accessibility of medications. Although patients in Ontario have to pay out of pocket for dispensing fees, the acquisition costs for statins are provided to all elderly patients free of charge. Moreover, our analyses also, to some extent, adjusted for baseline socioeconomic and geographic differences.

Statin therapy is a useful medication to examine because of the substantial reductions in cardiovascular mortality and the lower adverse effect profiles compared with thrombolytic therapy or invasive cardiac procedures. The relationship between baseline risk and statin avoidance in secondary prevention patients likely reflects a systematic bias, which may be generalizable to other evidence-based therapies. Studies demonstrating the diminishing use of thrombolytics, cardiac catheterizations, and β-blockers in elderly patients in the setting of acute myocardial infarction2,27,28 may represent a similar phenomenon—an aversion to treat patients at high risk of future adverse events. The inverse relationship between baseline risk and treatment aggressiveness implies suboptimal benefits of evidence-based therapies when applied to real-world settings. To our knowledge, the treatment-risk paradox has not been demonstrated in a similar fashion. Other studies are needed to confirm our findings in different patient subsets using different therapies.

Several factors may explain the treatment-risk paradox for statins. First, physicians may have misconceptions about the benefit-harm tradeoffs. For example, physicians may feel reluctant to generalize clinical trial results to elderly patients with comorbidities on the grounds that such patients may experience fewer benefits and greater harm from the adverse effects of therapy. However, the relative survival benefits associated with statins appear to be consistent across multiple subgroups, including elderly patients.915 Furthermore, the impact of any therapy in the population depends on baseline risk more than relative efficacy.1 Although the absolute rate of serious harmful adverse effects may be increased for patients at highest baseline risk compared with their healthier counterparts, the rate of life-threatening complications required to negate potential survival benefits from treatment rarely approaches the incidence encountered in real-world settings, especially for statins, where the rate of severe complications is extremely low.1,29,30 This overemphasis of harm combined with an underappreciation of benefits may favor a more conservative hands-off approach to treatment.

Second, physicians may prejudge the compliance of their patients and be less inclined to prescribe therapies to patients thought unlikely to adhere to treatment. Patients at higher baseline risk may not perceive the benefits of additional therapy and have an increasing unwillingness to be receptive to physicians' recommendations. Indeed, factors that contribute to poor compliance in elderly patients include cognitive, functional, and social decline31—all factors associated with higher baseline risk of adverse cardiac events. However, preconceived attitudes toward compliance may too be misguided, given the evidence suggesting improved compliance rates of statins among elderly patients with higher severity of cardiac illness.32 Therefore, it is important for physicians to address the diverse needs of elderly patients and emphasize therapies that would derive substantial benefits to promote adherence.

Finally, the treatment-risk paradox may be explained by physician inattentiveness to cardiovascular prevention, especially when multiple conditions coexist. For example, available evidence suggests that clinicians who care for patients with chronic diseases become less attentive when managing the necessities of other concurrent conditions due to constraints in time, expertise, and preferences.8

Several limitations of our study merit consideration. First, we did not have access to individual cholesterol levels, and it is not possible to determine the appropriateness of statin prescription on an individual basis. Since all patients in our cohort were eligible for secondary prevention, we believe that most of our cohort would have qualified for and derived substantial benefits from statin therapy. Furthermore, patients eligible for statins are likely equally distributed across the risk spectrum, and thus, our observed treatment pattern across the age-risk spectrum is unlikely to be affected. Second, patients' risk profiles characterized by administrative data may be subject to undercoding of comorbidity. Therefore, we designed our cohort to include patients with a prior history of cardiovascular disease or diabetes to maximize specificity. Third, we used all-cause mortality as our main determinant of baseline risk. Although admittedly, the benefits of statins are largely mediated through their effects on cardiovascular outcomes, randomized trials have demonstrated that statins exert consistent reductions in all-cause mortality. Moreover, studies33,34 have found that the determination of cardiac death may be inaccurate and could potentially lead to misinterpretation of data. Finally, our data reflected prescribing patterns approximately 5 years ago, and overall utilization rates of statins have likely increased in the interim.35,36 However, given the magnitude of discordance between baseline risk and treatment propensity observed in this study, it is unlikely that the treatment-risk paradox will cease to exist.

In conclusion, we demonstrate that physician aggressiveness in the prescription of statin therapy to elderly patients for secondary prevention in Ontario was inversely correlated with baseline cardiovascular risk independent of age. The treatment-risk paradox phenomenon was not only applicable at the extremes of illness severity but was also observed throughout the entire spectrum of illness severity. Given the importance of baseline risk in determining the impact of therapy in the population, the treatment-risk paradox implies that the survival benefits of statin therapy may never be fully realized until physicians appropriately attune their prescribing behaviors to the risk profiles of their patients.

Alter DA, Manuel DG, Gunraj N, Anderson G, Naylor CD, Laupacis A. Age, risk-benefit trade-offs, and the projected effects of evidence-based therapies.  Am J Med.2004;116:540-545.
Krumholz HM, Murillo JE, Chen J.  et al.  Thrombolytic therapy for eligible elderly patients with acute myocardial infarction.  JAMA.1997;277:1683-1688.
PubMed
Krumholz HM, Radford MJ, Ellerbeck EF.  et al.  Aspirin for secondary prevention after acute myocardial infarction in the elderly: prescribed use and outcomes.  Ann Intern Med.1996;124:292-298.
PubMed
Elad Y, French WJ, Shavelle DM, Parsons LS, Sada MJ, Every NR. Primary angioplasty and selection bias inpatients presenting late (>12 h) after onset of chest pain and ST elevation myocardial infarction.  J Am Coll Cardiol.2002;39:826-833.
PubMed
Alter DA, Naylor CD, Austin P, Tu JV. Effects of socioeconomic status on access to invasive cardiac procedures and on mortality after acute myocardial infarction.  N Engl J Med.1999;341:1359-1367.
PubMed
Alter DA, Khaykin Y, Austin PC, Tu JV, Hux JE. Processes and outcomes of care for diabetic acute myocardial infarction patients in Ontario: do physicians undertreat?  Diabetes Care.2003;26:1427-1434.
PubMed
Rathore SS, Mehta RH, Wang Y, Radford MJ, Krumholz HM. Effects of age on the quality of care provided to older patients with acute myocardial infarction.  Am J Med.2003;114:307-315.
PubMed
Redelmeier DA, Tan SH, Booth GL. The treatment of unrelated disorders in patients with chronic medical diseases.  N Engl J Med.1998;338:1516-1520.
PubMed
 Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S).  Lancet.1994;344:1383-1389.
PubMed
Shepherd J, Cobbe SM, Ford I.  et al. West of Scotland Coronary Prevention Study Group.  Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia.  N Engl J Med.1995;333:1301-1307.
PubMed
Sacks FM, Pfeffer MA, Moye LA.  et al. Cholesterol and Recurrent Events Trial Investigators.  The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels.  N Engl J Med.1996;335:1001-1009.
PubMed
The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group.  Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels.  N Engl J Med.1998;339:1349-1357.
PubMed
Downs JR, Clearfield M, Weis S.  et al.  Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS.  JAMA.1998;279:1615-1622.
PubMed
Heart Protection Study Collaborative Group.  MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial.  Lancet.2002;360:7-22.
PubMed
LaRosa JC, He J, Vupputuri S. Effect of statins on risk of coronary disease: a meta-analysis of randomized controlled trials.  JAMA.1999;282:2340-2346.
PubMed
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.  Executive summary of the third report of the National Cholesterol Education Program (NCEP) (Adult Treatment Panel III).  JAMA.2001;285:2486-2497.
PubMed
Tu JV, Naylor CD, Austin P. Temporal changes in the outcomes of acute myocardial infarction in Ontario, 1992-1996.  CMAJ.1999;161:1257-1261.
PubMed
Jong P, Gong Y, Liu PP, Austin PC, Lee DS, Tu JV. Care and outcomes of patients newly hospitalized for heart failure in the community treated by cardiologists compared with other specialists.  Circulation.2003;108:184-191.
PubMed
Hux JE, Ivis F, Flintoft V, Bica A. Diabetes in Ontario: determination of prevalence and incidence using a validated administrative data algorithm.  Diabetes Care.2002;25:512-516.
PubMed
Schneeweiss S, Seeger JD, Maclure M, Wang PS, Avorn J, Glynn RJ. Performance of comorbidity scores to control for confounding in epidemiologic studies using claims data.  Am J Epidemiol.2001;154:854-864.
PubMed
Krumholz HM, Chen J, Wang Y, Radford MJ, Chen YT, Marciniak TA. Comparing AMI mortality among hospitals in patients 65 years of age and older: evaluating methods of risk adjustment.  Circulation.1999;99:2986-2992.
PubMed
Fonarow GC, French WJ, Parsons LS, Sun H, Malmgren JA. Use of lipid-lowering medications at discharge in patients with acute myocardial infarction: data from the National Registry of Myocardial Infarction 3.  Circulation.2001;103:38-44.
PubMed
Lemaitre RN, Furberg CD, Newman AB.  et al.  Time trends in the use of cholesterol-lowering agents in older adults: the Cardiovascular Health Study.  Arch Intern Med.1998;158:1761-1768.
PubMed
Whincup PH, Emberson JR, Lennon L, Walker M, Papacosta O, Thomson A. Low prevalence of lipid lowering drug use in older men with established coronary heart disease.  Heart.2002;88:25-29.
PubMed
Majumdar SR, Gurwitz JH, Soumerai SB. Undertreatment of hyperlipidemia in the secondary prevention of coronary artery disease.  J Gen Intern Med.1999;14:711-717.
PubMed
Ford ES, Mokdad AH, Giles WH, Mensah GA. Serum total cholesterol concentrations and awareness, treatment, and control of hypercholesterolemia among US adults: findings from the National Health and Nutrition Examination Survey, 1999 to 2000.  Circulation.2003;107:2185-2189.
PubMed
Stone PH, Thompson B, Anderson HV.  et al.  Influence of race, sex, and age on management of unstable angina and non-Q-wave myocardial infarction: the TIMI III registry.  JAMA.1996;275:1104-1112.
PubMed
Rochon PA, Tu JV, Anderson GM.  et al.  Rate of heart failure and 1-year survival for older people receiving low-dose beta-blocker therapy after myocardial infarction.  Lancet.2000;356:639-644.
PubMed
Pasternak RC, Smith Jr SC, Bairey-Merz CN.  et al.  ACC/AHA/NHLBI clinical advisory on the use and safety of statins.  Circulation.2002;106:1024-1028.
PubMed
Staffa JA, Chang J, Green L. Cerivastatin and reports of fatal rhabdomyolysis.  N Engl J Med.2002;346:539-540.
PubMed
Anderson RT, Ory M, Cohen S, McBride JS. Issues of aging and adherence to health interventions.  Control Clin Trials.2000;21(5 suppl):171S-183S.
PubMed
Jackevicius CA, Mamdani M, Tu JV. Adherence with statin therapy in elderly patients with and without acute coronary syndromes.  JAMA.2002;288:462-467.
PubMed
Lauer MS, Blackstone EH, Young JB, Topol EJ. Cause of death in clinical research: time for a reassessment?  J Am Coll Cardiol.1999;34:618-620.
PubMed
Gottlieb SS. Dead is dead: artificial definitions are no substitute.  Lancet.1997;349:662-663.
PubMed
Wang TJ, Stafford RS, Ausiello JC, Chaisson CE. Randomized clinical trials and recent patterns in the use of statins.  Am Heart J.2001;141:957-963.
PubMed
Levy AR, O'Brien BJ, McMullen E.  et al.  Rapid increase in statins newly dispensed to Ontario seniors between 1994 and 2000.  Can J Cardiol.2003;19:665-669.
PubMed

Figures

Figure. Relationship of Adjusted Probability of Receiving Statins With Baseline Risk According to Age and Age According to Baseline Risk
Graphic Jump Location
The 95% confidence intervals were very small in the probability estimations of statin use across the whole spectrum of baseline risk and age (data not shown). A, Younger age is 71 years, median age is 75 years, and older age is 81 years. Baseline risk refers to the expected probability of death in 3 years as derived at inception. P<.001 for the probability of statin prescription for variations in age, risk, and age-risk interaction. B, Low risk is the 25th percentile for the expected probability of death in 3 years as derived at inception, median risk is the 50th percentile, and high risk is the 75th percentile. P<.001 for the probability of statin prescription for variations in age, risk, and age-risk interaction.

Tables

Table Graphic Jump LocationTable 1. Baseline Participant Characteristics*
Table Graphic Jump LocationTable 2. Observed and Expected Probability of 3-Year Mortality in Ontario According to Age and Baseline Risk*
Table Graphic Jump LocationTable 3. Adjusted Probability of Statin Prescription in Ontario According to Age and Baseline Risk*

References

Alter DA, Manuel DG, Gunraj N, Anderson G, Naylor CD, Laupacis A. Age, risk-benefit trade-offs, and the projected effects of evidence-based therapies.  Am J Med.2004;116:540-545.
Krumholz HM, Murillo JE, Chen J.  et al.  Thrombolytic therapy for eligible elderly patients with acute myocardial infarction.  JAMA.1997;277:1683-1688.
PubMed
Krumholz HM, Radford MJ, Ellerbeck EF.  et al.  Aspirin for secondary prevention after acute myocardial infarction in the elderly: prescribed use and outcomes.  Ann Intern Med.1996;124:292-298.
PubMed
Elad Y, French WJ, Shavelle DM, Parsons LS, Sada MJ, Every NR. Primary angioplasty and selection bias inpatients presenting late (>12 h) after onset of chest pain and ST elevation myocardial infarction.  J Am Coll Cardiol.2002;39:826-833.
PubMed
Alter DA, Naylor CD, Austin P, Tu JV. Effects of socioeconomic status on access to invasive cardiac procedures and on mortality after acute myocardial infarction.  N Engl J Med.1999;341:1359-1367.
PubMed
Alter DA, Khaykin Y, Austin PC, Tu JV, Hux JE. Processes and outcomes of care for diabetic acute myocardial infarction patients in Ontario: do physicians undertreat?  Diabetes Care.2003;26:1427-1434.
PubMed
Rathore SS, Mehta RH, Wang Y, Radford MJ, Krumholz HM. Effects of age on the quality of care provided to older patients with acute myocardial infarction.  Am J Med.2003;114:307-315.
PubMed
Redelmeier DA, Tan SH, Booth GL. The treatment of unrelated disorders in patients with chronic medical diseases.  N Engl J Med.1998;338:1516-1520.
PubMed
 Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S).  Lancet.1994;344:1383-1389.
PubMed
Shepherd J, Cobbe SM, Ford I.  et al. West of Scotland Coronary Prevention Study Group.  Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia.  N Engl J Med.1995;333:1301-1307.
PubMed
Sacks FM, Pfeffer MA, Moye LA.  et al. Cholesterol and Recurrent Events Trial Investigators.  The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels.  N Engl J Med.1996;335:1001-1009.
PubMed
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