statins

Choudhry NK, Patrick AR, Glynn RJ, Avorn J. The cost-effectiveness of C-reactive protein testing and rosuvastatin treatment for patients with normal cholesterol levels [Internet]. J Am Coll Cardiol 2011;57:784-91. WebsiteAbstract
OBJECTIVES: We sought to evaluate the cost-effectiveness of applying the JUPITER (Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) trial results into clinical practice. BACKGROUND: The JUPITER trial found that rosuvastatin reduces vascular events in apparently healthy subjects with elevated high-sensitivity C-reactive protein (hs-CRP) but normal low-density lipoprotein (LDL) cholesterol levels. The implications of expanding treatment recommendations based on these results have not been evaluated. METHODS: We constructed a cost-effectiveness model of men >/=50 years and women >/=60 years with LDL cholesterol levels of <130 mg/dl and no known cardiovascular disease. We compared: 1) hs-CRP testing followed by rosuvastatin treatment for patients with hs-CRP levels >/=2.0 mg/l; and 2) usual care (i.e., no testing and no treatment). Estimates of treatment effectiveness were based on the JUPITER trial and were varied in sensitivity analyses. RESULTS: Among patients with LDL <130 mg/dl and hs-CRP levels >/=2.0 mg/l, rosuvastatin had an incremental cost-effectiveness of $25,198 per quality-adjusted life year (QALY) gained compared to usual care. If the effectiveness of rosuvastatin were 50% of that observed in JUPITER, the incremental cost-effectiveness ratio would increase to $50,871 per QALY. Implementing this strategy only in patients with a Framingham risk score >/=10% yielded an incremental cost-effectiveness of $14,205 per QALY. Among such intermediate-risk patients, a JUPITER-based strategy becomes cost-saving at a rosuvastatin price of <$0.86 per day. CONCLUSIONS: Rosuvastatin treatment for JUPITER-eligible patients appears to be cost-effective, particularly among those with a Framingham risk score >/=10%.
Choudhry NK, Fischer MA, Avorn J, Liberman JN, Schneeweiss S, Pakes J, Brennan TA, Shrank WH. The implications of therapeutic complexity on adherence to cardiovascular medications [Internet]. Arch Intern Med 2011;171:814-822. WebsiteAbstract
BACKGROUND: Patients with chronic disease often take many medications multiple times per day. Such regimen complexity is associated with medication nonadherence. Other factors, including the number of pharmacy visits patients make to pick up their prescriptions, may also undermine adherence. Our objective was to estimate the extent of prescribing and filling complexity in patients prescribed a cardiovascular medication and to evaluate its association with adherence. METHODS: The study population comprised individuals prescribed a statin (n = 1 827 395) or an angiotensin- converting enzyme inhibitor or renin angiotensin receptor blocker (ACEI/ARB) (n = 1 480 304) between June 1, 2006, and May 30, 2007. We estimated complexity by measuring the number of medications, prescribers, pharmacies, pharmacy visits, and refill consolidation (a measure of the number of visits per fill) during the 3 months from the first prescription. The number of daily doses was also measured in ACEI/ARB users. After this period, adherence was evaluated over the subsequent year. The relationship between complexity and adherence was assessed with multivariable linear regression. RESULTS: The statin cohort had a mean age of 63 years and were 49% male. On average, during the 3-month complexity assessment period, statin users filled 11.4 prescriptions for 6.3 different medications, had prescriptions written by 2 prescribers, and made 5.0 visits to the pharmacy. Results for ACEI/ARB users were similar. Greater prescribing and filling complexity was associated with lower levels of adherence. In adjusted models, patients with the least refill consolidation had adherence rates that were 8% lower over the subsequent year than patients with the greatest refill consolidation. CONCLUSION: Medication use and prescription filling for patients with cardiovascular disease is complex, and strategies to reduce this complexity may help improve medication adherence.
Brunelli SM, Waikar SS, Bateman BT, Chang TI, Lii J, Garg AX, Winkelmayer WC, Choudhry NK. Preoperative statin use and postoperative acute kidney injury [Internet]. The American Journal of Medicine 2012;125:1195-1204 e3. WebsiteAbstract
BACKGROUND: Acute kidney injury is a frequent postoperative complication that confers increased mortality, morbidity, and costs. The purpose of this study was to evaluate whether preoperative statin use is associated with a decreased risk of postoperative acute kidney injury. METHODS: We assembled a retrospective cohort of 98,939 patients who underwent a major open abdominal, cardiac, thoracic, or vascular procedure between 2000 and 2010. Statin users were pair-matched to nonusers on the basis of surgery type, baseline kidney function, days from admission until surgery, and propensity score based on demographics, comorbid conditions, and concomitant medications. Acute kidney injury was defined based on changes in serum creatinine measurements applying Acute Kidney Injury Network and Risk-Injury-Failure staging systems, and on the need for renal replacement therapy. Associations between statin use and acute kidney injury were estimated by conditional logistic regression. RESULTS: Across various acute kidney injury definitions, statin use was consistently associated with a decreased risk: adjusted odds ratios (95% confidence intervals) varied from 0.74 (0.58-0.95) to 0.80 (0.71-0.90). Associations were similar among diabetics and nondiabetics, and across strata of baseline kidney function. The protective association of statins was most pronounced among patients undergoing vascular surgery and least among patients undergoing cardiac surgery. CONCLUSIONS: Preoperative statin use is associated with a decreased risk of postoperative acute kidney injury. Future randomized clinical trials are needed to determine causality.
Thavendiranathan P, Bagai A, Brookhart AM, Choudhry NK. Primary Prevention of Cardiovascular Diseases With Statin Therapy: A Meta-analysis of Randomized Controlled Trials [Internet]. Arch Intern Med 2006;166:2307-2313. WebsiteAbstract
Background While the role of hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins) in secondary prevention of cardiovascular (CV) events and mortality is established, their value for primary prevention is less clear. To clarify the role of statins for patients without CV disease, we performed a meta-analysis of randomized controlled trials (RCTs). Methods MEDLINE, EMBASE, Cochrane Collaboration, and American College of Physicians Journal Club databases were searched for RCTs published between 1966 and June 2005. We included RCTs with follow-up of 1 year or longer, more than 100 major CV events, and 80% or more of the population without CV disease. From each trial, demographic data, lipid profile, CV outcomes, mortality, and adverse outcomes were recorded. Summary relative risk (RR) ratios with 95% confidence intervals (CIs) were calculated using a random effects model. Results Seven trials with 42 848 patients were included. Ninety percent had no history of CV disease. Mean follow-up was 4.3 years. Statin therapy reduced the RR of major coronary events, major cerebrovascular events, and revascularizations by 29.2% (95% CI, 16.7%-39.8%) (P<.001), 14.4% (95% CI, 2.8%-24.6%) (P = .02), and 33.8% (95% CI, 19.6%-45.5%) (P<.001), respectively. Statins produced a nonsignificant 22.6% RR reduction in coronary heart disease mortality (95% CI, 0.56-1.08) (P = .13). No significant reduction in overall mortality (RR, 0.92 [95% CI, 0.84-1.01]) (P = .09) or increases in cancer or levels of liver enzymes or creatine kinase were observed. Conclusion In patients without CV disease, statin therapy decreases the incidence of major coronary and cerebrovascular events and revascularizations but not coronary heart disease or overall mortality.
Choudhry NK, Levin R, Winkelmayer WC. Statins in elderly patients with acute coronary syndrome: an analysis of dose and class effects in typical practice [Internet]. Heart 2007;93:945-51. WebsiteAbstract
OBJECTIVE: To compare the effectiveness of statins of different treatment intensity used to treat elderly patients with acute coronary syndrome (ACS) in typical care settings. DESIGN: Retrospective cohort study using linked hospital and pharmacy claims data. SETTING: Statewide pharmacy benefits programmes in Pennsylvania and New Jersey. PARTICIPANTS: 18,311 Medicare patients discharged alive after ACS who received a prescription for a statin within 90 days of hospital discharge. MAIN OUTCOME MEASURES: Using multivariable and propensity-matched Cox proportional hazards regression models, patients who were prescribed high-intensity and moderate-intensity statins were compared based on the drug-dose combination that they initially received. Individual drug-dose combinations were also compared. Our primary outcome was the composite of all-cause death or recurrent ACS. RESULTS: Patients who received moderate-intensity statins were as likely to experience a primary outcome as patients treated with high-intensity statins (adjusted HR 1.02, 95% CI 0.96 to 1.08). Propensity matching did not change the results. Individually, all moderate-intensity statins were as effective as high-intensity atorvastatin with the exception of lovastatin (adjusted HR 1.22, 95% CI 1.09 to 1.36). Similarly, all high-intensity statins seem as effective as high-intensity atorvastatin but the CIs surrounding these estimates were wide. CONCLUSIONS: This analysis of elderly patients with ACS treated in typical care settings does not demonstrate the superiority of high-intensity over moderate-intensity statin treatment or significant differences among individual statins.
Kulik A, Levin R, Ruel M, Mesana TG, Solomon DH, Choudhry NK. Patterns and predictors of statin use after coronary artery bypass graft surgery [Internet]. J Thorac Cardiovasc Surg 2007;134:932-8. WebsiteAbstract
OBJECTIVES: The benefits of statin therapy for patients with coronary artery disease have been well documented, including those occurring after coronary artery bypass graft surgery. The purposes of this study were to assess statin prescription rates in patients who have undergone coronary artery bypass graft surgery and to identify the determinants of postoperative statin administration. METHODS: A retrospective cohort of 9284 Medicare patients aged 65 years or older who underwent coronary artery bypass graft surgery (1995-2004) was assembled by using linked hospital and pharmacy claims data. Rates of statin use after hospital discharge were calculated, and predictors of postoperative statin use were identified by using generalized estimating equations. RESULTS: Overall, 35.9% of patients received statins within 90 days of coronary artery bypass graft surgery discharge. Use of statins within 90 days after coronary artery bypass graft surgery steadily improved during the study period, from 13.1% in 1995 to 60.9% in 2004. Patient factors independently associated with an increase in postoperative statin therapy included preoperative statin use (odds ratio, 7.69), later year of operation (odds ratio, 1.22 per additional year), and additional postoperative medications (odds ratio, 1.16 per additional medication). Factors independently associated with a decrease in postoperative statin therapy included peripheral vascular disease (odds ratio, 0.60), diabetes mellitus (odds ratio, 0.67), stroke (odds ratio, 0.77), and older age (odds ratio, 0.96 per additional year). Surgeon and hospital characteristics were not independently associated with postoperative statin use. CONCLUSIONS: Statins are considerably underused after coronary artery bypass graft surgery, although recent prescription rates are increasing. Patterns of use do not appear to correlate with coronary artery disease risk. These findings highlight the need for targeted quality improvement initiatives to increase the rate of statin administration to this at-risk population.
Kulik A, Brookhart MA, Levin R, Ruel M, Solomon DH, Choudhry NK. Impact of Statin Use on Outcomes After Coronary Artery Bypass Graft Surgery [Internet]. Circulation 2008; WebsiteAbstract
BACKGROUND: -The benefits of statins have been demonstrated for patients with a remote history of coronary artery bypass grafting (CABG); however, no investigation to date has evaluated whether initiation of statin therapy in the early months after surgery improves clinical outcomes. Methods and Results-A retrospective cohort of 7503 Medicare patients >/=65 years of age who underwent CABG (1995-2003) was assembled by use of linked hospital and pharmacy claims data. Rates of all-cause mortality and major adverse cardiovascular events were compared between patients who were (n=1745) and were not (n=5788) prescribed statins within 1 month of CABG discharge. Additional analyses evaluated the impact of statin initiation between 1 and 6 months after surgery. Multivariable and propensity score analysis demonstrated that statin use within 1 month of CABG discharge independently reduced the risk of all-cause mortality (adjusted hazard ratio 0.82, 95% confidence interval 0.72 to 0.94) compared with no statin use. Similarly, statin use within 1 month of CABG discharge independently reduced the risk of major adverse cardiovascular events (adjusted hazard ratio 0.89, 95% confidence interval 0.81 to 0.98). Initiation of statin therapy between 1 and 6 months after CABG discharge was also associated with reductions in major adverse cardiovascular events and mortality; however, outcome rates between early (
Chan DC, Shrank WH, Cutler D, Jan S, Fischer MA, Liu J, Avorn J, Solomon D, Brookhart MA, Choudhry NK. Patient, physician, and payment predictors of statin adherence [Internet]. Med Care 2010;48:196-202. WebsiteAbstract
BACKGROUND:: Although many patient, physician, and payment predictors of adherence have been described, knowledge of their relative strength and overall ability to explain adherence is limited. OBJECTIVES:: To measure the contributions of patient, physician, and payment predictors in explaining adherence to statins. RESEARCH DESIGN:: Retrospective cohort study using administrative data. SUBJECTS:: A total of 14,257 patients insured by Horizon Blue Cross Blue Shield of New Jersey who were newly prescribed a statin cholesterol-lowering medication. MEASURES:: Adherence to statin medication was measured during the year after the initial prescription, based on proportion of days covered. The impact of patient, physician, and payment predictors of adherence were evaluated using multivariate logistic regression. The explanatory power of these models was evaluated with C statistics, a measure of the goodness of fit. RESULTS:: Overall, 36.4% of patients were fully adherent. Older patient age, male gender, lower neighborhood percent black composition, higher median income, and fewer number of emergency department visits were significant patient predictors of adherence. Having a statin prescribed by a cardiologist, a patient's primary care physician, or a US medical graduate were significant physician predictors of adherence. Lower copayments also predicted adherence. All of our models had low explanatory power. Multivariate models including patient covariates only had greater explanatory power (C = 0.613) than models with physician variables only (C = 0.566) or copayments only (C = 0.543). A fully specified model had only slightly more explanatory power (C = 0.633) than the model with patient characteristics alone. CONCLUSIONS:: Despite relatively comprehensive claims data on patients, physicians, and out-of-pocket costs, our overall ability to explain adherence remains poor. Administrative data likely do not capture many complex mechanisms underlying adherence.
Kulik A, Singh JP, Levin R, Avorn J, Choudhry NK. Association between statin use and the incidence of atrial fibrillation following hospitalization for coronary artery disease [Internet]. Am J Cardiol 2010;105:1655-60. WebsiteAbstract
Mounting evidence suggests that statins possess antiarrhythmic properties and inhibit atrial fibrillation (AF). The goal of this study was to evaluate the relation between statin use and new-onset AF in a large cohort of patients with coronary artery disease. We identified all Medicare beneficiaries > or =65 years old who had been hospitalized for acute myocardial infarction or coronary revascularization from 1995 to 2004 and participated in 1 of 2 government-sponsored medication benefit programs. Patients with a history of AF before and during hospitalization were excluded. This yielded a cohort of 29,088. The incidence of new AF was compared between patients who were (n = 8,450) and were not (n = 20,638) prescribed statins within 1 month of hospital discharge after their cardiac event. New-onset AFs within 5 and 10 years were 32.6% and 51.2%, respectively, in patients who received statins compared to 38.3% and 58.0% in patients who did not receive statins (unadjusted hazard ratio 0.82, 95% confidence interval 0.78 to 0.86). Multivariable analysis controlling for demographic and clinical confounders indicated that statin use independently decreased the risk of developing new-onset AF compared to nonusers (adjusted hazard ratio 0.90, 95% confidence interval 0.85 to 0.94). Adjustment for propensity-score and health-seeking behaviors yielded nearly identical results. In conclusion, statin therapy initiated within 1 month after hospital discharge is independently associated with a decrease in the risk of new-onset AF after myocardial infarction or coronary revascularization. These findings lend support to the antiarrhythmic effects of statins and suggest another benefit for their use in patients with coronary artery disease.
Parikh S, Shrank WH, Mogun H, Choudhry NK. Statin Utilization in Nursing Home Patients after Cardiac Hospitalization [Internet]. J Gen Intern Med 2010; WebsiteAbstract
BACKGROUND: Coronary artery disease (CAD) is highly prevalent in nursing home residents and is associated with a substantial clinical and economic burden. Statins reduce mortality and hospitalization rates in older patients with CAD. OBJECTIVES: To assess rates and predictors of statin use among high-risk patients with symptomatic coronary artery disease (CAD) admitted to nursing homes after acute cardiac hospitalization. DESIGN: Cohort study. PARTICIPANTS: Medicare beneficiaries enrolled in either a state-run drug assistance program or Medicaid in nursing homes in New Jersey from 1994 through 2005. MEASUREMENTS: Statin utilization within 60 days of nursing home admission was determined for patients recently hospitalized with symptomatic CAD in whom statins are indicated consisting of those with: acute coronary syndrome (ACS) without revascularization, ACS with revascularization and congestive heart failure (CHF) with revascularization. Predictors of statin use were evaluated with multivariate logistic regression models. RESULTS: While statin use over the 11-year period increased from 1.2% to 31.8%, overall utilization was very low. Predictors of greater statin use included prior cardiac hospitalization [odds ratio (OR) 1.32, 95% confidence interval (95% CI) 1.13 to 1.57], prior statin use (OR 6.92, 95% CI 5.86 to 8.82) and receipt of a concurrent cardiac medication (range of odds ratios, 2.36-3.40). Older patients admitted for ACS with or without revascularization were less likely to receive a statin. Patients who had received anti-platelets or angiotensin-modifying agents prior to their hospitalization were less likely to receive statins after discharge. Renal disease, prior stroke, diabetes, hypertension and hyperlipidemia did not influence statin utilization. Predictors of treatment did not change when the cohort was dichotomized according to length of stay. CONCLUSIONS: Patients are infrequently treated with statins when discharged to nursing homes following hospitalization for a symptomatic cardiovascular event. Barriers to statin treatment in this setting require closer examination.
Kulik A, Shrank WH, Levin R, Choudhry NK. Adherence to Statin Therapy in Elderly Patients After Hospitalization for Coronary Revascularization [Internet]. Am J Cardiol 2011;107:1409-14. WebsiteAbstract
Low levels of statin adherence have been documented in patients with coronary artery disease (CAD), but whether coronary revascularization is associated with improved adherence rates has yet to be evaluated. We identified all Medicare beneficiaries enrolled in 2 statewide pharmacy assistance programs who were >/=65 years old, who had been hospitalized for CAD from 1995 through 2004, and who had been prescribed statin therapy within 90 days of discharge (n = 13,130). Statin adherence was measured based on the proportion of days covered with statin therapy after hospital discharge, and full adherence was defined as proportion of days covered >/=80%. Statin adherence was compared in patients with CAD treated with medical therapy (n = 3,714), percutaneous coronary intervention (n = 6,309), or coronary artery bypass graft surgery (n = 3,107). Statin adherence significantly increased over the period of the study from 70.5% to 75.4% (p <0.0001). After hospitalization for CAD, patients treated with percutaneous coronary intervention and coronary artery bypass graft surgery had full adherence rates of 70.6% and 70.2%, respectively. Full adherence rates were significantly lower for patients treated with coronary revascularization compared to patients treated with medical therapy (79.4%, p <0.0001). Independent predictors of higher statin adherence included treatment with medical therapy, later year of hospital admission, white race, previous statin use, and use of other cardiac medications after CAD hospitalization (p <0.01 for all comparisons). In conclusion, in patients receiving invasive coronary treatment, statin adherence remains suboptimal, despite strong evidence supporting their use. Given the health and economic consequences of nonadherence, these findings highlight the need for developing cost-effective strategies to improve medication adherence after coronary revascularization.