By P. Tom. Goshen College. 2019.
Percent change in proteinuria was noted to be –75% (95% CI buy anacin master card, –85 to –43) for lisinopril and –46% (95% CI order anacin overnight delivery, –60 to –24) for losartan purchase 525mg anacin amex. The notably broad confidence intervals likely stem from the very small sample size order anacin 525mg on-line. This study did note a statistically greater decline in proteinuria for those on lisinopril compared with losartan (P<0. No statistically significant differences in changes in creatinine clearance were noted between groups. No outcomes involving mortality, hospitalization, cardiovascular events, or end stage renal disease were reported. No differences in blood pressure control between monotherapy groups were reported. The rates of adverse events were similar for each therapy, with 10% (1 of 9) experiencing a potassium level of greater than 5. Similarly, 10% in each group (1 of 9) experienced dizziness while on therapy. No withdrawals due to adverse events were reported; the only withdrawal was related to non-adherence (specifically, inability to keep scheduled study appointments). Losartan compared with enalapril Losartan was compared with enalapril in 3 trials (N=145), all of which were conducted in Poland 93, 102, 103 by the same group. Losartan dose was 25 mg per day and enalapril dose was 10 mg per day in each trial. The trials ranged in duration from 3 DRIs, AIIRAs, and ACE-Is Page 50 of 144 Final Report Drug Effectiveness Review Project 103 102 93 months to 12 months with 1 intermediate range of 9 months. All 3 trials had a homogenous mix of participants including participants with mesangial glomerulonephritis, mesangiocapillary nephritis, and membranous nephropathy; 1 of these 3 trials also enrolled 103 participants with focal segmental glomerulosclerosis. Two trials specifically excluded 102, 103 participants with IgA nephropathy. All included participants had baseline proteinuria levels that spanned similar values (1. Each trial required a creatinine of less than 2 mg/dL for inclusion, and all participants had a creatinine clearance of greater than 80 2 ml/min/1. All 3 studies comparing losartan and enalapril (N=145) 93, 102, 103 93 reported percent decrease in proteinuria after therapy. Renke and colleagues reported percent decrease in proteinuria at 3 and 9 months as 26% and 44% for losartan and 43% and 50% 103 for enalapril respectively. Tylicki and colleagues reported percent decrease in proteinuria at 3 months of 25% for losartan and 45% for enalapril at 3 months. The difference between groups was found to not be statistically significant in either of these 2 trials (P=0. The third trial reported a 33% decline in proteinuria for those treated with losartan and a 41% decline for those treated with enalapril, but 102 no statistical analysis was reported between these 2 groups. These 3 trials did not report outcomes on mortality, end stage renal disease, or quality of life. One trial (N=51) reported percent decline in creatinine clearance for losartan compared 103 with enalapril at 3 months. The decline in creatinine clearance was noted to be greater in the enalapril (–15%) compared with the losartan group (percentage not reported), but the difference was not statistically significant (P=0. Two trials (N=94) reported changes in creatinine clearance but only as compared with 93, 102 baseline, without inter-group comparisons. One trial (N=54) showed slightly lower diastolic blood pressures among those treated with losartan 93 compared with enalapril (P=0. All 3 studies reported overall withdrawals, but those withdrawals were not consistently broken down by study groups, limiting the ability to make inter-group comparisons. One study reported a subgroup analysis comparing the effect of losartan therapy on participants delineated by baseline proteinuria level (greater than or less than 1. This trial also reported changes in proteinuria between 2 varied doses of losartan; as neither of these subgroups addressed a comparison question between ACE-I and AIIRA, those results will not be discussed here, but details are available in Evidence Table 9. Information on harms was not reported these 3 studies with the exception of the withdrawals related to allergic reactions. Each trail reported 1 withdrawal related to allergic reaction to study medication, but which medication was not specified. Losartan compared with benazepril 88 94, Losartan was compared with benazepril in 3 trials (N=420) conducted in China and Poland. The Reno protection of Optimal Antiproteinuric Doses (ROAD) study by Hou and colleagues is notable as the largest and longest duration trial comparing monotherapy with AIIRA compared with ACE-I with 360 94 participants and 3 years follow-up. The 2 remaining trials followed participants for 5 months 104 and 20 months and had 30 participants each. These trials were produced by the same research DRIs, AIIRAs, and ACE-Is Page 51 of 144 Final Report Drug Effectiveness Review Project group in Poland. Two trials used doses of benazepril 10mg daily and losartan 50mg daily 94, 104 exclusively, while 1 used benazepril 10 mg daily and losartan 50 mg daily as starting doses, but also included escalating doses to maximum of benazepril 40 mg daily and losartan 200 mg 88 94, 104 daily. Two of these 3 trials were homogeneous in terms of participants and enrolled participants with mesangial glomerulonephritis, mesangiocapillary glomerulonephritis, IgA nephropathy, and membranous nephropathy. The 1 remaining trial included a different range of chronic kidney disease, and enrolled participants with glomerulonephritis, polycystic kidney disease, hypertensive renal disease, interstitial renal disease, and those with renal disease of 88 unknown etiology. Two trials included participants with relatively normal renal function (mean 2 94, 104 baseline creatinine clearance greater than 80 ml/min/1. All participants were required to have proteinuria at the time of enrollment; baseline proteinuria was approximately 2 grams per day on average in all 3 studies. A trial (N=360) conducted at a single center in China reported a composite outcome of death, end stage renal disease, and doubling of serum creatinine 88 over 3 years of follow-up. This trial was unique in that half of its participants were randomized to benazepril 10 mg daily compared with losartan 50 mg daily, while the other half were randomized to “maximum” dose groups of benazepril and losartan. In the “maximum” dose groups, doses were titrated to the dose at which each individual achieved optimal antiproteinuric efficacy (as high as benazepril 40 mg daily and losartan 200 mg daily). There was no significant difference for percent reduction in the primary endpoint for losartan compared with benazepril at any dose (P values not reported), but a statistically significant lower percentage of participants reached the primary endpoint in each “maximum” group compared with group on the lower dosage of the same medication. Two trials (N=60) conducted at the University of Gdansk in Poland reported whether or not change in creatinine clearance was significant as compared with baseline (P values not 94, 104 reported). After 5 months, Renke and colleagues found no significant difference in creatinine clearance between groups (P values not reported). In the study by Rutkowski and colleagues, after 14 months no significant change in creatinine clearance was seen between groups or compared with baseline. They noted a numerically greater percent decline in proteinuria for losartan compared with benazepril, but that difference was not statistically significant (P=0. One group (N=360) reported only that change in proteinuria was not statistically significant between losartan and benazepril treatment 88 groups. Raw numbers were not provided for proteinuria changes, so no rough percent change was calculated. One group did not report reduction in proteinuria for monotherapy 94 comparisons. There were no significant differences in blood pressure control between treatment arms in either study. One study did perform a subgroup analysis examining reduction in proteinuria for those participants who started with baseline proteinuria of greater than or less than 2 grams per 104 day. Those with proteinuria of greater than 2 grams per day showed significantly greater reduction in comparison with those with less than 2 grams per day proteinuria at baseline (P=0. Two trials reported overall withdrawals, but did not break down those withdrawals by 94, 104 treatment group. This trial noted a 23% to 25% withdrawal rate in the 2 benazepril groups, compared with a 6% withdrawal rate in the 2 losartan groups. The majority of those withdrawals DRIs, AIIRAs, and ACE-Is Page 52 of 144 Final Report Drug Effectiveness Review Project in the benazepril groups were related to cough; if the withdrawal rate for the benazepril groups is calculated excluding withdrawals for cough, then the withdrawal rate ranges from 4% to 8%. One trial reported overall harms delineated by treatment groups; this study noted equivalent rates of hyperkalemia between groups, but a differential rate of cough. They described a statistically greater occurrence of cough in the benazepril arm compared with the losartan arm 88 (P value not reported). In the trial of 5-month duration, information on harms noted 2 hypotensive events, 1 allergic reaction to losartan, and 1 participant with cough, but these harms 94 were not clearly delineated by treatment groups. Similarly, the 14-month study reported 2 instances of cough and 2 instances of documented hypotension, but those harms were again not 104 clearly delineated by treatment groups.
It has to be noted that in this study the dosage of infliximab (3mg/kg) was lower than the recommended regimen (5 mg/kg) 525 mg anacin with mastercard. Therefore buy 525mg anacin visa, results have to be interpreted cautiously cheap anacin 525 mg with mastercard. With respect to the comparative effectiveness of etanercept and infliximab purchase 525mg anacin with mastercard, these studies reported similar findings as the head-to-head trial mentioned above. For example, in the nonrandomized, open-label trial, a Swedish population-based study that assessed the efficacy and safety of etanercept (n = 166), infliximab (n = 135), and leflunomide (n = 103), etanercept had statistically significantly greater American College of Rheumatology 20 response rates at 3 months (data NR; P<0. Comparisons at other time points, generally favored etanercept over infliximab although most differences failed to achieve statistical significance, which is probably attributable to a lack of power. Some of the six observational studies were based on data collected for registries in 45 44 43 48 42 Denmark, the Netherlands, Sweden, the United Kingdom, and the United States. These studies, therefore, reflect populations that are treated in daily clinical practice. Overall, results Targeted immune modulators 31 of 195 Final Update 3 Report Drug Effectiveness Review Project were consistent with findings mentioned above. In all of these studies etanercept led to numerically and sometimes statistically significantly greater response rates than infliximab after up to 3 years of follow-up. The largest of these observational studies was a prospective cohort study based on the 42 Rheumatoid Arthritis DMARD Intervention and Utilization Study program. This multicenter (509 rheumatology practices in the United States) registry enrolled patients who required changes in their rheumatoid arthritis treatment regimens. Data on 3034 patients on etanercept and 660 patients on infliximab were available for analysis after 12 months of follow-up. Etanercept- treated patients had numerically greater response rates on the modified American College of Rheumatology 20 (the modified American College of Rheumatology 20 omits erythrocyte sedimentation rate and C-reactive protein because they are infrequently measured in clinical practice) than infliximab-treated patients (etanercept + methotrexate: 43%; etanercept monotherapy: 41%; infliximab + methotrexate: 35%; infliximab monotherapy: 26%; P=NR). A good retrospective cohort study did not meet our eligibility criteria; nevertheless we presented findings because this study was the only one that compared radiographic progression 49 between etanercept and infliximab. This population-based study determined erosion progression and joint space narrowing on 372 Swiss patients who were monitored through the Swiss Clinical Quality Management System. Combination therapies of infliximab and disease- modifying antirheumatic drugs and etanercept and disease-modifying antirheumatic drugs did not present statistically significant differences in progression of erosion (Ratingen score; data NR; P=0. The combination of infliximab and disease- modifying antirheumatic drugs led to statistically significantly less joint space narrowing than etanercept and disease-modifying antirheumatic drugs (data NR; P<0. This difference, however, was not obvious when the analysis was limited to methotrexate as the concomitant disease-modifying antirheumatic drug. Targeted immune modulators combination strategies Two trials determined the potential for additive or synergistic effects of combination therapy of 50,51 two targeted immune modulators. The largest study, a 24-week randomized controlled trial, did not detect any synergistic effects of a combination treatment of etanercept (25 mg/week or 50 50 mg/week) and anakinra (100 mg/day) compared with etanercept monotherapy. Overall, 242 patients who were on stable doses of methotrexate treatment were enrolled. At endpoint, combination treatment did not lead to greater efficacy than etanercept only. Furthermore, the frequency of serious adverse events was substantially higher in the combination groups (14. Likewise, withdrawals because of adverse events were higher in the combination groups than in the etanercept group (8. The second study, examining a combination of abatacept (2 mg/kg) and etanercept (25 mg twice weekly) compared with abatacept (2 mg/kg) monotherapy reached similar 51 conclusions. The combination was associated with increased serious adverse events but only limited additional clinical benefit. Targeted immune modulators 32 of 195 Final Update 3 Report Drug Effectiveness Review Project Table 6. Summary of head-to-head studies in adult patients with rheumatoid arthritis Primary Secondary Quality Author, year Study design N Duration Comparisons outcome outcomes Population Results rating Abatacept compared with infliximab Active RA for at least 1 year; ACR Schiff et al. EULAR, Treatment response similar for 45 969 ACR 70 started a biologic; mean Fair 2010 (DANBIO months etanercept DAS28 adalimumab and etanercept disease duration: 8. EULAR, 45 1452 ACR 70 started a biologic; mean rates on ACR and EULAR for Fair 2010 (DANBIO months infliximab DAS28 disease duration: 8. ACR 50/70, had failed methotrexate 41 randomized 32 ACR 20 for etanercept than for infliximab at 12 Fair al, 2006 months Infliximab HAQ treatment; mean disease controlled trial months duration: NR Fernandez- Active RA ; had failed Prospective Etanercept vs. DAS 28, DAS 28 was statistically significantly Nebro et al. ACR had failed at least 1 DMARD significantly greater for etanercept than 40 301 DAS28 Fair 2002 trial months infliximab 20/50 treatment; mean disease for infliximab at 3 months and 6 months duration: 14. EULAR, 45 1333 ACR 70 started a biologic; mean rates on ACR and EULAR for Fair 2010 (DANBIO months infliximab DAS28 disease duration: 8. RA; patients who needed 42 cohort study (US ACR 20 HAQ greater for etanercept than for Fair 2006 months infliximab change in treatment regimen; registry) infliximab at 12 months mean disease duration: NR Combination strategies No additional benefit from etanercept- Etanercept + > 6 months history of active anakinra combination therapy; Adverse Genovese et 24 methotrexate vs. ACR 20/70, RA; stable methotrexate 50 RCT 242 ACR 50 events rates statistically significantly Fair al. Targeted immune modulators 34 of 195 Final Update 3 Report Drug Effectiveness Review Project Detailed assessment: Indirect evidence on the comparative effectiveness Because of the lack of direct head-to-head evidence for most comparisons, we conducted indirect comparisons based on metaregressions of placebo-controlled trials to compare the treatment effects of individual targeted immune modulators. We included data from published studies or from the US Food and Drug Administration Center for Drug Evaluation Research website. For all analyses we used only data derived from study arms at or near the recommended dosage. We limited analyses to comparisons of targeted immune modulators in combination with methotrexate compared with methotrexate monotherapy. We excluded treatment arms of targeted immune modulators without concomitant methotrexate. Our population of interest for indirect comparisons was patients who had active arthritis despite treatment with a disease-modifying antirheumatic drug. We excluded studies from indirect comparisons that enrolled patients who were disease-modifying antirheumatic drug- naïve or who had failed a trial with an antitumor necrosis factor drug. We also excluded studies that switched patients from the placebo group to the active treatment if they had an unsatisfactory response at a specific point in time during the study. We chose American College of Rheumatology 50 as the outcome measure because a 50% improvement is likely to translate to a clinically significant improvement in health-related quality of life. For example, a patient with 12 swollen and eight tender joints at baseline would need to have fewer than six swollen and four tender joints at the trial endpoint. This would be accompanied by at least a 50% improvement in at least three of the following five measures: the patient’s assessment of pain, the patient’s assessment of global disease activity, the physician’s assessment of global disease activity, the Health Assessment Questionnaire Disability Index, and either a C-reactive protein or sedimentation rate (Westergren erythrocyte sedimentation rate). The underlying assumption for indirect comparisons to be valid is that the relative 52 efficacy of an intervention is consistent across included studies. Included targeted immune modulator-studies primarily differ in study duration, disease duration, concomitant treatments, and some other baseline characteristics. Differences in study durations did not appear to be a factor altering the effect size. We included studies with duration of between 3 and 12 months. Sensitivity analyses based on different study durations did not substantially change the point estimates of the treatment effect. Results of indirect comparisons are depicted in Figure 2. Findings suggested that no substantial differences in efficacy exist among abatacept, adalimumab, anakinra, and infliximab. Given the wide confidence intervals, however, clinically significant differences could not be excluded with certainty. Findings of indirect comparisons also suggest that etanercept is statistically significantly more efficacious than abatacept, adalimumab, anakinra, and infliximab (Figure 2; range of relative risks, 2. For these analyses, we have excluded a landmark trial on etanercept, namely the TEMPO (Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes) 53,54 study. We excluded the TEMPO study because it enrolled a mixed population of methotrexate-naive patients (about 57%) and patients who had been on prior methotrexate treatment. Patients who had either failed prior methotrexate treatment or experienced toxic effects were also excluded from this study.
The number of trials and patients studied for each statin are as follows: fluvastatin (1 trial; N=429) order anacin amex, lovastatin (3 trials; N=1520) buy anacin 525mg without a prescription, pravastatin (5 trials; N=2220) cheap 525 mg anacin fast delivery, and simvastatin (3 trials; N=1118) purchase anacin 525 mg. The information about fluvastatin was inconclusive and the other 3 statins were already known to be effective from better studies. In general, most trials in which coronary heart disease events were not a prespecified endpoint found a trend towards a reduction in clinical events in favor of a statin. In the trials in which coronary heart disease events were a secondary endpoint, there was usually a significant reduction in 1 of the components of coronary heart disease events. While consistent, the results of these studies are difficult to interpret because of possible reporting bias. That is, these trials may have been more likely to report a result if it was statistically significant or indicated a trend favoring treatment. Similar trials of progression of atherosclerosis that found no trend probably did not report coronary events. For this reason, we did not conduct a meta-analysis to pool the results of these studies. Statins Page 52 of 128 Final Report Update 5 Drug Effectiveness Review Project Table 12. Studies of atherosclerotic progression that reported coronary heart disease outcomes Author or study acronym Pre-specified clinical event or Significant reduction in clinical a Statin spontaneous report event or trend towards statin LCAS 147 Spontaneous report Trend Fluvastatin ACAPS Reduction in major cardiovascular 148 Secondary endpoint Lovastatin events CCAIT 149 Spontaneous report Trend Lovastatin MARS 150 Spontaneous report Trend Lovastatin REGRESS Reduction in percutaneous 155 Pre-specified Pravastatin transluminal coronary angioplasty PLAC-I 151 Pre-specified Reduction in myocardial infarction Pravastatin PLAC-II Reduction in combined: nonfatal 152 Pre-specified Pravastatin myocardial infarction and death KAPS 153 Spontaneous report Trend Pravastatin Sato, et al 154 Pre-specified Reduction in overall death Pravastatin MAAS 156 Spontaneous report Trend Simvastatin CIS 157 Spontaneous report Trend Simvastatin SCAT 158 Pre-specified Reduction in revascularization Simvastatin a "Spontaneous report" means that the outcome was not a pre-specified endpoint for the study but was reported anyway. Revascularization studies with restenosis or clinical outcome endpoints This group (Table 13 and Evidence Table 6) included placebo-controlled trials in revascularized patients (coronary artery bypass graft, percutaneous transluminal coronary angioplasty, or 159-165, 167 coronary stent). The primary endpoint in 5 of the trials was the rate of restenosis. A reduction in clinical outcomes was the primary outcome in the 6th study (subgroup analysis of 161 CARE). Most of the studies were fair or fair-to-poor in quality for the question of whether treatment with a statin is associated with a reduction in clinical cardiovascular outcomes in patients with coronary heart disease. Sample sizes were relatively small and the studies were not powered to assess these types of events. The number of studies and patients per statin were as follows: fluvastatin (2 trials; N=2086), lovastatin (3 trials; N=1981), pravastatin (3 trials; N=3017; Table 9 presented data on 2245 patients already included in CARE). In these trials, pravastatin and fluvastatin had statistically significant effects on prespecified coronary disease outcomes. Statins Page 53 of 128 Final Report Update 5 Drug Effectiveness Review Project Table 13. Post-revascularization trials Study Drug, patients Clinical endpoint Clinical events 163 No effect on restenosis or on the preplanned FLARE Prespecified composite composite clinical end-point at 40 weeks (22. Spontaneous report the lovastatin group; no difference in fatal or placebo to reduce restenosis nonfatal events at 6 months after PTCA Pre-specified composite 159 No difference in composite outcome (12. No effect on restenosis; significant reduction in MI, revascularization, or lovastatin, before and after 2nd or 3rd re-PTCA (P=0. Rate of patients who under went or nonfatal MI, cardiac angina was reduced with pravastatin (30%) coronary balloon angioplasty st death, angina compared with control (59. In the Lescol Intervention Prevention Study (LIPS), patients who had undergone angioplasty or other percutaneous coronary intervention were randomized to fluvastatin 40 mg 167, 188 twice daily or placebo for 4 years. Patients with diabetes and those with multi- vessel disease experienced a comparable or greater benefit with fluvastatin than other subjects. Statins Page 54 of 128 Final Report Update 5 Drug Effectiveness Review Project Two subgroup analyses of the LIPS trial have recently been published; 1 in patients with 183 189 type 2 diabetes (discussed above) and another in patients with renal dysfunction. Fluvastatin reduced major coronary events in these subgroups. Miscellaneous studies Three trials that reported clinical outcomes did not fit the criteria for the other categories (Table 65, 166, 190 14 and Evidence Table 6). The study was open-label, but serious adverse events were classified by a safety committee blinded to allocation. The primary endpoint was safety, including noncardiac and cardiac events after 14 weeks of treatment. It was not designed to determine whether simvastatin and atorvastatin differed in their effects on coronary disease events but reported them as part of their safety analysis. Total adverse effect rates, serious adverse effect rates (A-2%, S-3%, NS), and withdrawal rates were similar for atorvastatin and simvastatin. The article states (page 10), “Serious cardiovascular events (including angina pectoris, myocardial infarction, and cerebral ischemia) were more frequent in the simvastatin group (19 patients, 2%) than in the atorvastatin group (21 patients, 1. This table shows that the number of these serious cardiovascular events was 11 (0. If deaths are included, the probabilities of serious cardiovascular events are 0. Because the study was of short duration, the investigators did not interpret any of the cardiovascular events to be related to therapy. The study was rated fair-to-poor quality because of the lack of blinding and the lack of clarity of the statistical analysis. Miscellaneous trials reporting clinical outcomes Study Drug Patients Clinical endpoint Clinical events 166 AVERT Atorvastatin vs. Are there differences in effectiveness of statins and fixed-dose combination products containing a statin and another lipid-lowering drug in different demographic groups or in patients with comorbid conditions (e. Summary of findings • There was good evidence from randomized trials that women and the elderly benefit from statin therapy. The rosuvastatin label has been revised to note that this increase should be considered when making rosuvastatin dosing decisions for Asian patients. Efficacy in demographic subgroups Women and the elderly Although women and the elderly were under-represented in the early major trials, we found 4 191-194 meta-analyses suggesting that statins are equally efficacious in men, women, and the elderly. Women accounted for an average of 17% of subjects and individuals age 65 and older accounted for an average of 29% of subjects with a range of 21% to 39% (WOSCOPS did not enroll women or anyone 65 years or older). The risk reduction in major coronary events was 29% (95% CI, 13 to 42) in women, 31% (95% CI, 26 to 35) for men, 32% (95% CI, 23 to 39) in those over age 65, and 31% (95% CI, 24 to 36) in those younger than age 65. Similarly, the Heart Protection 123, 178 Study found that simvastatin reduced cardiovascular events among women generally and particularly in women with diabetes, who benefited dramatically (number needed to treat, 23 to prevent 1 major vascular event). Nine trials of statins that enrolled 16 486 women and 4 additional studies that included 1405 women who used drug therapy other than statins were included in the analysis. For secondary prevention, lipid-lowering therapy reduced risk of coronary heart disease mortality (summary RR 0. In primary prevention studies, there was insufficient evidence of reduced risk of any clinical outcome in women, because of the small number of events in the trials. Sensitivity analyses including only studies using statins did not significantly affect the summary risk estimates. Statins Page 56 of 128 Final Report Update 5 Drug Effectiveness Review Project 193, 194 Two meta-analyses specifically evaluating statins in the elderly confirmed prior findings that these drugs are effective in this population. In particular, a hierarchial bayesian 193 meta-analysis included 9 placebo-controlled trials that enrolled 19 569 elderly patients who had a history of cardiovascular events. The pooled relative risk for all-cause mortality was 0. Coronary heart disease mortality, nonfatal myocardial infarction, need for revascularization, and stroke were all statistically significantly reduced with statins compared with placebo (Evidence Table 8). Of note, the Heart Protection study (which included primary prevention population) was included in the meta-analysis but a sensitivity analysis with and without this trial showed consistent treatment effects. Statins that were included were simvastatin 20-40 mg, pravastatin 40 mg, and fluvastatin 80 mg. African American, Hispanic, and other ethnic groups African Americans had the greatest overall coronary heart disease mortality and the highest out- 4 of-hospital coronary death rates of any other ethnic group in the United States. Other ethnic and minority groups in the United States included Hispanics, Native Americans, Asian and Pacific Islanders, and South Asians. However, these groups are underrepresented in randomized clinical trials reporting reductions in clinical outcomes. As a result there was no evidence to answer whether or not statins differ in their ability to reduce clinical events in the African American, Hispanic, or other ethnic groups.