Purpose
To determine whether the statin class of drug is protective against exudative age-related macular degeneration (AMD).
Design
Case-control study.
Methods
The study was conducted at Kaiser Permanente Southern California. Cases was defined as incident cases, identified using outpatient diagnosis data. Controls were patients who had seen an ophthalmologist during the same year without the diagnosis of AMD. Drug use information was obtained using computerized databases.
Results
In 2007, 86 635 patients older than 60 years underwent an eye examination. Cases comprised 719 patients newly diagnosed with exudative AMD. Controls (78 650) comprised everyone else who did not have any form of AMD. Use of statins was not associated with newly diagnosed exudative AMD.
Conclusions
Recent statin use is not associated with newly diagnosed exudative AMD. The current study had 80% statistical power to detect a protective effect of 0.70, but it cannot exclude a smaller effect.
Age-related macular degeneration (AMD) is the leading cause of blindness among older Americans. Although a number of new agents are now available for treating exudative AMD, preventive treatments still would be helpful. Epidemiologic studies have shown associations between cardiovascular disease and AMD. Genetic studies suggest that cardiovascular disease and AMD share susceptibility genes (e.g., complement factor H). C-reactive protein has been associated with both cardiovascular disease and AMD. With this background, some have suggested that modification of atherosclerotic changes also may prevent AMD. The statin (hydroxymethyl glutaryl co-enzyme A reductase inhibitors) class of drugs is one that may treat both diseases.
The current literature has been inconsistent regarding the effect of statin use and AMD. In 2001, one study reported the prevalence of AMD to be 3.7% in statin users and 21.6% in nonusers. Since that time, this association has been evaluated using a variety of study designs (retrospective and prospective), drug definitions (patient interview, filled prescriptions, or medical records), and definitions for AMD (early only, late only, combined, etc.). Some studies showed a protective effect, whereas others did not confirmed this effect. The current study investigated the association of statins use (filled prescriptions) and newly diagnosed cases of exudative AMD (incidence) in a case-control study design conducted within a defined population.
Methods
The study was conducted at Kaiser Permanente Southern California (KPSC) and was approved by the KPSC Institutional Review Board. KPSC provides care for 3.1 million residents of Southern California with more than 6000 physicians working in 11 medical centers. The study was a case-control study to determine whether incident cases with exudative AMD are less likely to be users of statins. Cases were identified using outpatient diagnosis data. AMD was identified as either exudative, nonexudative, or not specified. We identified all patients with a diagnosis of exudative AMD in the year 2007 and who did not have this diagnosis in 2006. Eligible patients were 60 years of age or older and had been enrolled in KPSC for at least 5 years in 2007. Controls were patients who had undergone an eye examination during the same year without the diagnosis of AMD.
The primary source of data to assess treatment with statins is the computer-stored data regarding outpatient prescriptions filled in Kaiser Permanente pharmacies, called the Pharmacy Information Management System (PIMS). The PIMS has been used in KPSC since 1991, with complete data available from January 1992. The PIMS actually consists of several databases, with records linked between databases using medical record numbers and other identifiers. Information available from the PIMS system includes details on known drug allergies as well as the following data for each prescription dispensed: date, location, person filling the order, the type of medication dispensed (identified by Generic Product Identification code), number of units dispensed, dosage, route of administration, ingredients (if medication mixed by pharmacist), and billing information. Approximately 93% of KPSC Health Plan members have prescription drug coverage as a benefit. It is estimated that more than 97% of all prescriptions written by KPSC physicians are filled at KPSC pharmacies, and therefore would be included in PIMS.
Statin use was defined as use of atorvastin, ezetimibe-simvastatin, lovastatin, pravastatin, and simvastatin. In analyses involving all lipid-lowering agents, cholestyramine, colestipol, ezetimibe, fenofibrate, and gemfibrozil were included. Drug use was defined as use before case determination. Recent use was defined as a filled prescription of statins in the year before the year of diagnosis, and recent longer-term use was defined as a filled prescription in each of the 3 years before the diagnosis. Myocardial infarction was defined as use of the diagnosis Internation Classification of Diseases Ninth Edition 410 and stroke, the codes 430 to 438.
Differences in proportions were tested using chi-square tests, supplemented by calculation of the odds ratio with associated 95% confidence limits. Means were tested using t tests. Logistic regression analyses were conducted to adjust for confounding variables.
Results
In 2007, 86 635 patients older than 60 years underwent an eye examination. Of these, 719 patients were newly diagnosed to have exudative AMD. To investigate the association with statin use, we selected all 719 cases of AMD. Controls were everyone else (n = 78 650) who did not have any form of AMD.
Table 1 shows the distribution of demographic variables between cases and controls. Case seemed to be older and more likely to be of white race. Cases also were more likely to have a history of myocardial infarction and stoke. We looked at whether recent use of a statin ( Table 2 ) and recent longer-term use ( Table 3 ) was associated with newly diagnosed exudative AMD. In both comparisons, there were no associations with statin use. There was also no association between lipid-lowering agents and incident exudative AMD ( Table 4 ). Logistic regression analysis was performed to adjust for differences the distribution of certain confounding variables. After adjustment for age, gender, and history of myocardial infarction and of stroke, statin use still was not associated with exudative AMD ( Table 5 ).
| Characteristics | Cases (n = 719) | Controls (n = 78 650) | P Value |
|---|---|---|---|
| Mean age (yrs) | 78.6 | 72.7 | .0001 |
| Age distribution (%) | .0001 | ||
| 61 to 69 | 15.4 | 37.6 | |
| 70 to 79 | 34.9 | 42.6 | |
| 80 to 89 | 43.0 | 18.4 | |
| 90+ | 6.7 | 1.5 | |
| Total | 100 | 100 | |
| Race (%) | |||
| White | 70.1 | 48.8 | .0001 |
| Black | 2.2 | 12.2 | |
| Latino | 12.1 | 16.7 | |
| Asian | 3.5 | 8.1 | |
| Other/unknown | 12.1 | 14.1 | |
| Total | 100 | 100 | |
| % Female | 54.5 | 57.3 | .13 |
| % with history of myocardial infarction (1981 through 2006) | 8.3 | 6.4 | .03 |
| % with history of stroke (1981 through 2006) | 17.4 | 13.7 | .006 |
| Exudative Age-Related Macular Degeneration | Statin Use | Total | |
|---|---|---|---|
| Yes % (n) | No % (n) | ||
| Yes | 51.5 (370) | 48.5 (349) | (100.0) 719 |
| No | 54.2 (42 656) | 45.8 (35 994) | (100.0) 78 650 |
| Exudative Age-Related Macular Degeneration | Statin Use | Total | |
|---|---|---|---|
| Yes, % (n) | No, % (n) | ||
| Yes | 38.5 (277) | 61.5 (442) | 100.0 (719) |
| No | 41.3 (32 466) | 58.7 (46 184) | 100.0 (78 650) |
| Exudative Age-Related Macular Degeneration | Use of Lipid-Lowering Agent | Total | |
|---|---|---|---|
| Yes, % (n) | No, % (n) | ||
| Yes | 5.3 (38) | 94.7 (681) | 100 (719) |
| No | 6.3 (4978) | 93.7 (73 672) | 100 (78 650) |
| Variable | Odds Ratio | 95% Confidence Interval | P Value (Chi-Square Test) |
|---|---|---|---|
| Statin use in 2006 | 0.9 | 0.8 to 1.0 | .15 |
| White race | 2.0 | 1.7 to 2.3 | < .0001 |
| Male gender | 1.1 | 1.0 to 1.3 | .07 |
| Age group (yrs) | |||
| > 90 vs 61 to 69 | 9.3 | 6.6 to 13.2 | < .0001 |
| 80 to 89 vs 61 to 69 | 5.0 | 4.0 to 6.3 | < .0001 |
| 70 to 79 vs 61 to 69 | 1.9 | 1.5 to 2.4 | < .0001 |
| History of myocardial infarction | 1.1 | 0.8 to 1.4 | .56 |
| History of stroke | 1.0 | 0.8 to 1.2 | .99 |
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