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Association of combination statin and antihypertensive therapy with reduced Alzheimer's disease and related dementia risk.

ABSTRACT: BACKGROUND:Hyperlipidemia and hypertension are modifiable risk factors for Alzheimer's disease and related dementias (ADRD). Approximately 25% of adults over age 65 use both antihypertensives (AHTs) and statins for these conditions. While a growing body of evidence found statins and AHTs are independently associated with lower ADRD risk, no evidence exists on simultaneous use for different drug class combinations and ADRD risk. Our primary objective was to compare ADRD risk associated with concurrent use of different combinations of statins and antihypertensives. METHODS:In a retrospective cohort study (2007-2014), we analyzed 694,672 Medicare beneficiaries in the United States (2,017,786 person-years) who concurrently used both statins and AHTs. Using logistic regression adjusting for age, socioeconomic status and comorbidities, we quantified incident ADRD diagnosis associated with concurrent use of different statin molecules (atorvastatin, pravastatin, rosuvastatin, and simvastatin) and AHT drug classes (two renin-angiotensin system (RAS)-acting AHTs, angiotensin converting enzyme inhibitors (ACEIs) or angiotensin-II receptor blockers (ARBs), vs non-RAS-acting AHTs). FINDINGS:Pravastatin or rosuvastatin combined with RAS-acting AHTs reduce risk of ADRD relative to any statin combined with non-RAS-acting AHTs: ACEI+pravastatin odds ratio (OR) = 0.942 (CI: 0.899-0.986, p = 0.011), ACEI+rosuvastatin OR = 0.841 (CI: 0.794-0.892, p<0.001), ARB+pravastatin OR = 0.794 (CI: 0.748-0.843, p<0.001), ARB+rosuvastatin OR = 0.818 (CI: 0.765-0.874, p<0.001). ARBs combined with atorvastatin and simvastatin are associated with smaller reductions in risk, and ACEI with no risk reduction, compared to when combined with pravastatin or rosuvastatin. Among Hispanics, no combination of statins and RAS-acting AHTs reduces risk relative to combinations of statins and non-RAS-acting AHTs. Among blacks using ACEI+rosuvastatin, ADRD odds were 33% lower compared to blacks using other statins combined with non-RAS-acting AHTs (OR = 0.672 (CI: 0.548-0.825, p<0.001)). CONCLUSION:Among older Americans, use of pravastatin and rosuvastatin to treat hyperlipidemia is less common than use of simvastatin and atorvastatin, however, in combination with RAS-acting AHTs, particularly ARBs, they may be more effective at reducing risk of ADRD. The number of Americans with ADRD may be reduced with drug treatments for vascular health that also confer effects on ADRD.

SUBMITTER: Barthold D

PROVIDER: S-EPMC7055882 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Association of combination statin and antihypertensive therapy with reduced Alzheimer's disease and related dementia risk.

Barthold Douglas D Joyce Geoffrey G Diaz Brinton Roberta R Wharton Whitney W Kehoe Patrick Gavin PG Zissimopoulos Julie J

PloS one 20200304 3

<h4>Background</h4>Hyperlipidemia and hypertension are modifiable risk factors for Alzheimer's disease and related dementias (ADRD). Approximately 25% of adults over age 65 use both antihypertensives (AHTs) and statins for these conditions. While a growing body of evidence found statins and AHTs are independently associated with lower ADRD risk, no evidence exists on simultaneous use for different drug class combinations and ADRD risk. Our primary objective was to compare ADRD risk associated wi ...[more]

PMID: 32130251

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Project description:IntroductionEstablishing efficacy of and molecular pathways for statins has the potential to impact incidence of Alzheimer's and age-related neurodegenerative diseases (NDD).MethodsThis retrospective cohort study surveyed US-based Humana claims, which includes prescription and patient records from private-payer and Medicare insurance. Claims from 288,515 patients, aged 45 years and older, without prior history of NDD or neurological surgery, were surveyed for a diagnosis of NDD starting 1 year following statin exposure. Patients were required to be enrolled with claims data for at least 6 months prior to first statin prescription and at least 3 years thereafter. Computational system biology analysis was conducted to determine unique target engagement for each statin.ResultsOf the 288,515 participants included in the study, 144,214 patients (mean [standard deviation (SD)] age, 67.22 [3.8] years) exposed to statin therapies, and 144,301 patients (65.97 [3.2] years) were not treated with statins. The mean (SD) follow-up time was 5.1 (2.3) years. Exposure to statins was associated with a lower incidence of Alzheimer's disease (1.10% vs 2.37%; relative risk [RR], 0.4643; 95% confidence interval [CI], 0.44-0.49; P < .001), dementia 3.03% vs 5.39%; RR, 0.56; 95% CI, 0.54-0.58; P < .001), multiple sclerosis (0.08% vs 0.15%; RR, 0.52; 95% CI, 0.41-0.66; P < .001), Parkinson's disease (0.48% vs 0.92%; RR, 0.53; 95% CI, 0.48-0.58; P < .001), and amyotrophic lateral sclerosis (0.02% vs 0.05%; RR, 0.46; 95% CI, 0.30-0.69; P < .001). All NDD incidence for all statins, except for fluvastatin (RR, 0.91; 95% CI, 0.65-1.30; P = 0.71), was reduced with variances in individual risk profiles. Pathway analysis indicated unique and common profiles associated with risk reduction efficacy.DiscussionBenefits and risks of statins relative to neurological outcomes should be considered when prescribed for at-risk NDD populations. Common statin activated pathways indicate overarching systems required for risk reduction whereas unique targets could advance a precision medicine approach to prevent neurodegenerative diseases.

Project description:To date, most clinical comparisons of ezetimibe-statin combination therapy versus statin monotherapy have relied entirely on surrogate variables. In this systematic review, we study the efficacy and safety of ezetimibe-statin combination therapy in comparison to statin monotherapy in terms of the prevention of cardiovascular events in hyperlipidemic patients with atherosclerosis and/or diabetes mellitus.This review is based on a systematic literature search (1995 to July 2015) in PubMed, the Excerpta Medica Database (EMBASE), the Cochrane Library, and the ClinicalTrials.gov registry.Nine randomized, controlled trials with data from a total of 19 461 patients were included. Ezetimibe-statin combination therapy was associated with a lower risk of cardiovascular events than statin monotherapy: 33% of the patients treated with ezetimibe and a statin, and 35% of those treated with a statin alone, had a cardiovascular event within seven years (number needed to treat [NNT]: 50 over 7 years). Combination therapy was also significantly more effective in preventing a composite endpoint consisting of death due to cardiovascular disease, nonfatal myocardial infarction, unstable angina pectoris, coronary revascularization, and nonfatal stroke (hazard ratio [HR] 0.94, 95% confidence interval [0,89; 0,99]; p = 0.016). Diabetic patients benefited from combination therapy rather than monotherapy with respect to cardiovascular morbidity (HR 0.87 [0.78; 0.94]). On the other hand, the addition of ezetimibe to statin therapy did not lessen either cardiovascular or overall mortality. Serious undesired events occurred in 38% of the patients taking ezetimibe and a statin nd in 39% of the patients taking a statin alone (relative risk 1.09 [0.77; 1.55]).In high-risk patients with an acute coronary syndrome, combination therapy with ezetimibe and a statin lowered the risk of cardiovascular events in comparison to statin monotherapy. The risk of dying or suffering an adverse drug effect was similar in the two treatment groups.

Project description:BackgroundSeveral previous studies showed that patients who received angiotensin II-stimulating antihypertensive medications had a lower incident dementia rate than those angiotensin II-inhibiting antihypertensive users, but no study has been conducted in long-term cancer survivors.ObjectivesTo determine the risk of Alzheimer's disease (AD) and related dementia (ADRD) associated with the types of antihypertensive medications in a large cohort of survivors with colorectal cancer in 2007-2015 with follow-up from 2007 to 2016.MethodsWe identified 58,699 men and women with colorectal cancer aged 65 or older from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database in 17 SEER areas in 2007-2015 with follow-up to 2016, who were free of any diagnosed ADRD at the baseline (within 12 months prior to and 12 months after the date of diagnosis for colorectal cancer). All patients who were defined as having hypertension by ICD diagnosis code or received antihypertensive drugs during this baseline 2-year period were classified into 6 groups based on whether they received angiotensin-II stimulating or inhibiting antihypertensive drugs.ResultsCrude cumulative incidence rates of AD and ADRD were similar between those who received angiotensin II-stimulating antihypertensive medications (4.3% and 21.7%) and those receiving angiotensin II-inhibiting antihypertensive medications (4.2% and 23.5%). As compared to patients who received angiotensin II-stimulating antihypertensive drugs, those who received angiotensin II-inhibiting antihypertensives were significantly more likely to develop AD (adjusted hazard ratio: 1.15, 95% CI: 1.01-1.32), vascular dementias (1.27, 1.06-1.53), and total ADRD (1.21, 1.14-1.28) after adjusting for potential confounders. These results remained similar after adjusting for medication adherence and considering death as a competing risk.ConclusionsThe risk of AD and ADRD in patients with hypertension who received angiotensin II-inhibiting antihypertensive medications was higher than in those receiving angiotensin II-stimulating antihypertensive drugs in patients with colorectal cancer.

Project description:Essentials A lowered risk of recurrent venous thrombosis (VT) with statin treatment is controversial. Among observational inception cohort of 2,798 adults with incident VT, 457 had recurrent VT. Time-to-event models with time-varying statin use and adjustment for potential confounders was used for analysis. Compared to nonuse, current statin use was associated with 26% lower risk of recurrent VT. Click to hear Prof. Büller's perspective on Anticoagulant Therapy in the Treatment of Venous ThromboembolismBackground Meta-analyses of randomized controlled trials suggest that treatment with hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) lowers the risk of incident venous thrombosis (VT), particularly among those without prevalent clinical cardiovascular disease (CVD). Whether this is true for the prevention of recurrent VT is debated. We used an observational inception cohort to estimate the association of current statin use with the risk of recurrent VT. Methods and Results The study setting was a large healthcare organization with detailed medical record and pharmacy information at cohort entry and throughout follow-up. We followed 2798 subjects 18-89 years of age who experienced a validated incident VT between January 1, 2002, and December 31, 2010, for a first recurrent VT, validated by medical record review. During follow-up, 457 (16%) developed a first recurrent VT. In time-to-event models incorporating time-varying statin use and adjusting for potential confounders, current statin use was associated with a 26% lower risk of recurrent VT: hazard ratio 0.74, 95% confidence interval 0.59-0.94. Among cohort members free of CVD (n = 2134), current statin use was also associated with a lower risk (38%) of recurrent VT: hazard ratio 0.62, 95% confidence interval 0.45-0.85. We found similar results when restricting to new users of statins and in subgroups of different statin types and doses. Conclusions In a population-based cohort of subjects who had experienced an incident VT, statin use, compared with nonuse, was associated with a clinically relevant lower risk of recurrent VT. These findings suggest a potential secondary benefit of statins among patients who have experienced an incident VT.

Project description:BackgroundDetecting patients with undiagnosed dementia is an important clinical challenge. Changes in medication adherence might represent an early sign of cognitive impairment. We sought to examine antihypertensive and statin adherence trajectories in community-dwelling older adults, comparing people who went on to develop dementia to those who did not.MethodsWe analyzed data from Adult Changes in Thought (ACT), a population-based cohort study embedded within an integrated healthcare delivery system. Analyses included 4368 participants aged ?65?years who had at least one follow-up visit. Research-quality dementia diagnoses were used to identify cases. We selected non-dementia control visits matched on age, sex, and study cohort that occurred at similar ACT follow-up time as the case's dementia onset; we treated this as the index date. Participants were included if they were prevalent users of either a statin or antihypertensive medication on the first day of follow up - 3?years prior to the index date. Using prescription fill dates and days supply, we calculated daily binary medication availability measures for each participant ('days covered') over 3?years leading up to the index date. We used group-based trajectory models to identify patterns of antihypertensive and statin adherence, and used conditional logistic regression to examine associations between adherence trajectories and dementia.ResultsFour trajectories were identified for antihypertensive users (292 cases, 3890 control visits), including near perfect (n =?1877, 36.6% cases, 45.5% controls), high (n =?1840, 43.2% cases, 44.1% controls), moderate (n =?365, 18.5% cases, 8.0% controls) and early poor adherence (n =?100, 1.7% cases, 2.4% controls). Odds of dementia was 3 times greater for those with moderate antihypertensive adherence compared to those with near perfect adherence (adjusted OR 3.0, 95% CI 2.0, 4.3). Four trajectories were identified for statin users (148 cases, 1131 control visits), including high (n =?1004, 75.0% cases, 79.0% controls), moderate (n =?192, 19.6% cases, 14.4% controls), early poor (n =?43, 2.0% cases, 3.5% controls), and delayed poor adherence (n =?40, 3.4% cases, 3.1% controls). No association was detected between statin adherence trajectories and dementia.ConclusionsPatterns of medication adherence may be useful to identify a subset of people at higher likelihood of developing dementia.

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Association of combination statin and antihypertensive therapy with reduced Alzheimer's disease and related dementia risk.

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Association of combination statin and antihypertensive therapy with reduced Alzheimer's disease and related dementia risk.

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