To JUPITER and beyond: statins, inflammation, and primary prevention.
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ABSTRACT:
SUBMITTER: Rao AD
PROVIDER: S-EPMC2911709 | biostudies-literature | 2010
REPOSITORIES: biostudies-literature
Publications
To JUPITER and beyond: statins, inflammation, and primary prevention.
Rao Ajay D AD Milbrandt Eric B EB
Critical care (London, England) 20100513 3
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Project description:BackgroundCholesterol guidelines typically prioritize primary prevention statin therapy on the basis of 10-year risk of cardiovascular disease. The advent of generic pricing may justify expansion of statin eligibility. Moreover, 10-year risk may not be the optimal approach for statin prioritization. We estimated the cost-effectiveness of expanding preventive statin eligibility and evaluated novel approaches to prioritization from a Scottish health sector perspective.MethodsA computer simulation model predicted long-term health and cost outcomes in Scottish adults ≥40 years of age. Epidemiologic analysis was completed using the Scottish Heart Health Extended Cohort, Scottish Morbidity Records, and National Records of Scotland. A simulation cohort was constructed with data from the Scottish Health Survey 2011 and contemporary population estimates. Treatment and cost inputs were derived from published literature and health service cost data. The main outcome measure was the lifetime incremental cost-effectiveness ratio, evaluated as cost (2020 GBP) per quality-adjusted life-year (QALY) gained. Three approaches to statin prioritization were analyzed: 10-year risk scoring using the ASSIGN score, age-stratified risk thresholds to increase treatment rates in younger individuals, and absolute risk reduction (ARR)-guided therapy to increase treatment rates in individuals with elevated cholesterol levels. For each approach, 2 policies were considered: treating the same number of individuals as those with an ASSIGN score ≥20% (age-stratified risk threshold 20, ARR 20) and treating the same number of individuals as those with an ASSIGN score ≥10% (age-stratified risk threshold 10, ARR 10).ResultsCompared with an ASSIGN score ≥20%, reducing the risk threshold for statin initiation to 10% expanded eligibility from 804 000 (32% of adults ≥40 years of age without CVD) to 1 445 500 individuals (58%). This policy would be cost-effective (incremental cost-effectiveness ratio, £12 300/QALY [95% CI, £7690/QALY-£26 500/QALY]). Incremental to an ASSIGN score ≥20%, ARR 20 produced ≈8800 QALYs and was cost-effective (£7050/QALY [95% CI, £4560/QALY-£10 700/QALY]). Incremental to an ASSIGN score ≥10%, ARR 10 produced ≈7950 QALYs and was cost-effective (£11 700/QALY [95% CI, £9250/QALY-£16 900/QALY]). Both age-stratified risk threshold strategies were dominated (ie, more expensive and less effective than alternative treatment strategies).ConclusionsGeneric pricing has rendered preventive statin therapy cost-effective for many adults. ARR-guided therapy is more effective than 10-year risk scoring and is cost-effective.
| S-EPMC9022692 | biostudies-literature
Project description:The elderly population is increasing worldwide, with subjects > 65 years of age constituting the fastest-growing age group. Furthermore, the elderly face the greatest risk and burden of cardiovascular disease mortality and morbidity. Although elderly patients, particularly those older > 75, have not been well represented in randomized clinical trials evaluating lipid-lowering therapy, the available evidence supporting the use of statin therapy in primary prevention in older individuals is derived mainly from subgroup analyses and post-hoc data. On the other hand, elderly patients often have multiple co-morbidities that require a high number of concurrent medications; this may increase the risk for drug-drug interactions, thereby reducing the potential benefits of statin therapy. The aim of this review was to present the relevant literature regarding statin use in the elderly for their primary cardiovascular disease, with the associated risks and benefits of treatment.
| S-EPMC4554788 | biostudies-other
Project description:AimsWe undertook a propensity match-weighted cohort study to investigate whether statin treatment recommendations for statins translate into improved cardiovascular (CV) outcomes in the current routine clinical care of the elderly.Methods and resultsWe included in our analysis (ISACS Archives -NCT04008173) a total of 5619 Caucasian patients with no known prior history of CV disease who presented to hospital with a first manifestation of CV disease with age of 65 years or older. The risk of ST-segment elevation myocardial infarction (STEMI) was much lower in statin users than in non-users in both patients aged 65-75 years [14.7% absolute risk reduction; relative risk (RR): 0.55, 95% CI 0.45-0.66] and those aged 76 years and older (13.3% absolute risk reduction; RR: 0.58, 95% CI 0.46-0.72). Estimates were similar in patients with and without history of hypercholesterolaemia (interaction test; P-values = 0.24 and 0.35). Proportional reductions in STEMI diminished with female sex in the old (P for interaction = 0.002), but not in the very old age (P for interaction = 0.26). We also observed a remarkable reduction in the risk of 30 day mortality from STEMI with statin therapy in both age groups (10.2% absolute risk reduction; RR: 0.39; 95% CI 0.23-0.68 for patients aged 76 or over and 3.8% absolute risk reduction; RR 0.37; 95% CI 0.17-0.82 for patients aged 65-75 years old; interaction test, P-value = 0.46).ConclusionsPreventive statin therapy in the elderly reduces the risk of STEMI with benefits in mortality from STEMI, irrespective of the presence of a history of hypercholesterolaemia. This effect persists after the age of 76 years. Benefits are less pronounced in women. Randomized clinical trials may contribute to more definitively determine the role of statin therapy in the elderly.
| S-EPMC9648819 | biostudies-literature
Project description:ObjectThe purpose of this study was to fully assess the role of statins in the primary prevention of coronary heart disease (CHD).MethodsWe searched six databases (PubMed, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Database, and Chinese Scientific Journal Database) to identify relevant randomized controlled trials (RCTs) from inception to 31 October 2017. Two review authors independently assessed the methodological quality and analysed the data using Rev Man 5.3 software. Risk ratios and 95% confidence intervals (95% CI) were pooled using fixed/random-effects models. Funnel plots and Begg's test were conducted to assess publication bias. The quality of the evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.ResultsSixteen RCTs with 69159 participants were included in this review. Statins can effectively decrease the occurrence of angina (RR=0.70, 95% CI: 0.58~0.85, I2 =0%), nonfatal myocardial infarction (MI) (RR=0.60, 95% CI: 0.51~0.69, I2 =14%), fatal MI (RR=0.49, 95% CI: 0.24~0.98, I2 =0%), any MI (RR=0.53, 95% CI: 0.42~0.67, I2 =0%), any coronary heart events (RR=0.73, 95% CI: 0.68~0.78, I2=0%), coronary revascularization (RR=0.66, 95% CI: 0.55~0.78, I2 = 0%), and any cardiovascular events (RR=0.77, 95% CI: 0.72~82, I2 = 0%). However, based on the current evidence, there were no significant differences in CHD deaths (RR=0.82, 95% CI: 0.66~1.02, I2=0%) and all-cause mortality (RR=0.88, 95% CI: 0.76 ~1.01, I2 =58%) between the two groups. Additionally, statins were more likely to result in diabetes (RR=1.21, 95% CI: 1.05~1.39, I2 =0%). There was no evidence of publication biases, and the quality of the evidence was considered moderate.ConclusionStatins seemed to be beneficial for the primary prevention of CHDs but have no effect on CHD death and all-cause mortality.
| S-EPMC6374814 | biostudies-literature
Project description:Background and objectivesMultiple meta-analyses of lipid-lowering therapies for cardiovascular primary prevention in the general population have been performed. Other meta-analyses of lipid-lowering therapies in CKD have also been performed, but not for primary prevention. This meta-analysis assesses lipid-lowering therapies for cardiovascular primary prevention in CKD.Design, setting, participants, & measurementsA systematic review and meta-analysis using a random-effects model was performed. MEDLINE was searched between January 2012 and September 2013 for new studies using predefined search criteria without language restrictions. A number of other sources including previously published meta-analyses were also reviewed. Inclusion criteria were randomized control trials of primary prevention with lipid-lowering therapy in non-end stage CKD.ResultsSix trials were identified, five including patients with stage 3 CKD only. These studies included 8834 participants and 32,846 person-years of follow-up. All trials were post hoc subgroup analyses of statins in the general population. Statins reduced the risk of cardiovascular disease (the prespecified primary outcome) by 41% in stages 1-3 CKD compared with placebo (pooled risk ratio, 0.59; 95% confidence interval [95% CI], 0.48 to 0.72). For the secondary outcomes, the risk ratios were 0.66 (95% CI, 0.49 to 0.88) for total mortality, 0.55 (95% CI, 0.42 to 0.72) for coronary heart disease events, and 0.56 (95% CI, 0.28 to 1.13) for stroke. In study participants with stage 3 CKD specifically, the results were similar.ConclusionsThis meta-analysis suggests that the use of statins in CKD for primary prevention of cardiovascular disease is effective. These findings are consistent with recent guidance for the use of statins in all patients with CKD.
| S-EPMC4422238 | biostudies-literature
Project description:ObjectivesEstimate the effect of statin prescription on mortality in the population of England and Wales with no previous history of cardiovascular disease.MethodsPrimary care records from The Health Improvement Network 1987-2011 were used. Four cohorts of participants aged 60, 65, 70, or 75 years at baseline included 118,700, 199,574, 247,149, and 194,085 participants; and 1.4, 1.9, 1.8, and 1.1 million person-years of data, respectively. The exposure was any statin prescription at any time before the participant reached the baseline age (60, 65, 70 or 75) and the outcome was all-cause mortality at any age above the baseline age. The hazard of mortality associated with statin prescription was calculated by Cox's proportional hazard regressions, adjusted for sex, year of birth, socioeconomic status, diabetes, antihypertensive medication, hypercholesterolaemia, body mass index, smoking status, and general practice. Participants were grouped by QRISK2 baseline risk of a first cardiovascular event in the next ten years of <10%, 10-19%, or ≥20%.ResultsThere was no reduction in all-cause mortality for statin prescription initiated in participants with a QRISK2 score <10% at any baseline age, or in participants aged 60 at baseline in any risk group. Mortality was lower in participants with a QRISK2 score ≥20% if statin prescription had been initiated by age 65 (adjusted hazard ratio (HR) 0.86 (0.79-0.94)), 70 (HR 0.83 (0.79-0.88)), or 75 (HR 0.82 (0.79-0.86)). Mortality reduction was uncertain with a QRISK2 score of 10-19%: the HR was 1.00 (0.91-1.11) for statin prescription by age 65, 0.89 (0.81-0.99) by age 70, or 0.79 (0.52-1.19) by age 75.ConclusionsThe current internationally recommended thresholds for statin therapy for primary prevention of cardiovascular disease in routine practice may be too low and may lead to overtreatment of younger people and those at low risk.
| S-EPMC5115824 | biostudies-literature
Project description:Background The 2013 American College of Cardiology/American Heart Association Cholesterol Treatment Guideline increased the number of primary prevention patients eligible for statin therapy, yet uptake of these guidelines has been modest. Little is known of how primary care provider ( PCP ) beliefs influence statin prescription. Methods and Results We surveyed 164 PCP s from a community-based North Carolina network in 2017 about statin therapy. We evaluated statin initiation among the PCP s' statin-eligible patients between 2014 and 2015 without a previous prescription. Seventy-two PCP s (43.9%) completed the survey. The median estimate of the relative risk reduction for high-intensity statins was 45% (interquartile range, 25%-50%). A minority of providers (27.8%) believed statins caused diabetes mellitus, and only 16.7% reported always/very often discussing this with patients. Most PCPs (97.2%) believed that statins cause myopathy, and 72.3% reported always/very often discussing this with patients. Most (77.7%) reported always/very often using the 10-year atherosclerotic cardiovascular disease risk calculator, although many reported that in most cases other risk factors or patient preferences influenced prescribing (59.8% and 43.1%, respectively). Of 6172 statin-eligible patients, 22.3% received a prescription for a moderate- or high-intensity statin at follow-up. Providers reporting greater reliance on risk factors beyond atherosclerotic cardiovascular disease risk were less likely to prescribe statins. Conclusions Although beliefs and approaches to statin discussions vary among community PCP s, new prescription rates are low and minimally associated with those beliefs. These results highlight the complexity of increasing statin prescriptions for primary prevention and suggest that strategies to facilitate standardized discussions and to address external influences on patient beliefs warrant future study.
| S-EPMC6405576 | biostudies-literature
Project description:BackgroundIn view of evidence that statin therapy increases risk of diabetes, the balance of benefit and risk of these drugs in primary prevention has become controversial. We undertook an analysis of participants from the JUPITER trial to address the balance of vascular benefits and diabetes hazard of statin use.MethodsIn the randomised, double-blind JUPITER trial, 17,603 men and women without previous cardiovascular disease or diabetes were randomly assigned to rosuvastatin 20 mg or placebo and followed up for up to 5 years for the primary endpoint (myocardial infarction, stroke, admission to hospital for unstable angina, arterial revascularisation, or cardiovascular death) and the protocol-prespecified secondary endpoints of venous thromboembolism, all-cause mortality, and incident physician-reported diabetes. In this analysis, participants were stratified on the basis of having none or at least one of four major risk factors for developing diabetes: metabolic syndrome, impaired fasting glucose, body-mass index 30 kg/m(2) or higher, or glycated haemoglobin A(1c) greater than 6%. The trial is registered at ClinicalTrials.gov, NCT00239681.FindingsTrial participants with one or more major diabetes risk factor (n=11,508) were at higher risk of developing diabetes than were those without a major risk factor (n=6095). In individuals with one or more risk factors, statin allocation was associated with a 39% reduction in the primary endpoint (hazard ratio [HR] 0·61, 95% CI 0·47-0·79, p=0·0001), a 36% reduction in venous thromboembolism (0·64, 0·39-1·06, p=0·08), a 17% reduction in total mortality (0·83, 0·64-1·07, p=0·15), and a 28% increase in diabetes (1·28, 1·07-1·54, p=0·01). Thus, for those with diabetes risk factors, a total of 134 vascular events or deaths were avoided for every 54 new cases of diabetes diagnosed. For trial participants with no major diabetes risk factors, statin allocation was associated with a 52% reduction in the primary endpoint (HR 0·48, 95% CI 0·33-0·68, p=0·0001), a 53% reduction in venous thromboembolism (0·47, 0·21-1·03, p=0·05), a 22% reduction in total mortality (0·78, 0·59-1·03, p=0·08), and no increase in diabetes (0·99, 0·45-2·21, p=0·99). For such individuals, a total of 86 vascular events or deaths were avoided with no new cases of diabetes diagnosed. In analysis limited to the 486 participants who developed diabetes during follow-up (270 on rosuvastatin vs 216 on placebo; HR 1·25, 95% CI 1·05-1·49, p=0·01), the point estimate of cardiovascular risk reduction associated with statin therapy (HR 0·63, 95% CI 0·25-1·60) was consistent with that for the trial as a whole (0·56, 0·46-0·69). By comparison with placebo, statins accelerated the average time to diagnosis of diabetes by 5·4 weeks (84·3 [SD 47·8] weeks on rosuvastatin vs 89·7 [50·4] weeks on placebo).InterpretationIn the JUPITER primary prevention trial, the cardiovascular and mortality benefits of statin therapy exceed the diabetes hazard, including in participants at high risk of developing diabetes.FundingAstraZeneca.
| S-EPMC3774022 | biostudies-literature
Project description:Purpose of reviewWhile people with HIV (PWH) are living longer due to advances in antiretroviral therapy, recent data have demonstrated an increased risk of cardiovascular disease (CVD) among this population. This increased risk is thought to be due to both traditional (for example, smoking, diabetes) and HIV-specific (for example, inflammation, persistent immune activation) risk factors. This review focuses on the potential for statin therapy to mitigate this increased risk.Recent findingsSeveral randomized clinical trials have demonstrated that statins, a class of lipid-lowering medications, are effective as a primary CVD prevention strategy among people without HIV. Among PWH, statins have been shown to lower cholesterol, exert immunomodulatory effects, stabilize coronary atherosclerotic plaque, and even induce plaque regression.SummaryPrevention of CVD among the aging population of people with controlled, but chronic, HIV is vital. Data exploring primary prevention in this context are thus far limited. The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) is ongoing; this trial will inform the field by investigating the effects of pitavastatin calcium as a primary prevention strategy for major adverse cardiovascular events among PWH on antiretroviral therapy (ART) at low-to-moderate traditional CVD risk.
| S-EPMC9415230 | biostudies-literature
Project description:Background/objectivesWe sought to determine whether statin use for primary prevention is associated with a lower risk of cardiovascular events or mortality in older men.DesignProspective cohort study.SettingPhysicians' Health Study participants.Participants7,213 male physicians ≥70 years without a history of cardiovascular disease (CVD).MeasurementsMultivariable propensity score for statin use with greedy matching (1:1) to minimize confounding by indication.ResultsMedian baseline age was 77 (70-102), median follow-up was 7 years. Non-users were matched to 1,130 statin users. Statin use was associated with an 18% lower risk of all-cause mortality, HR 0.82 (95% CI 0.69-0.98) and non-significant lower risk of CVD events, HR 0.86 (95% CI 0.70-1.06) and stroke, HR 0.70 (95% CI 0.45-1.09). In subgroup analyses, results did not change according to age group at baseline (70-76 or >76 years) or functional status. There was a suggestion that those >76 at baseline did not benefit from statins for mortality, HR 1.14 (95% CI 0.89-1.47), compared to those 70-76 at baseline, HR 0.83 (95% CI 0.61-1.11); however the CIs overlap between the two groups, suggesting no difference. Statin users with elevated total cholesterol had fewer major CVD events than non-users, HR 0.68 (95% CI 0.50-0.94) and HR 1.43 (95% CI 0.99-2.07)), respectively.ConclusionsStatin use was associated with a significant lower risk of mortality in older male physicians ≥70 and a nonsignificant lower risk of CVD events. Results did not change in those who were >76 years at baseline or according to functional status. There was a suggestion that those with elevated total cholesterol may benefit. Further work is needed to determine which older individuals will benefit from statins as primary prevention.
| S-EPMC5681374 | biostudies-literature