Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial

Shepherd, James; Blauw, Gerard J.; Murphy, Michael B.; Bollen, Edward L.E.M.; Buckley, Brendan M.; Cobbe, Stuart M.; Ford, Ian; Gaw, Allan; Hyland, Michael E.; Jukema, J. Wouter; Kamper, Adriaan M.; Macfarlane, Peter W.; Meinders, A. E.; Norrie, John; Packard, Chris J.; Perry, Ivan J.; Stott, David J.; Sweeney, Brian; Twomey, Gillian; Westendorp, Rudi G.J.

doi:10.1016/s0140-6736(02)11600-x

Cited by 3,042 publications

(1,898 citation statements)

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“…Clinical trial data suggest a clinical benefit of moderate‐intensity statins in those aged ≥75 years when used for secondary prevention, and prior observational studies have demonstrated a significant risk reduction gleaned from statin therapy in this population 11, 15, 16, 19. Similarly, a recent observational study suggests a significant survival advantage exists among older adults with ASCVD treated with high‐ versus moderate‐intensity statins, amplified at maximal doses of high‐intensity statins 20.…”

Section: Discussionmentioning

confidence: 95%

“…The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults acknowledges the limitations of existing data on older individuals and recommends individualizing the decision to initiate statins for primary prevention in adults >75 years 1. For secondary prevention, 3 trials found that high‐intensity statin therapy reduced cardiovascular events more than moderate‐intensity statin therapy, but these trials enrolled few patients >75 years and none >80 years8, 9, 10; however, there was sufficient evidence for moderate‐intensity statin therapy in secondary prevention patients of any age 11. The most recent 2016 US Preventive Services Task Force Recommendation Statement on Statin Use for the Primary Prevention of Cardiovascular Disease similarly avoids firm recommendations about statins for older adult patients (>75 years old), as do the European Society of Cardiology/European Atherosclerosis Society guidelines for the management of dyslipidemias in patients >80 years old, with insufficient evidence to make a recommendation in this population 12, 13…”

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confidence: 99%

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Statin Use and Adverse Effects Among Adults >75 Years of Age: Insights From the Patient and Provider Assessment of Lipid Management (PALM) Registry

Nanna

Návar

Wang

et al. 2018

JAHA

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BackgroundCurrent statin use and symptoms among older adults in routine community practice have not been well characterized since the release of the 2013 American College of Cardiology/American Heart Association guideline.Methods and ResultsWe compared statin use and dosing between adults >75 and ≤75 years old who were eligible for primary or secondary prevention statin use without considering guideline‐recommended age criteria. The patients were treated at 138 US practices in the Patient and Provider Assessment of Lipid Management (PALM) registry in 2015. Patient surveys also evaluated reported symptoms while taking statins. Multivariable logistic regression models examined the association between older age and statin use and dosing. Among 6717 people enrolled, 1704 (25%) were >75 years old. For primary prevention, use of any statin or high‐dose statin did not vary by age group: any statin, 62.6% in those >75 years old versus 63.1% in those ≤75 years old (P=0.83); high‐dose statin, 10.2% versus 12.3% in the same groups (P=0.14). For secondary prevention, older patients were slightly less likely to receive any statin (80.1% versus 84.2% [P=0.003]; adjusted odds ratio, 0.81; 95% confidence interval, 0.66–1.01 [P=0.06]), but were much less likely to receive a high‐intensity statin (23.5% versus 36.2% [P<0.0001]; adjusted odds ratio, 0.54; 95% confidence interval, 0.45–0.65 [P=0.0001]). Among current statin users, older patients were slightly less likely to report any symptoms (41.3% versus 46.6%; P=0.003) or myalgias (27.3% versus 33.3%; P<0.001).ConclusionsOverall use of statins was similar for primary prevention in those aged >75 years versus younger patients, yet older patients were less likely to receive high‐intensity statins for secondary prevention. Statins appear to be similarly tolerated in older and younger adults.

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Section: Discussionmentioning

confidence: 95%

mentioning

confidence: 99%

Statin Use and Adverse Effects Among Adults >75 Years of Age: Insights From the Patient and Provider Assessment of Lipid Management (PALM) Registry

Nanna

Návar

Wang

et al. 2018

JAHA

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“…Moreover, glycaemic goals were more often achieved by patients in the older subgroups regardless the presence of a CVD, in accordance with the results from clinical trials and observational studies suggesting that a global control of cardiovascular risk factors in older patients provides a greater benefit regarding morbidity and mortality than an intensive glycaemic control 13, 14, 15, 16, 17. Antihypertensive treatment, for instance, has benefits even in very old patients 18, 19, 20, 21, and there are also compelling evidences of the benefit of statins and antiplatelet agents in older adults in secondary prevention of CVD, while its use in primary prevention is controversial, and individual characteristics and the risk of related adverse events should be taken into account 5, 7, 22, 23, 24, 25.…”

Section: Discussionmentioning

confidence: 99%

Older type 2 diabetic patients are more likely to achieve glycaemic and cardiovascular risk factors targets than younger patients: analysis of a primary care database

et al. 2015

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SummaryBackgroundOlder subjects with type 2 diabetes mellitus (T2DM) have differential characteristics compared with middle‐aged or younger populations, and require tailored management of the disease.AimsTo evaluate how clinical characteristics, degree of control of glycaemia and cardiovascular risk factors, presence of chronic complications and treatments differ between older T2DM patients and younger adults.MethodsCross‐sectional study using data from a population‐based electronic database. We retrieved data from 318,020 patients ≥ 30 years diagnosed with T2DM, attended during 2011 in primary care centres in Catalonia, Spain. We performed descriptive and comparative analyses stratified by gender and age subgroups: ≤ 65, 66–75, 76–85 and >85 years.ResultsBoth men and women across older age subgroups (> 65 years) had longer diabetes duration than younger adults (8.0 vs. 5.6 in men and 8.4 vs. 6.9 years in women; p < 0.001), but better glycaemic control (mean glycated haemoglobin 7.1 vs. 7.7 in men and 7.1 vs. 7.4 in women; p < 0.001), and better combined control of different cardiovascular risk factors (p < 0.001). Moreover, older patients were more likely to achieve glycaemic targets irrespective of having cardiovascular disease. The use of oral antidiabetics decreased with increasing age, and insulin in monotherapy was more frequently prescribed among patients in the older age subgroups. Diabetes‐related complications were more frequent in men of all group ages. In the older age subgroups, patients of both sexes had a longer duration of T2DM but better glycaemic control. In this context, the prevalence of diabetic retinopathy decreased unexpectedly with increasing age.ConclusionControl of glycaemia and cardiovascular risk factors was better among older T2DM patients. There is a need for prospective studies to quantify the weight of risk factors in each complication to adapt the therapeutic and care approaches in elderly people.

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“…Progress has been achieved in reducing cardiovascular disease morbidity and mortality, largely through increased use of lipid‐lowering therapies such as low‐density lipoprotein‐cholesterol (LDL‐C)‐lowering HMG‐CoA reductase inhibitors (statins) 1, 2, 3, 4. However, therapies targeting other lipid‐related risk factors are needed to address the residual risk of cardiovascular events that persists in many patients.…”

Section: Introductionmentioning

confidence: 99%

CYP‐mediated drug–drug interactions with evacetrapib, an investigational CETP inhibitor: in vitro prediction and clinical outcome

Cannady

Suico

Wang

et al. 2015

Brit J Clinical Pharma

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AimsEvacetrapib is a cholesteryl ester transfer protein (CETP) inhibitor under development for reducing cardiovascular events in patients with high risk vascular disease. CETP inhibitors are likely to be utilized as ‘add‐on’ therapy to statins in patients receiving concomitant medications, so the potential for evacetrapib to cause clinically important drug–drug interactions (DDIs) with cytochromes P450 (CYP) was evaluated.MethodsThe DDI potential of evacetrapib was investigated in vitro, followed by predictions to determine clinical relevance. Potential DDIs with possible clinical implications were then investigated in the clinic.Results In vitro, evacetrapib inhibited all of the major CYPs, with inhibition constants (K i) ranging from 0.57 µm (CYP2C9) to 7.6 µm (CYP2C19). Evacetrapib was a time‐dependent inhibitor and inducer of CYP3A. The effects of evacetrapib on CYP3A and CYP2C9 were assessed in a phase 1 study using midazolam and tolbutamide as probe substrates, respectively. After 14 days of daily dosing with evacetrapib (100 or 300 mg), midazolam exposures (AUC) changed by factors (95% CI) of 1.19 (1.06, 1.33) and 1.44 (1.28, 1.62), respectively. Tolbutamide exposures (AUC) changed by factors of 0.85 (0.77, 0.94) and 1.06 (0.95, 1.18), respectively. In a phase 2 study, evacetrapib 100 mg had minimal impact on AUC of co‐administered simvastatin vs. simvastatin alone with a ratio of 1.25 (1.03, 1.53) at steady‐state, with no differences in reported hepatic or muscular adverse events.ConclusionsTaken together, the extent of CYP‐mediated DDI with the potential clinical dose of evacetrapib is weak and clinically important DDIs are not expected to occur in patients taking concomitant medications.

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Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial

Cited by 3,042 publications

References 27 publications

Statin Use and Adverse Effects Among Adults >75 Years of Age: Insights From the Patient and Provider Assessment of Lipid Management (PALM) Registry

Statin Use and Adverse Effects Among Adults >75 Years of Age: Insights From the Patient and Provider Assessment of Lipid Management (PALM) Registry

Older type 2 diabetic patients are more likely to achieve glycaemic and cardiovascular risk factors targets than younger patients: analysis of a primary care database

CYP‐mediated drug–drug interactions with evacetrapib, an investigational CETP inhibitor: in vitro prediction and clinical outcome

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