Impact of age and sex on primary preventive treatment for cardiovascular disease in the West Midlands, UK: cross sectional study
Cite this as: BMJ 2012;345:e4535
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Are statins necessary in very elderly patients?
The results reported by Sheppard et al are quite disturbing . In this study, although there was an increase in the prescription of statins up to the age of 74 years, after that age, the use of statins markedly decreased at general practices in United Kingdom. This is even more relevant, taking into account that the history of cardiovascular disease was progressively more common according to age, from 1% in those subjects aged between 40 and 44 years to 37% in those ≥85 years . In fact, in those patients aged between 70 and 74 years, in which the prescription of statins reached only 29% of patients, the proportion of patients with previous cardiovascular disease was 23% . But, can these results be extended to other clinical settings?
In a study performed with the aim to determine the differences according to age (≤65 years [mean age 55.6±6.8] versus >65 years [mean age 73.3±5.3]) in the clinical profile and management of outpatients with chronic ischemic heart disease attended by cardiologists in Spain, nearly 83% of patients were taking statins, without significant differences according to age . All these data indicate first that statins are clearly underused, not only in primary prevention but more importantly, in secondary prevention, and second, although in mid age and elderly the prescription of statins increases, in very elderly patients the use of statins dramatically decreases.
But, is this underuse of statins relevant in very elderly patients? Or in other words, is the use of statins associated with lesser outcomes in very elderly populations?
Unfortunately, the available evidence regarding this point is scarce . In a study including patients ≥80 years with a diagnosis of acute myocardial infarction, all-cause, cardiovascular and myocardial infarction mortalities were significantly lower in those who received statins treatment at discharge . In the JUPITER (Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) study, patients with an LDL-cholesterol <3.37 mmol/L (130 mg/dL), a high-sensitivity C-reactive protein levels ≥2.0 mg/L and without cardiovascular disease were randomly allocated to receive rosuvastatin 20 mg/daily or placebo. About 32% of patients were ≥70 years old. In this subgroup of patients, rosuvastatin reduced by 39% the risk of the primary end point, the occurrence of a first cardiovascular event (HR 0.61 95% CI 0.46-0.82; P < 0.001). Remarkably, no significant heterogeneity was found in treatment effects by age. However, absolute reductions in event rates were greater in older persons. Importantly, rates of any adverse event were similar in statin and placebo groups .
Although it is evident that there is a need to define the cost, benefit, and risk of statin use in the very elderly population , available evidence suggests that reducing LDL-cholesterol to targets appears beneficial and safe in very elderly population, as current guidelines recommend . Therefore, more efforts are needed to emphasize the use of statins in elderly population.
1. Sheppard JP, Singh S, Fletcher K, McManus RJ, Mant J. Impact of age and sex on primary preventive treatment for cardiovascular disease in the West Midlands, UK: cross sectional study. BMJ. 2012;345:e4535. doi: 10.1136/bmj.e4535.
2. Barrios V, Escobar C, Murga N, Quijano JJ. Clinical profile and management of patients with chronic ischemic heart disease according to age in the population daily attended by cardiologists in Spain The ELDERCIC study. Eur J Intern Med. 2010;21:180-4.
3. Gravina CF, Bertolami M, Rodrigues GH. Dyslipidemia: evidence of efficacy of the pharmacological and non-pharmacological treatment in the elderly. J Geriatr Cardiol. 2012;9:83-90.
4. Gränsbo K, Melander O, Wallentin L, Lindbäck J, Stenestrand U, Carlsson J, Nilsson J. Cardiovascular and cancer mortality in very elderly post-myocardial infarction patients receiving statin treatment. J Am Coll Cardiol. 2010;55:1362-9.
5. Glynn RJ, Koenig W, Nordestgaard BG, Shepherd J, Ridker PM. Rosuvastatin for primary prevention in older persons with elevated C-reactive protein and low to average low-density lipoprotein cholesterol levels: exploratory analysis of a randomized trial. Ann Intern Med. 2010;152:488-96.
6. Chokshi NP, Messerli FH, Sutin D, Supariwala AA, Shah NR. Appropriateness of Statins in Patients Aged ≥80 Years and Comparison to Other Age Groups. Am J Cardiol. 2012 Aug 14. [Epub ahead of print]
7. Reiner Z, Catapano AL, De Backer G, Graham I, Taskinen MR, Wiklund O, et al. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J. 2011;32:1769-818.
Competing interests: None declared
Hospital Ramon y Cajal, Carretera de Colmenar Vievo, Km 9,100, 28034, Madrid, Spain
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Sheppard et al report an interested study describing differences in prescribing by age and sex for patients without cardiovascular disease in primary care1. Readers might be interested to cross reference this study with existing literature. The results confirm from a study published in 2004 examining age inequalities in primary prevention for coronary heart disease in UK general practices. This study found that compared with patients aged <75 years, older patients were significantly less likely to have a serum cholesterol level recorded, to be on lipid lowering drugs and to have well controlled blood pressure2.
Secondly, the authors state that cardiovascular risk calculators have only been validated for patients under 75 years. This is indeed true for Framingham and ASSIGN and the original version of QRISK2 (2008). However subsequent versions of QRISK2 have been published and validated in patients aged 30-84 years3 4 (although the second article was published after the authors had submitted their article).
1. Sheppard JP, Singh S, Fletcher K, McManus RJ, Mant J. Impact of age and sex on primary preventive treatment for cardiovascular disease in the West Midlands, UK: cross sectional study. BMJ 2012;345.
2. Hippisley-Cox J, Pringle M, Coupland C, Cater R, A. M. Coronary heart disease prevention and age inequalities: the first year of the National Service Framework for CHD. BJGP 2005;514:369-75.
3. Hippisley-Cox J, Coupland C, Robson J, Brindle P. Derivation, validation, and evaluation of a new QRISK model to estimate lifetime risk of cardiovascular disease: cohort study using QResearch database. BMJ 2010;341:c6624.
4. Collins GS, Altman DG. Predicting the 10 year risk of cardiovascular disease in the United Kingdom: independent and external validation of an updated version of QRISK2. BMJ 2012;344.
Competing interests: Author of QISK2 algorithm. Medical director of ClinRisk Ltd which provides open and close source software to implement QRISK2 ino clinical practice.
University of Nottingham, University of Nottingham
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I would like to join the discussion, about the impact of sex on primary preventive treatment for cardiovascular disease, by providing our own data. In agreement with the view of Emberson, J1, concluding that the greatest benefit from taking statins is obtained when the levels of C-Reactive Protein (CRP) are elevated, as well as, with observations from Gutierrez J2 about the lower preventive efficacy of statins in women, our data, obtained from a study in a small sample of outpatients on Clozapine, an agent that consistently elevates CRP levels, and a following up longer than 2 years, women had CRP values below those of men, 2.9 ± 3.3 vs 5.4 ± 5.1 mg/dL, which would explain, according to conclusions of Emberson J, the observations made for Gutierrez J about the lower preventive effect of statin therapy in women and that would be caused by their lower levels of CRP, as we describe below in a brief summary of our research:
OBJECTIVE: Quantify the relative risk of thrombovascular events in patients on Clozapine, according to their CRP levels.
METHODS: Sample of 26 outpatients (68% men, 43 ± 2 years old) on clozapine for at least 2 years. The experimental data of CRP and Prolactin plus those from “Emerging Risk Factors Collaboration”3 and “Copenhagen General Population Study”4 studies, were used to calculate the risk of thrombovascular events.
RESULTS: CRP= 4.71±4.7 mg/dL, Prolactin = 523 ± 537 μIU/ml. According to the results, the patients were grouped according to their overall risk, in: low risk, CRP <1 (19%), moderate risk, 1 CONCLUSIONS: Patients on Clozapine have, therefore, a higher risk for venous thromboembolism events than for cardiovascular disease or stroke, as many authors have published. REFERENCES
1. Heart Protection Study Collaborative Group. C-reactive protein concentration and the vascular benefits of statin therapy: an analysis of 20 536 patients in the Heart Protection Study. Lancet, 2011;377 (9764): 469 76.
2. Gutierrez et al. Statin Therapy in the Prevention of Recurrent Cardiovascular Events. Arch Intern med, 2012; 172 (12):909-19
3.. The Emerging Risk Factors Collaboration. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis.
Lancet. 2010; 375 (9709):132-40.
4.. Zacho J, Tybjærg-Hansen A, Nordestgaard BG. C-reactive protein and risk of venous thromboembolism in the general population. Arterioscler Thromb Vasc Biol 2010; 1672-8.
CONCLUSIONS: Patients on Clozapine have, therefore, a higher risk for venous thromboembolism events than for cardiovascular disease or stroke, as many authors have published.
Competing interests: None declared
Hospital Real Ntra Sra de Gracia, Ramon y cajal 60 50004 Zaragoza (Spain)
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The recently published contribution from Sheppard and colleagues1 provides interesting findings concerning older patients. Given a lack of clarity on eligibility and a lack of data concerning prescribing and outcomes in those aged 75 years and over, they suggest a very real public health need in this group.
I would, however, question their presentation of data in the 40 to 74 year age group. Specifically, I worry about their use of the whole population, not eligible, as the denominator for primary prevention prescribing. Is this informative? Concentrating on statins, current UK guidelines focus on ≥ 20 percent risk of a CVD event in ten years as the central threshold for statin eligibility.2 All procedures, no matter how small, possess an opportunity cost. Guidelines, therefore, promote cost-effectiveness, and also prevent unnecessary exposure to harm. Not basing findings on this eligible group may limit their use to public health, making them somewhat abstract. We have no baseline estimate of global CVD risk, and therefore need. This leaves it necessary to unpack the relevance of the findings from the younger ages. The presentation of anti-hypertensive prescribing in a ‘general’ population, especially given a failure to exclude patients with hypertension, strikes me as even more difficult to relate to practice.
In order to make population health gains using a screening strategy such as the NHS Health Check programme – currently employed in England, high prescribing amongst eligible patients is vital.3 It is unlikely, given age-stratified estimates of statin eligibility in the primary prevention population,4 that the levels of prescribing presented by Shepphard and colleagues will make the required impact. One can, for example, expect a considerable proportion of the 70 to 74 years group to be eligible:4 the quoted 29 percent prescribing represents poor coverage. Their choice of methods does, however, hinder the ease of this important comparison.
Findings using similar data offer a clearer view, with estimates of 45 percent statin prescribing in eligible patients following a NHS Health Check. 5 Given the recent formalisation of CVD primary prevention, during the study period described by Shepphard et al., previous findings, in conjunction with those extracted from the research here point to one important conclusion. If the NHS Health Check programme is to be effective, rates of intervention must increase. This is, after all, a risk assessment and risk management programme. If this cannot be achieved in near future, one must quickly begin to question the merit of this costly programme.3
1. Sheppard JP, Singh S, Fletcher K, McManus RJ, Mant J. Impact of age and sex on primary preventive treatment for cardiovascular disease in the West
Midlands, UK: cross sectional study. BMJ 2012;345.
4. Dalton ARH, Soljak M, Samarasundera E, Millett C, Majeed A. Prevalence of cardiovascular disease risk amongst the population eligible for the NHS
Health Check Programme. European journal of cardiovascular prevention and rehabilitation: 2011.
5. Dalton ARH, Bottle A, Okoro C, Majeed A, Millett C. Uptake of the NHS Health Checks programme in a deprived, culturally diverse setting:
cross-sectional study. Journal of Public Health 2011;33(3):422-29.
Competing interests: None declared
Imperial College London, The Reynold Building, St Dunstan's Road, London, W6 8RP
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