- Email: [email protected]
Limitations of the utilization of cardiovascular risk tables and statins
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Letters to the Editor / Med Clin (Barc). 2015;144(7):332–335
is diagnosed at advanced stages, as occurred in our case. Nevertheless, the prognosis of these patients is favourable if they are treated with adequate chemotherapy. References 1. Ferreri A, Govi S, Pileri S, Savage K. Anaplastic large cell lymphoma, ALK-positive. Crit Rev Oncol Hematol. 2012;83:293–302. 2. Zhang Y, Wang J, Huang J, Qian J, Jin J. Anaplastic large cell lymphoma presenting as an endobronchial polypoid mass. Leuk Lymphoma. 2012;53:2078–9. 3. Chen SC, Shih CM, Su JL, Yeh SP, Chen CH, Tseng GC, et al. Anaplastic largecell lymphoma presenting as an endobronchial polypoid tumor. J Clin Oncol. 2008;26:4845–7. 4. Escobosa OM, Herrero A, Acha T. Linfoma anaplásico de células grandes endobronquial en la infancia. An Pediatr (Barc). 2009;70:449–52. 5. Guerra J, Echevarria-Escudero M, Barrio N, Velez-Rosario R. Primary endobronchial anaplastic large cell lymphoma in a pediatric patient. P R Health Sci J. 2006;25:159–61. 6. Barthwal MS, Deoskar RB, Falleiro JJ, Singh P. Endobronchial non-Hodgkin’s lymphoma. Indian J Chest Dis Allied Sci. 2005;47:117–20. 7. Bhalla R, McClure S. Pathologic quiz case: a 17-year-old adolescent girl with a short history of dyspnea. Arch Pathol Lab Med. 2003;127:e430–1.
Limitations of the utilization of cardiovascular risk tables and statins夽 Limitaciones en la utilización de las tablas de riesgo cardiovascular y de las estatinas Dear Editor, We hope you allow us to present our point of view on 2 important aspects of cardiovascular prevention. On the one hand, regarding the limitations on the use of risk charts, and on the other hand, regarding the excesses in the use of statins. The status of cardiovascular prevention in Spain, especially of the health care process and not so much of the health results, is increasingly known thanks to the studies like the one by RoyoBordonada et al., recently published in your magazine.1 This study states that all the autonomous communities have a cardiovascular prevention programme and/or clinical practice guideline and that they calculate the risk preferably with SCORE charts. With the purpose of facilitating their interpretation and usage, we have performed a SCORE risk calculator from the algebraic function of the original article, to which we have incorporated a bar chart that allows the physician and the assessed person to visualise the percentages of: (a) baseline risk; (b) added risk associated with risk factors; and (c) survivors. This can be obtained at evalmed.es, in the “Training” (Formación) tab.2 Having said that, we cannot forget that the SCORE prognostic equations are extracted from a “cohort of extraction,” and they need to be validated in one or more cohorts of validation, and, in Spain, they have not been validated in a “cohort of validation” representative of the entire Spanish population of 40 to 65 years,3 which is why there is a scientific uncertainty regarding their validity. The study that was nearest to validation in Spain was conducted by Buitrago Ramírez et al. in a cohort of 608 patients from a healthcare centre in Badajoz, without cardiovascular disease at the beginning, in which they analysed the adequacy between the events expected by the Framingham-REGICOR and SCORE charts and the actual episodes occurred throughout 10 years.4,5 In regards
夽 Please cite this article as: Palomo L, Sánchez-Robles G. Limitaciones en la utilización de las tablas de riesgo cardiovascular y de las estatinas. Med Clin (Barc). 2015;144:334–335.
8. Kim DH, Ko YH, Lee MH, Ree HJ. Anaplastic large cell lymphoma presenting as an endobronchial polypoid mass. Respiration. 1998;65:156–8. 9. Liao WP, Dai MS, Hsu LF, Yao NS. Anaplastic large-cell lymphoma primarily infiltrating femoral muscles. Ann Hematol. 2005;84:764–6. 10. Minoo P, Wang HY. ALK-immunoreactive neoplasms. Int J Clin Exp Pathol. 2012;5:397–410.
Paola Zuluaga a,∗ , Salvador Martí a , José Tomás Navarro b , Edwin Mejía c a Servicio de Medicina Interna, Hospital Universitario Germans Trias i Pujol, Badalona, Barcelona, Spain b Servicio de Hematología, Hospital Universitario Germans Trias i Pujol, Badalona, Barcelona, Spain c Servicio de Anatomía patológica, Hospital Universitario Germans Trias i Pujol, Badalona, Barcelona, Spain ∗ Corresponding author. E-mail address: [email protected] (P. Zuluaga).
to the SCORE chart, they obtained the flowing validity values (95% confidence interval [95% CI]): positive predictive value 10.7% (95% CI 5–21.5); negative predictive value 99.5% (95% CI 98.4–99.8); sensitivity 66.7% (95% CI 35.4–87.9); specificity 91.7% (95% CI 89.2–93.6); positive Bayes factor 8. The positive predictive value of 10.7% means there is an overdiagnosis (risk overestimation), since 89.3% of the patients catalogued as “high risk” patients do not suffer from an episode of cardiovascular mortality. And if they had been treated with drugs, they would have been overmedicated. On the other hand, the notion of “risk” is a probability function (validated algebraic) in a determined unit of time. A risk of cardiovascular mortality of 4% in 10 years indicates that out of 100 individuals with similar conditions, in a 10-year period, 4 are may die due to cardiovascular causes and 96 may not. The risk function is categorical (4 out of 100 individuals will and 96 will not) and not continuous, i.e., it should not be interpreted that each one of the 100 individuals has a risk of 4%. In regards to the recommendations to use statins for the prevention of cardiovascular risk, sometimes they are based on wrong calculations as the one we have mentioned. In a recent meta-analysis, Savarese et al.6 assessed 5 health results that are important for patients: mortality for any cause, mortality for cardiovascular cause, acute myocardial infarction (AMI), cerebrovascular accident (CVA) and new cancer diagnosis. The study was not carried out on all the cohorts of intervention and control of the reviewed clinical trials, but on the subgroups of older people, so the quality of the evidence found is reduced. We have detected a calculation error that may alter your conclusions. A number needed to treat (NNT) of 24/year for infarction is erroneously highlighted, when from your own calculations an NNT of 240/year is inferred. Moreover, an NNT of 42/year for strokes is erroneously highlighted, when from your own calculations an NNT of 408/year is inferred. The statistically significant differences in favour of the statins group would be the following: (1) AMI, since in a 3.5-year followup there was 0.64% of episodes/year in the statins group vs 1.06% of episodes/year in the placebo group; RR 0.61 (95% CI 0.43–0.85); ARR 0.42% (95% CI 0.16–0.6); NNT 240 (95% CI 167–618) per year, whose magnitude of effect is estimated as low in accordance with the GRADE7 assessment criteria, and (2) CVA, since in a 3.5-year followup there was 0.78% episodes/year in the statins group vs 1.03% episodes/year in the placebo group; RR 0.76 (95% CI 0.63–0.93); ARR 0.24% (95% CI 0.08–0.38); NNT 408 (95% CI 260–1.314) per
Letters to the Editor / Med Clin (Barc). 2015;144(7):332–335
year, whose magnitude of effect is estimated as very low. No statistically significant differences were found in mortality for any cause, mortality for cardiovascular cause and new cancer diagnosis. These clarifications may help the reader situate the cardiovascular risk charts in a scale more adjusted to their scientific validity. The usefulness of cardiovascular risk charts is sometimes overdimensioned and they are even used for diagnosis purposes. If we try to lessen a misinterpreted risk by adding a statin based on calculations that are also erroneous, we will be scaring the patients and submitting them to the adverse effects of a medication they do not need. References 1. Royo-Bordonada MA, Lobos JM, Brotons C, Villar F, Pablo C, Armario P, ˜ Med Clin (Barc). et al. El estado de la prevención cardiovascular en Espana. 2014;142:7–14. 2. Grupo evalmed-GRADE. Resumen analítico del proyecto SCORE: Estimación ˜ en Europa. Evalmed [elecdel riesgo de mortalidad cardiovascular en 10 anos tronic journal]; 2014. Available from: http://evalmedicamento.weebly.com/ 6/post/2014/03/resumen-analtico-del-proyecto-score-estimacin-del-riesgo-demortalidad-cardiovascular-en-10-aos-en-europa.html [consulted 25.04.14]. 3. Brotons C, Moral I, Soriano N, Cuixart L, Osorio D, Bottaro L, et al. Impacto de la utilización de las diferentes tablas SCORE en el cálculo del riesgo cardiovascular. Rev Esp Cardiol. 2014;67:94–100.
335
˜ 4. Buitrago Ramírez F, Canón Barroso L, Díaz Herrera N, Cruces Muro E, Bravo Simón B, Pérez Sánchez I. Comparación entre la tabla del SCORE y la función de Framingham-REGICOR en la estimación del riesgo cardiovascular en una ˜ población urbana seguida durante 10 anos. Med Clin (Barc). 2006;127:368–73. ˜ 5. Buitrago Ramírez F, Canón Barroso L, García-Nogales A. Criterios de validez y validación de las funciones de riesgo SCORE y REGICOR en la población de un centro de salud urbano. Rev Esp Salud Publica. 2010;84:335–8. 6. Savarese G, Gotto AM Jr, Paolillo S, D’Amore C, Losco T, Musella F, et al. Benefits of statins in elderly subjects without established cardiovascular disease: a metaanalysis. J Am Coll Cardiol. 2013;62:2090–9. ˜ Barrientos A, Baquero Barroso MJ, Rubio Núnez ˜ PL, 7. Álvarez-Cienfuegos A, Montano Candela Marroquín E, Gavilán Moral E, et al. ¿Es clínicamente relevante además ˜ [revista de estadísticamente significativo? Boletín Terapéutico Extremeno electrónica]; 2012, pp. 3. Available from: http://dl.dropboxusercontent.com/ u/20268175/20120915-BTE%20%C2%BFEs%20cl%C3%ADnicam%20relev%20adem %C3%A1s%20estad%20signif%C2%BF.pdf [consulted 25.04.14].
Luis Palomo a,∗ , Galo Sánchez-Robles b a b
Centro de Salud “Zona Centro”, Cáceres, Spain Centro de Salud Manuel Encinas, Cáceres, Spain
∗ Corresponding author. E-mail addresses: [email protected], [email protected] (L. Palomo).
Letters to the Editor / Med Clin (Barc). 2015;144(7):332–335
is diagnosed at advanced stages, as occurred in our case. Nevertheless, the prognosis of these patients is favourable if they are treated with adequate chemotherapy. References 1. Ferreri A, Govi S, Pileri S, Savage K. Anaplastic large cell lymphoma, ALK-positive. Crit Rev Oncol Hematol. 2012;83:293–302. 2. Zhang Y, Wang J, Huang J, Qian J, Jin J. Anaplastic large cell lymphoma presenting as an endobronchial polypoid mass. Leuk Lymphoma. 2012;53:2078–9. 3. Chen SC, Shih CM, Su JL, Yeh SP, Chen CH, Tseng GC, et al. Anaplastic largecell lymphoma presenting as an endobronchial polypoid tumor. J Clin Oncol. 2008;26:4845–7. 4. Escobosa OM, Herrero A, Acha T. Linfoma anaplásico de células grandes endobronquial en la infancia. An Pediatr (Barc). 2009;70:449–52. 5. Guerra J, Echevarria-Escudero M, Barrio N, Velez-Rosario R. Primary endobronchial anaplastic large cell lymphoma in a pediatric patient. P R Health Sci J. 2006;25:159–61. 6. Barthwal MS, Deoskar RB, Falleiro JJ, Singh P. Endobronchial non-Hodgkin’s lymphoma. Indian J Chest Dis Allied Sci. 2005;47:117–20. 7. Bhalla R, McClure S. Pathologic quiz case: a 17-year-old adolescent girl with a short history of dyspnea. Arch Pathol Lab Med. 2003;127:e430–1.
Limitations of the utilization of cardiovascular risk tables and statins夽 Limitaciones en la utilización de las tablas de riesgo cardiovascular y de las estatinas Dear Editor, We hope you allow us to present our point of view on 2 important aspects of cardiovascular prevention. On the one hand, regarding the limitations on the use of risk charts, and on the other hand, regarding the excesses in the use of statins. The status of cardiovascular prevention in Spain, especially of the health care process and not so much of the health results, is increasingly known thanks to the studies like the one by RoyoBordonada et al., recently published in your magazine.1 This study states that all the autonomous communities have a cardiovascular prevention programme and/or clinical practice guideline and that they calculate the risk preferably with SCORE charts. With the purpose of facilitating their interpretation and usage, we have performed a SCORE risk calculator from the algebraic function of the original article, to which we have incorporated a bar chart that allows the physician and the assessed person to visualise the percentages of: (a) baseline risk; (b) added risk associated with risk factors; and (c) survivors. This can be obtained at evalmed.es, in the “Training” (Formación) tab.2 Having said that, we cannot forget that the SCORE prognostic equations are extracted from a “cohort of extraction,” and they need to be validated in one or more cohorts of validation, and, in Spain, they have not been validated in a “cohort of validation” representative of the entire Spanish population of 40 to 65 years,3 which is why there is a scientific uncertainty regarding their validity. The study that was nearest to validation in Spain was conducted by Buitrago Ramírez et al. in a cohort of 608 patients from a healthcare centre in Badajoz, without cardiovascular disease at the beginning, in which they analysed the adequacy between the events expected by the Framingham-REGICOR and SCORE charts and the actual episodes occurred throughout 10 years.4,5 In regards
夽 Please cite this article as: Palomo L, Sánchez-Robles G. Limitaciones en la utilización de las tablas de riesgo cardiovascular y de las estatinas. Med Clin (Barc). 2015;144:334–335.
8. Kim DH, Ko YH, Lee MH, Ree HJ. Anaplastic large cell lymphoma presenting as an endobronchial polypoid mass. Respiration. 1998;65:156–8. 9. Liao WP, Dai MS, Hsu LF, Yao NS. Anaplastic large-cell lymphoma primarily infiltrating femoral muscles. Ann Hematol. 2005;84:764–6. 10. Minoo P, Wang HY. ALK-immunoreactive neoplasms. Int J Clin Exp Pathol. 2012;5:397–410.
Paola Zuluaga a,∗ , Salvador Martí a , José Tomás Navarro b , Edwin Mejía c a Servicio de Medicina Interna, Hospital Universitario Germans Trias i Pujol, Badalona, Barcelona, Spain b Servicio de Hematología, Hospital Universitario Germans Trias i Pujol, Badalona, Barcelona, Spain c Servicio de Anatomía patológica, Hospital Universitario Germans Trias i Pujol, Badalona, Barcelona, Spain ∗ Corresponding author. E-mail address: [email protected] (P. Zuluaga).
to the SCORE chart, they obtained the flowing validity values (95% confidence interval [95% CI]): positive predictive value 10.7% (95% CI 5–21.5); negative predictive value 99.5% (95% CI 98.4–99.8); sensitivity 66.7% (95% CI 35.4–87.9); specificity 91.7% (95% CI 89.2–93.6); positive Bayes factor 8. The positive predictive value of 10.7% means there is an overdiagnosis (risk overestimation), since 89.3% of the patients catalogued as “high risk” patients do not suffer from an episode of cardiovascular mortality. And if they had been treated with drugs, they would have been overmedicated. On the other hand, the notion of “risk” is a probability function (validated algebraic) in a determined unit of time. A risk of cardiovascular mortality of 4% in 10 years indicates that out of 100 individuals with similar conditions, in a 10-year period, 4 are may die due to cardiovascular causes and 96 may not. The risk function is categorical (4 out of 100 individuals will and 96 will not) and not continuous, i.e., it should not be interpreted that each one of the 100 individuals has a risk of 4%. In regards to the recommendations to use statins for the prevention of cardiovascular risk, sometimes they are based on wrong calculations as the one we have mentioned. In a recent meta-analysis, Savarese et al.6 assessed 5 health results that are important for patients: mortality for any cause, mortality for cardiovascular cause, acute myocardial infarction (AMI), cerebrovascular accident (CVA) and new cancer diagnosis. The study was not carried out on all the cohorts of intervention and control of the reviewed clinical trials, but on the subgroups of older people, so the quality of the evidence found is reduced. We have detected a calculation error that may alter your conclusions. A number needed to treat (NNT) of 24/year for infarction is erroneously highlighted, when from your own calculations an NNT of 240/year is inferred. Moreover, an NNT of 42/year for strokes is erroneously highlighted, when from your own calculations an NNT of 408/year is inferred. The statistically significant differences in favour of the statins group would be the following: (1) AMI, since in a 3.5-year followup there was 0.64% of episodes/year in the statins group vs 1.06% of episodes/year in the placebo group; RR 0.61 (95% CI 0.43–0.85); ARR 0.42% (95% CI 0.16–0.6); NNT 240 (95% CI 167–618) per year, whose magnitude of effect is estimated as low in accordance with the GRADE7 assessment criteria, and (2) CVA, since in a 3.5-year followup there was 0.78% episodes/year in the statins group vs 1.03% episodes/year in the placebo group; RR 0.76 (95% CI 0.63–0.93); ARR 0.24% (95% CI 0.08–0.38); NNT 408 (95% CI 260–1.314) per
Letters to the Editor / Med Clin (Barc). 2015;144(7):332–335
year, whose magnitude of effect is estimated as very low. No statistically significant differences were found in mortality for any cause, mortality for cardiovascular cause and new cancer diagnosis. These clarifications may help the reader situate the cardiovascular risk charts in a scale more adjusted to their scientific validity. The usefulness of cardiovascular risk charts is sometimes overdimensioned and they are even used for diagnosis purposes. If we try to lessen a misinterpreted risk by adding a statin based on calculations that are also erroneous, we will be scaring the patients and submitting them to the adverse effects of a medication they do not need. References 1. Royo-Bordonada MA, Lobos JM, Brotons C, Villar F, Pablo C, Armario P, ˜ Med Clin (Barc). et al. El estado de la prevención cardiovascular en Espana. 2014;142:7–14. 2. Grupo evalmed-GRADE. Resumen analítico del proyecto SCORE: Estimación ˜ en Europa. Evalmed [elecdel riesgo de mortalidad cardiovascular en 10 anos tronic journal]; 2014. Available from: http://evalmedicamento.weebly.com/ 6/post/2014/03/resumen-analtico-del-proyecto-score-estimacin-del-riesgo-demortalidad-cardiovascular-en-10-aos-en-europa.html [consulted 25.04.14]. 3. Brotons C, Moral I, Soriano N, Cuixart L, Osorio D, Bottaro L, et al. Impacto de la utilización de las diferentes tablas SCORE en el cálculo del riesgo cardiovascular. Rev Esp Cardiol. 2014;67:94–100.
335
˜ 4. Buitrago Ramírez F, Canón Barroso L, Díaz Herrera N, Cruces Muro E, Bravo Simón B, Pérez Sánchez I. Comparación entre la tabla del SCORE y la función de Framingham-REGICOR en la estimación del riesgo cardiovascular en una ˜ población urbana seguida durante 10 anos. Med Clin (Barc). 2006;127:368–73. ˜ 5. Buitrago Ramírez F, Canón Barroso L, García-Nogales A. Criterios de validez y validación de las funciones de riesgo SCORE y REGICOR en la población de un centro de salud urbano. Rev Esp Salud Publica. 2010;84:335–8. 6. Savarese G, Gotto AM Jr, Paolillo S, D’Amore C, Losco T, Musella F, et al. Benefits of statins in elderly subjects without established cardiovascular disease: a metaanalysis. J Am Coll Cardiol. 2013;62:2090–9. ˜ Barrientos A, Baquero Barroso MJ, Rubio Núnez ˜ PL, 7. Álvarez-Cienfuegos A, Montano Candela Marroquín E, Gavilán Moral E, et al. ¿Es clínicamente relevante además ˜ [revista de estadísticamente significativo? Boletín Terapéutico Extremeno electrónica]; 2012, pp. 3. Available from: http://dl.dropboxusercontent.com/ u/20268175/20120915-BTE%20%C2%BFEs%20cl%C3%ADnicam%20relev%20adem %C3%A1s%20estad%20signif%C2%BF.pdf [consulted 25.04.14].
Luis Palomo a,∗ , Galo Sánchez-Robles b a b
Centro de Salud “Zona Centro”, Cáceres, Spain Centro de Salud Manuel Encinas, Cáceres, Spain
∗ Corresponding author. E-mail addresses: [email protected], [email protected] (L. Palomo).