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BIBLIOGRAFIA 1. Wald N J, Law MR. A Strategy to reduce cardiovascular disease by more than 80% BMJ 2003; 326:1419-29 2. British Medical Association, Royal Pharmaceutical Society of Great Britain. British national formulary. London: BMA, RPS, 2002. (No 44.) 3. Law MR, Wald NJ, Thompson SG. By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischaemic heart disease? BMJ 1994;308: 367-72. 4. Homocysteine Lowering Triallists Collaboration. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. BMJ 1998;316: 894-8. 5. Wald DS, Bishop L, Wald NJ, Law M, Hennessy E, Weir D, et al. Randomized trial of folic acid supplementation and serum homocysteine levels. Arch Intern Med 2001;161: 695-700. 6. Law MR, Wald NJ, Morris JK, Jordan R. Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials. BMJ 2003;326: 1427-31 7. ISIS-2 Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988;ii: 349-59. 8. Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002;360: 1903-13 9. Law MR, Wald NJ, Morris JK. Lowering blood pressure to prevent myocardial infarction and stroke: a new prevention strategy. Health Technol Assess (in press). 10.MR, Wald NJ. Risk factor thresholds: their existence under scrutiny. BMJ 2002;324:1570-6. 11. Antithrombotic Trialists' Collaboration. Collaborative meta- analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002;324: 71-86. 12. Antiplatelet Trialists' Collaboration. Collaborative overview of randomised trials of antiplatelet therapy. I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. BMJ 1994;308: 81-105 13. Law MR, Watt HC, Wald NJ. The underlying risk of death after myocardial infarction in the absence of treatment. Arch Intern Med 2002;162: 2405-10. 14. Law MR, Wald NJ, Thompson SG.By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischaemic heart disease? BMJ 1994; 308:367/72 15. Homocysteine Lowering Triallist Collaboration. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. BMJ 1998; 316:894/8 16.Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of indivisual data for one million adults in 61 prospective studies. Lancet 2002; 360:1903-13 17. ISIS-2 Collaborative Group. Randomised trial of intravenosus streptokinase, oral aspirin, both or neither among 17.187 cases of suspected acute myocardial infarction : ISIS - 2 Lancet 1998; ii:349-59 18. Sachs FM, Pfeffer MA, Moye LA et Al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 1996;335:1001-9 11

12 Nel Settembre di quest'anno dopo aver letto l'articolo di Wald e Law il Giornale Italiano di Cardiologia Pratica /Italian Journal of Practice Cardiology ha ritenuto utile interpellare alcuni esponenti della Cardiologia Italiana per chiedere il loro parere in merito a questo Lavoro, certamente inusuale e per alcuni versi "innovativo". Pubblichiamo qui di seguito le prime risposte pervenuteci, ripromettendoci di continuare anche nel prossimo numero del Giornale. Profittiamo, comunque, per chiedere a tutti i nostri lettori il loro parere che sarà ben accolto e che ci aiuterà a far chiarezza su un tema cosi difficile. After having read the article by Wald and Law in the September issue, the editorial office of Giornale Italiano di Cardiologia Pratica/Italian Journal of Practice Cardiology thought it would be interesting to contact some of the Italian experts in cardiology and ask them for their opinion about this certainly unusual and in some ways “innovative” Paper. The first answers we received are published here below, and others will be published on the next issue of the Journal. However, we also ask all our readers to express their opinion, which will be welcome and much appreciated, and will contribute to clarifying such a difficult question. G.F. Gensini, A.A. Conti Dipartimento di Area Critica Medico Chirurgica - Università degli Studi di Firenze. Fondazione Don Carlo Gnocchi, IRCCS Firenze. Centro Italiano per la Medicina Basata sulle Prove, Firenze Corresponding author: Gian Franco Gensini Direttore Dipartimento Area Critica Medico Chirurgia - Università di Firenze Via P. della Valle,1 - 50139- Firenze Tel. 055-4360976, E-mail gensini@dfc.unifi.ite Prevenzione e terapia cardiovascolare tra evidenze, sogni ed incubi. L’articolo di NJ Wald e MR Law recentemente pubblicato sul British Medical Journal, in cui gli Autori lanciano l’idea di una nuova strategia di riduzione e contenimento del carico delle malattie cardiovascolari, ci è apparso subito un incubo, piuttosto che un sogno di mezza estate (1). In effetti, la proposta della cosiddetta “Polypill”, la super pillola contenente 6 principi attivi mirati alla prevenzione e alla terapia cardiovascolare globale, per quanto sia il risultato di una “simulazione”, potenzialmente racchiude notevoli rischi. Gli Autori hanno quantificato l’efficacia e la sicurezza di una formulazione contenente acido acetilsalicilico (75 mg), una statina (atorvastatina 10 mg o simvastatina 40 mg), tre anti-ipertensivi (selezionati in una rosa di cinque comprendenti un tiazidico, un beta-bloccante, un ACE-inibitore, un antagonista del recettore dell’angiotensina II e un calcio-antagonista, ognuno a dosaggio standard dimezzato) e 0,8 mg di acido folico. Wald e Law hanno stimato, nella loro “simulazione” ricavata dai dati presenti in letteratura, che la Polypill sarebbe in grado di ridurre gli eventi coronarici ischemici dell’88% (IC al 95%: da 84% a 91%) e gli eventi cerebrovascolari acuti dell’80%

BIBLIOGRAFIA<br />

1. Wald N J, Law MR. A Strategy to reduce cardiovascular disease by more than 80%<br />

BMJ 2003; 326:1419-29<br />

2. British Medical Association, Royal Pharmaceutical Society of Great Brita<strong>in</strong>. British national<br />

formulary. London: BMA, RPS, 2002. (No 44.)<br />

3. Law MR, Wald NJ, Thompson SG. By how much and how quickly does reduction <strong>in</strong> serum<br />

cholesterol concentration lower risk of ischaemic heart disease? BMJ 1994;308: 367-72.<br />

4. Homocyste<strong>in</strong>e Lower<strong>in</strong>g Triallists Collaboration. Lower<strong>in</strong>g blood homocyste<strong>in</strong>e with folic<br />

acid based supplements: meta-analysis of randomised trials. BMJ 1998;316: 894-8.<br />

5. Wald DS, Bishop L, Wald NJ, Law M, Hennessy E, Weir D, et al. Randomized trial of<br />

folic acid supplementation and serum homocyste<strong>in</strong>e levels. Arch Intern Med 2001;161:<br />

695-700.<br />

6. Law MR, Wald NJ, Morris JK, Jordan R. Value of low dose comb<strong>in</strong>ation treatment with<br />

blood pressure lower<strong>in</strong>g drugs: analysis of 354 randomised trials. BMJ 2003;326:<br />

1427-31<br />

7. ISIS-2 Collaborative Group. Randomised trial of <strong>in</strong>travenous streptok<strong>in</strong>ase, oral aspir<strong>in</strong>,<br />

both or neither among 17,187 cases of suspected acute myocardial <strong>in</strong>farction: ISIS-2.<br />

Lancet 1988;ii: 349-59.<br />

8. Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular<br />

mortality: a meta-analysis of <strong>in</strong>dividual data for one m<strong>il</strong>lion adults <strong>in</strong> 61 prospective<br />

studies. Lancet 2002;360: 1903-13<br />

9. Law MR, Wald NJ, Morris JK. Lower<strong>in</strong>g blood pressure to prevent myocardial <strong>in</strong>farction<br />

and stroke: a new prevention strategy. Health Technol Assess (<strong>in</strong> press).<br />

10.MR, Wald NJ. Risk factor thresholds: their existence under scrut<strong>in</strong>y. BMJ 2002;324:1570-6.<br />

11. Antithrombotic Trialists' Collaboration. Collaborative meta- analysis of randomised trials<br />

of antiplatelet therapy for prevention of death, myocardial <strong>in</strong>farction, and stroke <strong>in</strong> high<br />

risk patients. BMJ 2002;324: 71-86.<br />

12. Antiplatelet Trialists' Collaboration. Collaborative overview of randomised trials of antiplatelet<br />

therapy. I: Prevention of death, myocardial <strong>in</strong>farction, and stroke by prolonged<br />

antiplatelet therapy <strong>in</strong> various categories of patients. BMJ 1994;308: 81-105<br />

13. Law MR, Watt HC, Wald NJ. The underly<strong>in</strong>g risk of death after myocardial <strong>in</strong>farction<br />

<strong>in</strong> the absence of treatment. Arch Intern Med 2002;162: 2405-10.<br />

14. Law MR, Wald NJ, Thompson SG.By how much and how quickly does reduction <strong>in</strong> serum<br />

cholesterol concentration lower risk of ischaemic heart disease? BMJ 1994;<br />

308:367/72<br />

15. Homocyste<strong>in</strong>e Lower<strong>in</strong>g Triallist Collaboration. Lower<strong>in</strong>g blood homocyste<strong>in</strong>e with folic<br />

acid based supplements: meta-analysis of randomised trials. BMJ 1998; 316:894/8<br />

16.Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to<br />

vascular mortality: a meta-analysis of <strong>in</strong>divisual data for one m<strong>il</strong>lion adults <strong>in</strong> 61 prospective<br />

studies. Lancet 2002; 360:1903-13<br />

17. ISIS-2 Collaborative Group. Randomised trial of <strong>in</strong>travenosus streptok<strong>in</strong>ase, oral aspir<strong>in</strong>,<br />

both or neither among 17.187 cases of suspected acute myocardial <strong>in</strong>farction : ISIS<br />

- 2 Lancet 1998; ii:349-59<br />

18. Sachs FM, Pfeffer MA, Moye LA et Al. The effect of pravastat<strong>in</strong> on coronary events after<br />

myocardial <strong>in</strong>farction <strong>in</strong> patients with average cholesterol levels. N Engl J Med<br />

1996;335:1001-9<br />

11

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