Os bloqueadores dos receptores da angiotensina II (BRA-II) aumentam a incidência de infarto do miocárdio?
Florianópolis, SC
O editorial escrito por Verma e Strauss no
No estudo OPTIMAAL, 5.477 pacientes pós-IAM e com disfunção ventricular esquerda foram randomizados para losartan (50 mg/dia) ou captopril (150 mg/dia). Após um seguimento de 2,7 anos, houve um excesso de mortalidade no grupo losartan, entretanto, sem atingir significância estatística (18% vs 16%, p=0,07) e a incidência de IAM entre os grupos foi igual (14%).
No estudo VALIANT, 14.703 indivíduos pós-IAM foram randomizados para valsartan, captopril ou a combinação de ambos. Os resultados se mostraram neutros em termos do desfecho primário (morte) entre os 3 grupos. O número de indivíduos com IAM foi semelhante entre os grupos valsartan (820) e captopril (840), portanto, sem indicação estatisticamente significativa (16,7% vs 17,1%) de excesso entre os grupos.
Portanto, a hipótese apresentada pelos autores de excesso de mortalidade por IAM associada ao uso dos BRA-II peca pela tendenciosidade e pela análise incompleta. O cenário ideal para se testar tal hipótese seria o de um ensaio clínico com poder estatístico para detectar diferenças clinicamente relevantes, no caso específico, a incidência de infartos do miocárdio fatais e não-fatais, na comparação entre os BRA-II e os IECA. Os resultados dos estudos ONTARGET e TRANSCEND5 são aguardados para esclarecer ainda mais esta questão. Até lá, uma alternativa seria uma meta-análise6 com todos os estudos disponíveis realizada de forma isenta e não-enviesada.
Os IECA têm uma longa história de resultados positivos e de grande relevância clínica, incluindo a redução da incidência do infarto agudo do miocárdio em pacientes de alto risco cardiovascular. Os BRA-II, até aqui, não mostraram superioridade quando comparados aos IECA neste e em outros contextos, tais como na insuficiência cardíaca. Diante destes fatos, os IECA continuam sendo a primeira opção quando se trata de inibir o sistema-renina-angiotensina em busca de resultados relevantes para o paciente. Os BRA-II são úteis nos casos de intolerância (tosse e angioedema, principalmente) aos IECA. Estes casos ocorrem entre 5 a 20% dos casos de primeira exposição aos IECA, ou seja, pelo menos 80% dos indivíduos são tolerantes aos IECA e podem usá-los cronicamente. A afirmativa de que os BRA-II não são mais alternativos, mas "substitutos" dos IECA, não tem base científica sólida. Além disso, os aspectos de custo-efetividade devem ser considerados em um país como o Brasil, e também neste item, os IECA continuam sendo superiores aos BRA-II e, portanto, a primeira escolha.
1. Julius S, Kjeldsen SE,Weber M et al. VALUE Trial Group. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet 2004; 363: 2022-31.
2. Granger CB, McMurray JJ, Yusuf S et al. CHARM Investigators and Committees. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-alternative trial. Lancet. 2003; 362: 772-6.
3. Dickstein K, Kjekshus J. OPTIMAAL Steering Committee of the OPTIMAAL Study Group. Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Optimaal Trial in Myocardial Infarction with Angiotensin II Antagonist Losartan. Lancet. 2002; 360: 752-60.
4. Pfeffer MA, McMurray JJ, Velazquez EJ et al. Valsartan, captopril or both in myocardial infarction complicated by heart failure, left ventricular dysfunction or both. N Engl J Med. 2003; 349: 1893-906.
5. Teo K, Yusuf S, Anderson C et al. Rationale, design and baseline characteristics of 2 large, simple, randomised trials evaluating telmisartan, ramipril and their combination in high-risk patients: the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial/Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease (ONTARGET/TRANSCEND) trials. Am Heart J. 2004; 148: 52-61.
6. Lee VC, Rhew DC, Dylan M, Badamgarav E, Braustein GD, Weingarten SR. Meta-analysis: Angiotensin-Receptor blockers in chronic heart failure and high-risk acute myocardial infarction. Ann Intern Med. 2004; 141: 693-704.
Endereço para correspondência Mário Sérgio Soares de Azeredo Coutinho Rua Dr. Percy João de Borba 129 88036-200 - Florianópolis - SC E-mail:
Enviado em 21/01/2005
Aceito em 26/01/2005
Do angiotensin II receptor blockers (ARB-II) increase the incidence of myocardial infarction?
Florianópolis, SC - Brazil
The editorial written by Verma and Strauss in
In OPTIMAAL study, 5,477 post-AMI and left ventricular dysfunction patients were randomized for losartan (50 mg/day) or captopril (150 mg/day). After a 2.7-year follow-up, there was an excess of mortality in losartan group, but without reaching statistical significance (18% vs. 16%, p=0.07) and AMI incidence between groups was the same (14%).
In VALIANT study, 14,703 post-AMI individuals were randomized for valsartan, captopril or the combination of both. Results were shown neutral within limits of primary outcome (death) among the three groups. The number of AMI individuals was similar between valsartan (820) and captopril (840) groups, therefore, without statistically significant indication (16.7% vs. 17.1%) of excess between the groups.
Therefore, the hypothesis shown by the authors on mortality excess due to AMI associated to the use of ARB-II does wrong from tendenciousness and incomplete analysis. The ideal scenery to test such hypothesis would be the one of a clinical assay to detect clinically relevant differences, in the specific case, the incidence of fatal and non-fatal myocardial infarctions, in the comparison between ARB-IIs and ACEIs. Results from ONTARGET and TRANSCEND5 studies are expected to clarify that matter even more. By then, a decent alternative would be a meta-analysis6 with all available studies, in an impartial and non-oblique way.
ACEIs have a long positive history of positive results and great clinical relevance, including the reduction of acute myocardial infarction incidence among high cardiovascular risk patients. ARB-IIs, so far, have not shown superiority when compared to ACEIs in this and in other contexts, such as in heart failure. In the presence of such facts, ACEIs are still the best option when it comes to inhibit rennin-angiotensin system searching for relevant results for the patient. ARB-IIs are useful in cases of intolerance (especially cough and angioedema) to ACEIs. Those cases occur from 5 to 20% of the cases of first exposure to ACEIs, that is, at least 80% of the individuals are tolerant to ACEIs, and they can use them chronically. The affirmative that ARB-IIs are not alternative anymore, but "substitutes" for ACEIs, has no sound scientific basis. Besides, cost-effectiveness aspects must be considered in a country like Brazil, and also in this item, ACEIs remain superior to ARB-IIs and, therefore, the first choice.
1. Julius S, Kjeldsen SE,Weber M et al. VALUE Trial Group. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet 2004; 363: 2022-31.
2. Granger CB, McMurray JJ, Yusuf S et al. CHARM Investigators and Committees. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-alternative trial. Lancet. 2003; 362: 772-6.
3. Dickstein K, Kjekshus J. OPTIMAAL Steering Committee of the OPTIMAAL Study Group. Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Optimaal Trial in Myocardial Infarction with Angiotensin II Antagonist Losartan. Lancet. 2002; 360: 752-60.
4. Pfeffer MA, McMurray JJ, Velazquez EJ et al. Valsartan, captopril or both in myocardial infarction complicated by heart failure, left ventricular dysfunction or both. N Engl J Med. 2003; 349: 1893-906.
5. Teo K, Yusuf S, Anderson C et al. Rationale, design and baseline characteristics of 2 large, simple, randomised trials evaluating telmisartan, ramipril and their combination in high-risk patients: the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial/Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease (ONTARGET/TRANSCEND) trials. Am Heart J. 2004; 148: 52-61.
6. Lee VC, Rhew DC, Dylan M, Badamgarav E, Braustein GD, Weingarten SR. Meta-analysis: Angiotensin-Receptor blockers in chronic heart failure and high-risk acute myocardial infarction. Ann Intern Med. 2004; 141: 693-704.
Mário Sérgio Soares de Azeredo Coutinho Rua Dr. Percy João de Borba 129 88036-200 - Florianópolis, SC - Brasil E-mail:
Sent for publishing on 01/21/2005
Accepted on 01/26/2005