Amlodipine and enalapril in coronary disease

LETTER TO THE EDITOR

Universidade de Caxias do Sul, Caxias do Sul, RS - Brazil

Mailing address

Key words: Hypertension; coronary disease; enalaprilat; angiotensin-converting enzyme inhibitors.

Regarding the study "Combination of Amlodipine and Enalapril in Hypertensive Patients with Coronary Disease"¹, our group of research understands that the use of fixed associations, as the ones presented in this study, brings several advantages, especially regarding the good patient adherence when taking the medication and the possibility of using two drugs at smaller final doses to attain the control of arterial pressure, which must result in a higher adherence to treatment², and, consequently, in better therapeutic results³.

However, there are situations, such as in ischemic cardiopathy and diabetes mellitus, in which the "therapeutic space" corresponding to the arterial pressure must be used to attain the ideal dose of certain drugs before hypotension occurs⁴.

In the present case, to use higher doses of second-generation calcium channel blockers can be interesting to control angina, in case of ischemic cardiopathy, as well as the use of angiotensin-converting enzyme inhibitors for the secondary prevention of nephropathy. However, these are situations in which the association of other drugs can be troublesome.

Another important fact, from our point of view, is that the drugs that are involved in the association must have a similar half-life, so that the antihypertensive coverage is the same throughout the 24 hours of the day, with both drugs⁵.

References

1. Rienzo M, Saraiva JFK, Nogueira PR, Gomes EPSG, Moretti MA, Ferreira JFM, et al. Combinação de anlodipino e enalaprila em pacientes hipertensos com doença coronariana. Arq Bras Cardiol. 2009; 92 (3): 183-9.

2. Morris AB, Li J, Kroenke K, Bruner-England TE, Young JM, Murray MD. Factors associated with drug adherence and blood pressure control in patients with hypertension. Pharmacotherapy. 2006; 26 (4): 483-92.

3. Kettani FZ, Dragomir A, Cote R, Roy L, Berard A, Blais L, et al. Impact of a better adherence to antihypertensive agents on cerebrovascular disease for primary prevention. Stroke. 2009; 40 (1): 213-20.

4. Goncalves CB, Moreira LB, Gus M, Fuchs FD. Adverse events of blood-pressure-lowering drugs: evidence of high incidence in a clinical setting. Eur J Clin Pharmacol. 2007; 63 (10): 973-8.

5. Goodman LS, Gilman A, Brunton LL, Lazo JS, Parker KL. Goodman & Gilman's the pharmacological basis of therapeutics. 11th ed. New York: McGraw-Hill; 2006.

Response to Rosa et al

We understand that the benefit of certain antihypertensive drugs have a dose-dependent effect, as in the case of the angiotensin-converting enzyme inhibitors (ACEI) in diabetic patients, especially when one evaluates the progression of diabetic nephropathy, regardless of the presence or absence of systemic arterial hypertension^1,2. However, this was not the objective of our study. Moreover, in the studied sample, there was a small prevalence of diabetic patients (only two patients in group A [6.3%]).

Regarding the benefits of calcium-channel antagonists from the dihydropyridine group in chronic ischemic heart disease, in addition to the already established anti-angina effect of this type of medication, Amlodipine has also shown to be beneficial when compared to placebo and enalapril maleate, when evaluating the decrease in cardiovascular events and the progression of atherosclerosis in patients with normal blood pressure³.

Regarding the half-life of the drugs used in our study, the blood pressure was always measured in the morning, before the medication was taken, therefore at the lowest point of its effect and thus, we obtained excellent pressure control: diastolic arterial pressure < 85 mmHg in 93.8%-95.0% of the cases in groups A and B (p=ns), respectively, and systolic arterial pressure (mean ± SD) of 127.7 + 13.4 and 125.3 + 12.6 mmHg in groups A and B, respectively (p = 0.45).

Considering the results of the recently published ACCOMPLISH study⁴, which compared the fixed combination of ACEI (benazepril) and calcium-channel antagonist (Amlodipine) and showed a decrease in the cardiovascular morbimortality in hypertensive patients with chronic coronary disease that used the first fixed combination, it can be observed that the association of the two classes of drugs used in our study adds a benefit beyond the expected one, due to the frank decrease in blood pressure, subsequently demonstrated by the Ambulatory Blood Pressure Monitoring sub-study in the patients from the ACCOMPLISH study⁵, which did not show any difference in the blood pressure measurement between the two treatment groups. One must bear in mind that benazepril has exactly the same pharmacokinetic profile of enalapril.

References

Resposta

Entendemos que o benefício de determinados fármacos anti-hipertensivos tem efeito dose-dependente, como é o caso dos inibidores da enzima conversora de angiotensina (IECA) nos pacientes diabéticos, sobretudo quando se avalia a progressão da nefropatia diabética, independentemente da presença ou não de hipertensão arterial sistêmica^1,2. Porém, esse não foi nosso objetivo nesse estudo. Além disso, na amostra estudada, havia uma pequena prevalência de pacientes diabéticos (apenas dois pacientes no grupo A [6,3%]).

Quanto aos benefícios dos antagonistas do canal de cálcio do grupo dos di-idropiridínicos na doença isquêmica crônica do coração, além do já estabelecido poder antianginoso deste tipo de medicamento, o anlodipino mostrou-se também benéfico, quando comparado ao placebo e ao maleato de enalaprila, ao se avaliar a redução de eventos cardiovasculares e a progressão da aterosclerose em pacientes com pressão arterial normal³.

Quanto à meia-vida dos fármacos utilizados em nosso estudo, a pressão arterial foi aferida sempre pela manhã, antes da tomada diária do medicamento, portanto no vale do seu efeito, e assim conseguimos excelente controle pressórico: pressão arterial diastólica menor ou igual a 85 mmHg em 93,8%-95,0% dos casos nos grupos A e B (p = ns), respectivamente, e pressão arterial sistólica (média + DP) de 127,7 + 13,4 e 125,3 + 12,6 mmHg nos grupos A e B, respectivamente (p = 0,45).

Considerando os resultados do estudo ACCOMPLISH⁴, recentemente publicado, que comparou a combinação fixa de IECA (benazeprila) e antagonista do canal de cálcio (anlodipino) com a combinação fixa de IECA e diurético (hidroclorotiazida), e que mostrou redução da morbimortalidade cardiovascular em pacientes hipertensos portadores de doença coronária crônica que utilizaram a primeira combinação fixa, vê-se que a associação das duas classes de fármacos utilizadas no nosso estudo acrescenta benefício além do esperado pela simples redução na pressão arterial, comprovado posteriormente pelo subestudo de Monitorização Ambulatorial da Pressão Arterial de 24 horas nos pacientes do estudo ACCOMPLISH⁵, que não evidenciou nenhuma diferença nas medidas de pressão arterial entre os dois grupos de tratamento. Deve-se ter em mente que a benazeprila tem exatamente o mesmo perfil farmacocinético da enalaprila.

Dr. Luiz Antônio Machado César

Referências

Amlodipine and enalapril in coronarydisease

Eduardo Maffini da Rosa, Carolina Fedrizzi el Andari, Marcio Fernando Spagnól

Publication Dates

• Publication in this collection
  28 Apr 2010
• Date of issue
  Mar 2010