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Secondary Prevention of Coronary Disease with ACE Inhibition-does Blood Pressure Reduction with Perindopril Explain the Benefits in EUROPA?

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Abstract

Aims

We determined whether blood pressure (BP) lowering by perindopril was related to its benefit in the EUROPA study.

Methods and results

Twelve thousand two hundred eighteen patients with documented coronary artery disease received perindopril 8 mg once daily or matching placebo after a 4-week run-in period in which all patients received perindopril. Patients were excluded if systolic (S) BP was >180 or <100 mmHg. Mean age was 60 years (range 26–89). 27% had a history of hypertension. After 4.2 years of follow-up, the primary endpoint (cardiovascular death, nonfatal myocardial infarction, or resuscitated cardiac arrest) was observed in 603 (9.9%) placebo versus 488 (8.0%) perindopril patients [20% relative risk reduction (RRR), CI 9–29%, P = 0.003]. There was no interaction between baseline SBP levels (using JNC-7 cutoff values) and treatment effect. If anything, the greatest RRR of the primary endpoint (32%) occurred in patients with the lowest SBP (<120 mmHg) in whom perindopril did not reduce SBP. Also, RRR during blinded treatment was comparable, irrespective of whether BP decreased or not or of the extent of BP reduction during perindopril treatment.

Conclusion

The treatment benefit in EUROPA cannot be fully explained by baseline BP or BP reduction with perindopril. Other mechanisms including direct anti-atherosclerotic effects of ACE inhibition may play a role.

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Conflict of interest

The EUROPA study was funded by Servier.

Drs Remme, Deckers, Fox, Ferrari, Bertrand, and Simoons declare having received research grants and honoraria from Servier.

Author information

Authors and Affiliations

  1. Sticares Cardiovascular Research Institute, P.O. Box 882, 3160 AB, Rhoon, The Netherlands

    Willem J. Remme

  2. Thoraxcenter, Erasmus Medical Center, Rotterdam, The Netherlands

    Jaap W. Deckers & Maarten L. Simoons

  3. Department of Cardiology, Royal Brompton Hospital, London, UK

    Kim M. Fox

  4. Cardiovascular Research Center, Salvatore Maugeri Foundation, IRCCS, University Hospital of Ferrara, Gussago, Bressia, Italy

    Roberto Ferrari

  5. Hopital Cardiologique, Lille, France

    Michel Bertrand

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  1. Willem J. Remme
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  2. Jaap W. Deckers
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  4. Roberto Ferrari
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  5. Michel Bertrand
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EUROPA Investigators

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Correspondence to Willem J. Remme.

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Remme, W.J., Deckers, J.W., Fox, K.M. et al. Secondary Prevention of Coronary Disease with ACE Inhibition-does Blood Pressure Reduction with Perindopril Explain the Benefits in EUROPA?. Cardiovasc Drugs Ther 23, 161–170 (2009). https://doi.org/10.1007/s10557-008-6143-6

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  • DOI: https://doi.org/10.1007/s10557-008-6143-6

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