Skip to main content

The Antihypertensive Efficacy of the Triple Fixed Combination of Perindopril, Indapamide, and Amlodipine: The Results of the PETRA Study

Advances in Therapy volume 34, pages 1753–1763 (2017)Cite this article

Abstract

Introduction

The etiology of essential hypertension is multifactorial. Therefore, treatment with combinations of antihypertensive agents acting on multiple targets is necessary for successful therapy in the majority of patients. According to the experience and clinical data accumulated so far, combination therapy with three agents from different pharmacological classes is required in approx. 30% of patients in order to achieve long-term blood pressure control. The primary objective of the PETRA study was to evaluate the efficacy of blood pressure (BP) control with once daily administration of the different dosage strengths of the once-daily, triple fixed combination of perindopril, indapamide, and amlodipine. The evaluation was based on office BP readings and ambulatory blood pressure monitoring (ABPM) data gathered in routine clinical practice.

Methods

Data from 11,209 hypertensive patients (the proportion of female subjects was 47.6%) were processed and interpreted in a 3-month-long prospective, observational, non-interventional, open-label study conducted in 997 centers in Hungary.

Results

Mean baseline office BP was 156.58 ± 16.10/91.56 ± 9.33 mmHg (mean ± SD), whereas the mean duration of hypertension was 9.48 ± 7.19 years. Mean office BP decreased by 24.81 ± 15.47/11.41 ± 9.90 mmHg after switching to the triple fixed combination of perindopril, indapamide, and amlodipine (p < 0.0001). At the final visit 45.1% of patients took the 5/1.25/5 mg, 33.5% of them 10/2.5/5 mg, and 21.4% of them 10/2.5/10 mg strength of the perindopril/indapamide/amlodipine triple fixed combination. The 24-h blood pressure was obtained in 76 subjects. The mean 24-h BP decreased from 155.51 ± 17.43/85.28 ± 11.48 to 134.63 ± 12.51/77.83 ± 8.99 mmHg (p < 0.0001). Statistically significant (p < 0.0001) and clinically relevant improvement of a number of metabolic parameters—including total cholesterol (−8.6%), LDL-cholesterol (−11.4%), triglyceride (−12.1%), and fasting blood glucose (−6.6%) levels—was observed over the 3-month study period.

Conclusions

During the 3 months of the PETRA study, the outstanding 24-h antihypertensive efficacy of the triple fixed combination of perindopril, indapamide, and amlodipine was confirmed both by office BP readings and by ABPM recordings. This combination may offer a new therapeutic option for hypertensive patients who have failed to achieve the desired BP target on their previous dual combination therapy.

Funding

EGIS Pharmaceuticals PLC.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  1. Singh M, Mensah GA, Bakris G. Pathogenesis and clinical physiology of hypertension. Cardiol Clin. 2010;28(4):545–59.

    Article  PubMed  Google Scholar 

  2. Bakris GL. The importance of blood pressure control in the patient with diabetes. Am J Med. 2004;116(5A):30S–8S.

    Article  PubMed  Google Scholar 

  3. Dahlöf B, Sever PS, Poulter NR, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicenter randomised controlled trial. Lancet. 2005;366:895–906.

    Article  PubMed  Google Scholar 

  4. Jamerson K, Weber MA, Bakris GL, et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med. 2008;359:2417–28.

    Article  CAS  PubMed  Google Scholar 

  5. Gradman AH. Rationale for triple-combination therapy for management of high blood pressure. J Clin Hypertens (Greenwich). 2010;12:869–78.

    Article  Google Scholar 

  6. Mancia G, Robert Fagard R, Narkiewicz K, et al. 2013 ESH/ESC Guidelines for themanagement of arterial hypertension. The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2013;34:2159–219.

    Article  PubMed  Google Scholar 

  7. NICE. Clinical guideline 127. Hypertension in adults: diagnois and management. http://www.nice.org.uk/guidance/CG127/NICEGuidance. Accessed Nov 2016.

  8. Fox K, et al. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet. 2003;362:782–8.

    Article  CAS  PubMed  Google Scholar 

  9. Dézsi CA. Differences in the clinical effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: a critical review of the evidence. Am J Cardiovasc Drugs. 2014;14(3):167–73.

    Article  PubMed  PubMed Central  Google Scholar 

  10. PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack. Lancet. 2001;358:1033–41.

    Article  Google Scholar 

  11. ADVANCE Collaborative Group. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet. 2007;370:829–40.

    Article  Google Scholar 

  12. Beckett NS, Peters R, et al. (HYVET): Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008;358:1887–98.

    Article  CAS  PubMed  Google Scholar 

  13. Nissen S, et al. Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: a randomized controlled trial. JAMA. 2004;292:2217–26.

    Article  CAS  PubMed  Google Scholar 

  14. ALLHAT. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002;288(23):2981–97.

    Article  Google Scholar 

  15. Dahlöf B, Sever PS, Poulter NR, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet. 2005;366:895–906.

    Article  PubMed  Google Scholar 

  16. Thoenes M, Neuberger HR, Volpe M, et al. Antihypertensive drug therapy and blood pressure control in men and women: an international perspective. J Hum Hypertens. 2010;24:336–44.

    Article  CAS  PubMed  Google Scholar 

  17. Lithell H, Hansson L, Skoog I, et al. The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial. J Hypertens. 2003;21:875–86.

    Article  CAS  PubMed  Google Scholar 

  18. Páll D, Szántó I, Szabó Z. Triple combination therapy in hypertension: the antihypertensive efficacy of treatment with perindopril, amlodipine, and indapamide SR. Clin Drug Investig. 2014;34:701–8.

    Article  PubMed  Google Scholar 

  19. Tóth K. Antihypertensive efficacy of triple combination perindopril/indapamide plus amlodipine in high-risk hypertensives: results of the PIANIST Study (Perindopril-Indapamide plus AmlodipiNe in high rISk hyperTensive patients). Am J Cardiovasc Drugs. 2014;14(2):137–45.

    Article  PubMed  Google Scholar 

  20. Chalmers J, Arima H, Woodward M, Mancia G, et al. Effects of combination of perindopril, indapamide, and calcium channel blockers in patients with type 2 diabetes mellitus: results from the Action In Diabetes and Vascular Disease: Preterax and Diamicron Controlled Evaluation (ADVANCE) trial. Hypertension. 2014;63(2):259–64.

    Article  CAS  PubMed  Google Scholar 

  21. Chapman RH, Benner JS, Petrilla AA, et al. Predictors of adherence with antihypertensive and lipid-lowering therapy. Arch Intern Med. 2005;165:1147–52.

    Article  PubMed  Google Scholar 

  22. Bangalore S, Kamalakkannan G, Parkar S, Messerli FH, et al. Fixed-dose combinations improve medication compliance: a meta-analysis. Am J Med. 2007;120:713–9.

    Article  PubMed  Google Scholar 

  23. Esposti LD, Saragoni S, Benemei S, et al. Adherence to antihypertensive medications and health outcomes among newly treated hypertensive patients. Clin Econ Outcomes Res. 2011;3:47–54.

    Article  Google Scholar 

Download references

Acknowledgements

This study and the article processing charges for publication were funded by Egis Pharmaceuticals, Budapest, Hungary. The authors acknowledge the contribution of all 997 participating primary care medical centers in Hungary. In addition to the other members of the PETRA investigator group, the authors would like to acknowledge the assistance of Norbert Habony MD (Coordinator). All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval for the version to be published.

Disclosures

Gyorgy Abraham and Csaba András Dézsi have nothing to disclose.

Compliance with Ethics Guidelines

Patients received written and verbal information, and they signed a statement of consent. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964, as revised in 2013. Informed consent was obtained from all patients for being included in the study. Study official approval number (ETT-TUKEB): 39513-1-/2015/EKU (0281/15).

Author information

Authors and Affiliations

  1. Hypertension-Nephrology Center, 1st Department of Internal Medicine, ‘Albert Szent-Györgyi’ Health Center, University of Szeged Faculty of Medicine, Szeged, Hungary

    György Ábrahám

  2. Department of Cardiology, Petz Aladár County Teaching Hospital, Gyor, Hungary

    Csaba András Dézsi

Authors
  1. György Ábrahám
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Csaba András Dézsi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Csaba András Dézsi.

Additional information

Enhanced content

To view enhanced content for this article go to http://www.medengine.com/Redeem/0898F06076F223F6.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Ábrahám, G., Dézsi, C.A. The Antihypertensive Efficacy of the Triple Fixed Combination of Perindopril, Indapamide, and Amlodipine: The Results of the PETRA Study. Adv Ther 34, 1753–1763 (2017). https://doi.org/10.1007/s12325-017-0572-1

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12325-017-0572-1

Keywords

  • ABPM
  • Metabolic parameters
  • Non-interventional study
  • Office blood pressure
  • Triple fixed combination