Preview

Rational Pharmacotherapy in Cardiology

Advanced search

Efficacy, Safety and Long-term Outcomes of Nicorandil Use in Patients with Stable Ischemic Heart Disease According to the Results of Randomized and Observational Studies

https://doi.org/10.20996/1819-6446-2019-15-5-641-648

Full Text:

Abstract

Working Group of the NIKEA Study. Yekaterinburg: Akulina E.N., Reznik I.I.; Izhevsk: Grebnev S.A., Yezhov A., Shinkareva S.E.; Krasnodar: Kudryashov E.A., Skibitsky A.V., Skibitsky V.V., Fendrikova A.V.; Krasnoyarsk: Altayev V.D., Matyushin G.V., Nemik D.B., Pitaev R.R., Samokhvalov E.V., Stolbikov Yu.Yu.; Moscow: Balashov I.S., Voronina V.P., Gaisenok O.V., Dmitrieva N.A., Zagrebelny A.V., Zakharova A.V., Zelenova T.I., Kolganova E.V., Leonov A.S., Lerman O.V., Maximova M.A., Sladkova T.A., Shestakova G.N.; Novosibirsk: Kuimov A.D., Shurkevich A.A.; Omsk: Goodilin V.A., Loginova E.N., Nechaeva G.I.; Orel: Zhuravleva L.L., Lobanova G.N., Luneva M.M., Mitroshina T.N.; Orenburg: Kondratenko V.Yu., Libis R.A.; Rostov-on-Don: Dubishcheva N.F., Kalacheva N.M., Kolomatskaya O.E., Romadina G., Skarzhinskaya N.S., Chesnikova A.I., Chugunova I.B.; Ryazan: Dobrynina N.V., Nikolaev A.S., Trofimova Ya.M., Yakushin S.S.; Tula: Berberfish L.D., Gomova T.A., Gorina G.I., Dabizha V.G., Zubareva L.A., Nadezhkina K.N., Nikitina V.F., Renko I.E., Soin I.A., Yunusova K.N.

Background. Nicorandil is an antianginal drug for which, the ability to positively influence the prognosis of patients (pts) with stable ischemic heart disease (IHD) was confirmed in a randomized controlled trial (RCT) of IONA (the Impact Of Nicorandil in Angina). To study whether the results of RCTs are reproduced in real clinical practice seems to be an actual scientific and practical task.

Aim. To compare the data on the effectiveness and safety of nicorandil in pts with stable IHD obtained in the NIKEA observational study (OS) and in the IONA randomized study.

Material and methods. 590 pts with IHD and stable angina pectoris were included in the OS NIKEA. All pts were recommended to take nicorandil in addition to the standard antiischemic therapy. 21 months after being included in the study, 524 pts received a phone call. During the telephone contact with pts or their relatives, the life status of pts was determined. According to these results of the survey data were obtained, that 15 people died and 509 pts were alive. The events included in the primary combined endpoint (PCEP) were also determined: death from all causes, new cases of acute myocardial infarction and acute cerebrovascular accident, unscheduled operations of myocardial revascularization, hospitalization for decompensation of chronic heart failure, atrial fibrillation, unstable angina, information on taking nicorandil and other drug therapy, adverse events of drug treatment have been reported. A comparative analysis of the results of the OS NIKEA and RCT IONA was carried out. The results of the IONA study were taken according to the publication in the Lancet 2002. A comparative analysis of the results of the effectiveness of nicorandil in real practice (according to the OS results) was performed with the data obtained in the RCT: the nicorandil/placebo groups in the RCT were compared with the adherent/non-adherent nicorandil groups in the OS.

Results. The follow-up duration in both studies was similar and averaged 1.6±0.5 years at RCT IONA and 1.8±0.4 years at NIKEA study. The average age of pts was 67,0±8,0 years in RCT and 65.1±9.6 years in OS. In pts of OS more pronounced comorbidity was noted (cardiovascular diseases, diabetes mellitus). Drugs that favorably affect the prognosis in pts with IHD were more often prescribed to NIKEA study pts (p<0.05). In both RCTs and OS, the antianginal effectiveness of nicorandil was confirmed. According to the OS results, a reduction in the number of angina attacks and a decrease in the need for short-acting nitrates were demonstrated. The frequency of PCEP components was higher in RCT.

Conclusion. Long-term outcomes according to the NIKEA observational program for various components of the PCEP turned out to be similar to the results of RCT IONA. It is demonstrated the efficacy of nicorandil in real clinical practice. 

About the Authors

Yu. V. Lukina
National Medical Research Center for Preventive Medicine
Russian Federation

MD, PhD, Leading Researcher, Laboratory of Pharmacoepidemiological Research, Department of Preventive Pharmacotherapy,

Petroverigsky per. 10, Moscow, 101990



N. P. Kutishenko
National Medical Research Center for Preventive Medicine
Russian Federation

MD, PhD, Head of Laboratory of Pharmacoepidemiological Research, Department of Preventive Pharmacotherapy,

Petroverigsky per. 10, Moscow, 101990



S. Yu. Martsevich
National Medical Research Center for Preventive Medicine
Russian Federation

MD, PhD, Professor, Head of Department of Preventive Pharmacotherapy, 

Petroverigsky per. 10, Moscow, 101990



References

1. Kim S.Y. Efficacy versus effectiveness. Korean J Fam Med. 2013;34(4):227. DOI:10.4082/kjfm.2013.34.4.227.

2. IONA Study Group. Trial to show the impact of nicorandil in angina (IONA): design, methodology, and management. Heart. 2001;85(6):E9. DOI:10.1136/heart.85.6.e9.

3. The IONA Study Group. Effect of nicorandil on coronary events in patients with stable angina: the Impact Of Nicorandil in Angina (IONA): randomized trial. Lancet. 2002;359(9314):1269-75. DOI:10.1016/S0140-6736(02)08265-X.

4. Japanese Coronary Artery Disease (JCAD) Study Investigators. Current status of the background of patients with coronary artery disease in Japan. Circ J. 2006;70(10):1256-62. DOI:10.1253/circj.70.1256.

5. Sakata Y., Nakatani D., Shimizu M., et al. Oral treatment with nicorandil at discharge is associated with reduced mortality after acute myocardial infarction. Journal of Cardiology. 2012;59(1):14-21. DOI:10.1016/j.jjcc.2011.08.001.

6. Martsevich S.Y., Lukina Y.V., Kutishenko N.P., et al. Observational multicenter trial of nicorandil use in stable coronary heart disease high-risk patients (NIKEA): Design and first results. Russian Journal of Cardiology. 2017;(9):75-82 (In Russ.) DOI:10.15829/1560-4071-2017-9-75-82.

7. Martsevich S.Y., Lukina Y.V., Kutishenko N.P., et al. The First Results of the Evaluation of Long-Term Nicorandil Treatment Effect on the Probability of Cardiovascular Complications in Patients with Stable Coronary Artery Disease (Data of Observational NIKEA Study). Rational Pharmacotherapy in Cardiology. 2019;15(3):335-42. DOI:10.20996/1819-6446-2019-15-3-335-342 (In Russ.)

8. Martsevich S.Y., Kutishenko N.P., Tolpygina S.N., et al. The effectiveness and safety of drug therapy in primary and secondary prevention of cardiovascular diseases. VNOC recommendations. Rational Pharmacotherapy in Cardiology. 2011;7(5):6-14 (In Russ) DOI:10.20996/1819-6446-2011-7-5.

9. Sherman R.E., Anderson S.A., Dal Pan G.J., et al. Real-World-Evidence - what is it and what can it tell us? N Engl J Med. 2016;375:2293-7. DOI:10.1056/NEJMsb1609216.

10. Trentino K., Farmer S., Gross I., et al. Observational studies - should we simply ignore them in assessing transfusion outcomes? BMC Anesthesiol. 2016;16(1):96. DOI:10.1186/s12871-016-0264-4.

11. Faraoni D., Schaefer S.T. Randomized controlled trials vs. observational studies: why not just live together? BMC Anesthesiol. 2016;16(1):102. DOI:10.1186/s12871-016-0265-3.

12. Kim H.S., Lee S., Kim J.H. Real-world Evidence versus Randomized Controlled Trial: Clinical Research Based on Electronic Medical Records. J Korean Med Sci. 2018;33(34):e213. DOI:10.3346/jkms.2018.33.e213.

13. Stuart B.L., Grebel L.E., Butler C.C., et al. Comparison between treatment effects in a randomised controlled trial and an observational study using propensity scores in primary care. Br J Gen Pract. 2017;67(662):e643-e649. DOI:10.3399/bjgp17X692153.

14. Bolland M.J., Grey A., Gamble G.D., Reid I.R. Concordance of Results from Randomized and Observational Analyses within the Same Study: A Re-Analysis of the Women's Health Initiative Limited-Access Dataset. PLoS One. 2015;10(10):e0139975. DOI:10.1371/journal.pone.0139975.

15. Trotta F. Discrepancies between observational studies and randomized controlled trials. Focus Farmacovigilanza. 2012;73(11):1 [cited by Oct 01, 2019]. Available from: https://www.pharmaco-vigilance.eu/content/discrepancies-between-observational-studies-and-randomized-controlled-trials.

16. Singh S., Loke Y.K. Drug safety assessment in clinical trials: methodological challenges and opportunities. Trials. 2012;13:138. DOI:10.1186/1745-6215-13-138.

17. Naci H., Ioannidis J.P. How good is “evidence” from clinical studies of drug effects and why might such evidence fail in the prediction of the clinical utility of drugs? Annu Rev Pharmacol Toxicol. 2015;55:169-89. DOI:10.1146/annurev-pharmtox-010814-124614.

18. Lepahin V.K., Sturov N.V., Astakhova A.V. Methods of identification and registration of adverse drug reactions during their widespread use. Trudnii Patsient. 2008;9:42-6 (In Russ.).

19. Hammad T.A., Pinheiro S.P., Neyarapally G.A. Secondary use of randomized controlled trials to evaluate drug safety: a review of methodological considerations. Clin Trials. 2011;8(5):559-70. DOI:10.1177/1740774511419165.


For citation:


Lukina Y.V., Kutishenko N.P., Martsevich S.Y. Efficacy, Safety and Long-term Outcomes of Nicorandil Use in Patients with Stable Ischemic Heart Disease According to the Results of Randomized and Observational Studies. Rational Pharmacotherapy in Cardiology. 2019;15(5):641-648. (In Russ.) https://doi.org/10.20996/1819-6446-2019-15-5-641-648

Views: 25


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)