Top

Published in:

01-12-2021 | ß-Blockers | Research article

Impact of multiple cardiovascular medications on mortality after an incidence of ischemic stroke or transient ischemic attack

Authors: Tian-Tian Ma, Ian C. K. Wong, Cate Whittlesea, Kenneth K. C. Man, Wallis Lau, Zixuan Wang, Ruth Brauer, Thomas M. MacDonald, Isla S. Mackenzie, Li Wei

Published in: BMC Medicine | Issue 1/2021

Abstract

Background

To manage the risk factors and to improve clinical outcomes, patients with stroke commonly receive multiple cardiovascular medications. However, there is a lack of evidence on the optimum combination of medication therapy in the primary care setting after ischemic stroke. Therefore, this study aimed to investigate the effect of multiple cardiovascular medications on long-term survival after an incident stroke event (ischemic stroke or transient ischemic attack (TIA)).

Methods

This study consisted of 52,619 patients aged 45 and above with an incident stroke event between 2007 and 2016 in The Health Improvement Network database. We estimated the risk of all-cause mortality in patients with multiple cardiovascular medications versus monotherapy using a marginal structural model.

Results

During an average follow-up of 3.6 years, there were 9230 deaths (7635 in multiple cardiovascular medication groups and 1595 in the monotherapy group). Compared with patients prescribed monotherapy only, the HRs of mortality were 0.82 (95% CI 0.75–0.89) for two medications, 0.65 (0.59–0.70) for three medications, 0.61 (0.56–0.67) for four medications, 0.60 (0.54–0.66) for five medications and 0.66 (0.59–0.74) for ≥ six medications. Patients with any four classes of antiplatelet agents (APAs), lipid-regulating medications (LRMs), angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs), beta-blockers, diuretics and calcium channel blockers (CCBs) had the lowest risk of mortality (HR 0.51, 95% CI 0.46–0.57) versus any one class. The combination containing APAs, LRMs, ACEIs/ARBs and CCBs was associated with a 61% (95% CI 53–68%) lower risk of mortality compared with APAs alone.

Conclusion

Our results suggested that combination therapy of four or five cardiovascular medications may be optimal to improve long-term survival after incident ischemic stroke or TIA. APAs, LRMs, ACEIs/ARBs and CCBs were the optimal constituents of combination therapy in the present study.

Available only for authorised users

World Health Organization. The top 10 causes of death. 2020. https://www.who.int/es/news-room/fact-sheets/detail/the-top-10-causes-of-death. Accessed 10 Dec 2020.

British Heart Foundation. Heart and circulatory disease statistics 2020. 2020. https://www.bhf.org.uk/what-we-do/our-research/heart-statistics/heart-statistics-publications/cardiovascular-disease-statistics-2020.

National Institute for Health and Care Excellence. Stroke rehabilitation in adults [CG162]. National Institute for Health and Care Excellence; 2013. https://www.nice.org.uk/guidance/cg162.

Kernan WN, Ovbiagele B, Black HR, Bravata DM, Chimowitz MI, Ezekowitz MD, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack 2014. doi:https://doi.org/10.1161/STR.0000000000000024.

O’Donnell MJ, Xavier D, Liu L, Zhang H, Chin SL, Rao-Melacini P, et al. Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case-control study. Lancet. 2010;376:112–23. https://doi.org/10.1016/S0140-6736(10)60834-3.CrossRefPubMed

Rashid P, Leonardi-Bee J, Bath P. Blood pressure reduction and secondary prevention of stroke and other vascular events. Stroke. 2003;34:2741–8. https://doi.org/10.1161/01.STR.0000092488.40085.15.CrossRefPubMed

Ní Chróinín D, Asplund K, Åsberg S, Callaly E, Cuadrado-Godia E, Díez-Tejedor E, et al. Statin therapy and outcome after ischemic stroke. Stroke. 2013;44:448–56. https://doi.org/10.1161/STROKEAHA.112.668277.CrossRefPubMed

Thijs V, Lemmens R, Fieuws S. Network meta-analysis: simultaneous meta-analysis of common antiplatelet regimens after transient ischaemic attack or stroke. Eur Heart J. 2008;29:1086–92. https://doi.org/10.1093/eurheartj/ehn106.CrossRefPubMed

Zhang Q, Wang C, Zheng M, Li Y, Li J, Zhang L, et al. Aspirin plus clopidogrel as secondary prevention after stroke or transient ischemic attack: a systematic review and meta-analysis. Cerebrovasc Dis. 2015;39:13–22. https://doi.org/10.1159/000369778.CrossRefPubMed

10.

Verro P, Gorelick PB, Nguyen D. Aspirin plus dipyridamole versus aspirin for prevention of vascular events after stroke or TIA. Stroke. 2008;39:1358–63. https://doi.org/10.1161/STROKEAHA.107.496281.CrossRefPubMed

11.

Ge F, Lin H, Liu Y, Li M, Guo R, Ruan Z, et al. Dual antiplatelet therapy after stroke or transient ischaemic attack - how long to treat? The duration of aspirin plus clopidogrel in stroke or transient ischaemic attack: a systematic review and meta-analysis. Eur J Neurol. 2016;23:1051–7. https://doi.org/10.1111/ene.12982.CrossRefPubMed

12.

Geeganage CM, Diener H-C, Algra A, Chen C, Topol EJ, Dengler R, et al. Dual or mono antiplatelet therapy for patients with acute ischemic stroke or transient ischemic attack. Stroke. 2012;43:1058–66. https://doi.org/10.1161/STROKEAHA.111.637686.CrossRefPubMed

13.

Arima H, Chalmers J, Woodward M, Anderson C, Rodgers A, Davis S, et al. Lower target blood pressures are safe and effective for the prevention of recurrent stroke: the PROGRESS trial. J Hypertens. 2006;24:1201–8. https://doi.org/10.1097/01.hjh.0000226212.34055.86.CrossRefPubMed

14.

The Health Improvement Network. What is THIN data? https://www.the-health-improvement-network.co.uk/. Accessed 23 Nov 2020.

15.

Blak BT, Thompson M, Dattani H, Bourke A. Generalisability of The Health Improvement Network (THIN) database: demographics, chronic disease prevalence and mortality rates. Inform Prim Care. 2011;19:251–5. doi:https://doi.org/10.14236/jhi.v19i4.820.

16.

Davé S, Petersen I. Creating medical and drug code lists to identify cases in primary care databases. Pharmacoepidemiol Drug Saf. 2009;18:704–7. https://doi.org/10.1002/pds.1770.CrossRefPubMed

17.

Collins GS, Altman DG. An independent and external validation of QRISK2 cardiovascular disease risk score: a prospective open cohort study. BMJ. 2010;340(2):c2442. https://doi.org/10.1136/bmj.c2442.CrossRefPubMedPubMedCentral

18.

Azur MJ, Stuart EA, Frangakis C, Leaf PJ. Multiple imputation by chained equations: what is it and how does it work? Int J Methods Psychiatr Res. 2011;20:40–9. https://doi.org/10.1002/mpr.329.CrossRefPubMedPubMedCentral

19.

Rubin DB. Multiple imputation for nonresponse in surveys. New York: Wiley; 1987.CrossRef

20.

Hernán MÁ, Brumback B, Robins JM. Marginal structural models to estimate the causal effect of zidovudine on the survival of HIV-positive men. Epidemiology. 2000;11:561–70. https://doi.org/10.1097/00001648-200009000-00012.CrossRefPubMed

21.

Herderich M, Beckert C, Veit M. Establishing styrylpyrone synthase activity in cell free extracts obtained from gametophytes of Equisetum arvense L. by high performance liquid chromatography-tandem mass spectrometry. Phytochem Anal. 1997;8:194–7.CrossRef

22.

VanderWeele TJ, Ding P. Sensitivity analysis in observational research: introducing the E-value. Ann Intern Med. 2017;167:268. https://doi.org/10.7326/M16-2607.CrossRefPubMed

23.

Law MR. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ. 2003;326:1423–0. doi:https://doi.org/10.1136/bmj.326.7404.1423.

24.

Collaboration AT, Antiplatelet Trialists’ Collaboration. Collaborative overview of randomised trials of antiplatelet therapy prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. BMJ. 1994;308:81–106. doi:https://doi.org/10.1136/bmj.308.6921.81.

25.

National Institute for Health and Care Excellence. Secondary prevention following stroke and TIA. 2020. https://cks.nice.org.uk/topics/stroke-tia/management/secondary-prevention-following-stroke-tia/. Accessed 11 Dec 2020.

26.

National Institute for Health and Care Excellence. Hypertension in adults: diagnosis and management. [CG127]. 2011.

27.

Park J-H, Ovbiagele B. Optimal combination secondary prevention drug treatment and stroke outcomes. Neurology. 2015;84:50–6. https://doi.org/10.1212/WNL.0000000000001099.CrossRefPubMedPubMedCentral

28.

De Lima LG, Saconato H, Atallah ÁN, da Silva EM. Beta-blockers for preventing stroke recurrence. Cochrane Database Syst Rev. 2014;2014. https://doi.org/10.1002/14651858.CD007890.pub3.

29.

Sheppard JP, Fletcher K, McManus RJ, Mant J. Missed opportunities in prevention of cardiovascular disease in primary care: a cross-sectional study. Br J Gen Pract. 2014;64:e38–46. https://doi.org/10.3399/bjgp14X676447.CrossRefPubMed

30.

Wu J, Zhu S, Yao GL, Mohammed MA, Marshall T. Patient factors influencing the prescribing of lipid lowering drugs for primary prevention of cardiovascular disease in UK general practice: a national retrospective cohort study. PLoS One. 2013;8:e67611. https://doi.org/10.1371/journal.pone.0067611.CrossRefPubMedPubMedCentral

31.

Hobbs F. European survey of primary care physician perceptions on heart failure diagnosis and management (Euro-HF). Eur Heart J. 2000;21:1877–87. https://doi.org/10.1053/euhj.2000.2170.CrossRefPubMed

32.

Bryan S, Gill P, Greenfield S, Gutridge K, Marshall T. The myth of agency and patient choice in health care? The case of drug treatments to prevent coronary disease. Soc Sci Med. 2006;63:2698–701. https://doi.org/10.1016/j.socscimed.2006.07.008.CrossRefPubMed

33.

Montgomery AA, Harding J, Fahey T. Shared decision making in hypertension: the impact of patient preferences on treatment choice. Fam Pract. 2001;18:309–13. https://doi.org/10.1093/fampra/18.3.309.CrossRefPubMed

34.

Murray CJL, Lauer JA, Hutubessy RCW, Niessen L, Tomijima N, Rodgers A, et al. Effectiveness and costs of interventions to lower systolic blood pressure and cholesterol: a global and regional analysis on reduction of cardiovascular-disease risk. Lancet. 2003;361:717–25. https://doi.org/10.1016/S0140-6736(03)12655-4.CrossRefPubMed

35.

National Institute for Health and Care Excellence. Appraising life-extending, end of life treatments. 2009.

36.

Sacco RL, Adams R, Albers G, Alberts MJ, Benavente O, Furie K, et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack. Stroke. 2006;37:577–617. https://doi.org/10.1161/01.STR.0000199147.30016.74.CrossRefPubMed

37.

Furie KL, Kasner SE, Adams RJ, Albers GW, Bush RL, Fagan SC, et al. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack. Stroke. 2011;42:227–76. https://doi.org/10.1161/STR.0b013e3181f7d043.CrossRefPubMed

38.

Intercollegiate Stroke Working Party. National clinical guideline for stroke, 3rd edition. 2008. http://www.wales.nhs.uk/document/167935/info/. Accessed 10 Dec 2020.

39.

Intercollegiate Stroke Working Party. National clinical guideline for stroke, 4th edition. 2012. https://www.strokeaudit.org/Guideline/Historical-Guideline.aspx. Accessed 10 Dec 2020.

40.

Intercollegiate Stroke Working Party. National clinical guideline for stroke, 5th edition. 2016. https://www.strokeaudit.org/Guideline/Full-Guideline.aspx. Accessed 10 Dec 2020.

Title: Impact of multiple cardiovascular medications on mortality after an incidence of ischemic stroke or transient ischemic attack
Authors: Tian-Tian Ma
Ian C. K. Wong
Cate Whittlesea
Kenneth K. C. Man
Wallis Lau
Zixuan Wang
Ruth Brauer
Thomas M. MacDonald
Isla S. Mackenzie
Li Wei
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: ß-Blockers
Stroke
Published in: BMC Medicine / Issue 1/2021
Electronic ISSN: 1741-7015
DOI: https://doi.org/10.1186/s12916-021-01900-1

At a glance: The STEP trials

Springer Medicine

Impact of multiple cardiovascular medications on mortality after an incidence of ischemic stroke or transient ischemic attack

Abstract

Background

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2021

What neurological and psychiatric effects does COVID-19 have on its survivors?

Within- and across-day patterns of interplay between depressive symptoms and related psychopathological processes: a dynamic network approach during the COVID-19 pandemic

The rates and medical necessity of cesarean delivery in China, 2012–2019: an inspiration from Jiangsu

IRF7 and RNH1 are modifying factors of HIV-1 reservoirs: a genome-wide association analysis

Risk of incident fractures in individuals hospitalised due to unexplained syncope and orthostatic hypotension

Metabolic signatures of greater body size and their associations with risk of colorectal and endometrial cancers in the European Prospective Investigation into Cancer and Nutrition