Physicians' Academy for Cardiovascular Education

Poor adherence to antihypertensive therapy increases stroke risk

Literature - Herttua K, Tabák AG, Martikainen P et al. - Eur Heart J 16 July 2013


Adherence to antihypertensive therapy prior to the first presentation of stroke in hypertensive adults: population-based study

 
Herttua K, Tabák AG, Martikainen P et al.
Eur  Heart J 16 July 2013 doi:10.1093/eurheartj/eht219
 

Background

Stroke is the second most common cause of death after ischemic heart disease, and accounts for 11% of all deaths worldwide [1]. Stroke-related disability is furthermore one of the commonest causes of reduced, disability-adjusted life years [2]. High blood pressure is a leading risk factor for stroke and heart disease and antihypertensive therapy is the most effective primary prevention strategy against stroke [3-7].
To obtain this effect, patient’s adherence to antihypertensive medication is crucial. Previous studies have looked into the relation between antihypertensive therapy adherence and successful primary prevention of stroke and other CV events. However, adherence was measured at only one time point.
This study therefore estimated the year-by-year trajectories between adherence and stroke risk prior to the first presentation of non-fatal and fatal incident stroke. Nationwide prescription, hospitalisation and death registers were used to determine the excess risk of stroke associated with non-adherence to antihypertensive therapy among hypertensive patients without pre-existing stroke or CV events. Data of 73527 hypertensive patients from between 1995 and 2007 was included.
 

Main results

  • At 2, 5 and 10 years of follow-up adjusted OR for stroke death, were 3.81 (95%CI: 2.85-5.10), 3,68 (95%CI: 2.92-4.65) and 3.01 (95%CI: 2.37-3.83) in non-adherent as compared to adherent patients. ORs for stroke hospitalisation were 2.74 ((5%CI: 2.35-3.20), 2.28 (95%CI: 2.0-2.60), and 1.71 (95%CI: 1.49-1.96) respectively.
  • Retrospective analysis  showed that in the year of stroke death, non-adherent patients had a 5.68 (95%CI: 5.05-6.39) times higher risk as compared to adherent patients. ORs for non-adherence decreased when further away from the stroke event.
  • Analyses specified by class of prescribed antihypertensive drugs revealed the strongest associations with adherence for agents acting on the renin-angiotensin system combined with diuretics and/or β-blockers.
  • When specifying high, intermediate and poor adherence, patients with poor adherence had a higher risk (OR: 7.99 (95%CI: 6.28-10.18) than those with high adherence. OR for participants with intermediate adherence was 3.60 (95%CI: 2.95-4.39). These and similar findings for hospitalisation due to stroke suggest a dose-response association between poorer adherence to antihypertensive medication and a greater risk of a stroke event.
 

Conclusion

This large-scale population base study suggests that the near- and long-term risk of fatal and non-fatal stroke increases with decreasing adherence to antihypertensive medication. Although filling a prescription is no proof that a patient actually took the medicine, this study may be the closest one can get to studying adherence, since trials randomising to different adherence levels would be unethical. This observational study showed lower adherence already 9 years before a stroke event. The observed dose-response relationship across the entire follow-up period highlights the importance of prolonged adherence to antihypertensive therapy to reduce possibly fatal complications.
 

References

1. The GBDS consortium. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380:2095–2128.
2. The GBDS consortium. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380:2197–2223.
3. World Health Organization. TheWorld Health Report 2002 – Reducing Risks, Promoting Healthy Life. Geneva:World Health Organization, 2002.
4. Law MR, Morris JK,Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. Br Med J 2009;338:b1665.
5. Psaty BM, Lumley T, Furberg CD, et al. Health outcomes associated with various antihypertensive therapies
used as first-line agents: a network meta-analysis. JAMA 2003;289:2534–2544.
6. Turnbull F, Blood Pressure Lowering Treatment Trialists’Collaboration. Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials. Lancet 2003;362:1527–1535.
7. Turnbull F, Neal B, Ninomiya T, et al. Blood pressure lowering treatment trialists’ collaboration. Effects of different regimens to lower blood pressure on major cardiovascular events in older and younger adults: meta-analysis of randomised trials. Br Med J 2008;336:1121–1123.
 

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