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Keywords:

  • CABG ;
  • cardiovascular disease;
  • optimal medical therapy;
  • PCI ;
  • stable angina

Summary

  1. Top of page
  2. Summary
  3. What is Known and Objective
  4. Comment
  5. What is New and Conclusion
  6. References

What is known and objective

Cardioprotective drug regimens improve outcomes in patients with stable coronary artery disease. Revascularization is recommended for the persistence of symptoms despite optimal medical therapy (OMT) or in patients likely to derive prognostic benefit. Our objective is to comment on recent evidence that initiation of OMT is suboptimal in patients undergoing percutaneous coronary intervention (PCI) but conversely adherence to medication may be higher in patients treated with PCI.

Comment

Large randomized controlled trials demonstrate that the risk of death or myocardial infarction is similar in patients treated by OMT alone and those treated with PCI and OMT. Despite the recommendations of international practice guidelines, OMT remains underutilized in recent analyses of patients referred for PCI. Notwithstanding the underutilization of proven therapies, a recent study suggests that adherence to medication is significantly higher in patients treated with PCI than in those treated with OMT alone. We discuss the potential factors that may contribute to underprescription of OMT and predict adherence in patients undergoing PCI.

What is new and conclusion

Contemporary studies continue to demonstrate underutilization of OMT in patients referred for PCI but increased medication adherence in patients treated by PCI. We argue for increased recognition of OMT as the definitive treatment for stable angina, so that we can be sure those patients who require PCI ‘are taking’ and ‘keep taking’ the tablets.


What is Known and Objective

  1. Top of page
  2. Summary
  3. What is Known and Objective
  4. Comment
  5. What is New and Conclusion
  6. References

Stable angina pectoris affects 2·9% of men and 4·3% of women aged 40–59 years, with the prevalence rising to 11·9% in men and 9·2% in women aged 80 years and above.[1] Optimal medical therapy (OMT), with antiplatelet agents, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors and statins, is recommended by international guidelines to control symptoms and reduce the risk of cardiovascular events.[2, 3] Randomized controlled trials, such as the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation Trial[4] (COURAGE) and the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial[5], indicated no difference in rates of cardiovascular events (death or non-fatal myocardial infarction) in patients with stable coronary artery disease treated with OMT and revascularization compared with OMT alone. However, despite the persuasive evidence of clinical benefit, OMT is underutilized in patients with coronary artery disease.[6] Our objective was to review the evidence that OMT is underprescribed in patients referred for percutaneous coronary intervention (PCI) and comment on recent data demonstrating that adherence to medication is greater in patients receiving PCI than in those treated by OMT alone.

Comment

  1. Top of page
  2. Summary
  3. What is Known and Objective
  4. Comment
  5. What is New and Conclusion
  6. References

Uptake of PCI has increased substantially in recent years such that PCI now dominates coronary artery bypass surgery as the commonest mode of coronary revascularization.[7] Revascularization is recommended in stable coronary artery disease for patients with ongoing symptoms despite OMT or in whom revascularization is thought to confer prognostic benefit.[8] Trial of an initial strategy of antianginal therapy, aiming to control symptoms and reduce resting heart rate to 60 bpm or lower, is therefore appropriate in patients with stable coronary artery disease before considering revascularization.[2, 3] Utilization of OMT in the COURAGE trial was high with use of statins in 95%, aspirin in 95%, beta-blocker in 89% and ACE inhibitor or angiotensin receptor blocker (ARB) in 72% of participants at one year.[4] However, there is substantial evidence that OMT is less commonly prescribed in routine clinical practice.

It has long been recognized that medical therapy is underused in patients referred for coronary angiography.[9] Borden et al.[10] reported OMT use in an observational study of patients with stable coronary artery disease undergoing PCI in the US National Cardiovascular Data Registry between 2005 and 2009 – a period spanning the publication of COURAGE trial results in 2007. Before the publication of COURAGE, OMT was applied in 43·5% of patients (95% CI, 43·2–43·7%) before PCI and in 63·5% (95% CI, 63·3–63·7%) at hospital discharge. There was only a very modest increase in the use of OMT after publication of COURAGE, reaching 44·7% (95% CI, 44·5–44·8%) before PCI and 66·0% at hospital discharge (95% CI, 65·8–66·1%). The failure of clinicians to adopt substantially more prevalent use of OMT, leaving over half of all patients undertreated, after the COURAGE trial is surprising and is in stark contrast to the 17% decline in referrals for PCI observed in response to COURAGE.[11]

More recent data sets provide ongoing evidence of underutilization of OMT in patients with stable coronary artery disease referred for PCI. Antianginal therapy was underprescribed in patients undergoing PCI recorded in the US CathPCI Registry and Dartmouth Atlas data collected between 2009 and 2011.[12] Among 300772 PCI procedures, 32·8%, 48·3%, 16·1% and 2·8% of patients were taking 0, 1, 2 or ≥3 antianginal medications, respectively. Only 18·6% (median) were taking 2 or more antianginal drugs at the time of PCI. Wide regional variations in medication prescription were noted in this study, but interestingly medication use in each hospital region was not related to rates of PCI. Elder et al.[13] reported on implementation of OMT in patients undergoing elective PCI at six hospitals in the United Kingdom. Of 500 patients, 85% were receiving a statin, 78% were prescribed a beta-blocker, and 76% were taking ACE inhibitor or ARB. Antiplatelet use was not recorded. 51%, 32%, 7% and 1% of patients were receiving 1, 2, 3 or 4 antianginal agents, respectively. Only 33% had a resting heart rate less than 60 bpm.

We undertook a prospective analysis of OMT utilization in consecutive patients with stable coronary artery disease referred for PCI or angiography with follow-on PCI at our institution (a large regional cardiac centre in the United Kingdom). Medication prescription was recorded at a cardiac rehabilitation nurse-led pre-admission clinic (Table 1). We found utilization of aspirin in 95%; beta-blocker in 71%; ACE inhibitor in 48% and statin in 87%. Additional antianginal agents included oral nitrates in 56%; calcium channel blockers in 11%; nicorandil in 17% and ivabradine in 0·9%. In our series, 32% had a resting heart rate greater or equal to 70 bpm, which is known to be associated with adverse cardiovascular outcomes in patients with coronary artery disease.[14]

Table 1. Utilization of optimal medical therapy in 108 consecutive patients attending a pre-admission clinic prior to elective PCI at Leeds General Infirmary, United Kingdom
ParameterNumber of patients (%)
Aspirin102 (95)
Beta-blocker77 (71)
ACE inhibitor52 (48)
Statin94 (87)
Oral nitrate60 (56)
Calcium channel blocker12 (11)
Nicorandil18 (17)
Ivabradine1 (0·9)
Resting heart rate ≥70 bpm35 (32)

Despite suboptimal use of OMT in patients referred for PCI, admission to hospital for the PCI procedure can provide an opportunity to re-evaluate prescription of cardioprotective medication. Ardatti et al.[15] assessed medical therapy before and after PCI in 60 386 patients with stable coronary artery disease undergoing revascularization. OMT (defined in this study as aspirin, beta-blocker and statin pre-PCI and clopidogrel, beta-blocker and statin post-PCI) was used in 53·0% of patients before PCI and 82·1% at discharge.[15]

Several factors are likely to contribute to the current underutilization of OMT in patients referred for PCI. For example, there is evidence that cardiologists underestimate the benefits of optimal medical therapy and overestimate the benefits of revascularization.[16] In a qualitative focus group-based study in California, cardiologists generally believed that PCI would confer prognostic benefit in patients with stable coronary artery disease, despite acknowledging the fact that published data show no reduction in the risk of death or myocardial infarction in this group.[17]Other factors may potentially limit the opportunity and time available for a trial of OMT in stable angina before making the decision to refer for PCI. These include the evolution of rapid access chest pain clinics,[18] national targets for service delivery (e.g. the advent of the National Health Service's 18-week referral-to-treatment pathways in England[19]) and the increasing tendency to carry out PCI as an ad hoc procedure at the time of diagnostic coronary angiography.[20]

Notwithstanding the evidence for underprescription of OMT in patients undergoing PCI, the question of whether patients actually treated by PCI are more or less likely to remain adherent to medical therapy than those treated by OMT alone remained unanswered until recently. Kocas et al.[21] carried out the first prospective comparison of medication adherence in patients treated by PCI vs. those in whom medical management is recommended. In a single-centre study, adherence to beta-blockers, statins and ACE inhibitors was compared in 152 patients undergoing PCI vs. 80 patients receiving medical therapy alone. 53·6% of patients in the PCI group were adherent to medial therapy at 6 months compared with 33·8% in the OMT group (P = 0·004). The proportion of days with adherence to medical therapy was significantly higher in the PCI group than in the OMT (87% vs. 67%; P < 0·001). PCI emerged as an independent predictor of medication adherence in logistic regression analysis.

The enhanced adherence to medical therapy in patients undergoing PCI observed in Kocas's study is intriguing. Intuitively, one might have expected medication adherence to be lower in patients undergoing PCI, as such patients may believe they have undergone a ‘definitive’ procedure and no longer require intensive medication. Certainly, patients may underestimate the benefits of medical therapy and overestimate the benefits of PCI. In a study of 650 stable patients referred for elective coronary revascularization, 82% of patients who were offered PCI believed that revascularization would improve survival.[22] These assumptions were at odds with those of their treating cardiologists.[22] It is recognized that patients’ perception of their risk of future cardiovascular events after PCI correlates poorly with the true calculated future risk.[23] However, as Kocas et al. speculate in their report, patients in their PCI group may have adopted more health conscious behaviour following an invasive procedure; or the requirement to take dual antiplatelet therapy may have improved adherence to other medication. It is noteworthy that the mode of revascularization is relevant to patients' perception of the importance of ongoing medical therapy. For example, more patients are adherent to OMT in the first year after PCI than after coronary artery bypass surgery.[24] Although not specifically examined in that study, it is possible that realization of the requirement for dual antiplatelet therapy following PCI selectively fosters improved adherence in this group. Certainly, there is an association between patients' beliefs, knowledge, understanding and misconceptions about medication and their adherence to medication after PCI.[25] Cardiac rehabilitation may provide a further opportunity to enhance OMT prescription and adherence in patients undergoing PCI. Participation in a comprehensive cardiac rehabilitation programme encourages adherence to medication and pursuit of lifestyle changes, although adherence remains lower in older patients and in those with comorbidities.[26]

What is New and Conclusion

  1. Top of page
  2. Summary
  3. What is Known and Objective
  4. Comment
  5. What is New and Conclusion
  6. References

Contemporary data continue to demonstrate underutilization of OMT in patients with stable coronary artery disease referred for PCI. Given the overwhelming evidence of benefit, there is a persuasive argument for a change in mindset of cardiologists and recognition of OMT as the ‘definitive’ treatment for stable coronary artery disease. Clinical priorities should focus on establishing treatment with aspirin, beta-blocker, ACE inhibitor and statin in all eligible patients. Revascularization should be reserved for patients with stable coronary disease who remain symptomatic despite appropriate initiation and titration of OMT or in whom prognostic benefit from revascularization is likely. If more patients are established on OMT prior to undergoing PCI, it is likely that most will remain adherent following PCI. In this way, patients undergoing PCI would be more likely to be taking, and to keep taking, the tablets.

References

  1. Top of page
  2. Summary
  3. What is Known and Objective
  4. Comment
  5. What is New and Conclusion
  6. References
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  • 20
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  • 21
    Kocas C, Abaci O, Oktay V et al. Percutaneous coronary intervention vs. optimal medical therapy - the other side of the coin: medication adherence. J Clin Pharm Ther, 2013;38:476479.
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