Editor's Note: This Expert Analysis is part of a series presenting perspectives on major ESC Congress 2019 trials. Please follow this link for the companion articles.

Coronary artery bypass grafting (CABG) is the most commonly performed cardiac surgical procedure, with approximately 400,000 procedures performed in the United States annually, and the preferred method of revascularization in patients with multivessel coronary artery disease (CAD).¹ European data indicate 44 CABG procedures per 10,000 people per year. Patients undergoing CABG in the current era are increasingly more complex with multiple cardiac and non-cardiac comorbidities including hypertension, dyslipidemia, sleep apnea, left ventricular (LV) dysfunction, heart failure, renal disease, and neurovascular disease. These comorbidities not only increase surgical risk but also impact long-term prognosis after CABG. Additionally, CABG does not prevent the progression of CAD in either the native vessels or in the bypass grafts. It is important to recognize, therefore, that aggressive secondary prevention is essential to ameliorate the risk of both vein graft failure and progression of native CAD.¹

It has been shown previously that patients are less likely to fill prescriptions and to use medications for secondary prevention after CABG than after percutaneous coronary intervention.² The European guidelines recommend statins and platelet inhibitors for all CABG patients without contraindications: renin-angiotensin-aldosterone system (RAAS) inhibitors for those with LV ejection fraction <40%, hypertension, or previous myocardial infarction (MI); and (long-term) beta-blockers for patients with LV ejection fraction <35% or recent MI.³ The American Heart Association in its 2015 guideline document recommends that aspirin should be started within 6 hours of surgery and continued indefinitely.⁴ Dual antiplatelet therapy with clopidogrel should be used for 1 year in patients undergoing off-pump bypass. Statins also form an important part of secondary prevention, inhibiting the development of vein graft disease and improving graft patency.⁵ Therefore, all patients <75 years of age should be on high-intensity statin. Additionally, peri-operative beta-blockers are recommended to prevent post-operative atrial fibrillation. The US guidelines also recommend that patients should be on appropriate beta-blockers, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers if they have a history of previous MI or LV dysfunction. Lastly, smoking cessation and referral for cardiac rehabilitation are strongly recommended by the American Heart Association (Class I).⁵

The current study (presented at the recent European Society of Cardiology Congress 2019) used longitudinal data from the SWEDEHEART Registry (Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies) to assess trends in the use of post-CABG secondary prevention and its association with clinical outcomes. The SWEDEHEART Registry is a nationwide Swedish registry comprising patients hospitalized with acute coronary syndrome or undergoing coronary or valvular interventions for any indication. In this report, the authors studied 28,812 patients from the registry who were admitted between 2006 and 2015 for first-time CABG in Sweden. The authors used data at 6 months after discharge as baseline. Medication exposure status was updated every 3 months. Mortality data as well as data on prescribed medications were collected until death, emigration, or until the end of the study period (December 31, 2015). Cox regression models adjusted for age, sex, comorbidities, and other secondary prevention medications were used to investigate correlations between medication exposure and all-cause mortality. Median follow-up was 4.9 years; 0% of patients were lost to follow-up.

At 6 months after discharge, the authors reported excellent prescription rate of evidenced-based secondary prevention medications, with 93.9% of patients on statins, 91% on beta-blockers, 72.9% on RAAS inhibitors, and 93% on antiplatelet medications. Alarmingly, at 8 years, the prescription rates reduced to 77.3% for statins, 76.4% for beta-blockers, 65.9% for RAAS inhibitors, and 79.8% for antiplatelet drugs. The study showed a significant inverse association between all-cause mortality and use of RAAS inhibitors (hazard ratio [HR] 0.78; 95% confidence interval [CI], 0.73-0.84), antiplatelet drugs (HR 0.74; 95% CI, 0.69-0.81), and statin drugs (HR 0.56; 95% CI, 0.52-0.6) after adjusting for age, sex, comorbidities, and use of other prevention medications. No association was found between use of beta-blockers and risk of mortality. There were no major differences in the use of medications between women and men. Importantly, every additional year using statins, platelet inhibitors, and RAAS inhibitors was linked with 10%, 7%, and 2% lower relative risk of mortality, respectively. Key strengths of the SWEDEHEART Registry are the use of real-world data with a large, nationwide contemporary cohort and complete follow-up. However, there is lack of data on lifestyle parameters and reasons for patients discontinuing use of medications post-CABG.

There are several possible reasons for the decrease in medication prescriptions over time. The authors comment that perhaps the lack of follow-up with a cardiologist beyond 12 months of CABG may have impacted drug prescriptions. It is also possible that these patients developed concomitant conditions that prevented use of some of these medications, such as bleeding, renal toxicity, liver toxicity, or hypotension, for example. Advanced age (especially over the age of 75) can also be a deterrent to continued prescription of medications such as statins. Indeed, the authors noted that those older than 75 were less likely to receive secondary prevention medications. However, despite the possible explanations, this study demonstrates a worrisome trend: a lack of long-term focus on secondary prevention of heart disease. Cardiologists and cardiothoracic surgeons should be involved in the long-term care of these patients with at least annual visits after the first year in stable patients. The fact remains, however, that the average patient will likely interact more frequently with his or her primary care doctor than a specialist. Also, primary care physicians have a long-standing relationship with these patients, and the trust they have built can be harnessed to improve medication compliance. Therefore, it would serve us well to increase involvement of primary care doctors in secondary prevention after surgical revascularization. It is also important to ensure that medication prescription not be reduced to a checklist in the electronic medical record. This is an active process, requiring careful modulation and slow up-titration while watching for side effects and tolerance. This active approach can pay huge dividends, especially in patients with heart failure and LV dysfunction who often require target doses much higher than the starting dose of beta-blockers, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers. An important finding of this study was the lack of mortality benefit with beta-blockers, even in the subgroup of patients with LV dysfunction. These findings need to be interpreted with caution. Several factors such as ejection fraction, dosage, compliance, and type of beta-blocker used can affect its efficacy. We await the complete results of this study to further investigate this relationship.

Finally, although medications are the focus of the current investigation, non-pharmacological interventions such as smoking cessation, cardiac rehabilitation, diet, and exercise are just as important and should be stressed on the first and subsequent office visits after CABG. Cardiovascular medicine is a team-based approach; a fruitful collaboration among the primary care doctor, cardiologist, cardiac surgeon, pharmacist, physical therapist, and nutritionist can maximize benefit to our patients.

References

1. Alexander JH, Smith PK. Coronary-Artery Bypass Grafting. N Engl J Med 2016;375:e22.
2. Hlatky MA, Solomon MD, Shilane D, Leong TK, Brindis R, Go AS. Use of medications for secondary prevention after coronary bypass surgery compared with percutaneous coronary intervention. J Am Coll Cardiol 2013;61:295-301.
3. Sousa-Uva M, Head SJ, Milojevic M, et al. 2017 EACTS Guidelines on perioperative medication in adult cardiac surgery. Eur J Cardiothorac Surg 2018;53:5-33.
4. Kulik A, Ruel M, Jneid H, et al. Secondary prevention after coronary artery bypass graft surgery: a scientific statement from the American Heart Association. Circulation 2015;131:927-64.
5. Kulik A, Voisine P, Mathieu P, et al. Statin therapy and saphenous vein graft disease after coronary bypass surgery: analysis from the CASCADE randomized trial. Ann Thorac Surg 2011;92:1284-90.

Keywords: ESC Congress, esc 2019, ESC 19, Cardiac Surgical Procedures, Adrenergic beta-Antagonists, Acute Coronary Syndrome, American Heart Association, Angiotensin-Converting Enzyme Inhibitors, Angiotensin Receptor Antagonists, Aortic Valve, Aortic Valve Stenosis, Aspirin, Atrial Fibrillation, Australia, Cohort Studies, Cardiac Rehabilitation, Comorbidity, Confidence Intervals, Coronary Artery Bypass, Coronary Artery Disease, Diabetes Mellitus, Dilatation, Dyslipidemias, Drug Prescriptions, Echocardiography, Electronic Health Records, Diet, Follow-Up Studies, Heart Failure, Heart Diseases, Heart Valve Prosthesis, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Heart Ventricles, Hospitalization, Hypertension, Hypotension, Incidence, Life Style, Long-Term Care, Mitral Valve, Mitral Valve Insufficiency, Myocardial Infarction, Nutritionists, Odds Ratio, Office Visits, Outcome Assessment, Health Care, Papillary Muscles, Percutaneous Coronary Intervention, Pharmacists, Physical Therapists, Physicians, Primary Care, Platelet Aggregation Inhibitors, Primary Health Care, Prospective Studies, Pulmonary Circulation, Referral and Consultation, Prognosis, Registries, Renal Insufficiency, Research, Renin-Angiotensin System, Risk, Secondary Prevention, Sleep Apnea Syndromes, Stroke, Stroke Volume, Smoking Cessation, Surgeons, Systole, Taxus, Thoracic Surgery, Transcatheter Aortic Valve Replacement, Ventricular Dysfunction, Ticlopidine, Ventricular Function, Left

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