Interact CardioVasc Thorac Surg 2008;7:231-234. doi:10.1510/icvts.2007.168948
© 2008 European Association of Cardio-Thoracic Surgery
Institutional report - Cardiac general |
Secondary prevention following coronary artery bypass grafting has improved but remains sub-optimal: the need for targeted follow-up
Andrew J. Turley*,
Anthony P. Roberts,
Robert Morley,
Andrew R. Thornley,
W. Andrew Owens and
Mark A. de Belder
Department of Cardiology and Cardiothoracic Surgery, James Cook University Hospital, Marton Road, Middlesbrough, TS4 3BW, UK
Received 24 September 2007;
received in revised form 8 January 2008;
accepted 8 January 2008
 Manuscript presented at the European Intensive Care Society Meeting, Brussels, March 2007.
*Corresponding author. Tel.: +44 1642 854623; fax: +44 1642 854190.
E-mail address: a.turley{at}btopenworld.com (A.J. Turley).
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Abstract
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A focused review of secondary preventive medication following revascularisation provides an opportunity to ensure optimal use of these agents. A retrospective analysis of our in-house cardiothoracic surgical database was performed to identify patients undergoing non-emergency, elective surgical revascularisation discharged on four secondary preventive medications: aspirin; beta-blockers; ACE-inhibitors and statins. Of 2749 patients studied, 2302 underwent isolated coronary artery bypass grafting (CABG), mean age 65.5 years (S.D. 9.15). Overall, 2536 (92%) patients were prescribed aspirin. Beta-blockers were prescribed in 2171 (79%) patients overall, in 1096/1360 (81%) of patients with a history of myocardial infarction and in 465/619 (75%) of patients with left ventricular systolic dysfunction (LVSD). Overall, 1518 (55%) patients were prescribed an ACE-inhibitor and 179 (6.5%) an angiotensin receptor blocker (ARB); one of these agents was prescribed in 446/619 (72%) patients with LVSD and 915/1360 (67%) patients with a history of previous myocardial infarction. Overall, 2518 (92%) patients were prescribed a statin. Secondary preventive therapies are prescribed more commonly on discharge after CABG than in previous studies, but there is a continuing under-utilisation of ACE-inhibitors. To maximise the potential benefits of these agents, further study is required to understand why they are not prescribed.
Key Words: Coronary artery disease; Coronary artery bypass grafting; Secondary prevention; Angiotensin converting enzyme inhibitors; Statins
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1. Introduction
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Over the last decade, increased rates of coronary revascularisation have helped reduce mortality and morbidity from coronary heart disease (CHD). Long-term prognosis in these patients is dependent on successful implementation of secondary prevention, in particular the use of aspirin, statins, angiotensin converting enzyme inhibitors (ACE-inhibitors) and in many, beta-blockers. A focused review of secondary preventive medication at the time of coronary revascularisation provides an opportunity to ensure optimal use of these agents in line with the National Service Framework (NSF) for CHD recommendations.
The prognostic benefit of prescribing statins in patients with CHD is well known [1]. The use of ACE-inhibition in patients with LV systolic dysfunction (LVSD) is also firmly established [2]. Evidence now exists that an ACE-inhibitor provides prognostic benefit in most patients with CHD, irrespective of LV systolic function [2]. Previous studies have highlighted gaps between the evidence base and practical implementation of secondary prevention strategies in the revascularised population, especially the use of ACE-inhibitors and statins [3]. Our aim was to identify the proportion of patients undergoing non-emergency, elective surgical revascularisation discharged on four secondary preventive medications (aspirin, beta-blocker, ACE-inhibitor and statin), in a single centre, tertiary cardiothoracic unit.
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2. Materials and methods
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A retrospective review of our in-house cardiothoracic database was performed on all non-emergency patients who underwent surgical revascularisation between January 2003 and November 2006. All patients referred for surgical revascularisation had been reviewed by a cardiologist.
Patient demographic details were recorded at the time of surgery plus the variables required to calculate the European System for Cardiac Operative Risk Evaluation score (EuroSCORE). EuroSCORE defines impaired LV systolic function as ejection fraction <50%. Recent myocardial infarction was defined as within 90 days of surgery and unstable angina as rest angina requiring intravenous nitrates until arrival in the anaesthetic room. Previous cardiac surgery was defined as surgery involving opening of the pericardium.
At the time of hospital discharge, discharge letters including discharge medications are electronically generated and stored. All drug use is recorded.
Data were analysed using SPSS (Chicago, IL, USA) for Windows, version 13 statistical software. Descriptive statistics are presented, mean (±S.D.) and median (range) as appropriate.
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3. Results
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The study population comprised 2749 patients of whom 2302 underwent isolated CABG and 292 underwent a combined procedure. Most patients, 2705/2749 (98%) were undergoing cardiac surgery for the first time.
Demographics of the study population are presented in Table 1. The mean age for males was 64.7 years and for females 68.5 years (P<0.01).
At the time of revascularisation, 1360 (50%) patients had a history of previous myocardial infarction, of whom 591 (21%) had suffered a myocardial infarction within 90 days of surgery. There were 174 patients (6.3%) classified as suffering unstable angina at the time of surgery. The majority, 2130 (78%), had good LV systolic function at the time of surgery. The prescribing of secondary preventative medications following surgical revascularisation is summarised in Table 2 and a comparison with published case series is presented in Table 3 [3–8].
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Table 2 The prescribing of secondary preventative medications in patients undergoing non-emergency surgical revascularisation
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Table 3 The prescribing of secondary preventative medications in patients undergoing non-emergency surgical revascularisation a comparison with published case series and registries. Results expressed as percentages
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3.1. Aspirin prescription
Aspirin was prescribed in 2536 (92%), with use being consistently over 90% over the four years of study. Clopidogrel alone was prescribed in 163 patients, and 29 received both aspirin and clopidogrel. Warfarin was prescribed in 287 patients (10%). We did not review the indications for warfarin use or the incidence of atrial fibrillation in the postoperative period.
3.2. Beta-blocker prescription
Beta-blockers were prescribed in 2171 (79%) overall. They were prescribed in 1096/1360 (81%) patients with a history of previous myocardial infarction and in 465/619 (75%) of those patients with LVSD.
3.3. ACE-Inhibitor/ARB prescription
Fewer patients were discharged on an ACE-inhibitor (at any dose). In all, 1518 (55%) patients were prescribed an ACE-inhibitor and 179 (6.5%) an angiotensin receptor blocker (ARB). Evidence of LVSD was present in 619 (23%) patients. In these patients an ACE-inhibitor was prescribed in 393/619 (64%) and an ARB in 53/619 (8.6%) patients. In patients with a history of a previous myocardial infarction [1360/2749 (50%)], an ACE-inhibitor was prescribed in 833/1360 (62%) and an ARB in 82/1360 (6%). Thus, an ACE-inhibitor or ARB was prescribed in 446 (73%) patients with LVSD and 915 (67%) patients with a history of a previous myocardial infarction. This was consistent over the four years of study.
3.4. Statins
Overall, 2518 (92%) were prescribed a statin, with equivalent usage whether the patient had suffered a previous myocardial infarction or not.
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4. Discussion
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The utilisation of secondary preventive therapies within our unit is higher than previously reported. Our analysis has evaluated ‘all-comers’, not just eligible patients without contraindications. As such the true percentage of eligible patients discharged on secondary preventative medications was probably higher than the figures we report. However, there is a continuing under-utilisation of ACE-inhibitors amongst this high-risk group.
In our study, the discharge prescription of aspirin was 92% and for beta-blockade 79%, which compares favourably to case series and registries [3, 4, 7].
Many patients undergoing surgical revascularisation have suffered a previous myocardial infarction and/or have documented LVSD. There is unequivocal evidence that these patients derive prognostic benefit from the use of ACE-inhibitors. Evidence also suggests that any patient with CHD irrespective of LV systolic function benefit prognostically from ACE-inhibitors [2]. A missed opportunity for effective secondary prevention in patients undergoing surgical revascularisation has previously been reported with only 12–25% of patients prescribed ACE-inhibitors at the time of hospital discharge [5, 7]. In our study, 55% of patients were prescribed an ACE-inhibitor and 6% an angiotensin receptor antagonist (ARB). An ACE-inhibitor or ARB was prescribed in 72% patients with LVSD and 67% patients with a history of previous myocardial infarction.
The Heart Outcomes Prevention Evaluation (HOPE) study recruited over 9000 patients of which 80% had CHD but no evidence of LVSD [9]. Patients prescribed an ACE-inhibitor had a significant reduction in myocardial infarction, stroke, or death rates compared to the placebo group. The EUROPA study demonstrated a 20% relative risk reduction in the endpoint of cardiovascular death, non-fatal myocardial infarction and cardiac arrest with the use of ACE-inhibition in over 13,000 patients with stable CHD [10]. The Prevention of Events with Angiotensin Converting Enzyme Inhibition (PEACE) trial enrolled 8290 patients with CHD without evidence of LVSD [11]. No significant difference in death from cardiovascular causes, myocardial infarction, or coronary revascularisation between the treatment groups was observed. This may reflect inadequate power of the study given its lower risk population. A combined analysis of the above three trials has concluded that the use of ACE-inhibitors should be considered in all patients with atherosclerosis reporting an 18% reduction in odds ratio for the combined outcomes of cardiovascular mortality, non-fatal myocardial infarction or stroke [2]. These benefits are in addition to other preventative medications including aspirin, beta-blockers and statins.
The evidence for the use of ARBs in the secondary prevention of acute coronary events is limited. There is evidence of an equivalent protective effect in patients with left ventricular systolic dysfunction, including those post myocardial infarction, but there is some concern about a neutral effect on prevention of future myocardial infarction in other patients with cardiovascular disease and in some studies an increased risk relative to the comparator treatments [12].
The reason why ACE-inhibitors are not prescribed following coronary surgery requires further study. There are good theoretical reasons for a lower utilisation of these drugs in the postoperative period. Patients undergoing elective surgical revascularisation may have their ACE-inhibitors discontinued at the time of hospital admission. Clinicians may be wary of their use in the presence of peri-operative hypotension or temporary renal dysfunction. EuroSCORE uses creatinine value as one variable in calculating peri-operative risk in patients undergoing cardiac surgery. It is recognised that creatinine values are a poor reflection of true renal function and measures of glomerular filtration rate provide a more objective marker of renal function. Those patients with an eGFR <60 ml/min/1.73 m2 of body surface area (chronic kidney disease stage 3–5) have substantially increased risks of cardiovascular events and premature death. In our surgical cohort, this accounts for 25% of patients. The paradox is that these patients may particularly benefit from ACE-inhibitor therapy and thus it is worth challenging current anxieties about their early use following surgery. Our data highlight an improvement in use when compared with published data, with over 61% of patients receiving either an ACE-inhibitor or an ARB. Whilst this represents progress, this almost certainly represents an under-utilisation of this important prognostic intervention. Further study is required to evaluate the prescription and dose-titration of these drugs following discharge.
4.1. Statins
The use of statins in our patient population was high at over 90%. This compares favourably with other case series and is comparable to statin use in acute coronary syndrome patients [4, 8]. As with other major trials, the placebo controlled Heart Protection Study (HPS) demonstrated a reduction in major vascular events including first event rate for non-fatal myocardial infarction or coronary death, for non-fatal or fatal stroke and for coronary or non-coronary revascularisation in those patients prescribed simvastatin [13]. The statins were tolerated well with no significant difference between groups in terms of liver enzyme derangements.
The use of preoperative statin therapy in patients undergoing elective surgical revascularisation has also demonstrated reduced early mortality rates. The post CABG trial has demonstrated that aggressive lipid lowering in patients following surgical revascularisation results in a 30% reduction in revascularisation procedures and a 24% reduction in the composite end point of cardiovascular death, myocardial infarction or need for revascularisation. It also slows the angiographic progression of atherosclerosis within saphenous vein grafts over a 7.5-year follow-up period [14].
Given that patients treated in cardiothoracic surgical units are referred from multiple sources and are discharged back for continuing care, there is a need for a co-ordinated response to optimise the treatments these patients receive and to ensure all patients are considered. There are a number of strategies to ensure this. Like others, we have previously shown the effectiveness of nurse-led secondary prevention clinics established in primary care using agreed clinical guidelines [6, 15]. This system probably provides the best way to improve uptake of secondary care medications, as well as medium- and long-term compliance.
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5. Limitations
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Our study highlights the use of secondary prevention at only one timepoint, hospital discharge. As such no attempts were made to review admission medication, nor subsequent changes to medication initiated by primary care providers. Furthermore, we did not identify reasons for non-prescribing of secondary preventive medications. This study represents what happens in daily clinical practice, and although we did not specifically investigate the reasons for drug contraindications, absolute contraindications for these medications are generally low. This retrospective review covers a 3–4 year period. During this time, the evidence base has evolved and prescribing practices have potentially changed in accordance with published recommendations.
We were not able in this retrospective study to analyse reasons why ACE-inhibitors or ARBs were not prescribed on discharge, nor whether they might have been temporarily discontinued peri-operatively. A study evaluating decision-making behaviour in this setting may be worthwhile and further research should be performed to establish actual rather than perceived risks of early prescription of ACE-inhibitors in the postoperative setting.
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6. Conclusion
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Although utilisation of secondary preventive therapies has improved compared with previous studies, there is a need for a greater emphasis on ACE-inhibitor use. Our results reinforce the need to have a secondary prevention review process as part of the chosen revascularisation strategy. Within the UK, the NSF and Quality Outcomes Framework (QOF) have stimulated the introduction of mechanisms to ensure a regular review of patients with CHD. The most efficient way of implementing such a review process for patients following revascularisation may be in community secondary prevention clinics with agreed local guidelines and internal audit processes. Such a review process should also be included at the time of surgical follow-up.
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Abstract
1. Introduction
