Glycemic Control in Non-ST-Segment Elevation Acute Myocardial Infarction and Unstable Angina
There is no RCT evidence for tight glycemic control improving outcomes in diabetic patients with non-ST-segment elevation acute myocardial infarction and unstable angina. Conventionally, however, intravenous insulin infusions are used for 24 hours in hyperglycemic patients, but the warnings of the CREATE/OASIS analysis should be heeded, so minimizing fluid volumes and careful monitoring of serum potassium are important. However, regardless of management during the index event, good glycemic control (e.g. HbA1c < 7.0%, 53 mmol/mol) in PCI patients is associated with a lower risk of the need for target vessel revascularization at 12 months. The specific regimen used to achieve this level of control is probably not important.
Percutaneous Coronary Intervention in Diabetes and ACS
Primary PCI has replaced thrombolysis in STEMI. It has the same advantages over thrombolysis as for non-diabetic patients and should be undertaken wherever possible, though 30-day mortality is nearly twice as high . Periprocedural glycoprotein (GP)IIa/IIIb inhibitor treatment and 12 months of clopidogrel decrease the risk of longer-term events, but they are still more common in people with diabetes. Although there is controversy over the use of bare-metal versus drug-eluting stents, diabetic patients appear to have a generally better outlook with drug-eluting stents, although secondary prevention medication is more intensive in these patients, and may account for some of the benefit.
Coronary intervention versus optimum medical treatment in stable multivessel disease: BARI and COURAGE
The first BARI study (1996), in the pre-stent era, found that coronary artery bypass graft (CABG) carried a better 5-year survival in diabetic (but not in non-diabetic) patients, and this advantage was maintained up to 10 years. CABG also reduced the risk of fatal reinfarctions. BARI 2D (2009)  studied only type 2 patients with stable symptoms and angiographically characterized coronary artery disease. A complex study, it was designed to mimic real-life decision-making and to promote joint clinical decision-making between cardiologists and diabetologists. A decision for either PCI or CABG was made on the angiographic findings, and therefore importantly this was not a randomized trial of PCI versus CABG in multivessel disease (the FREEDOM trial is currently addressing this ). There were two subsequent randomizations:
- prompt intervention (target within 4 weeks) as decided at angiography (and intensive medical treatment) versus intensive medical treatment alone, reserving the predetermined intervention to a later time if clinically needed;
- insulin-sensitizing regimen (metformin and rosiglitazone) versus insulin-providing regimen (various insulins, sulphonylureas and meglitinides). Targets for control of blood pressure and low-density lipoprotein (LDL) were exceeded, though the HbA1c target was not quite reached:
- HbA1c 7.2% (55 mmol/mol), target < 7.0% (53 mmol/mol);
- blood pressure 125/70 mmHg, target < 130/80 mmHg;
- LDL 2.05 mmol/L (80 mg/dL), target < 2.6 mmol/L (100 mg/dL).
The PCI-intended group had, not surprisingly, less advanced coronary artery disease (two versus three significant coronary lesions, 10% vs. 20% proximal left anterior descending artery lesions). The key findings are summarized in Box 3.1.
Post-Coronary Interventions (adapted from COURAGE, 2007)
These recent studies have reinforced the importance of lifestyle modification and medications after a coronary event.
- Exercise: post-myocardial infarction rehabilitation programmes can be effectively and more economically delivered at home than at a formal centre . COURAGE recommended 30–45 min of moderate-intensity exercise five times per week and an increase in daily lifestyle activity.
- Smoking cessation: bizarrely, patients with diabetes appear less likely to receive inpatient smoking cessation counselling after myocardial infarction than non-diabetic people. For those who receive counselling, there is a significant mortality benefit . Currently, varenicline is the most effective pharmacological adjunctive treatment, although side-effects, including nausea, headache, sleep disturbance and gastrointestinal symptoms, are common. Because of its pharmacology (partial agonist of the a4/J32 nicotinic acetylcholine receptor while competitively inhibiting nicotine binding), there has been concern that it may increase cardiovascular risk factors, but it is probably safe in stable coronary artery disease, though it should not be used in the phase immediately after myocardial infarction. Severe recurrent hypoglycemia has also been reported in a type 1 patient, so use with caution in this situation.
- Diet: there is limited RCT evidence, but adherence to a portfolio of diet advice and components is likely to be beneficial:
- Weight reduction: target BMI 27.5
- ‘Mediterranean’ diet  (see Chapter 5)
- Low total and saturated fat and low dietary cholesterol
- Low salt
- Recommended alcohol intake where appropriate
- Increased soluble/insoluble fibre
- Increased oily fish (two portions per week)
- Avoid ‘antioxidant’ vitamin supplements
- ~50 g dark (> 70% cocoa) chocolate/day.
- HbA1c ~ 7.0–7.5% (53–58 mmol/mol) without hypoglycemia; emphasize insulin-sensitizing drugs.
- Avoid glibenclamide.
- Role of GLP-1 analogues in cardioprotection not yet established in RCTs.
Lipids (see Chapter 12)
- LDL target < 1.7–1.8 mmol/L (66–70 mg/dL). Intensive statin therapy started within 14 days of hospitalization for ACS reduces death and cardiovascular events after 4 months of treatment. Most clinical trials have used high-dose atorvastatin (80 mg daily), which has a good safety record in this situation. Compliance with statin treatment is also higher if it is started in hospital rather than after discharge .
- HDL as high as possible; triglycerides <1.7 mmol/L (150 mg/dL) (consider niacin or pharmacological doses of fish oils).
- Omega (ω)-3 fatty acids: DHA (docosahexenoic acid) plus EPA (eicosapentenoic acid) 1 g daily starting within 3 months of event.
- ACE inhibitor (ACE-i) to maximum recommended dose; ARB only if ACE-i side-effects.
- Aspirin with or without clopidogrel.
Class 3 obesity (BMI > 40) is associated with an increased risk of sustained atrial fibrillation (AF), and this effect is in part mediated by diabetes. Diabetes is one of the factors in the CHADS risk score (www.mdcalc.com) that identifies aspirin-treated AF patients at increased risk of stroke. Patients with a score of 3 or more have a stroke risk of about 4 per 100 patient-years of aspirin, and long-term warfarin should be considered. In GISSI-AF (2009) the ARB valsartan did not prevent recurrence of AF, but several studies have found that new-onset AF is less frequent in patients treated with ARBs. Although an ARB can be used for other cardiovascular risk factors (albuminuria, hypertension), there is no RCT evidence yet for their routine use in hypertensive patients without ventricular hypertrophy or diastolic dysfunction in the primary prevention of AF .
For more information and to purchase this book, just follow this link:
David Levy, MD, FRCP, Consultant Physician, Gillian Hanson Centre, Whipps Cross University Hospital; Honorary Senior Lecturer
Queen Mary University of London London, UK
This edition first published 2011, © 2011 by David Levy. 1st edition 1998 (Greenwich Medical Media/Cambridge University Press) 2nd edition 2006 (Altman Publications)