What are the adverse effects of bile acid binding resins?
GI effects limit the max dose and are a common reason for nonadherence - need to take with lots and lots of water to minimise upper GIT disturbance
ConstipatingCan interfere with drdug absorption esp anticoagulants, thyroxine, cyclosporin, and digoxin
What is third line after a statin plus ezetimibe for dyslipidemia of LDL-C variant?
Bile acid binding resin
What is fourth line therapy for dyslipidemia of the LDL-C kind?
Nicotinc acid - rarely used as is poorly tolerated mainly due to flushing (can give with food and prophylactic aspirin)Can also cause gastric irration, gout and impaired glucose tolerance.Need to monitor BSL, CK, and liver.
Use with caution with a statin (but can be done)
Can you use fibrates with a statin to reduce LDL-C? What do you need to consider?
May lead to 5-10% reduction in LDL-CDoes not increase risk of myopathy beyond the level of statin monotherapy, EXCEPT...
Gemfibrozil - DO NOT DO IT, significantly increases the risk of myositis when given with a statin.
Use fenofibrate instead and monitor CK.
How do you treat hypertriglyceridaemia?
Dietary/behaviour/diabetic control are central.
If severe (>10), or >4 and have low HDL-C (<1) or is associated with increased absolute CVD risk:
Fibrate plus fish oil (Two Fs!) - and probably need to max both out.
Nicotinic acid is third line. Statins are inappropriate
High CVD riskElevated LDL-CMild to moderate elevation of TGLs
What is the treatment?
Statins are first line
High absolute CVD riskLDL-C elevatedTGLs >4
What is first line therapy?
How safely do you treat mixed hyperlipidaemia that is severe? (Mixed = high cholesterol and TGL)
Statin plus fish oilFibrate plus ezetimibe
Statin plus fenofibrate or statin plus nicotinic acid can be done but only with caution.
What are the side effects of Ezetimibe?
SteatorrheaMyalgia and rhabdo have been repeatedRaise ALT/AST
NOT CYP450 so limited drug interactionsAvoid in mod-severe liver impairment (no data)
What are the risk factors for developing liver and muscle problems from lipid-modifying therapy?
Risk factors for these adverse effects include pre-existing muscle, liver or kidney disease, high-dose therapy, concomitant interacting drugs, intercurrent illness, frailty and advanced age.
How do you monitor lipid modifying therapy?
Basleine LFTS and when you assess response to lipids - 1-2 months post initiation/dose adjustment
No need to routinely monitor CK/LFT if asymptomatic - unless on combination therapy
If asymptomatic CK elevation - avoid exercise for a few days. Continiue if CK is not >5 ULN
When should you stop lipid-modifying therapy?
Mild muscle sx - still benefit from max dose, try second daily or twice weekly
previously normal ALT is persistently more than 3 times ULN
CK is more than 10 times ULN
CK is more than 5 times ULN and patient has muscle symptoms
patient has persistent unexplained muscle pain
patient has persistent unexplained muscle weakness.
What do you do if someones muscles or liver enzymes normalise after you stop lipid-modifying therapy?
If the symptoms were mild, drug can be restarted (at a lower dose), if it recurs - change statin or go to alternative lipid modifying drug
Which lipid-modifying agents impair glucose metabolism?
High-dose statins may slightly impair glucose metabolism, while nicotinic acid can cause impaired glucose tolerance as well as hyperuricaemia and gout. Check blood glucose before starting therapy, and repeat 1 to 2 months after starting therapy or adjusting the dose.
Which lipid modifying drugs affect the CK and ALT respectively?
CK: statin > fibrate > nicotinic acid or ezetimibe
ALT: nicotinic acid > ezetimibe > fibrate > statin
What lipid tests are required to calculate absolute CVD risk?
What are the drawbacks of this?
TC (total cholesterol) and HDL-C
TC may overestimate risk of HDL-C is raisedTC may underestimate risk of TGLs are raised
Predictive value is improved by considering LDL-C and HDL-C independently
What impact does significantly elevated triglycerides have on the measurement of cholesterol and LDL-C?
LDL composition changes when TGL >2mmol - in this case, non-HDL-c becomes a better indicator than LDL-c - LDL-C requires a fasting sample and becomes unreliable if TGLs exceed 4mmol
How do statins reduce LDL?
Reduce liver cholesterol synthesisIncreased LDLr and SREBP gene expressionReceptors produced by normal gene (even in familial disease) will reduce LDL cholesterol levels.
What are the target lipid levels for patients on lipid-modifying therapy?
total cholesterol (TC) - less than 4.0 mmol/L
low-density lipoprotein cholesterol (LDL-C) - less than 2.0 mmol/L
high-density lipoprotein cholesterol (HDL-C) - more than 1.0 mmol/L
triglycerides -less than 2.0 mmol/L
non–high-density lipoprotein cholesterol (non–HDL-C) - less than 2.5 mmol/L
What are the target LDL-C levels in those with familial hypercholesterolaemia?
Target plasma levels for LDL-cholesterol for low, intermediate an d high risk FH are < 4, < 3 and < 2 mmol/L, respectively
Which subset of familial hypercholesterolaemia patients benefits the most from statins?
Statin treatment of FH males is one of the most cost-effective medical interventions available and several lines of evidence point towards major improvements in CVD event rates and total mortality of FH patients since its introduction. Still evolving for younger patients.
What does this ECG show?
Broad QRS >120msRSR pattern in V1-V3Wide slurred S wave in lateral leads (I, AVL, V5-V6)
What syndrome do you need to be mindful of when diagnosing a RBBB on ECG?
An RSR’ pattern in V1-3 may also be caused by Brugada syndrome – an ECG pattern associated with malignant ventricular arrhythmias.
When is treatment stress testing indicated?
Symptoms of known or probably ischaemic heart diseaseStable chest painUnstable chest pain stabilised by medical therapyPost MIPost revascularisation
What are the absolute contraindications to EST?
Acute MIUnstable anginaSymptomatic uncontrolled cardiac arrhythmiaSevere ASAcute PE or pulm infarctAcute myocarditis or pericarditisAcute aortic dissection
What are the most important pre-test predictive parameters of CAD?
Diagnostic power of EST is maximal when the pretest probability is intermediate (30-70%)
What are the indications for PCI?
Clinical indications for PCI include the following:
Acute ST-elevation MI (STEMI) Non–ST-elevation acute coronary syndrome (NSTE-ACS) Stable angina Anginal equivalent (eg, dyspnea, arrhythmia, or dizziness or syncope) Asymptomatic or mildly symptomatic patient with objective evidence of a moderate-sized to large area of viable myocardium or moderate to severe ischemia on noninvasive testing
Angiographic indications include hemodynamically significant lesions in vessels serving viable myocardium (vessel diameter >1.5 mm).
What is the evidence behind CTCA?
Meta-analyses of over 45 single-centre studies have consistently shown CTCA to have excellent sensitivity (98%) and very good specificity (88%) compared with invasive coronary angiography for significant disease (stenosis > 50%).5,8,9 The negative predictive values (96%–100%) were better than positive predictive values (93%), demonstrating CTCA to be an excellent tool for ruling out significant disease in patients with low-to-intermediate pretest probability of CAD.
What are the indications for CTCA in the evaluation of non-acute chest pain?
Evaluation of chest pain with no previous known disease:
able to exercise and no previous tests (intermediate risk)
unable to exercise or ECG uninterpretable (low-to-intermediate risk)
equivocal or uninterpretable stress test results
normal ECG exercise test but ongoing symptoms.
What are the indications for CTCA with acute chest pain?