Guidelines on the Management of Stable Angina Pectoris ... - Cardio

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44 ESC <strong>Guidelines</strong>CHD death and MI is greater in men than in women at allages, the incidence of angina in women exceeds that ofmen in post-menopausal age groups. Therefore, it is not surprisingthat at population level, some studies report an evenhigher prevalence of Rose angina questionnaire in middleaged and elderly women than in men of comparableage. 31–33,621,622 However, in population-based studies, theincidence of fatal CHD is higher in men with angina thanwomen with angina, 620 possibly partly due to misclassificationof angina as CHD in a proportion of women.The diagnosis of angina in women is more difficult than inmen for several reasons. Atypical symptoms are morecommon in women, but this is ‘atypical ’ compared withthe typical symptoms described by men. Patient perceptionof pain and the language used to report symptoms aredifferent between men and women. 623To compound the problem, the correlation betweensymptoms and ‘significant’ luminal obstruction at coronaryangiography is weaker in women than in men. In theCoronary Artery Surgery Study, 624 62% of women withtypical angina had significant coronary stenoses, when comparedwith 40% of women with atypical angina and 4% ofwomen with non-ischaemic pain, illustrating the lowerprevalence of angiographically verified CHD in women thanin men for all forms of chest pain, including typical andatypical angina and non-cardiac chest pain.Angina, the symptom complex, may still be associatedwith ischaemia even in the absence of obstructive coronarylesions, as in Syndrome X, a phenomenon which is morecommon in women. Microvascular disease and coronaryvasospasm are also more common in women. Ischaemia, inthis context, may be demonstrated electrocardiographically,by perfusion scintigraphy, or other methods and mayrespond appropriately to anti-ischaemic therapy withoutangiographic evidence of epicardial stenosis. Although theabsence of obstructive coronary lesions remains an indicatorof better infarct-free survival than the presence of obstructivedisease, there are some emerging data suggesting thatthe prognosis associated with ‘normal’ coronary arteries isnot as benign as once thought. 305When used for the detection of significant coronarydisease, exercise ECG testing has a higher false-positiverate in women (38–67%) than in men (7–44%), 140 largelybecause of the lower pretest likelihood of disease, 142 but alower false-negative rate in women. 625 This results in a highnegative predictive value, signifying that a negative resultof non-invasive testing reliably excludes the presence ofCAD. The difficulties of using exercise testing for diagnosingobstructive CAD in women have led to speculation thatstress imaging may be preferred over standard stresstesting. Myocardial perfusion scintigraphy or echocardiographycould be a logical addition to treadmill testing inthis circumstance. However, the sensitivity of radionuclideperfusion scans may be lower in women than men. 626Artefacts due to breast attenuation, usually manifest in theanterior wall, can be an important caveat in the interpretationof women’s perfusion scans, especially when 201 Tl isused as a tracer. More recently, the use of gated 99 mTc sestamibiSPECT imaging has been associated with an apparentreduction in breast artefacts. 627 Similarly, exercise orpharmacological stress echocardiography may help avoidartefacts specifically due to breast attenuation. Indeed,numerous studies have indicated the value of stressechocardiography as an independent predictor of cardiacevents in women with known or suspected CAD. 171,628,629Despite its limitations in women, routine exercise ECGtesting has been shown to reduce procedures without loss ofdiagnostic accuracy. Indeed, only 30% of women (in whom areasonably certain diagnosis of CAD could not be reached orexcluded) need to be referred for further testing. 630Although the optimal strategy for diagnosing obstructive CADin women remains to be defined, the Task Force believesthat there are currently insufficient data to justify replacingstandard exercise testing with stress imaging in all womenbeing evaluated for CAD. In many women with a low pretestlikelihood of disease, a negative exercise test result will be sufficientand imaging procedures will not be required. 630It is important to emphasize that women with objectiveevidence of moderate-to-severe ischaemia at non-invasivetesting should have equal access to coronary arteriographyas men. Furthermore, limited female representation in clinicaltrials of secondary prevention to date is not a justificationto apply guidelines differently to men and womenafter CAD is diagnosed.It is known that women have a higher morbidity and mortalityafter suffering MI than men, and it has been suggestedby some that less vigorous treatment in women may impacton reduced survival in women after MI. 631 A review of 27studies concluded that the reasons for increased early mortalityamong women were older age and the presence ofother unfavourable baseline clinical characteristics. 632Subsequent investigation found an interaction betweengender and age, with a female excess of mortality inyounger patients (,50 years of age) that diminishes withage. 633Reports of the impact of gender on utilization of investigationsand therapies and on subsequent clinical outcomein stable settings are similarly divergent. In a recent Dutchstudy, 1894 patients (1526 men and 368 women) with angiographicallydocumented CAD were evaluated over a 16-yearperiod (1981–97). Over time, the number of angioplasty proceduresincreased significantly from 11.6–23.2% for men andfrom 17.6–28.0% for women, whereas the number of coronaryartery bypass procedures decreased in men from 34.9%to 29.5% and from 42.6–30.6% in women. 634 However,interpretation of this and other coronary arteriographyregistries is limited by their intrinsic referral bias. Datafrom the Euro Heart Survey of Stable Angina conducted in2003 suggest that significant bias exists against the use,not just of arteriography but also of exercise testing inwomen, even after adjustment for factors such as age,comorbidity, severity of symptoms, and, in the case of arteriography,results of non-invasive testing. 635 In the samestudy, women were less likely to receive revascularizationand were less likely to receive effective secondary preventivemedical therapy. Such findings suggest that the perceiveddifficulties in diagnosis and limited female-specificliterature regarding the treatment of angina, alongperhaps with more complex social issues, have perpetuatedthe situation where women with stable angina often remainunder-investigated and under-treated.Diabetes mellitusBoth insulin-dependent diabetes mellitus (type 1) andnon-insulin-dependent diabetes mellitus (type 2) are associatedwith an increased risk of CVD. Furthermore, CHD
ESC <strong>Guidelines</strong> 45mortality is increased three-fold in diabetic men and two- tofive-fold in diabetic women, compared with age- and sexmatchednon-diabetic persons. 81,636–638 Moreover, anumber of epidemiological reports indicate that in patientswith diabetes, the higher the blood glucose, the greater theincidence of CVD. 639,640The clinical manifestations of CHD in diabetic subjects aresimilar to those in non-diabetic patients, with angina, MI,and heart failure being the most prominent, but the symptomstend to occur at an earlier age in diabetic patients.It is generally accepted that the prevalence of asymptomaticischaemia is increased in patients with diabetes.However, because of considerable variation in inclusionand exclusion criteria as well as screening tests in studiesto date, it is somewhat difficult to estimate the increasedfrequency of silent ischaemia accurately. 641There is growing interest in the use of myocardial perfusionscanning and other techniques to detect ischaemia in asymptomaticdiabetic individuals 642 and firm evidence of the prognosticpower of perfusion imaging specifically in diabeticpatients. 643 There are also data to suggest that individualswith diabetes may have subclinical ventricular dysfunctionwhich negatively impacts on exercise capacity, 644 an importantendpoint of exercise testing, but the impact of thisfinding on the diagnostic and prognostic information yieldedby conventional testing in a symptomatic population is notclear. Thus, the cardiac assessment of symptomatic ischaemiain diabetic patients should, in general, parallel that in nondiabeticsubjects, with similar indications for exercisetesting, myocardial perfusion testing, and coronary arteriography.As CVD accounts for 80% of mortality in patientswith diabetes mellitus, 645 emphasis should be placed onearly diagnosis and aggressive treatment in this population.Current strategies for optimal care of patients with diabetesmellitus include vigorous and persistent efforts toachieve physiological control of blood glucose and controlof other risk factors such as dyslipidaemia, renal disease,obesity, and smoking. Abundant evidence that long-termmaintenance of near-normal blood glucose levels is protectiveof patients with diabetes and substantially reducescomplications and mortality in both diabetes type 1 andtype 2 is now available. 645–648Conventional therapies for CHD with nitrates, betablockers,calcium-channel blockers, statins, antiplateletsagents, and coronary revascularization procedures havesimilar indications in diabetic and non-diabetic patients.Additionally, ACE-inhibitors are indicated in diabeticpatients with proven vascular disease. 253 The relativemerits of PCI and CABG in diabetic patients are discussedin the section on Revascularization. Unfortunately, owingto the chronic metabolic disturbances of diabetes mellitus,these patients usually have a continuous progression ofnative atherosclerotic disease, leading to an extensiveCHD with high rates of multi-vessel disease and of restenosis.649,650 Thus, even after successful invasive procedures,good management of CVD risk factors and a tight glycaemiccontrol are essential for good long-term outcome. 638ElderlyAfter the age of 75 years there is an equal prevalence of CADin men and women. 651 The disease is more likely to bediffuse and severe; LM coronary artery stenosis and threevesseldisease are more prevalent in older patients, as isimpaired LV function. The evaluation of chest pain syndromesin the elderly can be difficult because complaintsof chest discomfort, weakness, and dyspnoea are common,and co-morbid conditions that mimic angina pectoris arefrequently present. Reduced activity levels and bluntedappreciation of ischaemic symptoms become the norm withadvancing age. 652 In large community studies of men andwomen .65-years old, those with atypical symptoms andtypical angina were shown to have similar 3 year cardiacmortality rates. 20 The performance of exercise testingposes additional problems in the elderly. Functional capacityoften is compromised from muscle weakness and deconditioning.More attention must be given to the mechanicalhazards of exercise, and less challenging protocols may bemore appropriate. Arrhythmias occur more frequently withincreasing age, especially at higher workloads. 653 Theinterpretation of exercise test results in the elderly differsfrom that in the young. The higher prevalence of diseasemeans that more test results are false negative. 654 Falsepositivetest results also are more frequent because of thehigher prevalence of confounders such as prior MI, LV hypertrophyfrom valvular diseases, hypertension and conductiondisturbances. Despite these differences, exercise testingremains important also in the elderly. The Task Forcebelieves that exercise ECG testing should remain the initialtest in evaluating elderly patients with suspected of CADunless the patient cannot exercise, in which case it may bereplaced by pharmacological stress imaging.It is important to emphasize that elderly patients withobjective evidence of moderate-to-severe ischaemia at noninvasivetesting should have similar access to coronary arteriographyas younger patients. Notably, diagnostic coronaryarteriography has relatively little increased risk (comparedwith younger patients) in older patients undergoing electiveevaluation. 243 However, age .75 is an important predictorof contrast-induced nephropathy. 655Medical treatment is more complex in elderly patients.Indeed, changes in drug bioavailability, elimination, andsensitivity mean that dose modification is essential whenprescribing cardiovascular drugs to elderly patients. 656Further issues which should be taken into account whenprescribing for the elderly include risk of drug interactions,polypharmacy, and compliance problems. Nevertheless, inthis patient population, anti-anginal medications are asefficacious in reducing symptoms and statins in improvingprognosis, 438 as they are in young patients. Consideringsymptoms as well as prognosis, elderly patients have thesame benefit from medical therapy, angioplasty, andbypass surgery as younger patients. 657–659Chronic refractory anginaDrugs and revascularization procedures, i.e. CABG and percutaneoustransluminal angioplasty, can adequatelymanage the majority of patients suffering from ischaemicheart disease. However, there are patients who remainseverely disabled by angina pectoris in spite of differentforms of conventional treatment. It is an unfortunate ironythat the prolongation of life due to the improvement ofcardiovascular care and treatment are responsible for anincrease in the number of patients with end-stage ischaemiccoronary disease, some who complain from intractable episodesof angina. The problem of chronic refractory angina
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