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

32 ESC <strong>Guidelines</strong>24 h and a 17/8 mmHg difference during the night, comparedwith 8/2 mmHg with office measurements in thesame study. 464 In EUROPA, patients with uncontrolled hypertension(.180/100 mmHg) were also excluded, and themean blood pressure at baseline was 137/82 mmHg. Theoverall blood pressure difference between perindopril andplacebo treatment was 5/2 mmHg, 461 but larger differencesmay have occurred in subgroups of patients. However, analysisof the effect of treatment according to tertiles or quartilesof baseline blood pressure or fall in blood pressure ontreatment shows significant benefit in all groups, eventhose in the lowest baseline blood pressure or smallestreduction in blood pressure with treatment. 465 Benefits ofblood pressure reductions may be expected in subgroupsof patients with clearly elevated blood pressure, but loweringblood pressure is associated with a lowering of cardiovascularrisk also in the ‘normal’ range. 466 Thus, it is difficult toseparate blood pressure-related effects from bloodpressure-independent protection afforded by ACE-inhibitionin stable angina pectoris.Further clues regarding the effect of blood pressure loweringand ACE-inhibition in stable coronary disease may beobtained from the CAMELOT trial. 467 In this study, patientswith angiographic evidence of coronary disease, althoughnot necessarily obstructive, and normal blood pressure(mean BP 129/78 mmHg) were randomized to amlodipine,enalapril, or placebo and followed-up for 2 years. Sixtypercent of the patients had hypertension and they werewell treated in other respects (83% on statins, 75% on a betablocker,and 95% on aspirin). Blood pressure reductions(5 mm/2 mm) were almost identical in the two active treatmentgroups. The study was not powered to show effects on‘hard’ endpoints (670 patients per group), but a ‘post hoc’analysis of the combined endpoint of cardiovascular death,stroke, and MI showed similar non-significant relative riskreductions with enalapril (29%) and amlodipine (30%).Furthermore, an IVUS substudy in 274 patients showed a significantcorrelation between the progression of atheromaand the reduction in blood pressure even at this ‘normal’range of blood pressure. The recently presented VALUEstudy, which compared antihypertensive treatment withamlodipine or valsartan in 15 245 patients (46% of whomhad CAD) during 4.2 years, found that blood pressure loweringwas more important than the type of drug used. 468 Thesestudies support the contention that the benefits of loweringblood pressure extend into the ‘normal’ blood pressurerange, as suggested by epidemiological data, 466 and thateffects on outcome of blood pressure lowering are similarwith ACE-inhibitors or ARBs when compared with calciumantagonists. 457,458 A report from the ASCOT study claimsthat blood pressure alone does not account for differencesin outcome between different blood pressure treatmentregimens, with the combination of CCBs and ACE-inhibitortherapy achieving greater reduction in clinical events thanthe combination of beta-blocker and diuretic. 469 However,the accompanying editorial points out that blood pressuredifferences may fully explain the differences in outcomebetween the two groups. 470 The benefits of blood pressurelowering in the normal range, are likely to be greatest inthose at highest absolute risk, 471 particularly those withestablished vascular disease, but the level of blood pressurebelow which clinically appreciable benefit may be observedhas not been established.The blood pressure lowering effects of ramipril and perindoprilcompared with placebo, thus probably contributedto the risk reduction in the HOPE and EUROPA studies, butadditional cardioprotection may also be afforded byACE-inhibitors. 441 Furthermore, ACE-inhibition is well establishedin the treatment of heart failure or LV dysfunction, 472and in the treatment of diabetic patients with renal involvement.370 Thus, it is appropriate to consider ACE-inhibitorsfor the treatment of patients with stable angina pectorisand co-existing hypertension, diabetes, heart failure,asymptomatic LV dysfunction, or post-MI. In angina patients,without co-existing indications for ACE-inhibitor treatmentthe anticipated benefit of treatment (possible ARR)should be weighed against costs and risks for side-effects,and the dose and agent used of proven efficacy for thisindication.Effects of ARB treatment on prognosis in ischaemic heartdisease are less well studied, but the VALIANT studyshowed similar effects of valsartan and captopril treatmentin post-MI patients with heart failure. 473 However, theCHARM-preserved study 474 showed no significant benefit ofcandesartan compared with placebo in patients with preservedventricular function. Thus, ARB treatment may beappropriate therapy for the treatment of heart failure,hypertension, or diabetic renal dysfunction in patientswith angina when ACE-inhibition is indicated but not tolerated,but there is no indication for ARB therapy in patientswith preserved ventricular function without diabetes as asecondary preventive agent.Hormone replacement therapy. Epidemiological evidencesuggested substantial cardiovascular benefits of postmenopausaluse of hormone replacement therapy (HRT).More recently, however, properly designed prospective,double-blind, placebo-controlled trials have shown thatHRT with a combination of oral oestrogen/progestinoffered no cardiovascular benefit among women withestablished disease 475,476 and that there is an increasedrisk of developing CVD in primary prevention, and also anincreased risk of suffering breast cancer. 477 Primaryprevention with unopposed oestrogen therapy in hysterectomizedwomen offered no cardiovascular protection. 478New guidelines therefore recommend against routine useof HRT for chronic conditions 349 and current users havebeen advised to taper doses downwards towardsdiscontinuation. 479Beta-blockers. The risk of suffering cardiovascular death orMI was reduced by beta-blockers by some 30% in post-MItrials. 480 A recent meta-regression analysis of the effectsof different beta-blockers on mortality found non-significantbenefits of acute treatment, but a significant 24% relativerisk reduction in mortality with long-term secondary preventivetreatment. 481 Beta-blockers with intrinsic sympathomimeticactivity appeared to provide less protection, and itwas pointed out that the most frequently prescribedagent, atenolol, had poor documentation regarding mortalityafter MI. 481 Also, a recent meta-analysis of atenololtrials in hypertension questioned the prognostic benefitafforded by this drug 482 even though beta-blockers as agroup provided similar protection as other antihypertensivedrugs in previous meta-analyses. 457,458 It has beenextrapolated from the post-MI trials that beta-blockersmay be cardioprotective also in patients with stable