Sanne E. Hoeks

The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials

Objectives To investigate whether statins reduce all cause mortality and major coronary and cerebrovascular events in people without established cardiovascular disease but with cardiovascular risk factors, and whether these effects are similar in men and women, in young and older (>65 years) people, and in people with diabetes mellitus. Design Meta-analysis of randomised trials. Data sources Cochrane controlled trials register, Embase, and Medline. Data abstraction Two independent investigators identified studies on the clinical effects of statins compared with a placebo or control group and with follow-up of at least one year, at least 80% or more participants without established cardiovascular disease, and outcome data on mortality and major cardiovascular disease events. Heterogeneity was assessed using the Q and I2 statistics. Publication bias was assessed by visual examination of funnel plots and the Egger regression test. Results 10 trials enrolled a total of 70 388 people, of whom 23 681 (34%) were women and 16 078 (23%) had diabetes mellitus. Mean follow-up was 4.1 years. Treatment with statins significantly reduced the risk of all cause mortality (odds ratio 0.88, 95% confidence interval 0.81 to 0.96), major coronary events (0.70, 0.61 to0.81), and major cerebrovascular events (0.81, 0.71 to 0.93). No evidence of an increased risk of cancer was observed. There was no significant heterogeneity of the treatment effect in clinical subgroups. Conclusion In patients without established cardiovascular disease but with cardiovascular risk factors, statin use was associated with significantly improved survival and large reductions in the risk of major cardiovascular events.

Guidelines for pre-operative cardiac risk assessment and perioperative cardiac management in non-cardiac surgery

The American College of Cardiology, American Heart Association, and the European Society of Cardiology are all in the process of completing updated versions of our Guidelines for Perioperative Care. Our respective writing committees are undertaking a careful analysis of all relevant validated studies and always incorporate appropriate new trials and meta-analyses into our evidence review. In the interim, our current joint position is that the initiation of beta blockers in patients who will undergo non-cardiac surgery should not be considered routine, but should be considered carefully by each patients treating physician on a case-by-case basis. Please see the expression of concern which is free to view in Eur Heart J (2013) 34 (44): 3460; doi: 10.1093/eurheartj/eht431. AAA : abdominal aortic aneurysm ACC : American College of Cardiology ACE : angiotensin-converting enzyme ACS : acute coronary syndrome AHA : American Heart Association AR : aortic regurgitation ARB : angiotensin receptor blocker AS : aortic stenosis AF : atrial fibrillation BBSA : β-blocker in spinal anaesthesia BNP : brain natriuretic peptide CABG : coronary artery bypass grafting CARP : coronary artery revascularization prophylaxis CASS : coronary artery surgery study CI : confidence interval COX-2 : cyclooxygenase-2 COPD : chronic obstructive pulmonary disease CPET : cardiopulmonary exercise testing CPG : Committee for Practice Guidelines CRP : C-reactive protein CT : computed tomography cTnI : cardiac troponin I cTnT : cardiac troponin T CVD : cardiovascular disease DECREASE : Dutch Echocardiographic Cardiac Risk Evaluating Applying Stress Echo DES : drug-eluting stent DIPOM : Diabetes Postoperative Mortality and Morbidity DSE : dobutamine stress echocardiography ECG : electrocardiography ESC : European Society of Cardiology FEV1 : forced expiratory volume in 1 s FRISC : fast revascularization in instability in coronary disease HR : hazard ratio ICU : intensive care unit IHD : ischaemic heart disease INR : international normalized ratio LMWH : low molecular weight heparin LQTS : long QT syndrome LR : likelihood ratio LV : left ventricular MaVS : metoprolol after surgery MET : metabolic equivalent MI : myocardial infarction MR : mitral regurgitation MRI : magnetic resonance imaging MS : mitral stenosis NICE-SUGAR : normoglycaemia in intensive care evaluation and survival using glucose algorithm regulation NSTEMI : non-ST-segment elevation myocardial infarction NT-proBNP : N-terminal pro-brain natriuretic peptide NYHA : New York Heart Association OPUS : orbofiban in patients with unstable coronary syndromes OR : odds ratio PaCO2 : mixed expired volume of alveolar and dead space gas PAH : pulmonary arterial hypertension PETCO2 : end-tidal expiratory CO2 pressure PCI : percutaneous coronary intervention PDA : personal digital assistant POISE : PeriOperative ISchaemic Evaluation trial QUO-VADIS : QUinapril On Vascular ACE and Determinants of ISchemia ROC : receiver operating characteristic SD : standard deviation SMVT : sustained monomorphic ventricular tachycardia SPECT : single photon emission computed tomography SPVT : sustained polymorphic ventricular tachycardia STEMI : ST-segment elevation myocardial infarction SVT : supraventricular tachycardia SYNTAX : synergy between percutaneous coronary intervention with taxus and cardiac surgery TACTICS : treat angina with aggrastat and determine cost of therapy with an invasive or conservative strategy TIA : transient ischaemic attack TIMI : thrombolysis in myocardial infarction TOE : transoesophageal echocardiography UFH : unfractionated heparin VCO2 : carbon dioxide production VE : minute ventilation VHD : valvular heart disease VKA : vitamin K antagonist VO2 : oxygen consumption VPB : ventricular premature beat VT : ventricular tachycardia Guidelines and Expert Consensus Documents aim to present management and recommendations based on the relevant evidence on a particular subject in order to help physicians to select the best possible management strategies for the individual patient suffering from a specific condition, taking into account not only the impact on outcome, but also the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines are no substitutes for textbooks. The legal implications of medical guidelines have been discussed previously.1 A great number of Guidelines and Expert Consensus Documents have been issued in recent years by the European Society of Cardiology (ESC) and also by other organizations or related societies. Because of the impact on clinical practice, quality criteria for development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC guidelines and Expert Consensus Documents can be found on the ESC website in the guidelines section (www.escardio.org). In brief, experts in the field are selected and undertake a comprehensive review of the published evidence for management and/or prevention of a given condition. …

Guidelines for pre-operative cardiac risk assessment and perioperative cardiac management in non-cardiac surgery: The task force for preoperative cardiac risk assessment and perioperative cardiac management in non-cardiac surgery of the European society of Cardiology (ESC) and endorsed by the European society of anaesthesiology (ESA)

ESC Committee for Practice Guidelines (CPG): Alec Vahanian (Chairperson) (France), Angelo Auricchio (Switzerland), Jeroen J. Bax (The Netherlands), Claudio Ceconi (Italy), Veronica Dean (France), Gerasimos Filippatos (Greece), Christian Funck-Brentano (France), Richard Hobbs (UK), Peter Kearney (Ire

Percutaneous left ventricular assist devices vs. intra-aortic balloon pump counterpulsation for treatment of cardiogenic shock: a meta-analysis of controlled trials

AIMS Studies have compared safety and efficacy of percutaneous left ventricular assist devices (LVADs) with intra-aortic balloon pump (IABP) counterpulsation in patients with cardiogenic shock. We performed a meta-analysis of controlled trials to evaluate potential benefits of percutaneous LVAD on haemodynamics and 30-day survival. METHODS AND RESULTS Two independent investigators searched Medline, Embase, and Cochrane Central Register of Controlled Trials for all controlled trials using percutaneous LVAD in patients with cardiogenic shock, where after data were extracted using standardized forms. Weighted mean differences (MDs) were calculated for cardiac index (CI), mean arterial pressure (MAP), and pulmonary capillary wedge pressure (PCWP). Relative risks (RRs) were calculated for 30-day mortality, leg ischaemia, bleeding, and sepsis. In main analysis, trials were combined using inverse-variance random effects approach. Two trials evaluated the TandemHeart and a recent trial used the Impella device. After device implantation, percutaneous LVAD patients had higher CI (MD 0.35 L/min/m(2), 95% CI 0.09-0.61), higher MAP (MD 12.8 mmHg, 95% CI 3.6-22.0), and lower PCWP (MD -5.3 mm Hg, 95% CI -9.4 to -1.2) compared with IABP patients. Similar 30-day mortality (RR 1.06, 95% CI 0.68-1.66) was observed using percutaneous LVAD compared with IABP. No significant difference was observed in incidence of leg ischaemia (RR 2.59, 95% CI 0.75-8.97) in percutaneous LVAD patients compared with IABP patients. Bleeding (RR 2.35, 95% CI 1.40-3.93) was significantly more observed in TandemHeart patients compared with patients treated with IABP. CONCLUSION Although percutaneous LVAD provides superior haemodynamic support in patients with cardiogenic shock compared with IABP, the use of these more powerful devices did not improve early survival. These results do not yet support percutaneous LVAD as first-choice approach in the mechanical management of cardiogenic shock.

Long-Term Prognosis of Patients With Peripheral Arterial Disease: A Comparison in Patients With Coronary Artery Disease

OBJECTIVES This study was designed to compare the long-term outcomes of patients with peripheral arterial disease (PAD) with a risk factor matched population of coronary artery disease (CAD) patients, but without PAD. BACKGROUND The PAD is considered to be a risk factor for adverse late outcome. METHODS A total of 2,730 PAD patients undergoing vascular surgery were categorized into groups: 1) carotid endarterectomy (n = 560); 2) elective abdominal aortic surgery (AAA) (n = 923); 3) acute AAA surgery (r-AAA) (n = 200), and 4) lower limb reconstruction procedures (n = 1,047). All patients were matched using the propensity score, with 2,730 CAD patients who underwent coronary angioplasty. Survival status of all patients was obtained. In addition, the cause of death and complications after surgery in PAD patients were noted. The Kaplan-Meier method was used to compare survival between the matched PAD and CAD population and the different operation groups. Prognostic risk factors and perioperative complications were identified with the Cox proportional hazards regression model. RESULTS The PAD patients had a worse long-term prognosis (hazard ratio 2.40, 95% confidence interval 2.18 to 2.65) and received less medication (beta-blockers, statins, angiotensin-converting enzyme inhibitors, aspirin, nitrates, and calcium antagonists) than CAD patients did (p < 0.001). Cerebro-cardiovascular complications were the major cause of long-term death (46%). Importantly, no significant difference in long-term survival was observed between the AAA and lower limb reconstruction groups (log rank p = 0.70). After vascular surgery, perioperative cardiac complications were associated with long-term cardiac death, and noncardiac complications were associated with all-cause death. CONCLUSIONS Long-term prognosis of vascular surgery patients is significantly worse than for patients with CAD. The vascular surgery patients receive less cardiac medication than CAD patients do, and cerebro-cardiovascular events are the major cause of late death.

Pre-Operative Risk Assessment and Risk Reduction Before Surgery

Perioperative myocardial infarctions are the predominant cause of morbidity and mortality in patients undergoing noncardiac surgery. The pathophysiology of perioperative myocardial infarction is complex. Prolonged myocardial ischemia due to the stress of surgery in the presence of a hemodynamically significant coronary lesion, leading to subendocardial ischemia, and acute coronary artery occlusion after plaque rupture and thrombus formation contribute equally to these devastating events. Perioperative management aims at optimizing the patients condition by identification and modification of underlying cardiac risk factors and diseases. During recent decades there has been a shift from the assessment and treatment of the underlying culprit coronary lesion toward a systemic medical therapy aiming at prevention of myocardial oxygen supply demand mismatch and coronary plaque stabilization. Beta-blockers, statins, and aspirin are widely used in this setting. The role of prophylactic coronary revascularization has been restricted to the same indications as the nonoperative setting. Therefore pre-operative cardiac testing is recommended only if test results will change perioperative management. In addition to the limited perioperative period, physicians should benefit from this opportunity to initiate lifestyle changes and medical therapy to lessen the impact of cardiac risk factors, as patients should live long enough after the operation to enjoy the benefits of surgery.

Impact of Cardioselective β-Blockers on Mortality in Patients with Chronic Obstructive Pulmonary Disease and Atherosclerosis

RATIONALE beta-Blocker use is associated with improved health outcomes in patients with cardiovascular disease. There is a general reluctance to prescribe beta-blockers in patients with chronic obstructive pulmonary disease (COPD) because they may worsen symptoms. OBJECTIVES We investigated the relationship between cardioselective beta-blockers and mortality in patients with COPD undergoing major vascular surgery. METHODS We evaluated 3,371 consecutive patients who underwent major vascular surgery at one academic institution between 1990 and 2006. The patients were divided into those with and without COPD on the basis of symptoms and spirometry. The major endpoints were 30-day and long-term mortality after vascular surgery. Patients were defined as receiving low-dose therapy if the dosage was less than 25% of the maximum recommended therapeutic dose; dosages higher than this were defined as intensified dose. MEASUREMENTS AND MAIN RESULTS There were 1,205 (39%) patients with COPD of whom 462 (37%) received cardioselective beta-blocking agents. beta-Blocker use was associated independently with lower 30-day (odds ratio, 0.37; 95% confidence interval, 0.19-0.72) and long-term mortality in patients with COPD (hazards ratio, 0.73; 95% confidence interval, 0.60-0.88). Intensified dose was associated with both reduced 30-day and long-term mortality in patients with COPD, whereas low dose was not. CONCLUSIONS Cardioselective beta-blockers were associated with reduced mortality in patients with COPD undergoing vascular surgery. In carefully selected patients with COPD, the use of cardioselective beta-blockers appears to be safe and associated with reduced mortality.

Timing of Noncardiac Surgery After Coronary Artery Stenting With Bare Metal or Drug-Eluting Stents

The current guidelines have recommended postponing noncardiac surgery (NCS) for > or =6 weeks after bare metal stent (BMS) placement and for > or =1 year after drug-eluting stent (DES) placement. However, much debate has ensued about these intervals. The aim of the present study was to assess the influence of different intervals between stenting and NCS and the use of dual antiplatelet therapy on the occurrence of perioperative major adverse cardiac events (MACEs). We identified 550 patients (376 with a DES and 174 with a BMS) by cross-matching the Erasmus Medical Center percutaneous coronary intervention (PCI) database with the NCS database. The following intervals between PCI-BMS (<30 days, <3 months, and >3 months) or PCI-DES (<30 days, <3 months, 3 to 6 months, 6 to 12 months, and >12 months) and NCS were studied. MACEs included death, myocardial infarction, and repeated revascularization. In the PCI-BMS group, the rate of MACEs during the intervals of <30 days, 30 days to 3 months, and >3 months was 50%, 14%, and 4%, respectively (overall p <0.001). In the PCI-DES group, the rate of MACE changed significantly with the interval after PCI (35%, 13%, 15%, 6%, and 9% for patients undergoing NCS <30 days, 30 days to 3 months, 3 to 6 months, 6 to 12 months, and >12 months, respectively, overall p <0.001). Of the patients who experienced a MACE, 45% and 55% were receiving single and dual antiplatelet therapy at NCS, respectively (p = 0.92). The risk of severe bleeding in patients with single and dual therapy at NCS was 4% and 21%, respectively (p <0.001). In conclusion, we found an inverse relation between the interval from PCI to NCS and perioperative MACEs. Continuation of dual antiplatelet therapy until NCS did not provide complete protection against MACEs.

Clinical ResearchPeripheral Vascular DiseaseLong-Term Prognosis of Patients With Peripheral Arterial Disease: A Comparison in Patients With Coronary Artery Disease

OBJECTIVES This study was designed to compare the long-term outcomes of patients with peripheral arterial disease (PAD) with a risk factor matched population of coronary artery disease (CAD) patients, but without PAD. BACKGROUND The PAD is considered to be a risk factor for adverse late outcome. METHODS A total of 2,730 PAD patients undergoing vascular surgery were categorized into groups: 1) carotid endarterectomy (n = 560); 2) elective abdominal aortic surgery (AAA) (n = 923); 3) acute AAA surgery (r-AAA) (n = 200), and 4) lower limb reconstruction procedures (n = 1,047). All patients were matched using the propensity score, with 2,730 CAD patients who underwent coronary angioplasty. Survival status of all patients was obtained. In addition, the cause of death and complications after surgery in PAD patients were noted. The Kaplan-Meier method was used to compare survival between the matched PAD and CAD population and the different operation groups. Prognostic risk factors and perioperative complications were identified with the Cox proportional hazards regression model. RESULTS The PAD patients had a worse long-term prognosis (hazard ratio 2.40, 95% confidence interval 2.18 to 2.65) and received less medication (beta-blockers, statins, angiotensin-converting enzyme inhibitors, aspirin, nitrates, and calcium antagonists) than CAD patients did (p < 0.001). Cerebro-cardiovascular complications were the major cause of long-term death (46%). Importantly, no significant difference in long-term survival was observed between the AAA and lower limb reconstruction groups (log rank p = 0.70). After vascular surgery, perioperative cardiac complications were associated with long-term cardiac death, and noncardiac complications were associated with all-cause death. CONCLUSIONS Long-term prognosis of vascular surgery patients is significantly worse than for patients with CAD. The vascular surgery patients receive less cardiac medication than CAD patients do, and cerebro-cardiovascular events are the major cause of late death.

Prognostic implications of asymptomatic left ventricular dysfunction in patients undergoing vascular surgery.

Background:The prognostic value of heart failure symptoms on postoperative outcome is well acknowledged in perioperative guidelines. The prognostic value of asymptomatic left ventricular (LV) dysfunction remains unknown. This study evaluated the prognostic implications of asymptomatic LV dysfunction in vascular surgery patients assessed with routine echocardiography. Methods:Echocardiography was performed preoperatively in 1,005 consecutive vascular surgery patients. Systolic LV dysfunction was defined as LV ejection fraction less than 50%. Ratio of mitral-peak velocity during early and late filling, pulmonary vein flow, and deceleration time was used to diagnose diastolic LV dysfunction. Troponin-T measurements and electrocardiograms were performed routinely perioperatively. Multivariate regression analyses evaluated the relation between LV function and the study endpoints, 30-day cardiovascular events, and long-term cardiovascular mortality. Results:Left ventricular dysfunction was diagnosed in 506 (50%) patients of which 80% were asymptomatic. In open vascular surgery (n = 649), both asymptomatic systolic and isolated diastolic LV dysfunctions were associated with 30-day cardiovascular events (odds ratios 2.3, 95% confidence interval [CI] 1.4–3.6 and 1.8, 95% CI 1.1–2.9, respectively) and long-term cardiovascular mortality (hazard ratios 4.6, 95% CI 2.4–8.5 and 3.0, 95% CI 1.5–6.0, respectively). In endovascular surgery (n = 356), only symptomatic heart failure was associated with 30-day cardiovascular events (odds ratio 1.8, 95% CI 1.1–2.9) and long-term cardiovascular mortality (hazard ratio 10.3, 95% CI 5.4–19.3). Conclusions:This study demonstrated that asymptomatic LV dysfunction is predictive for 30-day and long-term cardiovascular outcome in open vascular surgery patients. These data suggest that preoperative risk stratification should include not only solely heart failure symptoms but also routine preoperative echocardiography to risk stratify open vascular surgery patients.