Stumme Ischämie beim Diabetiker: Behandeln? Wenn Ja, wie?

Präsentation zum Thema: "Stumme Ischämie beim Diabetiker: Behandeln? Wenn Ja, wie?"—  Präsentation transkript:

1 Stumme Ischämie beim Diabetiker: Behandeln? Wenn Ja, wie?
C.A. Schneider Klinik III für Innere Medizin, Universität zu Köln

2 Hätten Sie es gewusst? Bei Patienten mit Diabetes und KHK kommt auf 1 Angina pectoris-Anfall xxx Phasen einer stummen Ischämie? Antwort 3 Phasen ! Eisbergphänomen

3 Prävalenz Ischämie / Narbe
Detection of silent myocardial ischemia in asymptomatic diabetic subjects The DIAD study Prävalenz Ischämie / Narbe Adenosin MIBI SPECT N=522, Diabetes II, Alter Jahre Diabetes seit ca. 8 Jahre bekannt Keine KHK, keine Ap, keine Q-Zacken F Wackers Diabetes Care 2004; 27:

4 N = 370 asymptomatische Patienten Normales Ruhe EKG
Predictive Value of Silent Myocardial Ischemia for Cardiac Events in Diabetic Patients N = 370 asymptomatische Patienten Normales Ruhe EKG Keine Infarktanamnese HbA1c 8,1%, 15 Jahre Diabetes Mindestens 2 zusätzl. Risikofaktoren Szintigraphie oder Belastungs-EKG Nachbeobachtung 38 Monate OBJECTIVE— Silent myocardial ischemia (SMI) in asymptomatic subjects with no history of myocardial infarction or angina is a frequent condition in diabetic patients. The aim of the study was to examine the predictive value of SMI for cardiac events in a multicenter cohort and to determine whether this value is higher in patients with a particular clinical profile. RESEARCH DESIGN AND METHODS— A total of 370 asymptomatic diabetic patients with at least two additional cardiovascular risk factors was recruited in four departments of diabetology. SMI was assessed by either exercise or dipyridamole single-photon emission– computed tomography myocardial perfusion imaging with thallium-201. If dipyridamole stress was used, an electrocardiogram stress test was performed separately on another day. Follow-up duration was 3–89 months ( months). RESULTS— There was evidence of SMI in 131 patients (35.4%) on at least one positive noninvasive test. The patients with SMI were significantly older and had significantly higher serum triglycerides and lower HDL cholesterol levels. Cardiac events occurred in 53 patients (14.3%). Major cardiac events (death or myocardial infarction) occurred in 38 patients (10%) and other events (unstable angina, heart failure, or coronary revascularization) occurred in 15 patients. The patients who had cardiac events were older and had higher serum triglyceride levels at baseline. There was a significant association between SMI and cardiac events (hazard ratio 2.79 [95% CI 1.54 –5.04]) and in particular major cardiac events (3 [1.53–5.87]). In the patients60 years of age, the prevalence of SMI was higher (43.4 vs. 30.2% in those 60 years). SMI was associated with a significant risk of cardiac events (2.89 [1.31– 6.39]) and in particular major cardiac events (3.66 [1.36 –9.87]) for the patients60 years old but not for those60 years old. CONCLUSIONS— In asymptomatic diabetic patients with additional cardiovascular risk factors, SMI is a potent predictor of cardiac events and should be assessed preferably in the patients 60 years of age. PAUL VALENSI et al. Diabetes Care 28:2722–2727, 2005

5 Prävalenz stumme Myokardischämie =
Predictive Value of Silent Myocardial Ischemia for Cardiac Events in Diabetic Patients Prävalenz stumme Myokardischämie = 35% OBJECTIVE— Silent myocardial ischemia (SMI) in asymptomatic subjects with no history of myocardial infarction or angina is a frequent condition in diabetic patients. The aim of the study was to examine the predictive value of SMI for cardiac events in a multicenter cohort and to determine whether this value is higher in patients with a particular clinical profile. RESEARCH DESIGN AND METHODS— A total of 370 asymptomatic diabetic patients with at least two additional cardiovascular risk factors was recruited in four departments of diabetology. SMI was assessed by either exercise or dipyridamole single-photon emission– computed tomography myocardial perfusion imaging with thallium-201. If dipyridamole stress was used, an electrocardiogram stress test was performed separately on another day. Follow-up duration was 3–89 months ( months). RESULTS— There was evidence of SMI in 131 patients (35.4%) on at least one positive noninvasive test. The patients with SMI were significantly older and had significantly higher serum triglycerides and lower HDL cholesterol levels. Cardiac events occurred in 53 patients (14.3%). Major cardiac events (death or myocardial infarction) occurred in 38 patients (10%) and other events (unstable angina, heart failure, or coronary revascularization) occurred in 15 patients. The patients who had cardiac events were older and had higher serum triglyceride levels at baseline. There was a significant association between SMI and cardiac events (hazard ratio 2.79 [95% CI 1.54 –5.04]) and in particular major cardiac events (3 [1.53–5.87]). In the patients60 years of age, the prevalence of SMI was higher (43.4 vs. 30.2% in those 60 years). SMI was associated with a significant risk of cardiac events (2.89 [1.31– 6.39]) and in particular major cardiac events (3.66 [1.36 –9.87]) for the patients60 years old but not for those60 years old. CONCLUSIONS— In asymptomatic diabetic patients with additional cardiovascular risk factors, SMI is a potent predictor of cardiac events and should be assessed preferably in the patients 60 years of age. PAUL VALENSI et al. Diabetes Care 28:2722–2727, 2005 SMI = Stumme Myokardischämie

6 Prävalenz stumme Ischämie beim Diabetiker Prognose Therapie
Medikamentös Interventionell / operativ

7 Predictive Value of Silent Myocardial Ischemia for Cardiac Events in Diabetic Patients
Tod, Myokardinfarkt OBJECTIVE— Silent myocardial ischemia (SMI) in asymptomatic subjects with no history of myocardial infarction or angina is a frequent condition in diabetic patients. The aim of the study was to examine the predictive value of SMI for cardiac events in a multicenter cohort and to determine whether this value is higher in patients with a particular clinical profile. RESEARCH DESIGN AND METHODS— A total of 370 asymptomatic diabetic patients with at least two additional cardiovascular risk factors was recruited in four departments of diabetology. SMI was assessed by either exercise or dipyridamole single-photon emission– computed tomography myocardial perfusion imaging with thallium-201. If dipyridamole stress was used, an electrocardiogram stress test was performed separately on another day. Follow-up duration was 3–89 months ( months). RESULTS— There was evidence of SMI in 131 patients (35.4%) on at least one positive noninvasive test. The patients with SMI were significantly older and had significantly higher serum triglycerides and lower HDL cholesterol levels. Cardiac events occurred in 53 patients (14.3%). Major cardiac events (death or myocardial infarction) occurred in 38 patients (10%) and other events (unstable angina, heart failure, or coronary revascularization) occurred in 15 patients. The patients who had cardiac events were older and had higher serum triglyceride levels at baseline. There was a significant association between SMI and cardiac events (hazard ratio 2.79 [95% CI 1.54 –5.04]) and in particular major cardiac events (3 [1.53–5.87]). In the patients60 years of age, the prevalence of SMI was higher (43.4 vs. 30.2% in those 60 years). SMI was associated with a significant risk of cardiac events (2.89 [1.31– 6.39]) and in particular major cardiac events (3.66 [1.36 –9.87]) for the patients60 years old but not for those60 years old. CONCLUSIONS— In asymptomatic diabetic patients with additional cardiovascular risk factors, SMI is a potent predictor of cardiac events and should be assessed preferably in the patients 60 years of age. N = 370 asymptomatische Patienten Normales Ruhe EKG Keine Infarktanamnese HbA1c 8,1%, 15 Jahre Diabetes Mindestens 2 zusätzl. Risikofaktoren Szintigraphie oder Belastungs-EKG Nachbeobachtung 38 Monate PAUL VALENSI et al. Diabetes Care 28:2722–2727, 2005 SMI = Stumme Myokardischämie

8 Prognostic relevance of symptoms versus objective evidence of coronary artery disease in diabetic patients Tod und Myokardinfarkt Aim Little is known about the prognostic significance of silent versus symptomatic coronary artery disease (CAD) in diabetic patients. We therefore assessed the incidence of scintigraphic evidence of CAD in diabetic patients without known CAD and the impact of symptoms and scintigraphic findings on prognosis. Methods and results A consecutive series of 1737 diabetic patients without known CAD underwent dual-isotope myocardial perfusion SPECT (MPS) and 1430 were followed- up for a median of 2 (1–8.5) years. Critical events were defined as myocardial infarction or cardiac death. Objective evidence of CAD was found in 39% of 826 asymptomatic diabetic patients, in 51% of 151 diabetic patients with shortness of breath (SOB), and in 44% of 760 diabetic patients with angina. During follow-up, 98 critical events occurred. Annual critical event rates were 2.2% in asymptomatic, 3.2% in angina, and 7.7% in diabetic patients with shortness of breath (p < 0:001 versus other groups). With MPS evidence of CAD, critical event rates increased to 3.4% (asymptomatic), 5.6% (angina), and 13.2% (SOB) (p60:009 versus no evidence of CAD). Age, hypertension, shortness of breath, scarring and ischaemia were independent predictors of critical events. MPS findings added incremental information to prescan information regarding outcome prediction. Conclusions In asymptomatic diabetic patients, the rate of objective evidence of CAD and annual critical events were similar to those found in diabetic patients with angina. The outcome was three times worse in diabetic patients with shortness of breath. MPS findings were strongly predictive of outcome and proved valuable for risk stratification. MPS= myocardial perfusion scintigraphy N=1737 Patienten ohne bekannte KHK, FU 2 Jahre Michael J. Zellweger et al. European Heart Journal (2004) 25, 543–550

9 Prävalenz stumme Ischämie beim Diabetiker Prognose Therapie
Medikamentös Interventionell / operativ

10 Anti-ischemic effect of atenolol versus nifedipine in patients with coronary artery disease and ambulatory silent ischemia Crossover trial of the effect of therapy on 24 patients with silent ischemia. Compared with placebo, both atenolol and nifedipine significantly decreased the number (left) and duration (right) of silent ischemic events during the monitoring period. However, atenolol was significantly more effective than nifedipine. Data from Deedwania, PC, Carbajal, EV, Nelson, JR, et al. J Am Coll Cardiol 1991; 17:963. Anti-ischemic effects of atenolol versus nifedipine in patients with coronary artery disease and ambulatory silent ischemia. AUDeedwania PC; Carbajal EV; Nelson JR; Hait H SOJ Am Coll Cardiol 1991 Mar 15;17(4):   The anti-ischemic effects of atenolol and nifedipine were compared in a randomized double-blind crossover manner in 24 patients with stable exertional angina and transient silent ischemia during ambulatory electrocardiographic (ECG) monitoring. Both atenolol and nifedipine were effective (p less than 0.005) in reducing the average number and duration of transient ischemic events, but therapy with atenolol was associated with a significantly greater reduction in the mean number (p less than 0.05) and duration (p less than 0.01) of silent ischemic events. Analyses of the silent ischemic activity during the morning hours revealed that only therapy with atenolol produced a significant reduction in the average duration per patient (139 +/- 54 vs. 1,609 +/- 468 s, p less than 0.01) and in the average duration of silent ischemia per event between 6 AM and 12 noon (62 +/- 21 vs /- 24 s, p less than 0.005). There were fewer adverse experiences during therapy with atenolol. These results show that although both atenolol and nifedipine are effective in reducing silent ischemic events, treatment with atenolol is associated with significantly greater efficacy, particularly on the morning surge of silent myocardial ischemia. N=20 Männer Rand., doppel-blind, cross-over Deedwania P et al. 1991; 17: 963-9

11 Prognostic significance of transient ischemic episodes: response to treatment shows improved prognosis Results of the Total Ischemic Burden Bisoprolol Study (TIBBS) Follow-up 10-20 mg 20 mg 2x/d After a one year follow-up, the 97 patients who responded to bisoprolol (100 percent responders) had a significantly better event-free survival (death, nonfatal myocardial infarction, hospitalization for angina, need for revascularization) than the 186 patients who continued to have episodes of silent ischemia (non-100 percent responders) (p = 0.015). Data from Von Arnim, T, for the TIBBS Investigators. J Am Coll Cardiol 1996; 28:20. N= 520 Nachbeobachtung Endpunkte: Tod, Myokardinfarkt, Hospitalisierung V Arnim et al. J Am Coll Cardiol 1996; 28: 20-4

12 Prognostic significance of transient ischemic episodes: response to treatment shows improved prognosis Results of the Total Ischemic Burden Bisoprolol Study (TIBBS) Follow-up V Arnim et al. J Am Coll Cardiol 1996; 28: 20-4

13 Effect of free fatty acid inhibition on silent myocardial ischemia in diabetic patients with coronary artery disease Langzeit EKG-Befunde N= 30, bek. KHK 6 Monate HbA1c 7,3%, Diabe. Dauer 7 Jahre Trimetazidine 3*20 mg/ Tag (Vastarel MR) Marazzi G et al. Int J Cardiol 2007; 120: 79-84

14 Effect of Cholesterol Reduction on Myocardial Ischemia in Patients With Coronary Disease
Langzeit -EKG P<0.008 Background Cholesterol lowering is associated with a reduction in cardiovascular morbidity and mortality. This study sought to determine whether cholesterol lowering also results in a reduction of myocardial ischemia during daily life. Methods and Results We enrolled 40 patients with proven coronary artery disease, total serum cholesterol between 191 and 327 mg/dL, and at least one episode of ST-segment depression on ambulatory ECG monitoring. Twenty patients were randomized to an American Heart Association Step 1 diet plus placebo (placebo group) and 20 to the same diet plus lovastatin (treatment group). Serum cholesterol and LDL cholesterol levels and ambulatory monitoring were repeated after 4 to 6 months of therapy. The two groups were comparable with respect to baseline characteristics, number of episodes of ST-segment depression, and baseline serum cholesterol levels. The treatment group had lower mean total and LDL cholesterol levels at study end and experienced a significant reduction in the number of episodes of ST-segment depression compared with the placebo group. ST-segment depression was completely resolved in 13 of 20 patients (65%) in the treatment group versus 2 of 20 (10%) in the placebo group. The treatment group exhibited a highly significant reduction in ischemia (P<.001). By logistic regression, treatment with diet and lovastatin was an independent predictor of ischemia resolution. Conclusions Cholesterol lowering with lovastatin appears to be effective in eliminating myocardial ischemia during daily life in a significant proportion of patients. N= 40, bek KHK Lovastatin mg LDL – 54 mg dl Andrews T et al. Circulation. 1997;95:

15 Effects of anti-ischaemic drug therapy in silent myocardial ischaemia type I: the Swiss Interventional Study on Silent Ischaemia type I (SWISS I): a randomized, controlled pilot study (Tod, Myokardinfarkt, instabile Angina) Bisoprolo, Amlodipin, Molsidomin Aspirin Risk Factor Control Aims To determine the effect of anti-ischaemic drug therapy on long-term outcomes of asymptomatic patients without coronary artery disease (CAD) history but silent exercise ST-depression. Methods and results In a randomizedmulticentre trial, 263 of 522 asymptomatic subjects without CAD but at least one CAD risk factor in whom silent ischaemia by exercise ECG was confirmed by stress imaging were asked to participate. The 54 (21%) consenting patients were randomized to anti-anginal drug therapy in addition to risk factor control (MED, n ¼ 26) or risk factor control-only (RFC, n ¼ 28). They were followed yearly for years. During 483 patient-years, cardiac death, non-fatal myocardial infarction, or acute coronary syndrome requiring hospitalization or revascularization occurred in 3 (12%) of MED vs. 17 (61%) of RFC patients (P , 0.001). In addition, MED patients had consistently lower rates of exercise induced ischaemia during follow-up, and left ventricular ejection fraction remained unchanged (20.7%, P ¼ 0.597) in contrast to RFC patients in whom it decreased over time (26.0%, P ¼ 0.006). Conclusion Anti-ischaemic drug therapy and aspirin seem to reduce cardiac events in subjects with asymptomatic ischaemia type I. In such patients, exercise-induced ST-segment depression should be verified by stress imaging; if silent ischaemia is documented, anti-ischaemic drug therapy and aspirin should be considered. N=54 Patienten Asymptomatisch, keine KHK, Path. Bel EKG und Szinti + 1 RF Erne P et al. European Heart Journal (2007) 28, 2110–2117

16 Davies RF et al. Circulation. 1997;95:2037-2043
Asymptomatic Cardiac Ischemia Pilot (ACIP) Study Two-Year Follow-up Outcomes of Patients Randomized to Initial Strategies of Medical Therapy Versus Revascularization Gesamtsterblichkeit Background Patients with ischemia during stress testing and ambulatory ECG monitoring have an increased risk of cardiac events, but it is not known whether their prognosis is improved by more aggressive treatment with anti-ischemic drugs or revascularization. Methods and Results The Asymptomatic Cardiac Ischemia Pilot study randomized 558 such patients who had coronary anatomy suitable for revascularization to three treatment strategies: angina-guided drug therapy (n=183), angina plus ischemia–guided drug therapy (n=183), or revascularization by angioplasty or bypass surgery (n=192). Two years after randomization, the total mortality was 6.6% in the angina-guided strategy, 4.4% in the ischemia-guided strategy, and 1.1% in the revascularization strategy (P<.02). The rate of death or myocardial infarction was 12.1% in the angina-guided strategy, 8.8% in the ischemia-guided strategy, and 4.7% in the revascularization strategy (P<.04). The rate of death, myocardial infarction, or recurrent cardiac hospitalization was 41.8% in the angina-guided strategy, 38.5% in the ischemia-guided strategy, and 23.1% in the revascularization strategy (P<.001). Pairwise testing revealed significant differences between the revascularization and angina-guided strategies for each comparison. Conclusions A strategy of initial revascularization appears to improve the prognosis of this population compared with angina-guided medical therapy. A larger long-term study is needed to confirm this benefit and to adequately test the potential of more aggressive drug therapy. N=558 Bek. KHK, Atenolol / Nifedipin Diltiazem / ISDN Davies RF et al. Circulation. 1997;95:

17 Effects of Percutaneous Coronary Interventions in Silent Ischemia After Myocardial Infarction The SWISSI II Randomized Controlled Trial Tod, Myokardinfarkt, Revaskularisierung Bisoprolo, Amlodipin, Molsidomin Aspirin, Statin Context The effect of a percutaneous coronary intervention (PCI) on the long-term prognosis of patients with silent ischemia after a myocardial infarction (MI) is not known. Objective To determine whether PCI compared with drug therapy improves longterm outcome of asymptomatic patients with silent ischemia after an MI. Design, Setting, and Participants Randomized, unblinded, controlled trial (Swiss Interventional Study on Silent Ischemia Type II [SWISSI II]) conducted from May 2, 1991, to February 25, 1997, at 3 public hospitals in Switzerland of 201 patients with a recent MI, silent myocardial ischemia verified by stress imaging, and 1- or 2-vessel coronary artery disease. Follow-up ended on May 23, 2006. Interventions Percutaneous coronary intervention aimed at full revascularization (n=96) or intensive anti-ischemic drug therapy (n=105). All patients received 100 mg/d of aspirin and a statin. Main Outcome Measures Survival free of major adverse cardiac events defined as cardiac death, nonfatal MI, and/or symptom-driven revascularization. Secondary measures Included exercise-inducedi schemia andresting leftventricular ejectionfraction during follow-up. Results During a mean (SD) follow-up of 10.2 (2.6) years, 27 major adverse cardiac events occurred in the PCI group and 67 events occurred in the anti-ischemic drug therapy group (adjusted hazard ratio, 0.33;95%confidence interval, ; P.001), which corresponds to an absolute event reduction of 6.3% per year (95% confidence interval, 3.7%-8.9%; P.001). Patients in the PCI group had lower rates of ischemia (11.6% vs 28.9% in patients in the drug therapy group at final follow-up; P=.03) despite fewer drugs. Left ventricular ejection fraction remained preserved in PCI patients (mean [SD] of 53.9% [9.9%] at baseline to 55.6% [8.1%] at final follow-up) and decreased significantly (P.001) in drug therapy patients (mean [SD] of 59.7% [11.8%] at baseline to 48.8% [7.9%] at final follow-up). Conclusion Among patients with recent MI, silent myocardial ischemia verified by stress imaging, and 1- or 2-vessel coronary artery disease, PCI compared with antiischemic drug therapy reduced the long-term risk of major cardiac events. Trial Registration clinicaltrials.gov Identifier: NCT JAMA. 2007;297: N=201 Herzinfarkt, 1-2 GE, Stumme Ischämie Paul Erne, JAMA. 2007;297:

18 Optimal Medical Therapy with or without PCI for Stable Coronary Disease
William E. Boden et al. N Engl J Med 2007;356:

19 Prävalenz stumme Ischämie beim Diabetiker : 30-70%
Prognose: 2-3 fach erhöhtes Risiko Therapie -> Ischämiereduktion Medikamentös ? Interventionell / operativ ?

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