Thomas Riemer

Short-term comprehensive cardiac rehabilitation after AMI is associated with reduced 1-year mortality: results from the OMEGA study

Background The prognostic effect of early, comprehensive short-term cardiac rehabilitation on top of current, guideline-adjusted treatment of acute myocardial infarction has not sufficiently been evaluated. Design Prospective cohort study. Methods Within the OMEGA study population, the clinical course of 3560 patients still alive 3 months after acute myocardial infarction were evaluated by comparing patients who had attended to cardiac rehabilitation (70.6%) with those who did not. Total mortality and major adverse cerebrovascular and cardiovascular events, as well as non-fatal events, were evaluated within the time period of 4–12 months after hospital admission for acute myocardial infarction. The effect of cardiac rehabilitation on clinical events was estimated by using the propensity score method to adjust for confounding parameters in multivariate analysis. Results Patients participating in cardiac rehabilitation were younger, more often had acute revascularization, less often experienced non-ST-elevation myocardial infarction, and less often had a history of diabetes or cardiovascular events. Total mortality (OR 0.46, 95% CI 0.27–0.77) and major adverse cerebrovascular and cardiovascular events (OR 0.53, 95% CI 0.38–0.75) were significantly lower in the rehabilitation group. Subgroup analysis including major clinical characteristics also revealed significantly reduced rates of total death and major adverse cerebrovascular and cardiovascular events in the rehabilitation group. Conclusions Attendance to early, comprehensive short-term cardiac rehabilitation programmes on top of current guideline-adjusted treatment of acute myocardial infarction is associated with a significantly improved 1-year prognosis.

Disproportional Decrease in Office Blood Pressure Compared With 24-Hour Ambulatory Blood Pressure With Antihypertensive TreatmentNovelty and Significance: Dependency on Pretreatment Blood Pressure Levels

The long-term relationship between 24-hour ambulatory blood pressure (ABP) and office BP in patients on therapy is not well documented. From a registry we included all patients in whom antihypertensive therapy needed to be uptitrated. Drug treatment included the direct renin inhibitor aliskiren or an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker or drugs not blocking the renin–angiotensin system, alone or on top of an existing drug regimen. In all patients, office BP and 24-hour ABP were obtained at baseline and after 1 year with validated devices. In the study population of 2722 patients, there was a good correlation between the change in office BP and 24-hour ABP (systolic: r=0.39; P<0.001; diastolic: r=0.34; P<0.001). However, the numeric decrease in office BP did not correspond to the decrease in ABP in a 1:1 fashion, for example, a decrease of 10, 20, and 30 mm Hg corresponded to a decrease of ≈7.2, 10.5, and 13.9 mm Hg in systolic ABP, respectively. The disproportionally greater decrease in systolic office BP compared with ABP was dependent on the level of the pretreatment BP, which was consistently higher for office BP than ABP. The white coat effect (difference between office BP and ABP) was on average 10/5 mm Hg lower 1 year after intensifying treatment and the magnitude of that was also dependent on pretreatment BP. There was a disproportionally greater decrease in systolic office BP than in ABP, which for both office BP and ABP seemed to depend on the pretreatment BP level.

Disproportional Decrease in Office Blood Pressure Compared With 24-Hour Ambulatory Blood Pressure With Antihypertensive Treatment: Dependency on Pretreatment Blood Pressure Levels

The long-term relationship between 24-hour ambulatory blood pressure (ABP) and office BP in patients on therapy is not well documented. From a registry we included all patients in whom antihypertensive therapy needed to be uptitrated. Drug treatment included the direct renin inhibitor aliskiren or an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker or drugs not blocking the renin–angiotensin system, alone or on top of an existing drug regimen. In all patients, office BP and 24-hour ABP were obtained at baseline and after 1 year with validated devices. In the study population of 2722 patients, there was a good correlation between the change in office BP and 24-hour ABP (systolic: r=0.39; P<0.001; diastolic: r=0.34; P<0.001). However, the numeric decrease in office BP did not correspond to the decrease in ABP in a 1:1 fashion, for example, a decrease of 10, 20, and 30 mm Hg corresponded to a decrease of ≈7.2, 10.5, and 13.9 mm Hg in systolic ABP, respectively. The disproportionally greater decrease in systolic office BP compared with ABP was dependent on the level of the pretreatment BP, which was consistently higher for office BP than ABP. The white coat effect (difference between office BP and ABP) was on average 10/5 mm Hg lower 1 year after intensifying treatment and the magnitude of that was also dependent on pretreatment BP. There was a disproportionally greater decrease in systolic office BP than in ABP, which for both office BP and ABP seemed to depend on the pretreatment BP level.

Self-referral to chest pain units: results of the German CPU-registry.

Background: Chest pain units (CPUs) are increasingly established in emergency cardiology services. With improved visibility of CPUs in the population, patients may refer themselves directly to these units, obviating emergency medical services (EMS). Little is known about characteristics and outcomes of self-referred patients, as compared with those referred by EMS. Therefore, we described self-referral patients enrolled in the CPU-registry of the German Cardiac Society and compared them with those referred by EMS. Methods and results: From 2008 until 2010, the prospective CPU-registry enrolled 11,581 consecutive patients. Of those 3789 (32.7%) were self-referrals (SRs), while 7792 (67.3%) were referred by EMS. SR-patients were significantly younger (63.6 vs. 70.1 years), had less prior myocardial infarction or coronary artery bypass surgery, but more previous percutaneous coronary interventions (PCIs). Acute coronary syndromes were diagnosed less frequently in the SR-patients (30.3 vs. 46.9%; p<0.0001). SR-patients showed ST-segment changes in their initial ECG in 19.6% of cases. EMS-patients underwent more coronary angiographies (60.0 vs. 47.5%; p<0.0001), while SR-patients underwent more stress tests (11.3 vs. 7.8%; p<0.001). PCI was performed in 32.6% of the EMS- and in 24.0% of the SR-group (p<0.0001). Conclusion: These data demonstrate that patients who contact a CPU as a self-referral are younger, less severely ill and have more non-coronary problems than those calling an emergency medical service. Nevertheless, 30% of self-referral patients had an acute coronary syndrome.

Competing time-to-event endpoints in cardiology trials: A simulation study to illustrate the importance of an adequate statistical analysis:

Background: Clinical trials in cardiology commonly consider time-to-event endpoints that are often influenced by competing risks. In the presence of competing risks, standard survival analysis techniques, such as the Kaplan-Meier estimator, can yield seriously biased results. Although methods to account for competing risks are well known in the statistical literature, they are rarely applied in clinical trials. Design: Simulation study, to demonstrate the appropriate application and interpretation of the competing risks methodology with respect to time-to-event endpoints. Methods: In this paper, different statistical approaches to account for competing risks are systematically compared, based on a simulation study and using the original data from a cardiology trial. Results: Group comparisons in clinical trials that have competing time-to-event endpoints should be based on the cause-specific hazard functions. In contrast, group comparisons based on event rates should be carried out with care, as event rates are directly influenced by competing events. Conclusion: Ignoring or not fully accounting for competing risks may yield misleading or even erroneous results, which could hinder understanding of survival trends; therefore, it is important that competing risks methodology be routinely incorporated into clinical trial standards.

Usefulness of Heart Rate to Predict One-Year Mortality in Patients With Atrial Fibrillation and Acute Myocardial Infarction (from the OMEGA Trial)

In the setting of acute myocardial infarction and sinus rhythm, the heart rate (HR) has been demonstrated to correlate closely with mortality. In patients presenting with acute myocardial infarction and atrial fibrillation (AF) on admission, however, the prognostic relevance of the HR has not yet been systematically addressed. A post hoc subgroup analysis of the data from the OMEGA trial was conducted to analyze whether the admission HR determines the 1-year mortality in patients presenting with AF in the setting of acute myocardial infarction. Of 3,851 patients enrolled in the OMEGA study, 211 (6%) presented with AF on admission. This subgroup was dichotomized according to the admission HR (cutoff 95 beats/min). Multiple regression analysis revealed that an admission HR of ≥95 beats/min independently determined the 1-year mortality in patients with AF (odds ratio 4.69, 95% confidence interval 1.47 to 15.01; p = 0.01). In conclusion, this is the first study demonstrating that a high HR (≥95 beats/min) on admission in patients with AF and acute myocardial infarction is associated with an almost fivefold mortality risk.

Everolimus-eluting bioresorbable scaffolds in patients with coronary artery disease: results from the German-Austrian ABSORB RegIstRy (GABI-R)

AIMS The aim of this study was to analyse the procedural results and midterm safety of everolimus-eluting bioresorbable vascular scaffolds (BVS) used for percutaneous coronary intervention in a large all-comers cohort from the German-Austrian ABSORB RegIstRy (GABI-R). METHODS AND RESULTS A total of 3,231 patients were included in this prospective, observational, multicentre study (ClinicalTrials.gov NCT02066623) of consecutive patients undergoing BVS implantation between November 2013 and January 2016. Endpoints were major adverse cardiac events (MACE; a composite endpoint of death, target vessel revascularisation, and myocardial infarction), and target lesion failure (TLF; a composite endpoint of cardiac death, target vessel myocardial infarction, and target lesion revascularisation). Scaffold thrombosis was a further endpoint. Of all patients, 51.5% presented with acute coronary syndrome. Predilatation and post-dilatation were performed in 91.5% and 71.9% of patients, respectively. Procedural success was 98.9%. After six months, the incidence of MACE was 4.1% and of TLF 2.4%. The rate of target vessel MI was 1.5%, and target lesion revascularisation was performed in 1.8%. Definite/ probable scaffold thrombosis was documented in 1.4% of patients. CONCLUSIONS GABI-R, the largest registry to provide data regarding safety after BVS implantation in a real-world setting, reveals high procedural success and low six-month event rates.

1-Year outcomes of hypertension management in 13,000 outpatients under practice conditions: prospective 3A registry.

BACKGROUND Current data on characteristics and outcomes of patients with high blood pressure (BP) managed under clinical practice conditions are limited. METHODS AND RESULTS The 3A registry is an open, prospective observational cohort study in German primary care offices, with a 4:1:1 inclusion ratio to either aliskiren (ALIS), an ACE inhibitor/angiotensin receptor blocker (ACEI/ARB), or to an antihypertensive agent not affecting the renin angiotensin system (non-RAS). A nonlinear mixed regression model was used to assess BP changes during follow-up regarding different BP values at inclusion in the various groups. ClinicalTrial.gov identifier is NCT01454583. In the total cohort of 13,433 patients with 1-year follow-up results, the mean age of patients was 64.7 years, 54% were men. Mean number of antihypertensive drugs was higher in the ALIS group compared to the other groups (3.0 drugs versus 2.5 in ACEI/ARB versus 1.6 in non-RAS; p<0.0001). Statistical regression analysis revealed baseline BP as the dominant covariate. After adjustment for baseline BP and 12 other confounders, no significant differences in BP reduction between the three groups were observed. The rate of major cardiac events (death, myocardial infarction, and stroke) was 1.3% in the total cohort, and did not differ across groups. CONCLUSIONS ALIS at beginning of the observation was mostly used by the physicians in patients with higher BP at entry and in higher risk populations. By study end, in all groups, stringent BP lowering measures, usually with combination therapy, led to significant improvements; more than half of these at-risk patients reached the BP targets.

Benefits and Risks of Aliskiren Treatment in Patients With Type 2 Diabetes: Analyses of the 3A Registry.

The authors sought to retrospectively analyze the real‐world evidence on aliskiren in diabetic patients with or without concomitant renin‐angiotensin system (RAS) blocker use based on the Registry for Ambulant Therapy With RAS Inhibitors in Hypertension Patients in Germany (3A). Of 14,986 patients included, 3772 patients had diabetes and 28.5% received aliskiren, 14.3% received angiotensin‐converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs), 35.4% received aliskiren plus an ACE inhibitor/ARB, and 10.5% received other drugs. Ambulatory blood pressure (BP) monitoring (baseline BP 148±15.8/84.0±10.9 mm Hg) revealed stronger diastolic BP reduction for aliskiren plus ACE inhibitor/ARB than aliskiren alone in the low (2.8±0.5 vs 0.6±0.6; P=.004) and intermediate (5.9±0.5 vs 4.5±0.5; P=.04) baseline BP groups. There was a lesser ambulatory BP reduction observed for patients receiving non‐RAS in the high baseline category for both systolic (12.5±1.8 vs 17.1±1.0; P=.02) and diastolic (6.9±1.0 vs 9.8±0.6; P=.01) BP. In patients with hypertension and type 2 diabetes, aliskiren was beneficial in lowering BP, with no observed increases in major adverse effects compared with RAS‐blocking therapy alone.

Two-Year Outcomes of Patients Treated With Aliskiren Under Clinical Practice Conditions: Non-Interventional Prospective Study.

The authors investigated the long‐term effectiveness and safety of aliskiren (ALIS) with particular attention on its association with dual blockade of the renin‐angiotensin system (RAS). The open, prospective 3A Registry (N=8723) in Germany assigned patients in a 4:1:1 ratio to ALIS, angiotensin‐converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), or non‐RAS drugs. Patients taking ALIS compared with those taking ACE inhibitors/ARBs or non‐RAS had more comorbidities and risk factors, were taking more antihypertensive agents, and had higher blood pressure (BP) values at entry. At 2 years, BP reduction from baseline was similar in all groups (mean, −20.5/−9.9 mm Hg). A total of 2.3% of patients died, 0.5% had myocardial infarction, 0.6% had stroke, 2.9% were hospitalized, and 5.5% had any event (not significant between groups). ALIS alone or combined with another RAS inhibitor was well tolerated and effective in lowering BP in typical unselected patients with hypertension. Given the methodical limitations of the design, the study cannot be used to confirm or refute safety concerns for dual RAS blockade as suggested by the Aliskiren Trial in Type 2 Diabetes Using Cardio‐Renal Endpoints (ALTITUDE) trial.