Increased Bleeding Risk With Concurrent Use of Selective Serotonin Reuptake Inhibitors and Coumarins
Tom Schalekamp, PharmD, PhD; J H. Klungel, PharmD, PhD; Patrick C. Souverein, PhD; Anthonius de Boer, MD, PhD
Arch Intern Med. 2008;168(2):180-185.
Background Treatment with vitamin K antagonists (coumarins) is associated with an increased risk of bleeding. Because use of selective serotonin reuptake inhibitors (SSRIs) is also associated with an increased risk of bleeding, we assessed the odds ratio (OR) of abnormal bleeding associated with SSRI use in users of the coumarins acenocoumarol or phenprocoumon and compared this with the OR of bleeding as a result of use of nonsteroidal anti-inflammatory drugs.
Methods We used data from a Dutch linkage system including pharmacy and linked hospitalization records for approximately 2 million subjects to conduct a case-control study in a cohort of new users of coumarins. Cases were patients who were hospitalized having a primary diagnosis of abnormal major bleeding while taking a coumarin and were matched with up to 4 control subjects. Conditional logistic regression analysis was used to determine ORs and 95% confidence intervals (CIs) for the risk of hospitalization because of abnormal bleeding associated with concurrent use of SSRIs or nonsteroidal anti-inflammatory drugs.
Results We identified 1848 case patients with abnormal bleeding. Users of SSRIs were at significantly increased risk of hospitalization because of nongastrointestinal tract bleeding (hereafter referred to as "nongastrointestinal bleeding") (adjusted OR, 1.7; 95% CI, 1.1-2.5) but not because of gastrointestinal tract bleeding (hereafter referred to as "gastrointestinal bleeding") (adjusted OR, 0.8; 95% CI, 0.4-1.5). Users of nonsteroidal anti-inflammatory drugs had a similar increased risk of nongastrointestinal bleeding (adjusted OR, 1.7; 95% CI, 1.3-2.2), whereas the risk of gastrointestinal bleeding was higher (adjusted OR, 4.6; 95% CI, 3.3-6.5).
Conclusion In users of coumarins, SSRI usage was associated with increased risk of hospitalization because of nongastrointestinal bleeding but not because of gastrointestinal bleeding.
Wednesday, January 30, 2008
Tuesday, January 29, 2008
Ventricular Arrhythmias During Clinical Treadmill Testing and Prognos
Ventricular Arrhythmias During Clinical Treadmill Testing and Prognosis
Frederick E. Dewey, BA; John R. Kapoor, MD, PhD; Ryan S. Williams, MD; Michael J. Lipinski, MD; Euan A. Ashley, MRCP, DPhil; David Hadley, PhD; Jonathan Myers, PhD; Victor F. Froelicher, MD
Arch Intern Med. 2008;168(2):225-234.
Background Although exercise-associated ventricular arrhythmias are frequently observed during exercise testing, their prognostic significance remains uncertain. Therefore, we aimed to evaluate the clinical correlates and prognostic significance of exercise-associated premature ventricular complexes (PVCs) during and after exercise testing.
Methods We studied 1847 heart failure–free patients who underwent clinical treadmill testing between March 13, 1997, and January 15, 2004, in the Veterans Affairs Palo Alto Health Care System. Logistic regression was used to evaluate the clinical and exercise test associations of exercise and recovery PVCs. Propensity score–adjusted Cox survival analyses were used to evaluate the prognostic significance of exercise-associated PVCs.
Results Of the 1847 subjects, 850 (46.0%) developed exercise PVCs (median rate, 0.43 per minute) and 620 (33.6%) had recovery PVCs (median rate, 0.60 per minute). Resting PVCs, age, and systolic blood pressure were key predictors of both exercise and recovery PVCs. Whereas exercise PVCs were related to the heart rate increase with exercise, recovery PVCs were related to coronary disease (previous myocardial infarction, coronary revascularization procedure, or pathological Q waves on resting electrocardiogram) and ST-segment depression. During a 5.4-year mean follow-up, 161 subjects (8.7%) died, and 53 of these deaths (32.9%) were due to cardiovascular causes. Recovery PVCs, but not exercise PVCs, were associated with 71% to 96% greater propensity-adjusted mortality rates (hazard ratio, 1.96 [95% confidence interval, 1.31-2.91] for infrequent PVCs; hazard ratio, 1.71 [95% confidence interval, 1.07-2.73] for frequent PVCs compared with subjects without PVCs), and occurrence of recovery PVCs reclassified 33.2% of subjects with intermediate-risk Duke Treadmill Scores into higher-risk subgroups.
Conclusion In our heart failure–free population, recovery PVCs were associated with increased mortality and augmented established risk markers.
Frederick E. Dewey, BA; John R. Kapoor, MD, PhD; Ryan S. Williams, MD; Michael J. Lipinski, MD; Euan A. Ashley, MRCP, DPhil; David Hadley, PhD; Jonathan Myers, PhD; Victor F. Froelicher, MD
Arch Intern Med. 2008;168(2):225-234.
Background Although exercise-associated ventricular arrhythmias are frequently observed during exercise testing, their prognostic significance remains uncertain. Therefore, we aimed to evaluate the clinical correlates and prognostic significance of exercise-associated premature ventricular complexes (PVCs) during and after exercise testing.
Methods We studied 1847 heart failure–free patients who underwent clinical treadmill testing between March 13, 1997, and January 15, 2004, in the Veterans Affairs Palo Alto Health Care System. Logistic regression was used to evaluate the clinical and exercise test associations of exercise and recovery PVCs. Propensity score–adjusted Cox survival analyses were used to evaluate the prognostic significance of exercise-associated PVCs.
Results Of the 1847 subjects, 850 (46.0%) developed exercise PVCs (median rate, 0.43 per minute) and 620 (33.6%) had recovery PVCs (median rate, 0.60 per minute). Resting PVCs, age, and systolic blood pressure were key predictors of both exercise and recovery PVCs. Whereas exercise PVCs were related to the heart rate increase with exercise, recovery PVCs were related to coronary disease (previous myocardial infarction, coronary revascularization procedure, or pathological Q waves on resting electrocardiogram) and ST-segment depression. During a 5.4-year mean follow-up, 161 subjects (8.7%) died, and 53 of these deaths (32.9%) were due to cardiovascular causes. Recovery PVCs, but not exercise PVCs, were associated with 71% to 96% greater propensity-adjusted mortality rates (hazard ratio, 1.96 [95% confidence interval, 1.31-2.91] for infrequent PVCs; hazard ratio, 1.71 [95% confidence interval, 1.07-2.73] for frequent PVCs compared with subjects without PVCs), and occurrence of recovery PVCs reclassified 33.2% of subjects with intermediate-risk Duke Treadmill Scores into higher-risk subgroups.
Conclusion In our heart failure–free population, recovery PVCs were associated with increased mortality and augmented established risk markers.
Diuretics Most Effective Blood Pressure Medication For People With Metabolic Syndrome
Commentaries:
The ALLHAT study originally reported in 2002 that diuretics were the most beneficial of the drug classes studied for treating high blood pressure and for protecting against adverse cardiovascular outcomes. The study compare a diuretic (chlorthalidone) with three classes of medications to treat high blood pressure: a calcium-channel blocker (amlodipine besylate), an alpha-blocker (doxazosin mesylate), and an angiotensin-converting enzyme (ACE) inhibitor (lisinopril).
Diuretic-based treatment was more protective against heart failure and also against overall cardiovascular disease (coronary heart disease, stroke, heart failure, or peripheral arterial disease combined) when compared with the ACE-inhibitor and alpha-blocker-based treatments.
Diuretic-based treatment was more protective against heart failure when compared with the calcium channel blocker-based treatment.
Clinical Outcomes by Race in Hypertensive Patients With and Without the Metabolic Syndrome Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)
Jackson T. Wright Jr, MD, PhD; Sonja Harris-Haywood, MD; Sara Pressel, MS; Joshua Barzilay, MD; Charles Baimbridge, MS; Charles J. Bareis, MD; Jan N. Basile, MD; Henry R. Black, MD; Richard Dart, MD; Alok K. Gupta, MD; Bruce P. Hamilton, MD; Paula T. Einhorn, MD, MS; L. Julian Haywood, MD; Syed Z. A. Jafri, MD; Gail T. Louis, RN, BA; Paul K. Whelton, MD, MSc; Cranford L. Scott, MD; Debra L. Simmons, MD; Carol Stanford, MD; Barry R. Davis, MD, PhD
Arch Intern Med. 2008;168(2):207-217.
Background Antihypertensive drugs with favorable metabolic effects are advocated for first-line therapy in hypertensive patients with metabolic/cardiometabolic syndrome (MetS). We compared outcomes by race in hypertensive individuals with and without MetS treated with a thiazide-type diuretic (chlorthalidone), a calcium channel blocker (amlodipine besylate), an -blocker (doxazosin mesylate), or an angiotensin-converting enzyme inhibitor (lisinopril).
Methods A subgroup analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind hypertension treatment trial of 42 418 participants. We defined MetS as hypertension plus at least 2 of the following: fasting serum glucose level of at least 100 mg/dL, body mass index (calculated as weight in kilograms divided by height in meters squared) of at least 30, fasting triglyceride levels of at least 150 mg/dL, and high-density lipoprotein cholesterol levels of less than 40 mg/dL in men or less than 50 mg/dL in women.
Results Significantly higher rates of heart failure were consistent across all treatment comparisons in those with MetS. Relative risks (RRs) were 1.50 (95% confidence interval, 1.18-1.90), 1.49 (1.17-1.90), and 1.88 (1.42-2.47) in black participants and 1.25 (1.06-1.47), 1.20 (1.01-1.41), and 1.82 (1.51-2.19) in nonblack participants for amlodipine, lisinopril, and doxazosin comparisons with chlorthalidone, respectively. Higher rates for combined cardiovascular disease were observed with lisinopril-chlorthalidone (RRs, 1.24 [1.09-1.40] and 1.10 [1.02-1.19], respectively) and doxazosin-chlorthalidone comparisons (RRs, 1.37 [1.19-1.58] and 1.18 [1.08-1.30], respectively) in black and nonblack participants with MetS. Higher rates of stroke were seen in black participants only (RR, 1.37 [1.07-1.76] for the lisinopril-chlorthalidone comparison, and RR, 1.49 [1.09-2.03] for the doxazosin-chlorthalidone comparison). Black patients with MetS also had higher rates of end-stage renal disease (RR, 1.70 [1.13-2.55]) with lisinopril compared with chlorthalidone.
Conclusions The ALLHAT findings fail to support the preference for calcium channel blockers, -blockers, or angiotensin-converting enzyme inhibitors compared with thiazide-type diuretics in patients with the MetS, despite their more favorable metabolic profiles. This was particularly true for black participants.
Monday, January 28, 2008
ACE inhibitor prevents cardiac rupture after acute MI
Causes of death in patients with acute myocardial infarction treated with angiotensin-converting enzyme inhibitors: Findings from the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto (GISSI)–3 trial
American Heart Journal
Volume 155, Issue 2, Pages 388-394 (February 2008)
Giovanni Pedrazzini, MD, Eugenio Santoro, MS, Roberto Latini, MD, Laurie Fromm, PharmD, Maria Grazia Franzosi, BiolScD, Tiziano Mocetti, MD, Lidia Staszewsky, MD, Simona Barlera, MS, Gianni Tognoni, MD, Aldo P. Maggioni, MD
Background
The causes of death occurring in clinical trials of myocardial infarction (MI) are scarcely reported in the literature. The present analysis is aimed to describe the inhospital causes of death in patients with acute MI stratified to angiotensin converting enzyme (ACE) inhibitor treatment/no treatment, as described in the GISSI-3 trial. Furthermore, the 5-year survival analysis of GISSI-3 patients is reported.
Methods and Results
An independent committee assigned the definition of causes of death of GISSI-3 based on clinical and/or anatomical data. Univariate and multivariable analyses were performed to identify the predictors of early and late deaths. Kaplan-Meier mortality curves were used to describe the effects of ACE-I treatment on mortality on a median follow-up period of 56 months.
Patients receiving lisinopril had fewer inhospital cardiac deaths than patients allocated to the no-lisinopril group (4.7% vs 5.3%, P = .052), corresponding to a 12% relative risk reduction. The risk of dying from cardiac rupture was reduced by 39% by lisinopril treatment. The improvement in survival associated with the lisinopril treatment was mainly due to a reduction in cardiac rupture, electromechanical dissociation, and pump failure occurring early (within 4 days) from the onset of MI symptoms.
The beneficial effects of lisinopril observed at 6 weeks (8 fewer deaths per 1000 treated patients) were maintained up to nearly 5 years (10 fewer deaths per 1000).
Conclusions
Early administration of ACE inhibitors in unselected patients with acute MI should be considered standard therapy to reduce early deaths, specifically those due to cardiac rupture. The early beneficial effect persisted up to nearly 5 years.
American Heart Journal
Volume 155, Issue 2, Pages 388-394 (February 2008)
Giovanni Pedrazzini, MD, Eugenio Santoro, MS, Roberto Latini, MD, Laurie Fromm, PharmD, Maria Grazia Franzosi, BiolScD, Tiziano Mocetti, MD, Lidia Staszewsky, MD, Simona Barlera, MS, Gianni Tognoni, MD, Aldo P. Maggioni, MD
Background
The causes of death occurring in clinical trials of myocardial infarction (MI) are scarcely reported in the literature. The present analysis is aimed to describe the inhospital causes of death in patients with acute MI stratified to angiotensin converting enzyme (ACE) inhibitor treatment/no treatment, as described in the GISSI-3 trial. Furthermore, the 5-year survival analysis of GISSI-3 patients is reported.
Methods and Results
An independent committee assigned the definition of causes of death of GISSI-3 based on clinical and/or anatomical data. Univariate and multivariable analyses were performed to identify the predictors of early and late deaths. Kaplan-Meier mortality curves were used to describe the effects of ACE-I treatment on mortality on a median follow-up period of 56 months.
Patients receiving lisinopril had fewer inhospital cardiac deaths than patients allocated to the no-lisinopril group (4.7% vs 5.3%, P = .052), corresponding to a 12% relative risk reduction. The risk of dying from cardiac rupture was reduced by 39% by lisinopril treatment. The improvement in survival associated with the lisinopril treatment was mainly due to a reduction in cardiac rupture, electromechanical dissociation, and pump failure occurring early (within 4 days) from the onset of MI symptoms.
The beneficial effects of lisinopril observed at 6 weeks (8 fewer deaths per 1000 treated patients) were maintained up to nearly 5 years (10 fewer deaths per 1000).
Conclusions
Early administration of ACE inhibitors in unselected patients with acute MI should be considered standard therapy to reduce early deaths, specifically those due to cardiac rupture. The early beneficial effect persisted up to nearly 5 years.
Digitalis: a dangerous drug in atrial fibrillation? An analysis of the SPORTIF III and V data
Commentaries:
In this study patients were not randomized to digitalis use.
Digitalis: a dangerous drug in atrial fibrillation? An analysis of the SPORTIF III and V data
Heart 2008; 94: 191-196
Knut Gjesdal (University of Oslo, Norway) and colleagues
ABSTRACT
Objective: In heart failure, digitalis increases exercise capacity and reduces morbidity, but has no effect on survival. This raises the suspicion that the inotropic benefits of digitalis may be counteracted by serious adverse effects. Patients with atrial fibrillation (AF) were studied to clarify this.
Design: In the Stroke Prevention using an ORal Thrombin Inhibitor in atrial Fibrillation (SPORTIF) III and V studies, 7329 patients with AF at moderate-to-high risk were randomised to preventive treatment of thromboembolism, either with warfarin or the oral direct thrombin inhibitor ximelagatran. The survival of users and non-users of digitalis was investigated.
Results: At baseline, 53.4% of the study population used digitalis, and these patients had a higher mortality than non-users (255/3911 (6.5%) vs 141/3418 (4.1%), p<0.001; hazard ratio (HR) = 1.58 (95% CI 1.29 to 1.94)). Digitalis users also had more baseline risk factors. After multivariate risk factor adjustment, the increased mortality persisted (p<0.001; HR = 1.53 (95% CI 1.22 to 1.92 vs 1.23 to 1.92)).
Conclusions: The results suggest that digitalis, like other inotropic drugs, may increase mortality. This may be concealed in heart failure, but be revealed in patients with AF, who need the rate-reducing effect of digitalis, but do not benefit much from an increased inotropy. Cautious interpretation of the data is mandatory since the patients were not randomised with respect to digitalis use.
In this study patients were not randomized to digitalis use.
Digitalis: a dangerous drug in atrial fibrillation? An analysis of the SPORTIF III and V data
Heart 2008; 94: 191-196
Knut Gjesdal (University of Oslo, Norway) and colleagues
ABSTRACT
Objective: In heart failure, digitalis increases exercise capacity and reduces morbidity, but has no effect on survival. This raises the suspicion that the inotropic benefits of digitalis may be counteracted by serious adverse effects. Patients with atrial fibrillation (AF) were studied to clarify this.
Design: In the Stroke Prevention using an ORal Thrombin Inhibitor in atrial Fibrillation (SPORTIF) III and V studies, 7329 patients with AF at moderate-to-high risk were randomised to preventive treatment of thromboembolism, either with warfarin or the oral direct thrombin inhibitor ximelagatran. The survival of users and non-users of digitalis was investigated.
Results: At baseline, 53.4% of the study population used digitalis, and these patients had a higher mortality than non-users (255/3911 (6.5%) vs 141/3418 (4.1%), p<0.001; hazard ratio (HR) = 1.58 (95% CI 1.29 to 1.94)). Digitalis users also had more baseline risk factors. After multivariate risk factor adjustment, the increased mortality persisted (p<0.001; HR = 1.53 (95% CI 1.22 to 1.92 vs 1.23 to 1.92)).
Conclusions: The results suggest that digitalis, like other inotropic drugs, may increase mortality. This may be concealed in heart failure, but be revealed in patients with AF, who need the rate-reducing effect of digitalis, but do not benefit much from an increased inotropy. Cautious interpretation of the data is mandatory since the patients were not randomised with respect to digitalis use.
Similar outcome after thrombolysis or primary angioplasty in STEMI
Comparison of Left Ventricular Ejection Fraction and Inducible Ventricular Tachycardia in ST-Elevation Myocardial Infarction Treated by Primary Angioplasty Versus Thrombolysis
American Journal of Cardiology
Volume 101, Issue 2, Pages 153-157 (15 January 2008)
James J.H. Chong, MDa, Anand N. Ganesan, MD, PhD, Vicki Eippera, Pramesh Kovoor, MD, PhD
Electrophysiologic studies predict the risk for sudden death after myocardial infarction (MI). Although primary angioplasty has become the preferred method of treatment for ST-elevation MI, intravenous thrombolysis remains the first-line treatment in 30% to 70% of cases worldwide. Rates of ventricular tachyarrhythmias may vary according to type of reperfusion treatment. This study was undertaken to examine the hypothesis that the left ventricular ejection fraction (LVEF) and rates of inducible ventricular tachycardia may be more favorable in treatment with primary angioplasty rather than thrombolysis. Consecutive patients receiving primary angioplasty (n = 225) or thrombolysis (n = 195) for ST-elevation MI were included. The mean LVEF was 48 ± 12% for the primary angioplasty group and 46 ± 13% for the thrombolysis group (p = 0.30). The proportion of patients with LVEFs <40% was 30% in the primary angioplasty group and 30% in the thrombolysis group (p = 0.98). Patients with LVEFs <40% underwent electrophysiologic studies. Ventricular tachycardia was inducible in 23 of 66 primary angioplasty patients (34.8%) compared with 21 of 55 (38.1%) thrombolysis patients (p = 0.69). Implantable cardiac defibrillators were inserted in 30 patients, of whom 8 (27%) had appropriate device activations. The mean time from MI to first spontaneous activation was 387 ± 458 days.
In conclusion, patients treated with thrombolysis or primary angioplasty for ST-elevation MIs had similar resultant LVEFs and rates of inducible ventricular tachycardia. There was a surprisingly high rate of spontaneous defibrillator activations, often occurring late after MI.
American Journal of Cardiology
Volume 101, Issue 2, Pages 153-157 (15 January 2008)
James J.H. Chong, MDa, Anand N. Ganesan, MD, PhD, Vicki Eippera, Pramesh Kovoor, MD, PhD
Electrophysiologic studies predict the risk for sudden death after myocardial infarction (MI). Although primary angioplasty has become the preferred method of treatment for ST-elevation MI, intravenous thrombolysis remains the first-line treatment in 30% to 70% of cases worldwide. Rates of ventricular tachyarrhythmias may vary according to type of reperfusion treatment. This study was undertaken to examine the hypothesis that the left ventricular ejection fraction (LVEF) and rates of inducible ventricular tachycardia may be more favorable in treatment with primary angioplasty rather than thrombolysis. Consecutive patients receiving primary angioplasty (n = 225) or thrombolysis (n = 195) for ST-elevation MI were included. The mean LVEF was 48 ± 12% for the primary angioplasty group and 46 ± 13% for the thrombolysis group (p = 0.30). The proportion of patients with LVEFs <40% was 30% in the primary angioplasty group and 30% in the thrombolysis group (p = 0.98). Patients with LVEFs <40% underwent electrophysiologic studies. Ventricular tachycardia was inducible in 23 of 66 primary angioplasty patients (34.8%) compared with 21 of 55 (38.1%) thrombolysis patients (p = 0.69). Implantable cardiac defibrillators were inserted in 30 patients, of whom 8 (27%) had appropriate device activations. The mean time from MI to first spontaneous activation was 387 ± 458 days.
In conclusion, patients treated with thrombolysis or primary angioplasty for ST-elevation MIs had similar resultant LVEFs and rates of inducible ventricular tachycardia. There was a surprisingly high rate of spontaneous defibrillator activations, often occurring late after MI.
Saturday, January 26, 2008
Clinical Cases and Images: Noncompaction of the Left Ventricle – A Rare Cause Of Non-ischemic Cardiomyopathy
Clinical Cases and Images: Noncompaction of the Left Ventricle – A Rare Cause Of Non-ischemic Cardiomyopathy
Noncompaction of the Left Ventricle – A Rare Cause Of Non-ischemic Cardiomyopathy
Author: M. Auron, M.D, Department of Hospital Medicine, Cleveland ClinicReviewer: V. Dimov, M.D., Department of Hospital Medicine, Cleveland ClinicA 56 yo AAM with no significant past medical history presented to the ER with progressive dyspnea, epigastric pain and diaphoresis for one week.
Noncompaction of the Left Ventricle – A Rare Cause Of Non-ischemic Cardiomyopathy
Author: M. Auron, M.D, Department of Hospital Medicine, Cleveland ClinicReviewer: V. Dimov, M.D., Department of Hospital Medicine, Cleveland ClinicA 56 yo AAM with no significant past medical history presented to the ER with progressive dyspnea, epigastric pain and diaphoresis for one week.
Thursday, January 24, 2008
Drug-Eluting Stents vs. Coronary-Artery Bypass Grafting in Multivessel Coronary Disease
Drug-Eluting Stents vs. Coronary-Artery Bypass Grafting in Multivessel Coronary Disease
New England Journal of Medicine, January 24, 2008.
Edward L. Hannan, Ph.D., Chuntao Wu, M.D., Ph.D., Gary Walford, M.D., Alfred T. Culliford, M.D., Jeffrey P. Gold, M.D., Craig R. Smith, M.D., Robert S.D. Higgins, M.D., Russell E. Carlson, M.D., and Robert H. Jones, M.D.
ABSTRACT
Background Numerous studies have compared the outcomes of two competing interventions for multivessel coronary artery disease: coronary-artery bypass grafting (CABG) and coronary stenting. However, little information has become available since the introduction of drug-eluting stents.
Methods We identified patients with multivessel disease who received drug-eluting stents or underwent CABG in New York State between October 1, 2003, and December 31, 2004, and we compared adverse outcomes (death, death or myocardial infarction, or repeat revascularization) through December 31, 2005, after adjustment for differences in baseline risk factors among the patients.
Results In comparison with treatment with a drug-eluting stent, CABG was associated with lower 18-month rates of death and of death or myocardial infarction both for patients with three-vessel disease and for patients with two-vessel disease. Among patients with three-vessel disease who underwent CABG, as compared with those who received a stent, the adjusted hazard ratio for death was 0.80 (95% confidence interval [CI], 0.65 to 0.97) and the adjusted survival rate was 94.0% versus 92.7% (P=0.03); the adjusted hazard ratio for death or myocardial infarction was 0.75 (95% CI, 0.63 to 0.89) and the adjusted rate of survival free from myocardial infarction was 92.1% versus 89.7% (P<0.001). Among patients with two-vessel disease who underwent CABG, as compared with those who received a stent, the adjusted hazard ratio for death was 0.71 (95% CI, 0.57 to 0.89) and the adjusted survival rate was 96.0% versus 94.6% (P=0.003); the adjusted hazard ratio for death or myocardial infarction was 0.71 (95% CI, 0.59 to 0.87) and the adjusted rate of survival free from myocardial infarction was 94.5% versus 92.5% (P<0.001). Patients undergoing CABG also had lower rates of repeat revascularization.
Conclusions For patients with multivessel disease, CABG continues to be associated with lower mortality rates than does treatment with drug-eluting stents and is also associated with lower rates of death or myocardial infarction and repeat revascularization.
Wednesday, January 23, 2008
New Drugs for the Treatment of Diabetes Mellitus: Part I: Thiazolidinediones and Their Evolving Cardiovascular Implications
Merck Sharp & Dohme
Circulation:Volume 117(3)22 January 2008pp 440-449
New Drugs for the Treatment of Diabetes Mellitus: Part I: Thiazolidinediones and Their Evolving Cardiovascular Implications
Conclusions
In summary, thiazolidinedione effects on the cardiovascular system extend beyond their impact on glucose metabolism, yielding much interest in their effect on CVD risk, with numerous trials underway. Both rosiglitazone and pioglitazone are similarly associated with peripheral edema and, much less commonly, HF, warranting continued caution for their use in HF patients according to their product labels, Food and Drug Administration guidance, and AHA/American Diabetes Association recommendations.57 Pioglitazone has demonstrated favorable trends for CVD risk reduction in the PROactive study, the largest CVD outcomes trial of glucose-modifying therapy completed to date. The safety signal associated with potential increased CVD risk associated with rosiglitazone warrants caution for its use, but the paucity of evaluable data in this context justifies continued clinical trial assessment with judicious safety monitoring of ongoing clinical trials. Until such additional safety and efficacy data are available, in the context of what may now appear to be safer alternatives to rosiglitazone available, including but not limited to pioglitazone, its routine use in the treatment of hyperglycemia in patients with T2DM at increased CVD risk cannot be recommended.
Circulation:Volume 117(3)22 January 2008pp 440-449
New Drugs for the Treatment of Diabetes Mellitus: Part I: Thiazolidinediones and Their Evolving Cardiovascular Implications
Conclusions
In summary, thiazolidinedione effects on the cardiovascular system extend beyond their impact on glucose metabolism, yielding much interest in their effect on CVD risk, with numerous trials underway. Both rosiglitazone and pioglitazone are similarly associated with peripheral edema and, much less commonly, HF, warranting continued caution for their use in HF patients according to their product labels, Food and Drug Administration guidance, and AHA/American Diabetes Association recommendations.57 Pioglitazone has demonstrated favorable trends for CVD risk reduction in the PROactive study, the largest CVD outcomes trial of glucose-modifying therapy completed to date. The safety signal associated with potential increased CVD risk associated with rosiglitazone warrants caution for its use, but the paucity of evaluable data in this context justifies continued clinical trial assessment with judicious safety monitoring of ongoing clinical trials. Until such additional safety and efficacy data are available, in the context of what may now appear to be safer alternatives to rosiglitazone available, including but not limited to pioglitazone, its routine use in the treatment of hyperglycemia in patients with T2DM at increased CVD risk cannot be recommended.
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