|Year : 2019 | Volume
| Issue : 1 | Page : 34-40
Year in cardiology 2018
Alok Kumar Singh
Department of Cardiology, Opal Hospital, Varanasi, Uttar Pradesh, India
|Date of Web Publication||29-Mar-2019|
Dr. Alok Kumar Singh
Department of Cardiology, Opal Hospital, Varanasi, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Singh AK. Year in cardiology 2018. Heart India 2019;7:34-40
In this article, I will discuss the result of landmark trials published in 2018 which will have impact in future cardiology practice. The purpose of this article is to get a summary of all relevant studies published in 2018 at one place in a concise manner.
| Epinephrine for Out-Of-Hospital Cardiac Arrest|| |
Epinephrine has been part of the resuscitation of patients with cardiac arrest, recommended by almost every guideline. Despite widespread epinephrine use, data on the benefit of the drug comes primarily from observational studies with a little authenticity. The PARAMEDIC2 trial published in 2018 provides the largest set of randomized data on epinephrine use in out-of-hospital cardiac arrest so far. In this trial, patients with cardiac arrest were randomly assigned to receive parenteral epinephrine or saline, with trial-group assignments concealed from both the treating teams and the outcome assessors. All but 7 of 8014 patients were included in the primary analysis at 30 days. In adults with out-of-hospital cardiac arrest, the use of epinephrine resulted in a significantly higher rate of 30-day survival than the use of placebo, but there was no significant between-group difference in the rate of a favorable neurologic outcome because more survivors had severe neurologic impairment in the epinephrine group.
| Cardiovascular Outcomes and Mortality in Patients With Type 2 Diabetes|| |
It is well-known fact that patients with diabetes are at higher risk for death and cardiovascular outcomes than the general population. Rawshani et al. studied 71,174 patients with type 2 diabetes, who were registered in the Swedish National Diabetes Register and matched them with 1,355,870 controls on the basis of age, sex, and county. Patients with type 2 diabetes have risks of death and cardiovascular events that are 2–4 times as great as the risks in the general population. The extent to which the excess risk associated with type 2 diabetes may be mitigated, or potentially eliminated, by contemporary evidence-based treatment and multifactorial risk-factor modification is not known. Investigators assessed patients with diabetes according to age categories and according to the presence of five risk factors (elevated glycated hemoglobin level, elevated low-density lipoprotein (LDL) cholesterol level, albuminuria, smoking, and elevated blood pressure). The median follow-up among all the study participants was 5.7 years, during which 175,345 deaths occurred. In patients with type 2 diabetes, a glycated hemoglobin level outside the target range was the strongest predictor of stroke and acute myocardial infarction; smoking was the strongest predictor of death. Patients with type 2 diabetes who had five risk-factor variables within the target range appeared to have little or no excess risk of death, myocardial infarction, or stroke, as compared with the general population. The risk of hospitalization for heart failure was consistently higher among patients with diabetes than among controls (hazard ratio, 1.45). In my opinion, this study contribution to medical science is reinforcing the fact; the blood sugar control along with risk factor modification can alter the natural history of diabetes.
| Cardiovascular Safety of Febuxostat or Allopurinol in Patients With Gout|| |
It is well-known fact that the risk of cardiovascular events, including death, is substantially higher in people with gout than in those without gout. White et al. conducted a multicenter, double-blind, noninferiority trial involving patients with gout and cardiovascular disease; patients were randomly assigned to receive febuxostat or allopurinol and were stratified according to the kidney function. Investigators concluded that, in patients with gout and major cardiovascular coexisting conditions, febuxostat was noninferior to allopurinol with respect to the rates of adverse cardiovascular events. All-cause mortality and cardiovascular mortality were higher with febuxostat than with allopurinol. Important limitations of this study are a large number of participants who discontinued the trial treatment and the large number of participants who did not complete follow-up.
| Aspirin in Healthy Elderly (Aspree Study)|| |
Aspirin is a well-proven treatment for the secondary prevention of cardiovascular events; however, its role in primary prevention is not known. McNeil et al. have studied the role of aspirin in the primary prevention of cardiovascular diseases in older persons, who have an increased risk. In this study, the 19,114 persons who were enrolled in the trial, 9525 were assigned to receive aspirin and 9589 to receive placebo. After a median of 4.7 years of follow-up, the rate of cardiovascular disease was 10.7 events per 1000 person-years in the aspirin group and 11.3 events per 1000 person-years in the placebo group. Authors of this study have concluded that the use of low-dose aspirin as a primary prevention strategy in older adults resulted in a significantly higher risk of major hemorrhage and did not result in a significantly lower risk of cardiovascular disease than placebo.
[TAG:2]Aspirin in Primary Prevention in Diabetes Mellitus (The Ascend Study)[/TAG:2]
Patients with diabetes mellitus have a risk of vascular events that is 2–3 times as high as the risk among those without diabetes, three but most of the diabetics do not have manifest vascular disease. Role of aspirin in secondary prevention is well proven, but no hard data were available in diabetics without apparent heart disease. In the ASCEND trial, 15,480 participants with diabetes were randomly assigned to receive aspirin at a dose of 100 mg daily or matching placebo.
During a mean follow-up of 7.4 years, the use of aspirin was associated with a 12% decrease in the rate of serious vascular events; however, this benefit came at the cost of a 29% increase in the rate of major bleeding events. Investigators of this study concluded that the absolute benefits were largely counterbalanced by the bleeding hazard.
[TAG:2]Aspirin to Reduce Risk of Initial Vascular Events – the Arrive Study[/TAG:2]
The goal of the ARRIVE trial was to evaluate aspirin compared with placebo among patients with moderate risk of cardiovascular disease without diabetes. In ARRIVE trial, the incidence of the composite primary outcome of myocardial infarction, stroke, unstable angina, transient ischemic attack, or death from cardiovascular causes was 4.3% with aspirin and 4.5% with placebo (hazard ratio, 0.96; 95% confidence interval [CI], 0.81–1.13; P = 0.60), whereas the incidence of gastrointestinal bleeding events with aspirin was twice the incidence with placebo. Hence, overall final conclusion of the study was among patients at moderate risk of coronary heart disease, the use of aspirin was not beneficial. However, the significant limitation of this trial was lower than expected event rate.
| Vitamin D Supplements for Prevention of Cancer and Cardiovascular Disease|| |
Observational studies have shown lower rates of death from cancer and cardiovascular disease in regions with greater sun exposure than in areas with less sun exposure. investigators conducted a nationwide, randomized, placebo-controlled trial, with a two-by-two factorial design, of Vitamin D (cholecalciferol) at a dose of 2000 IU/day and marine n−3 (also called omega-3) fatty acids at a dose of 1 g/day for the prevention of cancer and cardiovascular disease among men 50 years of age or older and women 55 years of age or older in the United States. Manson et al. in their study concluded that supplementation with Vitamin D did not result in a lower incidence of invasive cancer or cardiovascular events than placebo irrespective of baseline serum 25-hydroxyvitamin D levels during the trial follow-up of 5 years.
| Effects of N−3 Fatty Acid Supplements in Diabetes Mellitus|| |
The American Heart Association guidelines currently recommend n−3 fatty acid supplements for secondary prevention of coronary heart disease, and fish consumption for primary prevention is recommended in cardiovascular disease prevention guidelines. However, randomized trials of supplementation with n−3 (also called omega-3) fatty acids have shown conflicting results regarding the effects on fatal or nonfatal outcomes. These recommendations are based on observational studies, not supported by randomized clinical trial evidence. In ASCEND study, investigators randomly assigned 15,480 patients with diabetes but without evidence of atherosclerotic cardiovascular disease to receive 1-g capsules containing either n−3 fatty acids (fatty acid group) or matching placebo (olive oil) daily. Investigators of this study concluded that supplementation with n−3 (omega-3) fatty acids did not result in a lower incidence of serious vascular events than placebo during the trial follow-up of 7.4 years.
| Marine N−3 Fatty Acids for Prevention of Cardiovascular Disease and Cancer|| |
Multiple observational studies have shown higher intake of marine n−3 (also called omega-3) fatty acids has been associated with reduced risks of cardiovascular disease and cancer. Investigators conducted a nationwide, randomized, placebo-controlled trial, with a two-by-two factorial design, of Vitamin D (cholecalciferol) at a dose of 2000 IU per day and marine n−3 (also called omega-3) fatty acids at a dose of 1 g/day for the prevention of cancer and cardiovascular disease among men 50 years of age or older and women 55 years of age or older in the United States. Manson et al. in their study concluded that supplementation with n−3 Fatty Acids did not result in a lower incidence of invasive cancer or cardiovascular events than placebo during the trial follow-up of 5 years.
| Impact of Smoking Cessation on Type 2 Diabetes and Mortality|| |
Weight gain may occur in quitters after smoking cessation. Such weight may discourage quitting attempts and potentially attenuate the health benefits of smoking cessation through increasing the risk of cardiometabolic disease and premature death. Hu et al. studied the impact of smoking cessation on weight change and their effect on the development of diabetes and mortality. The temporary increase in the risk of type 2 diabetes was directly proportional to weight gain, and the risk was not increased among quitters without weight gain. The risk of type 2 diabetes was higher among recent quitters (2–6 years since smoking cessation) than among current smokers (hazard ratio, 1.22. The risk peaked 5–7 years after quitting and then gradually decreased. Overall smoking cessation that was accompanied by substantial weight gain was associated with an increased short-term risk of type 2 diabetes but did not neutralize the benefits of quitting smoking on reducing cardiovascular and all-cause mortality.
| Mediterranean Diet Supplemented With Extra-Virgin Olive Oil or Nuts Versus Low-Fat Diet|| |
In observational cohort studies and a secondary prevention trial (the Lyon Diet Heart Study), increasing adherence to the Mediterranean diet has been definitely associated with lower cardiovascular risk. Estruch et al. tested the efficacy of two Mediterranean diets (one supplemented with extra-virgin olive oil and another with nuts), as compared with a control diet (advice on a low-fat diet), in primary prevention in PREDIMED (Prevencion con Dieta Mediterranea) trial. In this study involving 7447 participants (55–80 years of age, 57% of women) who were at high cardiovascular risk, but with no cardiovascular disease, the incidence of major cardiovascular events was lower among those assigned to a Mediterranean diet supplemented with extra-virgin olive oil or nuts than among those assigned to a reduced-fat diet.
| Wearable Cardioverter–defibrillator for Sudden Death Prevention After Myocardial Infarction|| |
Implantable cardioverter–defibrillators (ICDs) reduce mortality among patients with a reduced ejection fraction when the devices are implanted months to years after myocardial infarction. However, two randomized trials did not show a long-term mortality benefit from ICDs that had been implanted immediately after myocardial infarction. Hence, therefore, guidelines recommend waiting for at least 40 days after myocardial infarction and 90 days after coronary revascularization for the implantation of an ICD for primary prevention. In VEST trial, investigators randomly assigned (in a 2:1 ratio) patients with acute myocardial infarction and an ejection fraction of 35% or less (assessed ≥8 h after myocardial infarction) to receive a wearable cardioverter-defibrillator plus guideline-directed therapy (the device group) or to receive only guideline-directed therapy (the control group) within 7 days after hospital discharge. Authors of this study concluded that among patients with a recent myocardial infarction and an ejection fraction of 35% or less, the wearable cardioverter-defibrillator did not lead to a significantly lower rate of the primary outcome of arrhythmic death than control.
| Outcomes After Angiography With Acetylcysteine and Sodium Bicarbonate|| |
Acute kidney injury associated with contrast administration during angiography can result in accelerated progression of underlying chronic kidney disease, death and the need for dialysis, along with substantial increases in health-care costs. Using a 2-by-2 factorial design, Weisbord et al. randomly assigned 5177 patients at high risk for renal complications who were scheduled for angiography to receive intravenous 1.26% sodium bicarbonate or intravenous 0.9% sodium chloride and 5 days of oral acetylcysteine or oral placebo; of these patients, 4993 were included in the modified intention-to-treat analysis. The primary endpoint was a composite of death, the need for dialysis, or a persistent increase of at least 50% from baseline in the serum creatinine level at 90 days. Contrast-associated acute kidney injury was a secondary endpoint. This trial was done in the population, who had an estimated glomerular filtration rate of 15–44.9 ml/min/1.73 m2 of the body-surface area or 45–59.9 ml/min/1.73 m2 among those with diabetes mellitus. In this multinational, randomized, controlled trial (PRESERVE) in patients with chronic kidney disease who were undergoing angiography, investigators found no benefit of intravenous sodium bicarbonate over intravenous sodium chloride or of oral acetylcysteine over oral placebo for the prevention of death, need for dialysis, or persistent kidney impairment at 90 days or for the prevention of contrast-associated acute kidney injury or other secondary endpoints.
[TAG:2]Coronary Computed Tomographic Angiography and 5-Year Risk of Myocardial Infarction[/TAG:2]
Coronary computed tomographic angiography (CTA) improves diagnostic certainty in the assessment of patients with stable chest pain, its effect on 5-year clinical outcomes were unknown. In this open-label, multicenter, parallel-group trial, investigators randomly assigned 4146 patients with stable chest pain who had been referred to a cardiology clinic for evaluation to standard care plus CTA (2073 patients) or to standard care alone (2073 patients). The primary endpoint was death from coronary heart disease or nonfatal myocardial infarction at 5 years. The 5-year rate of the primary end point was lower in the CTA group than in the standard-care group (2.3% [48 patients] vs. 3.9% [81 patients]; hazard ratio, 0.59). In this study, overall conclusion was that, the use of CTA in addition to standard care in patients with stable chest pain resulted in a significantly lower rate of death from coronary heart disease or nonfatal myocardial infarction at 5 years than standard care alone, without resulting in a significantly higher rate of coronary angiography or coronary revascularization. This is a new important finding that is in contrast to previous trials that have shown higher rates of invasive coronary angiography and coronary revascularization after anatomical imaging with CTA than after functional testing.
[TAG:2]Alirocumab and Cardiovascular Outcomes After Acute Coronary Syndrome[/TAG:2]
Despite the introduction of all current evidence-based treatments, patients who have had acute coronary syndrome remain at high risk for recurrent ischemic cardiovascular events. Before this study, the potential for a PCSK9 antibody to reduce cardiovascular risk after an acute coronary syndrome remains undetermined. In the ODYSSEY OUTCOMES trial, investigators conducted a multicenter, randomized, double-blind, placebo-controlled trial involving 18,924 patients who had an acute coronary syndrome 1–12 months earlier, had a LDL cholesterol level of at least 70 mg/dl (1.8 mmol/L), a nonhighdensity lipoprotein cholesterol level of at least 100 mg/dl (2.6 mmol/L), or an apolipoprotein B level of at least 80 mg/dl, and were receiving statin therapy at a high-intensity dose or at the maximum tolerated dose. The primary endpoint was a composite of death from coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization.
The median duration of follow-up was 2.8 years. Overall conclusion of the study was that among patients who had a previous acute coronary syndrome and who were receiving high intensity statin therapy, the risk of recurrent ischemic cardiovascular events was lower among those who received alirocumab than among those who received placebo. However, no significant differences between the trial groups were observed with respect to the risks of the secondary endpoints of death from coronary heart disease and death from cardiovascular causes.
[TAG:2]One-Year Outcomes After Percutaneous Coronary Intervention Strategies in Cardiogenic Shock (Culprit-Shock – one Year Follow-Up)[/TAG:2]
Among patients with acute myocardial infarction, cardiogenic shock, and multivessel coronary artery disease, the risk of a composite of death from any cause or severe renal failure leading to renal-replacement therapy at 30 days was found to be lower with percutaneous coronary intervention (PCI) of the culprit lesion only than with immediate multivessel PCI in CULPRIT – SHOCK. Investigators evaluated clinical outcomes at 1 year. At 1 year, death had occurred in 172 of 344 patients (50.0%) in the culprit lesion-only PCI group and in 194 of 341 patients (56.9%) in the multivessel PCI group (relative risk, 0.88). The rate of recurrent infarction was 1.7% with culprit-lesion-only PCI and 2.1% with multivessel PCI (relative risk, 0.85), and the rate of a composite of death or recurrent infarction was 50.9% and 58.4%, respectively (relative risk, 0.87).
Repeat revascularization occurred more frequently with culprit-lesion-only PCI than with multivessel PCI (in 32.3% of the patients vs. 9.4%; relative risk, 3.44;), as did rehospitalization for heart failure (5.2% vs. 1.2%; relative risk, 4.46). Overall conclusion of the study was, among patients with acute myocardial infarction and cardiogenic shock, the risk of death or renal-replacement therapy at 30 days was lower with culprit-lesion-only PCI than with immediate multivessel PCI, and mortality did not differ significantly between the two groups at 1 year of follow-up.
[TAG:2]Catheter Ablation for Atrial Fibrillation With Heart Failure[/TAG:2]
Heart failure and atrial fibrillation are common coexisting conditions, with atrial fibrillation increasing the risk of stroke, hospitalization for heart failure, and death. Investigators randomly assigned patients with symptomatic paroxysmal or persistent atrial fibrillation who did not have a response to antiarrhythmic drugs, had unacceptable side effects, or were unwilling to take these drugs to undergo either catheter ablation (179 patients) or medical therapy (rate or rhythm control) (184 patients) for atrial fibrillation in addition to guidelines-based therapy for heart failure. All the patients had New York Heart Association Class II, III, or IV heart failure, a left ventricular ejection fraction of 35% or less, and an implanted defibrillator.
After follow-up of 37.8 months, patients who were assigned to ablation were less likely to meet the primary composite endpoint of death from any cause or heart-failure-related admission or the secondary endpoints, which included death from any cause and death from cardiovascular disease. After 5 years, the LVEF had increased by 8% in the ablation group as compared with no increase in the medical-therapy group. In addition, 63% of patients in the ablation group were in sinus rhythm, as compared with 22% of those in the medical therapy group. Overall conclusion of the study was that catheter ablation for atrial fibrillation in patients with heart failure was associated with a significantly lower rate of a composite end point of death from any cause or hospitalization for worsening heart failure than was medical therapy.
[TAG:2]Relationship between Clinic and Ambulatory Blood-Pressure Measurements and Mortality[/TAG:2]
This study examined the associations of clinic blood pressure and 24-h ambulatory blood pressure with all-cause and cardiovascular mortality in a large cohort of patients in primary care in Spain. Banegas et al. analyzed data from a registry-based, multicenter, national cohort that included 63,910 adults recruited from 2004 to 2014 in Spain. During a median follow-up of 4.7 years, 3808 patients died from any cause, and 1295 of these patients died from cardiovascular causes. 24-h systolic pressure was more strongly associated with all-cause mortality (hazard ratio, 1.58 per 1-SD increase in pressure; 95% CI, 1.56–1.60, after adjustment for clinic blood pressure) than the clinic systolic pressure. Masked hypertension was more strongly associated with all-cause mortality (hazard ratio, 2.83; 95% CI, 2.12–3.79) than sustained hypertension (hazard ratio, 1.80) or white-coat hypertension (hazard ratio, 1.79). Ambulatory blood pressure measurements were a stronger predictor of all-cause and cardiovascular mortality than clinic blood-pressure measurements. The most important contribution of this study is that white-coat hypertension was not benign, and masked hypertension was associated with a greater risk of death than sustained hypertension.
[TAG:2]Percutaneous Repair or Medical Treatment for Secondary Mitral Regurgitation[/TAG:2]
In patients of chronic heart failure with reduced the left ventricular ejection fraction, the presence of severe secondary mitral valve regurgitation is associated with a poor prognosis. Obadia et al. randomly assigned patients who had severe secondary mitral regurgitation (defined as an effective regurgitant orifice area of >20 mm2 or a regurgitant volume of >30 ml per beat), a left ventricular ejection fraction between 15% and 40%, and symptomatic heart failure, in a 1:1 ratio, to undergo percutaneous mitral-valve repair in addition to receiving medical therapy (intervention group; 152 patients) or to receive medical therapy alone (control group; 152 patients). The primary efficacy outcome endpoint was a composite of death from any cause or unplanned hospitalization for heart failure at 12 months. Overall conclusion of the study was, among patients with severe secondary mitral regurgitation, the rate of death or unplanned hospitalization for heart failure at 1 year did not differ significantly between patients who underwent percutaneous mitral-valve repair in addition to receiving medical therapy and those who received medical therapy alone.
[TAG:2]Transcatheter Mitral-Valve Repair in Patients With Heart Failure[/TAG:2]
It is established fact among patients with heart failure who have mitral regurgitation due to the left ventricular dysfunction, the prognosis is poor. Stone et al. enrolled patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy. Patients were randomly assigned to transcatheter mitral-valve repair plus medical therapy (device group) or medical therapy alone (control group). Of 614 patients who were enrolled in the trial, 302 were assigned to the device group and 312 to the control group. The annualized rate of all hospitalizations for heart failure within 24 months was 35.8% per patient-year in the device group as compared with 67.9% per patient-year in the control group (hazard ratio, 0.53). The rate of freedom from device-related complications at 12 months was 96.6%. Death from any cause within 24 months occurred in 29.1% of the patients in the device group as compared with 46.1% in the control group (hazard ratio, 0.62). Overall conclusion of this study was among patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy, transcatheter mitral-valve repair resulted in a lower rate of hospitalization for heart failure and lower all-cause mortality within 24 months of follow-up than medical therapy alone.
[TAG:2]Five-Year Outcomes With Percutaneous Coronary Intervention Guided by Fractional Flow Reserve[/TAG:2]
PCI guided by fractional flow reserve (FFR) would be superior to medical therapy as initial treatment in patients with stable coronary artery disease. In this study among 1220 patients with angiographically significant stenoses, those in whom at least one stenosis was hemodynamically significant (FFR, ≤0.80) were randomly assigned to FFR-guided PCI plus medical therapy or to medical therapy alone. Patients in whom all stenoses had an FFR of more than 0.80 received medical therapy and were entered into a registry. The primary endpoint was a composite of death, myocardial infarction, or urgent revascularization. A total of 888 patients underwent randomization (447 patients in the PCI group and 441 in the medical-therapy group). At 5 years, the rate of the primary endpoint was lower in the PCI group than in the medical-therapy group (13.9% vs. 27.0%; hazard ratio, 0.46 P < 0.001). The difference was driven by urgent revascularizations, which occurred in 6.3% of the patients in the PCI group as compared with 21.1% of those in the medical-therapy group (hazard ratio, 0.27). There were no statistically significant differences between the PCI group and the medical-therapy group in the rates of death (5.1% and 5.2%, respectively; hazard ratio, 0.98) or myocardial infarction (8.1% and 12.0%; hazard ratio, 0.66). There was no significant difference in the rate of the primary endpoint between the PCI group and the registry cohort (13.9% and 15.7%, respectively; hazard ratio, 0.88). Overall conclusion of this study was in patients with stable coronary artery disease, an initial FFR-guided PCI strategy was associated with a significantly lower rate of the primary composite endpoint Of death, myocardial infarction, or urgent revascularization at 5 years than medical therapy alone.
[TAG:2]Rivaroxaban in Patients With Heart Failure, Sinus Rhythm, and Coronary Disease[/TAG:2]
Patients with heart failure and a reduced left ventricular ejection fraction are at high risk for death and complications, despite the proven benefits of established medications and devices. Heart failure is associated with activation of thrombin-related pathways, which predicts a poor prognosis. In this double-blind, randomized trial, 5022 patients who had chronic heart failure, a left ventricular ejection fraction of 40% or less, coronary artery disease, and elevated plasma concentrations of natriuretic peptides and who did not have atrial fibrillation were randomly assigned to receive rivaroxaban at a dose of 2.5 mg twice daily or placebo in addition to standard care after treatment for an episode of worsening heart failure. The primary efficacy outcome was the composite of death from any cause, myocardial infarction, or stroke. Overall conclusion of the study was that rivaroxaban at a dose of 2.5 mg twice daily was not associated with a significantly lower rate of death, myocardial infarction, or stroke than placebo among patients with worsening chronic heart failure, reduced left ventricular ejection fraction, coronary artery disease, and no atrial fibrillation.
[TAG:2]Tafamidis Treatment for Patients With Transthyretin Amyloid Cardiomyopathy[/TAG:2]
Transthyretin amyloid cardiomyopathy is a life-threatening condition characterized by the accumulation of amyloid fibrils composed of misfolded transthyretin protein in the heart. In a multicenter, international, double-blind, placebo-controlled, phase 3 trial, investigators randomly assigned 441 patients with transthyretin amyloid cardiomyopathy in a 2:1:2 ratio to receive 80 mg of tafamidis, 20 mg of tafamidis, or placebo for 30 months. In the primary analysis, all-cause mortality and rates of cardiovascular-related hospitalizations were lower among the 264 patients who received tafamidis than among the 177 patients who received placebo (P < 0.001). Tafamidis was associated with lower all-cause mortality than placebo (78 of 264 [29.5%] vs. 76 of 177 [42.9%]; hazard ratio, 0.70) and a lower rate of cardiovascular-related hospitalizations, with a relative risk ratio of 0.68 (0.48 per year vs. 0.70 per year). After 30 month, tafamidis was also associated with a lower rate of decline in distance for the 6-min walk test (P < 0.001) and a lower rate of decline in Kansas City Cardiomyopathy Questionnaire–Overall Summary score (P < 0.001). The incidence and types of adverse events were similar in the two groups. Overall conclusion of this study was in patients with transthyretin amyloid cardiomyopathy, tafamidis was associated with reductions in all-cause mortality and cardiovascular-related hospitalizations and reduced the decline in functional capacity and quality of life as compared with placebo. Reductions in cardiovascular-related hospitalizations were seen only after 9 months, and all cause mortality after 18 months, which may reflect the time necessary to influence the underlying pathology.
[TAG:2]Cardiovascular Safety of Lorcaserin in Overweight or Obese Patients[/TAG:2]
Lorcaserin, a selective serotonin 2C receptor agonist that modulates appetite, has proven efficacy for weight management in overweight or obese patients. Investigators of this study randomly assigned 12,000 overweight or obese patients with atherosclerotic cardiovascular disease or multiple cardiovascular risk factors to receive either lorcaserin (10 mg twice daily) or placebo. The primary safety outcome was major cardiovascular events (a composite of cardiovascular death, myocardial infarction, or stroke), and the primary cardiovascular efficacy outcome was extended major cardiovascular events (a composite of major cardiovascular events plus heart failure, hospitalization for unstable angina, or coronary revascularization). A key secondary outcome was the development of new-onset type 2 diabetes. In this study, the patient population had a high burden of coexisting illnesses, including diabetes (in 57%), hyperlipidemia (in 94%), hypertension (in 90%), and chronic kidney disease (in 20%). At 1 year, weight loss of at least 5% had occurred in 1986 of 5135 patients (38.7%) in the lorcaserin group and in 883 of 5083 (17.4%) in the placebo group (odds ratio, 3.01;). Adverse events of special interest were uncommon, and the rates were generally similar in the two groups, except for a higher number of patients with serious hypoglycemia in the lorcaserin group. Overall conclusion of this study was, in a high-risk population of overweight or obese patients, lorcaserin facilitated sustained weight loss without a higher rate of major cardiovascular events than that with placebo.
| References|| |
Perkins GD, Ji C, Deakin CD, Quinn T, Nolan JP, Scomparin C, et al.
A randomized trial of epinephrine in out-of-hospital cardiac arrest. N Engl J Med 2018;379:711-21.
Rawshani A, Rawshani A, Franzén S, Sattar N, Eliasson B, Svensson AM, et al.
Risk factors, mortality, and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 2018;379:633-44.
White WB, Saag KG, Becker MA, Borer JS, Gorelick PB, Whelton A, et al.
Cardiovascular safety of febuxostat or allopurinol in patients with gout. N Engl J Med 2018;379:1200-10.
McNeil JJ, Wolfe R, Woods RL, Tonkin AM, Donnan GA, Nelson MR, et al.
Effect of aspirin on cardiovascular events and bleeding in the healthy elderly. N Engl J Med 2018;379:1509-18.
ASCEND Study Collaborative Group, Bowman L, Mafham M, Wallendszus K, Stevens W, Buck G. Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med 2018;379:1529-39.
Gaziano JM, Brotons C, Coppolecchia R, Cricelli C, Darius H, Gorelick PB, et al.
Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): A randomised, double-blind, placebo-controlled trial. Lancet 2018;392:1036-46.
Manson JE, Cook NR, Lee I-M, et al
. Vitamin D supplements and prevention of cancer and cardiovascular disease. N Engl J Med 2018;379:33-44.
ASCEND Study Collaborative Group, Bowman L, Mafham M, Wallendszus K, Stevens W, Buck G. Effects of n-3 fatty acid supplements in diabetes mellitus. N Engl J Med 2018;379:1540-50.
Manson JE, Cook NR, Lee I-M, et al
. Marine n−3 fatty acids and prevention of cardiovascular disease and cancer. N Engl J Med 2018;380:23-32.
Hu Y, Zong G, Liu G, Wang M, Rosner B, Pan A, et al.
Smoking cessation, weight change, type 2 diabetes, and mortality. N Engl J Med 2018;379:623-32.
Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, Arós F, et al.
Primary prevention of cardiovascular disease with a Mediterranean diet supplemented with extra-virgin olive oil or nuts. N Engl J Med 2018;378:e34.
Olgin JE, Pletcher MJ, Vittinghoff E, Wranicz J, Malik R, Morin DP, et al.
Wearable cardioverter-defibrillator after myocardial infarction. N Engl J Med 2018;379:1205-15.
Weisbord SD, Gallagher M, Jneid H, Garcia S, Cass A, Thwin SS, et al.
Outcomes after angiography with sodium bicarbonate and acetylcysteine. N Engl J Med 2018;378:603-14.
SCOT-HEART Investigators, Newby DE, Adamson PD, Berry C, Boon NA, Dweck MR. Coronary CT angiography and 5-year risk of myocardial infarction. N Engl J Med 2018;379:924-33.
Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R, et al.
Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med 2018;379:2097-107.
Thiele H, Akin I, Sandri M, de Waha-Thiele S, Meyer-Saraei R, Fuernau G, et al.
One-year outcomes after PCI strategies in cardiogenic shock. N Engl J Med 2018;379:1699-710.
Marrouche NF, Brachmann J, Andresen D, Siebels J, Boersma L, Jordaens L, et al.
Catheter ablation for atrial fibrillation with heart failure. N Engl J Med 2018;378:417-27.
Banegas JR, Ruilope LM, de la Sierra A, Vinyoles E, Gorostidi M, de la Cruz JJ, et al.
Relationship between clinic and ambulatory blood-pressure measurements and mortality. N Engl J Med 2018;378:1509-20.
Obadia JF, Messika-Zeitoun D, Leurent G, Iung B, Bonnet G, Piriou N, et al.
Percutaneous repair or medical treatment for secondary mitral regurgitation. N Engl J Med 2018;379:2297-306.
Stone GW, Lindenfeld J, Abraham WT, Kar S, Lim DS, Mishell JM, et al.
Transcatheter mitral-valve repair in patients with heart failure. N Engl J Med 2018;379:2307-18.
Xaplanteris P, Fournier S, Pijls NH, Fearon WF, Barbato E, Tonino PA, et al.
Five-year outcomes with PCI guided by fractional flow reserve. N Engl J Med 2018;379:250-9.
Zannad F, Anker SD, Byra WM, Cleland JG, Fu M, Gheorghiade M, et al.
Rivaroxaban in patients with heart failure, sinus rhythm, and coronary disease. N Engl J Med 2018;379:1332-42.
Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M, et al.
Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med 2018;379:1007-16.
Bohula EA, Wiviott SD, McGuire DK, Inzucchi SE, Kuder J, Im K, et al.
Cardiovascular safety of lorcaserin in overweight or obese patients. N Engl J Med 2018;379:1107-17.