Anticoagulant and/or Antiplatelet Treatment in Patients with Atrial Fibrillation after Percutaneous Coronary Intervention Intensive oral antiplatelet therapy for reduction of ischaemic events including stent thrombosis in patients with acute coronary syndromes treated with percutaneous coronary intervention and stenting in the TRITON-TIMI 38 trial: a subanalysis of a randomised trial Dogma Disputed: Can Aggressively Lowering Blood Pressure in Hypertensive Patients with Coronary Artery Disease Be Dangerous? Comparison of the Effects of Antihypertensive Agents on Central Blood Pressure and Arterial Stiffness in Isolated Systolic Hypertension Subgroup and per-protocol analysis of the randomized European Trial on Isolated Systolic Hypertension in the Elderly. Blood Pressure and Clinical Outcomes in the International Stroke Trial Dual antiplatelet therapy versus oral anticoagulation plus dual antiplatelet therapy in patients with atrial fibrillation and low-to-moderate thromboembolic risk undergoing coronary stenting: design of the MUSICA-2 randomized trial. The Australian Therapeutic Trial in Mild Hypertension. Effectiveness of blood pressure-lowering drug treatment by levels of absolute risk: post hoc analysis of the Australian National Blood Pressure Study Mortality in primary angioplasty patients starting antiplatelet therapy with prehospital prasugrel or clopidogrel: a 1-year follow-up from the European MULTIPRAC Registry Thrombelastographic hypercoagulability and antiplatelet therapy after coronary artery bypass surgery (TEG-CABG trial): a randomized controlled trial Comparative effects of antiplatelet, anticoagulant, or combined therapy in patients with valvular and nonvalvular atrial fibrillation: a randomized multicenter study. Rationale and design of the dual antiplatelet therapy study, a prospective, multicenter, randomized, double-blind trial to assess the effectiveness and safety of 12 versus 30 months of dual antiplatelet therapy in subjects undergoing percutaneous coronary intervention with either drug-eluting stent  Rationale, Design, and Progress of the ENhanced Control of Hypertension ANd Thrombolysis Stroke Study (ENCHANTED) Trial: An International Multicenter 2 × 2 Quasi-Factorial Randomized Controlled Trial of Low- vs. Standard-Dose rt-PA and Early Intensive vs. Guideline-Recommended Blood Pressure Lowerin Impact of achieved blood pressure on cardiovascular outcomes in the Irbesartan Diabetic Nephropathy Trial. A comparative study of dual versus monoantiplatelet therapy in patients with acute large-artery atherosclerosis stroke. An analysis of mortality rates with dual-antiplatelet therapy in the primary prevention population of the CHARISMA trial.
Background : Atrial fibrillation ( AF ) is the most common cardiac arrhythmia sustained and frequently occurs in patients with coronary heart disease . Thus , a large number of patients requiring percutaneous coronary intervention ( PCI  ) also suffer from AF . An anticoagulant regimen has not been st and ardized for patients with AF after coronary stent implantation . Patients and Methods : The authors investigated data from 159 patients with AF who underwent PCI in their department . Baseline variables and incidence of a combined endpoint ( stroke , myocardial infa rct ion , cardiovascular death , severe bleeding ) were compared in patients receiving clopidogrel and acetylsalicylic acid ( ASA ; group 1 ) versus patients receiving the combination of clopidogrel and ASA with low-molecular-weight heparin ( LMWH ; group 2 ) versus patients receiving the combination of clopidogrel and ASA with oral anticoagulation ( OAC ; group 3 )  at discharge . Results : Patients discharged with triple therapy including OAC seemed to be at higher risk : patients in group 3 had decreased left ventricular ejection fraction and increased inflammatory state as measured by plasma fibrinogen and C-reactive protein . Moreover , previous OAC treatment and strokes were found more often in this subgroup of patients . In a median follow-up of 1.4 years , two severe bleeding events ( both in group 1 ) , four myocardial infa rct ions ( all in group 1 ) , 13 strokes ( nine in group 1 , four in group 2 ) , and nine cardiovascular deaths ( three in group 1 , five in group 2 , one in group 3 ) occurred . Conclusion : In this analysis , no treatment regimen seemed to be clearly superior . It underlines the importance of prospect i ve , r and omized trials to investigate the optimal antithrombotic/antiplatelet treatment for patients with AF after PCI.ZusammenfassungHintergrund : Vorhofflimmern ( VHF ) ist die häufigste Herzrhythmusstörung und wichtige Komorbidität bei Patienten mit koronarer Herzkrankheit . Welche antithrombotische/antithrombozytäre Therapiestrategie bei Patienten mit Vorhofflimmern nach perkutaner Koronarintervention ( PCI ) verfolgt werden sollte , ist aktuell nicht eindeutig zu beantworten . Patienten und Method ik : Die Autoren identifizierten retrospektiv 159 Patienten mit VHF , die in ihrer Abteilung in den Jahren 1999–2004 eine PCI erhalten hatten . Die Grunderkrankungen und die Inzidenz eines kombinierten Endpunkts ( Schlaganfall , Myokardinfarkt , kardiovaskulär bedingter Tod , schwere Blutung ) wurden bei Patienten verglichen , die Clopidogrel und Acetylsalicylsäure ( ASS ; Gruppe 1 ) , Clopidogrel und ASS in Kombination mit niedermolekularem Heparin ( Gruppe 2 ) sowie Clopidogrel und ASS und zusätzlich orale Antikoagulation erhalten hatten ( Gruppe 3).Ergebnisse : Die Grunderkrankungen der Patienten in den drei Gruppen waren nicht signifikant unterschiedlich . In einem medianen Beobachtungszeitraum von 1,4 Jahren konnten zwei schwere Blutungen ( in Gruppe 1 ) , vier Myokardinfarkte ( in Gruppe 1 ) , 13 Schlaganfälle ( neun in Gruppe 1 , vier in Gruppe 2 ) und neun kardiovaskulär bedingte Todesfälle ( drei in Gruppe 1 , fünf in Gruppe 2 , einer in Gruppe 3 ) nachgewiesen werden . Schlussfolgerung : In dieser Untersuchung erwies sich keine Therapiestrategie einer and eren gegenüber als eindeutig überlegen . Die erhobenen Date n zeigen , wie wichtig es ist , prospektive , r and omisierte Studien bezüglich der antithrombotischen/antithrombozytären Therapie durchzuführen , um Patienten mit AF nach PCI optimal beh and eln zu können BACKGROUND Intracoronary stenting can improve procedural success and reduce restenosis compared with balloon angioplasty in patients with acute coronary syndromes , but can also increase the rate of thrombotic complications including stent thrombosis . The TRITON-TIMI 38 trial has shown that prasugrel-a novel , potent thienopyridine-can reduce ischaemic events compared with st and ard clopidogrel therapy . We assessed the rate , outcomes , and prevention of ischaemic events in patients treated with prasugrel or clopidogrel with stents in the TRITON-TIMI 38 study . METHODS Patients with moderate-risk to high-risk acute coronary syndromes were included in our analysis if they had received at least one coronary stent at the time of the index procedure following r and omisation in TRITON-TIMI 38 , and were further subdivided by type of stent received . Patients were r and omly assigned in a 1 to 1 fashion to receive a loading dose of study drug ( prasugrel 60 mg or clopidogrel 300 mg ) as soon as possible after r and omisation , followed by daily maintenance therapy ( prasugrel 10 mg or clopidogrel 75 mg ) . All patients were to receive aspirin therapy . Treatment was to be continued for a minimum of 6 months and a maximum of 15 months . R and omisation was not stratified by stents used or stent type . The primary endpoint was the composite of cardiovascular death , non-fatal myocardial infa rct ion , or non-fatal stroke . Stent thrombosis was assessed using Academic Research Consortium definitions , and analysis was by intention to treat . TRITON-TIMI 38 is registered with Clinical Trials.gov , number NCT00097591 . FINDINGS 12,844 patients received at least one coronary stent ; 5743 received only drug-eluting stents , and 6461 received only bare-metal stents . Prasugrel compared with clopidogrel reduced the primary endpoint ( 9.7 vs 11.9 % , HR 0.81 , p=0.0001 ) in the stented cohort , in patients with only drug-eluting stents ( 9.0 vs 11.1 % , HR 0.82 , p=0.019 ) , and in patients with only bare-metal stents ( 10.0 vs 12.2 % , HR 0.80 , p=0.003 ) . Stent thrombosis was associated with death or myocardial infa rct ion in 89 % ( 186/210 ) of patients . Stent thrombosis was reduced with prasugrel overall ( 1.13 vs 2.35 % , HR 0.48 , p<0.0001 ) , in patients with drug-eluting stents only ( 0.84 vs 2.31 % , HR 0.36 , p<0.0001 ) , and in those with bare-metal stents only ( 1.27 vs 2.41 % , HR 0.52 , p=0.0009 ) . INTERPRETATION Intensive antiplatelet therapy with prasugrel result ed in fewer ischaemic outcomes including stent thrombosis than with st and ard clopidogrel . These findings were statistically robust irrespective of stent type , and the data affirm the importance of intensive platelet inhibition in patients with intracoronary stents Context Experts debate the consequences of excessive lowering of diastolic pressure in patients with hypertension and coronary artery disease . Contribution This report is a secondary analysis of data from a large trial of 2 antihypertensive drug regimens in patients with known coronary artery disease . The authors found a J-shaped relationship between diastolic blood pressure and all-cause death and myocardial infa rct ion , with the increased risk occurring at diastolic blood pressures below 70 to 80 mm Hg , that is , the lower the diastolic pressure , the higher the risk . Caution s The study examined associations between blood pressure and outcomes ; it could not prove that the antihypertensive therapy that lowered diastolic pressure too much caused the adverse outcomes . The Editors For 2 decades , the hypertension literature has been haunted by the phenomenon of a paradoxical increase in morbidity and mortality with an excessive decrease in blood pressure ( J-curve ) . Indeed , several reports have shown that low diastolic pressure is associated with an increased risk for coronary heart disease and related mortality in older adults and in patients taking antihypertensive medications ( 1 - 13 ) . After doing a review and meta- analysis of pertinent studies , Farnett and colleagues ( 14 ) concluded that although there was no consistent J-shaped relationship between stroke and systolic or diastolic pressure , there was a consistent J-shaped relationship for cardiac events and diastolic pressure . These authors stated that this dichotomy in the relationship between diastolic pressure and target organ disease may leave a clinician with the uncomfortable choice of whether to prevent stroke or renal disease at the expense of coronary heart disease . These findings were at variance with the generally accepted dogma formulated by the sixth report of the Joint National Committee on Prevention , Detection , Evaluation , and Treatment of High Blood Pressure ( JNC VI ) ( 15 ) , which stated that the relationship between pressure and risk was strong , continuous , independent , predictive and etiologically significant . Within the past decade , the phenomenon of a J-curve has been studied in several large trials of normotensive and hypertensive patients ( 16 - 30 ) . Not surprisingly , arguments regarding whether a J-curve could be clinical ly significant have become somewhat contentious . That is , some rely on evidence that on-treatment diastolic pressure below 70 mm Hg does not increase risk for cardiovascular disease and thus deny an impairment of vital organ perfusion within the usual values achievable by antihypertensive treatment . Others , however , consider the J-curve a more real possibility , particularly for the heart . In contrast to other organs , the heart is perfused mostly during diastole and thus could be more vulnerable to diastolic pressure reduction . If a J-curve did exist , it should be most evident in patients with limited coronary perfusion , in other words , in those with manifest coronary artery disease ( CAD ) . Optimal blood pressure in patients with hypertension and CAD remains controversial because few r and omized clinical trials have been done in this population ( 31 , 32 ) . The International Verapamil-Tr and olapril Study ( INVEST ) ( 33 ) , a r and omized trial , evaluated more than 22000 patients with CAD and hypertension . This patient profile , together with unprecedented levels of blood pressure control , provided a unique opportunity to critically investigate the hypothesis that the risk for CAD would increase with an excessive decrease in diastolic pressure . Methods Study Design and Intervention The INVEST design , methods , and principal results have been previously published ( 33 ) . The trial used an open design with blinded end point assessment . In brief , clinical ly stable patients with CAD and hypertension were r and omly assigned to a verapamil sustained-releasebased or atenolol-based strategy .  Patients with previous myocardial infa rct ion ( MI ) within 3 months of enrollment or class IV or V congestive heart failure were excluded .  Blood pressure goals were based on JNC VI ( systolic pressure < 140 mm Hg and diastolic pressure < 90 mm Hg or systolic pressure < 130 mm Hg and diastolic pressure < 85 mm Hg in patients with diabetes or renal impairment ) ( 15 ) . The addition of tr and olapril or hydrochlorothiazide was recommended when necessary to achieve blood pressure goals . Tr and olapril was also recommended for patients with heart failure , diabetes , or renal impairment . Documented CAD was defined as any of the following : remote ( 3 months before enrollment ) confirmed MI , coronary angiography showing more than 50 % narrowing of at least 1 major coronary artery , diagnosis of classic angina pectoris , or concordant abnormalities on 2 different signals ( electrocardiography , echocardiography , or radionuclide scans ) from stress test findings concordant for ischemia ( for example , ST-segment depression or perfusion defects on radionuclide scanning or wall-motion abnormalities on echocardiography or radionuclide scanning ) . Patient Monitoring and Follow-up Protocol visits were scheduled every 6 weeks for the first 6 months and then biannually until 2 years after the last patient was enrolled . Patients were assessed for response to treatment , symptoms , treatment adherence , and adverse effects at each visit and at the end of the study as detailed elsewhere ( 33 ) . Patient follow-up was complete when we received a final assessment form through the online data system or a death report . The Internet-based electronic data collection method used in INVEST did not accept the entry until all required fields were complete . Blood pressure  was measured by using a st and ard mercury sphygmomanometer with an appropriately sized cuff applied to the upper nondominant arm at heart level . By auscultation at the brachial artery , systolic pressure was recorded at the first Korotkoff sound and diastolic pressure was recorded at the disappearance of the fifth Korotkoff sound . Blood pressure was measured twice , at least 2 minutes apart , and the measurements were averaged . Study Outcomes The primary outcome was the first occurrence of all-cause death , nonfatal MI , or nonfatal stroke by intention-to-treat analysis . The MI and stroke definitions are detailed elsewhere ( 34 ) . These 3 components individually were the main secondary outcomes . For this analysis , additional outcomes included fatal and nonfatal MI , fatal and nonfatal stroke , and average on-treatment blood pressure before outcome or censoring . Ascertainment and blinded adjudication of outcomes were described previously ( 32 ) . Follow-up data were available for 22008 ( 97.5 % ) patients . Statistical Analysis The main conclusions of INVEST were that the 2 treatment strategies were equivalent with respect to the primary outcome , main secondary outcomes , and on-treatment systolic and diastolic pressures . Thus , data for all enrolled patients were combined and included in these analyses following the intention-to-treat principle . A P value of 0.05 or less was considered statistically significant . Patients without a primary outcome event were censored at their latest follow-up visit . Average follow-up systolic and diastolic pressures were calculated for each patient by using all post-baseline results , up to the date of primary outcome or censoring . The baseline value was substituted for patients with no post-baseline data ( n= 1154 ) . In this exploratory analysis , the proportions of patients were pooled by 10 mm Hg strata of average follow-up systolic pressure , and the distribution of primary outcome event rate was evaluated to determine whether the relationship was linear . A similar presentation was prepared for diastolic pressure . Because the frequency distributions seemed consistent with a quadratic curve , a quadratic Cox proportional hazards model was formed for the time to primary outcome for each blood pressure variable , with factors for blood pressure and blood pressure squared . Similarly , the relationship between each 10 mm Hg stratum of average systolic pressure and diastolic pressure and all-cause death , fatal and nonfatal MI , and fatal and nonfatal stroke was evaluated . For the time to primary outcome , a second model was fitted , adjusting for the following baseline covariates : age ( 10-year increments ) , sex , race and ethnicity ( white , Asian , black , Hispanic , multiracial , or other ) , previous MI , heart failure ( classes I to III ) , body mass index in increments of 5 kg/m2 , U.S. residency , renal impairment , peripheral vascular disease , left ventricular hypertrophy , smoking history , coronary revascularization , dyslipidemia , stroke or transient ischemic attack , angina pectoris , arrhythmia , diabetes , cancer , aspirin use , and average systolic pressure or diastolic pressure and systolic pressure squared or diastolic pressure squared . To identify clinical ly relevant interactions between the J-shaped curve and baseline diastolic pressure , demographic characteristics , and comorbid conditions for the primary outcome , a 2-step procedure was used . First , baseline covariates were tested individually by adding the variable and 2 interaction terms ( variablediastolic pressure and variable[diastolic pressure squared ] ) to the Cox proportional hazards model . Variables included were age older than 70 years , sex , previous MI , heart failure ( classes I to III ) , previous stroke or transient ischemic attack , diabetes , cancer , renal impairment , hypercholesterolemia , peripheral vascular disease , smoking history , U.S. residency , body mass index greater than 29 kg/m2 ( mean baseline body mass index ) , and diastolic pressure greater than 86 mm Hg ( mean baseline diastolic pressure ) . The change in log likelihood was used to assess the significance of simultaneously adding the 2 interaction terms . The second step in identifying clinical ly relevant interactions between the J-shaped curve and baseline covariates was to plot the hazard ratios for the primary outcome versus diastolic pressure in the Isolated systolic hypertension is an important risk factor for cardiovascular disease and results primarily from elastic artery stiffening . Although various drug therapies are used to lower peripheral blood pressure ( BP ) in patients with isolated systolic hypertension , the effects of the 4 major classes of antihypertensive agents on central BP , pulse pressure ( PP ) amplification , and arterial stiffness in this condition are not clear . Fifty-nine patients over the age of 60 years with untreated isolated systolic hypertension ( systolic BP ≥140 mm Hg and diastolic BP ≤90 mm Hg ) were r and omly assigned to receive 1 of the following 4 antihypertensive agents : perindopril , atenolol , lercanidipine , or bendrofluazide  . BP was measured using a mercury sphygmomanometer , and augmentation index and carotid-femoral ( aortic ) pulse wave velocity were measured at baseline , after 2 weeks of placebo therapy , and at the end of 10 weeks of active therapy . Peripheral systolic BP and peripheral PP were reduced similarly after treatment with all 4 classes of drug . However , central PP was only reduced significantly by perindopril , lercanidipine , and bendrofluazide , whereas atenolol had no effect . Lercanidipine reduced the augmentation index , whereas atenolol increased it . Aortic pulse wave velocity was not changed by any of the drugs . In summary , despite similar reductions in peripheral systolic and PPs with the 4 classes of drug , changes in central pressure and augmentation index varied . Because central PP and increased wave reflections are considered important risk factors in patients with isolated systolic hypertension , the choice of therapy may be influenced by these findings in the future BACKGROUND In 1989 , the European Working Party on High Blood Pressure in the Elderly started the double-blind , placebo-controlled , Systolic Hypertension in Europe Trial to test the hypothesis that antihypertensive drug treatment would reduce the incidence of fatal and nonfatal stroke in older patients with isolated systolic hypertension . This report addresses whether the benefit of antihypertensive treatment varied according to sex , previous cardiovascular complications , age , initial blood pressure ( BP ) , and smoking or drinking habits in an intention-to-treat analysis and explores whether the morbidity and mortality results were consistent in a per- protocol analysis . METHODS After stratification for center , sex , and cardiovascular complications , 4695 patients 60 years of age or older with a systolic BP of 160 to 219 mm Hg and diastolic BP less than 95 mm Hg were r and omized . Active treatment consisted of nitrendipine ( 10 - 40 mg/d ) , with the possible addition of enalapril maleate ( 5 - 20 mg/d ) and /or hydrochlorothiazide ( 12.5 - 25 mg/d ) , titrated or combined to reduce the sitting systolic BP by at least 20 mm Hg , to below 150 mm Hg . In the control group , matching placebo tablets were employed similarly . RESULTS In the intention-to-treat analysis , male sex , previous cardiovascular complications , older age , higher systolic BP , and smoking at r and omization were positively and independently correlated with cardiovascular risk . Furthermore , for total ( P = .009 ) and cardiovascular ( P = .09 ) mortality , the benefit of antihypertensive drug treatment weakened with advancing age ; for total mortality ( P = .05 ) , the benefit increased with higher systolic BP at entry , while for fatal and nonfatal stroke ( P = .01 ) , it was most evident in nonsmokers ( 92.5 % of all patients ) . In the per protocol analysis , active treatment reduced total mortality by 24 % ( P = .05 ) , reduced all fatal and nonfatal cardiovascular end points by 32 % ( P<.001 ) , reduced all strokes by 44 % ( P = .004 ) , reduced nonfatal strokes by 48 % ( P = .005 ) , and reduced all cardiac end points , including sudden death , by 26 % ( P = .05 ) . CONCLUSIONS In elderly patients with isolated systolic hypertension , stepwise antihypertensive drug treatment , starting with the dihydropyridine calcium channel blocker nitrendipine , improves prognosis . The per- protocol analysis suggested that treating 1000 patients for 5 years would prevent 24 deaths , 54 major cardiovascular end points , 29 strokes , or 25 cardiac end points . The effects of antihypertensive drug treatment on total and cardiovascular mortality may be attenuated in very old patients Background and Purpose — Among patients with acute stroke , high blood pressure is often associated with poor outcome , although the reason is unclear . We analyzed data from the International Stroke Trial ( IST ) to explore the relationship between  systolic blood pressure ( SBP ) , subsequent clinical events over the next 2 weeks , and functional outcome at 6 months in patients with acute stroke . Methods — We included in the analysis 17 398 patients from IST with confirmed ischemic stroke . A single measurement of SBP was made immediately before r and omization . Clinical events within 14 days of r and omization were recorded : recurrent ischemic stroke , symptomatic intracranial hemorrhage , death result ing from presumed cerebral edema , fatal coronary heart disease , and death . Survival and dependency were assessed at 6 months . Outcomes were adjusted for age , sex , clinical stroke syndrome , time to r and omization , consciousness level , atrial fibrillation , and treatment allocation ( aspirin , unfractionated heparin , both , or neither ) . Results — A U-shaped relationship was found between baseline SBP and both early death and late death or dependency : early death increased by 17.9 % for every 10 mm Hg below 150 mm Hg ( P < 0.0001 ) and by 3.8 % for every 10 mm Hg above 150 mm Hg ( P = 0.016 ) . The rate of recurrent ischemic stroke within 14 days increased by 4.2 % for every 10–mm Hg increase in SBP ( P = 0.023 ) ; this association was present in both fatal and nonfatal recurrence . Death result ing from presumed cerebral edema was independently associated with high SBP ( P = 0.004 ) . No relationship between symptomatic intracranial hemorrhage and SBP was seen . Low SBP was associated with a severe clinical stroke ( total anterior circulation syndrome ) and an excess of deaths from coronary heart disease ( P = 0.002 ) . Conclusions — Both high blood pressure and low blood pressure were independent prognostic factors for poor outcome , relationships that appear to be mediated in part by increased rates of early recurrence and death result ing from presumed cerebral edema in patients with high blood pressure and increased coronary heart disease events in those with low blood pressure . The occurrence of symptomatic intracranial hemorrhage within 14 days was independent of SBP BACKGROUND Oral anticoagulation ( OAC ) is the recommended therapy for patients with atrial fibrillation ( AF ) because it reduces the risk of stroke and other thromboembolic events . Dual antiplatelet therapy ( DAPT ) is required after percutaneous coronary intervention and stenting ( PCI-S ) . In patients with AF requiring PCI-S  , the association of DAPT and OAC carries an increased risk of bleeding , whereas OAC therapy or DAPT alone may not protect against the risk of developing new ischemic or thromboembolic events . OBJECTIVE The MUSICA-2 study will test the hypothesis that DAPT compared with triple therapy ( TT ) in patients with nonvalvular AF at low-to-moderate risk of stroke ( CHADS2 score ≤2 ) after PCI-S reduces the risk of bleeding and is not inferior to TT for preventing thromboembolic complications . DESIGN The MUSICA-2 is a multicenter , open-label r and omized trial that will compare TT with DAPT in patients with AF and CHADS2 score ≤2 undergoing PCI-S.  The primary end point is the incidence of stroke or any systemic embolism or major adverse cardiac events : death , myocardial infa rct ion , stent thrombosis , or target vessel revascularization at 1 year of PCI-S. The secondary end point is the combination of any cardiovascular event with major or minor bleeding at 1 year of PCI-S. The calculated sample size is 304 patients . CONCLUSIONS The MUSICA-2 will attempt to determine the most effective and safe treatment in patients with nonvalvular AF and CHADS2 score ≤2 after PCI-S. Restricting TT for AF patients at high risk for stroke may reduce the incidence of bleeding without increasing the risk of thromboembolic complications In the Australian Therapeutic Trial in Mild Hypertension treated patients had significantly lower cardiovascular mortality and a significantly lower incidence of cerebrovascular complications than patients given placebos .  There was , however , no difference in the incidence of nonfatal myocardial infa rct ion or other new manifestations of ischaemic heart disease . Although the evidence of benefit from treatment was clear-cut , the number of cardiovascular complications in the control group was small . This was due to several factors . Patients admitted to the trial had no preceding evidence of cardiovascular complications  , the blood pressure fell spontaneously to below 95 mm Hg in almost half the control group , and patients whose blood pressures rose to levels above 110 mm Hg were given treatment , but remained in the placebo group for analysis . In both treated and placebo groups , trial end-points occurred more frequently in persons whose average diastolic blood pressure during the study remained raised . Ischaemic heart disease and many cases of stroke are due to atherosclerotic arterial disease . This appears not to be favourably influenced by antihypertensive drug therapy Objectives In many current guidelines , blood pressure (BP)-lowering drug treatment for primary prevention of cardiovascular disease ( CVD ) is based on absolute risk . However , in clinical practice , therapeutic decisions are often based on BP levels alone . We sought to investigate which approach was superior by conducting a post hoc analysis of the Australian National Blood Pressure ( ANBP ) cohort , a seminal study establishing the efficacy of BP lowering in ‘ mild hypertensive ’ persons . Design A post hoc subgroup analysis of the ANBP trial results by baseline absolute risk tertile . Setting and participants 3244 participants aged 35–69 years in a community-based r and omised placebo controlled trial of blood pressure-lowering medication . Interventions Chlorothiazide500 mg versus placebo . Primary outcome measures All-cause mortality and non-fatal events ( non-fatal CVD , congestive cardiac failure , renal failure , hypertensive retinopathy or encephalopathy ) . Results Treatment effects were assessed by HR , absolute risk reduction and number needed to treat . Participants had an average 5-year CVD risk in the intermediate range ( 10.5±6.5 ) with moderately elevated BP ( mean 159/103 mmHg ) and were middle aged ( 52±8 years ) . In a subgroup analysis , the relative effects ( HR ) and absolute effects ( absolute risk reduction and number needed to treat ) did not statistically differ across the three risk groups except for the absolute benefit in all-cause mortality ( p for heterogeneity=0.04 ) . With respect to absolute benefit , drug treatment significantly reduced the number of events in the high-risk group regarding any event with a number needed to treat of 18 ( 10 to 64 ) , death from any cause with 45 ( 25 to 196 ) and major CVD events with 23 ( 12 to 193 ) . Conclusion Our analysis confirms that the benefit of treatment was substantial only in the high-risk tertile , reaffirming the rationale of treating elevated blood pressure in the setting of all risk factors rather than in isolation Aim MULTIPRAC was design ed to provide insights into the use and outcomes associated with prehospital initiation of antiplatelet therapy with either prasugrel or clopidogrel in the context of primary percutaneous coronary intervention . After a previous report on efficacy and safety outcomes during hospitalization , we report here the 1-year follow-up data , including cardiovascular ( CV ) mortality . Methods and results MULTIPRAC is a multinational , prospect i ve registry of patients with ST-elevation myocardial infa rct ion ( STEMI ) from 25 hospitals in nine countries , all of which had an established practice of prehospital start of dual antiplatelet therapy in place . The key outcome was CV death at 1 year . Among 2,036 patients followed-up through 1 year , 49 died ( 2.4 % ) , 10 during the initial hospitalization and 39 within 1 year after hospital discharge . The primary analysis was based on the P2Y12-inhibitor , used from prehospital loading dose through hospital discharge . Prasugrel ( n=824 ) was more commonly used than clopidogrel ( n=425 ) . The observed 1-year rates for CV death were 0.5 % with prasugrel and 2.6 % with clopidogrel . After adjustment for differences in baseline characteristics , treatment with prasugrel was associated with a significantly lower risk of CV death than treatment with clopidogrel ( odds ratio 0.248 ; 95 % confidence interval 0.06–0.89 ) . Conclusion In STEMI patients from routine practice undergoing primary angioplasty , who were able to start oral antiplatelet therapy prehospital , treatment with prasugrel as compared to clopidogrel was associated with a lower risk of CV death at 1-year follow-up Abstract A hypercoagulable state has , in observational studies , been associated with increased risk of thromboembolic events . The aim of this trial was to study whether dual antiplatelet therapy ( DAPT ) with clopidogrel in addition to aspirin could reduce the rate of graft occlusions , thromboembolic events , and death compared to aspirin monotherapy in hypercoagulable patients undergoing coronary artery bypass surgery . A total of 1683 patients were screened for eligibility , among which 165 patients were r and omized and 133 patients underwent multislice computed tomography scan to evaluate their grafts .  Thrombelastography ( TEG ) and multiplate aggregometry  were performed before and after surgery , and again at three months follow up . TEG hypercoagulability was defined as the maximum amplitude above 69 mm . At three months follow up , 17 out of 66 ( 25.7 % ) DAPT patients and 15 of 67 ( 22.4 % ) aspirin patients had significant graft stenosis or occlusions ( p = 0.839 ) . Saphenous vein grafts ( SVGs ) were stenosed or occluded in 15 ( 22.7 % ) patients in the DAPT group and 7 ( 10.4 % ) in the aspirin group ( p = 0.167 ) . Thromboembolic events and death after the second postoperative day ( when clopidogrel was started ) were numerically , but not statistically , lower in the DAPT group , 3 ( 3.8 % ) vs. 8 ( 9.9 % ) , p = 0.211 . In univariate logistic regression analysis , only postoperative day 4 platelet response to aspirin measured with multiplate was correlated with graft occlusion , OR 1.020 [ 1.002–1.039 ] , p = 0.033 . This is the first trial to test the hypothesis of intensified antiplatelet therapy in hypercoagulable patients . Due to the low enrollment and high loss to follow up , our results can only be viewed as hypothesis generating . We found a high rate of graft occlusions in this patient population . Our results were not suggestive of that DAPT improved saphenous vein graft patency . A trend was observed in patients on DAPT toward fewer MI and deaths . Postoperative response to aspirin therapy was found to be associated with early SVG occlusion OBJECTIVES This trial evaluated the efficacy and safety of the combination of antiplatelet and moderate-intensity anticoagulation therapy in patients with atrial fibrillation associated with recognized risk factors or mitral stenosis . BACKGROUND Warfarin was more effective than aspirin in preventing stroke in these patients ; combined therapy with low anticoagulant intensity was ineffective . Mitral stenosis patients were not investigated . METHODS We performed a multicenter r and omized trial in 1,209 patients at risk . The intermediate-risk group included patients with risk factors or age > 60 years : 242 received the cyclooxygenase inhibitor triflusal  , 237 received  acenocumarol , and 235 received a combination of both .  The high-risk group included patients with prior embolism or mitral stenosis : 259 received anticoagulants and 236 received the combined therapy . Median follow-up was 2.76 years . Primary outcome was a composite of vascular death and nonfatal stroke or systemic embolism . RESULTS Primary outcome was lower in the combined therapy than in the anticoagulant arm in both the intermediate- ( hazard ratio [ HR ] 0.33 [ 95 % confidence interval (CI)0.12 to 0.91 ] ; p = 0.02 ) and the high-risk group ( HR 0.51 [ 95 % CI 0.27 to 0.96 ] ; p = 0.03 ) . Primary outcome plus severe bleeding was lower with combined therapy in the intermediate-risk group . Nonvalvular and mitral stenosis patients had similar embolic event rates during anticoagulant therapy . CONCLUSIONS The combined antiplatelet plus moderate-intensity anticoagulation therapy significantly decreased the vascular events compared with anticoagulation alone and proved to be safe in atrial fibrillation patients BACKGROUND Dual antiplatelet therapy with aspirin and thienopyridines ( clopidogrel or prasugrel ) is required after placement of coronary stents to prevent thrombotic complications . Although current clinical practice guidelines recommend 12-month treatment after drug-eluting stent placement , even longer duration s may prevent thrombotic events . STUDY DESIGN The Dual Antiplatelet Therapy ( DAPT ) Study is comparing the benefits and risks of 12 versus 30 months of dual antiplatelet therapy in preventing stent thrombosis or major adverse cardiovascular and cerebrovascular events in subjects undergoing percutaneous coronary intervention ( PCI ) for the treatment of coronary artery obstructive lesions . The DAPT Study is a multicenter , international , r and omized , double-blind , placebo-controlled trial that will enroll 15,245 subjects treated with drug-eluting stent ( DES ) and 5,400 subjects treated with bare-metal stents ( BMS ) .  All subjects will receive 12 months of open-label thienopyridine treatment in addition to aspirin . After 12 months , subjects who are free from death , myocardial infa rct ion , or stroke ( MACCE ) , repeat revascularization , and GUSTO ( Global Use of Strategies to Open Occluded Coronary Arteries ) moderate or severe bleeding events will be r and omized to receive either 18 additional months of thienopyridine ( clopidogrel or prasugrel ) ( 30 month DAPT arm ) or placebo ( 12 month DAPT arm ) plus aspirin . Co primary end points are MACCE and stent thrombosis . The primary safety end point is GUSTO moderate or severe bleeding . CONCLUSIONS This r and omized trial is design ed to define the relative safety and effectiveness of 12 versus 30 months of dual antiplatelet therapy across the broad spectrum of patients receiving coronary stents Rationale Controversy exists over the optimal dose of intravenous ( iv ) recombinant tissue plasminogen activator ( rt-PA ) and degree of blood pressure ( BP ) control in acute ischaemic stroke ( AIS ) . Asian studies suggest low-dose ( 0·6 mg/kg ) is more efficacious than st and ard-dose ( 0·9 mg/kg ) iv rt-PA , and guidelines recommend reducing systolic BP to < 185 mmHg before and < 180 mmHg after use of iv rt-PA , despite observational studies indicating better outcomes at much lower ( < 140 mmHg ) systolic BP levels in this patient group . Aims The study aims to assess in thrombolysis-eligible AIS patients whether : ( i ) low-dose ( 0·6 mg/kg body weight ; maximum 60 mg ) iv rt-PA has non-inferior efficacy and lower risk of symptomatic intracerebral haemorrhage ( sICH ) compared to st and ard-dose ( 0·9 mg/kg body weight ; maximum 90 mg ) iv rt-PA ; and ( ii ) early intensive BP lowering ( systolic target 130–140 mmHg ) has superior efficacy and lower risk of any ICH compared to guideline -recommended BP control ( systolic target < 180 mmHg ) . Design The ENhanced Control of Hypertension And Thrombolysis strokE stuDy ( ENCHANTED ) trial is an independent , 2 × 2 quasi-factorial , active-comparison , prospect i ve , r and omized , open blinded endpoint ( PROBE ) , clinical trial that is evaluating Arm [ A ] ‘ rt-PA dose ’ and /or Arm [ B ] ‘ BP control ’ , using central Internet r and omization and data collection in patients fulfilling local criteria for thrombolysis and clinician uncertainty over the study treatments . The treatment arms will be analyzed separately . Study outcomes The primary study outcome in both trial Arms is death or disability according to the modified Rankin scale ( mRS , scores 2–6 ) assessed at 90 days . Secondary outcomes include sICH , any ICH , a shift ( ‘ improvement ’ ) in function across mRS scores , separately on death and disability , early neurological deterioration , recurrent major vascular events , health-related quality of life , length of hospital stay , need for permanent residential care , and health care costs . Results Following launch of the trial in February 2012 , the study has recruited more than 2500 patients across a global network of approximately 100 sites in 15 countries . The required sample sizes are 3300 for Arm [ A ] and 2300 for Arm [ B ] , which will provide > 90 % power to detect non-inferiority of low-dose iv rt-PA and superiority of intensive BP lowering on the primary clinical outcome , respectively . Conclusions Low-dose iv rt-PA and early intensive BP lowering could provide more affordable and safer use of thrombolysis treatment for patients with AIS worldwide Elevated arterial pressure enhances the risk for cardiovascular ( CV ) events in patients with diabetic nephropathy . The optimal BP and the component of the elevated BP that affect the risk have not been defined . A post hoc analysis was performed to assess the impact of achieved systolic , diastolic , and pulse pressures on CV outcomes in 1590 adults who had overt diabetic nephropathy and were enrolled in the Irbesartan Diabetic Nephropathy Trial ( IDNT ) and had a baseline serum creatinine above the normal range , up to 266 micromol/L ( 3.0 mg/dL ) , 24-h urine protein > 900 mg/d , and at least 6 mo of follow-up . Patients were r and omized to irbesartan , amlodipine , or placebo , with other antihypertensive agents to a BP goal of < or = 135/85 mmHg . Progressively lower achieved systolic BP ( SBP ) to 120 mmHg predicted a decrease in CV mortality and congestive heart failure ( CHF ) but not myocardial infa rct ions ( MI ) . A SBP below this threshold was associated with increased risk for CV deaths and CHF events . Achieved diastolic BP < 85 mmHg was associated with a trend to increase in all-cause mortality , significant increase in MI , but decreased risk for strokes . Increased pulse pressure predicted increased all-cause mortality , CV mortality , MI , and CHF . It is concluded that achieved SBP approaching 120 mmHg and diastolic BP of 85 mmHg are associated with the best protection against CV events in these patients . BP < or = 120/85 may be associated with an increase in CV events BACKGROUND Antiplatelet drugs are recommended for patients with acute noncardioembolic stroke . However , few r and omized clinical trials have investigated the safety and efficacy of dual antiplatelet therapy for these patients . The aim of this study was to evaluate the effects of treatment with clopidogrel and aspirin ( combination therapy ) and aspirin alone ( monotherapy ) on neurologic deterioration , platelet activation , and other short-term outcomes in patients with acute large-artery atherosclerosis stroke . MATERIAL S AND METHODS Altogether 574 patients with acute ( ≤2 days ) large-artery atherosclerosis stroke were r and omly assigned to receive either combined clopidogrel and aspirin or aspirin alone . Platelet aggregation and platelet-leukocyte aggregation studies were performed at days 1 and 30 . Primary outcomes including recurrent ischemic stroke , neurologic deterioration , periphery vascular events , and myocardial infa rct ion were monitored . Safety endpoints were hemorrhagic episodes and death . RESULTS The prevalence of neurologic deterioration and recurrent ischemic stroke were lower in patients in the combination therapy group than in those of the monotherapy group ( 3.52 % versus 9.78 % and 1.76 % versus 6.29 % , respectively ) . At day 30 of treatment , the platelet aggregations and platelet-leukocyte aggregates were lower in patients who were treated with clopidogrel and aspirin than in patients given aspirin alone ( P < .001 ) . CONCLUSIONS For patients with acute large-artery atherosclerosis stroke , treatment with clopidogrel and aspirin for 1 month provided significantly greater inhibition of platelet activity  than aspirin alone . Thus , dual therapy can be safer and more effective in reducing ischemic stroke recurrence and neurologic deterioration AIMS To examine the unanticipated , excess mortality observed in patients r and omized to clopidogrel and aspirin vs. aspirin alone  in the prespecified ' asymptomatic ' subgroup of CHARISMA , we investigated whether dual-antiplatelet therapy may be associated with adverse  cardiovascular ( CV )  events in a primary prevention population . METHODS AND RESULTS Of 15 603 patients enrolled , 3284 were initially categorized as asymptomatic with CV risk factors , but 995 had a prior CV event , leaving 2289 patients to represent the primary prevention cohort . This subset was compared with 13 148 symptomatic patients with established vascular disease and both were evaluated for CV death and bleeding . A multivariate analysis analysed predictors of CV death in this group . No post mortem data were available . Compared with aspirin alone , a significant increase in CV death ( P = 0.01 ) was observed in patients receiving dual-antiplatelet therapy in the asymptomatic population . Within the primary prevention cohort , this excess CV death was not significant ( P = 0.07 ) . Multivariate analysis of the primary prevention group showed a trend towards excess CV death ( P = 0.054 ; HR 1.72 ; CI 0.99 - 2.97 ) with dual-antiplatelet therapy ( aspirin plus clopidogrel ) . Other independent predictors of CV death included increasing age , hypertension , atrial fibrillation , and a history of heart failure . There was a non-significant increase in moderate or severe bleeding ( P = 0.218 ) with dual-antiplatelet therapy ; thus , bleeding was an unlikely explanation for the excess event rate . CONCLUSION These findings do not support the use of dual-antiplatelet therapy with clopidogrel and aspirin in a primary prevention population . In this subgroup analysis , CV death occurred more frequently than anticipated . The cause of this apparent harm is not eluci date d , may represent play of chance , but requires further prospect i ve evaluation
Acetylsalicylic acid ( ASA ) did not reduce stroke or ' all cardiovascular events ' compared to placebo in primary prevention patients with elevated blood pressure and no prior cardiovascular disease .
Antiplatelet therapy with ASA for primary prevention in patients with elevated blood pressure provides a benefit , reduction in myocardial infa rct ion , which is negated by a harm of similar magnitude , increase in major haemorrhage .
The benefit of antiplatelet therapy for secondary prevention in patients with elevated blood pressure is many times greater than the harm .
Benefit has not been demonstrated for warfarin therapy alone or in combination with aspirin in patients with elevated blood pressure .
BACKGROUND Elevated systemic blood pressure results in high intravascular pressure but the main complications , coronary heart disease ( CHD ) , ischaemic strokes and peripheral vascular disease ( PVD ) , are related to thrombosis rather than haemorrhage .
Some complications related to elevated blood pressure , heart failure or atrial fibrillation , are themselves associated with stroke and thromboembolism .
Therefore it is important to investigate if antithrombotic therapy may be useful in preventing thrombosis-related complications in patients with elevated blood pressure .
OBJECTIVES To conduct a systematic review of the role of antiplatelet therapy and anticoagulation in patients with high blood pressure , including those with elevations in both systolic and diastolic blood pressure , isolated elevations of either systolic or diastolic blood pressure , to address the following hypotheses : ( i ) antiplatelet agents reduce total deaths and /or major thrombotic events when compared to placebo or other active treatment ; and ( ii ) oral anticoagulants reduce total deaths and /or major thromboembolic events when compared to placebo or other active treatment .
Ticlopidine , clopidogrel and newer antiplatelet agents such as prasugrel and ticagrelor have not been sufficiently evaluated in patients with high blood pressure .