It Is Suitable For The Exploration Of Hypertension Drug Treatment Programs For Low-income Groups In China

Section 1 Study on real-world clinical outcomes between Generic and brand-name antihypertensive agents:a multicenter cohort studyObjectivesHypertension is still the biggest single contributor to the global burden of cardiovascular disease,and antihypertensive therapy has been widely proven to reduce cardiovascular risk,but treatment of hypertension by using brand-name drugs impose a significant economic burden on individuals and societies,especially in developing counties.Affordable and efficacy antihypertensive agents are urgently needed in developing countries.The generic agent is widely accepted by developing countries to reduce the economic burden of society and individuals because of the same active ingredients as the brand-name agent,the similar antihypertensive effect with the lower price.We investigated that whether generic antihypertensive agents could achieve the same cardiovascular benefits as the brand-name hypertensive agents in present medical era.MethodsThis is a practical clinical trial,8913 hypertensive patients aged 18 years to 74 years old were recruited between June 2014 to June 2015 and investigated for demographic characteristics,history of diseases,medical history by questionnaires in 20 secondary or tertiary hospitals of 18 cities,and were prospectively followed up until November,2018.These patients were divided into 2 groups according to used antihypertensive agents at baseline(generic agents group,n=3913 and brand-name agents group,n=5050).The primary endpoint was combination of myocardial infarction,percutaneous coronary intervention or coronary aortic bypass grafting due to angina pectoris,stroke and other cardiovascular deaths.The secondary endpoint events were cardiac events including myocardial infarction,percutaneous coronary intervention or coronary aortic bypass grafting due to angina pectoris and other cardiovascular deaths,stroke(hemorrhagic and ischemic stroke),cardiovascular and all-cause mortality.ResultsDuring the period of follow-up,the mean systolic blood pressure levels were 135.4±12.8 mmHg and 135.2±12.7 mmHg(P=0.01),and the diastolic blood pressure levels were 83.1±9.4 mmHg and 83.1±9.5 mmHg(P=0.37),respectively in generic and brand-name agents group.During the follow-up of 3.07±0.91 years,the primary end point events occurred in 207(5.3%)patients in the generic agents group and in 294(5-8%)in the brand-name agents group(log-rank P=0.58).After adjusting for confounding factors,the risk of primary endpoint events increased by 1%in generic agents group in comparation with the brand-name agents group,but not significantly.(adjusted HR=1.01,95%CI 0.84-1.21).There were 89 cardiac events(2.2%),127 stroke(3.2%),26 cardiovascular deaths(0.7%)and 36 all-cause deaths(0.9%)occurred in the generic agents group and 158 cardiac events(3.1%),148 stroke(2.9%),49 cardiovascular deaths(1.0%)and 64 all-cause deaths(1.3%)occurred in brand-name agents group(log-rank P=0.04,0.22,0.23,0.26),adjusted for confounding factors,there was no significant difference between brand-name and generic agents group(adjusted HR=1.20,95%CI 0.92-1.56,0.86,95%CI 0.67-1.09,1.39,95%CI 0.85-2.25,1.34,95%CI 0.89-2.03,respectively).Subgroup analysis showed that in the young and middle-aged hypertensive patients(age<60 years),the risk of the primary end point events(adjusted HR=1.32,95%CI 0.96-1.82),cardiac events(adjusted HR=1.39,95%CI 0.85-2.28),stroke(adjusted HR=1.30,95%CI 0.87-1.96)and ischemic stroke(adjusted HR=1.26,95%CI 0.82-1.94)were higher risk in the brand-name agents group than the generic agents group,but not significantly.In elderly hypertensive patients(aged 60-74 years),the risk of the primary end point events(adjusted HR=0.90,95%CI 0.72-1.12)and cardiac events(adjusted HR=1.16,95%CI 0.85-1.68)was not significant,whereas the brand-name agents group had a lower risk of future stroke(adjusted HR=0.65,95%CI 0.48-0.89)and ischemic stroke(adjusted HR=0.63,95%CI 0.46-0.86)in comparation with the generic agents group.ConclusionsGeneric and brand name hypertensive agents had comparable effects on lowering blood pressure,no significant difference was found between the two groups in reducing the risk of cardiovascular events and mortality as well.These data further support that choosing affordable antihypertensive agents to lower blood pressure is much more important than unaffordable brand name drugs,especially in rural area in developing countries.Brand-name hypertensive agents may have a better protective effect on stroke than generic hypertensive agents.Section 2 Pharmacogenetic association of ?1-and ?2-adrenergic receptor polymorphisms with cardiovascular outcomes in patients with hypertension treated with ?1-blockersObjectivesBeta-blockers in the treatment of hypertension can significantly reduce the risk of cardiovascular events,but recent meta-analysis showed that its clinical benefit is not as good as other antihypertensive drugs,a recent meta-analysis also indicated that?-blocker-induced heart rate reduction in hypertensive patients increased the risk of cardiovascular events.It is unclear that whether clinical benefits treated with ?-blockers is affected by polymorphism of ?-adrenergic receptor(ADRB)gene.This study was designed to investigate whether polymorphisms of ADRB1 Ser49Gly,Arg389Gly and ADRB2 Argl6Gly affect the clinical benefit of beta-blockers in the treatment of hypertension.MethodsA total of 2096 hypertensive patients were consecutively recruited from June 1st 2014 and June 1st 2015 in 20 secondary or tertiary hospitals of 18 cities in China and treated with ?-blockers.The DNA samples were genotyped for ADRB1 Ser49Gly and Arg389Gly and ADRB2 Argl6Gly.Patients were followed up and primary end point included cardiovascular death,myocardial infarction,percutaneous coronary intervention(PCI)/cardiac artery bypass graft(CABG)deu to angina pectoris,ischemic stroke and cerebral hemorrhage.Kaplan-Meier survival analysis and COX regression were used to analyze the association between genetic polymorphisms of ADRB1 as well as ADRB2 and risk of cardiovascular events.ResultsDuring a mean follow-up of 3.2 years(range,0.1 to 4.5 years),106(5.1%)primary end point events were identified,including 61(2.9%)cardiac events and 53(2.5%)ischemic strokes.There were 24 all-cause deaths(1.1%).Kaplan-Meier analysis showed a significantly lower risk of cardiac events in the Gly16 carriers than in ADRB2 Arg16 homozygous carriers in hypertensive patients(2.4%vs.4.2%,P=0.03),while no significant association was identified in primary end point events and ischemic stroke risk between these two groups(4.7%vs.5.7%,2.8%vs.2.1%,P>0.05).COX multivariate analysis showed a significant lower risk of cardiac events(HR=0.58,95%CI 0.35-0.95,P=0.03)in Gly16 carriers in comparation with patients with Arg16 homozygotes,but neither in primary end point events(HR=0.82,95%CI 0.55-1.22,P=0.32),nor in stroke(HR=1.31,95%CI 0.71-2.43,P=0.39).There was a significantly lower risk in primary end point events(HR=0.53,95%CI 0.29-0.97,P=0.04)and a not significantly lower trend in cardiac events(HR=0.45,95%CI 0.19-1.04,P=0.06)in patients with Gly16 homozygous in comparation with Arg16 carriers,while there was no significant difference in the risk of stroke(HR=0.76,95%CI 0.36-1.62,P=0.48).The risk of primary end point events(HR=2.7,95%CI 1.09-6.69,P=0.03)and ischemic stroke(HR=4.15,95%1.48-11.62,P=0.007)was significantly higher in patients with ADRB1 Gly49 homozygous than in Ser49 carriers.ConclusionsThe polymorphisms of ADRB1 Ser49Gly and ADRB2 Argl6Gly affect the clinical benefit of P-blockers in patients with hypertension.It will provide a basis for pharmacogenetics to guide the clinical selection on beta-blocker in patients that can significantly benefit from beta-blockers and contribute to development of precision medicine.Section 3 Status survey on resting heart rate and usage of ?-receptor blockers in patients with hypertension.ObjectivesBeta-blockers have been excluded from first-line antihypertensive drugs by the European and American guidelines for the management of hypertension,and recent meta-analysises indicated question for the clinical benefit of ?-blockers?pointing out that the use of?-blockers in patients suffering stable coronary heart disease and acute myocardial infarction with left ventricular ejection fraction after reperfusion therapy was not associated with nonfatal myocardial infarction,cardiovascular death,and all-cause death.Also,a meta-analysis indicated that ?-blocker-induced heart rate reduction in hypertensive patients increased the risk of cardiovascular events.This attitude may result in physicians worry about ?-blockers.However,resting heart rate is an independent risk factor for cardiovascular death,with a resting heart rate>80 beats/min,which is thought to increase cardiovascular events and death risk.Inadequate use of ?-blockers due to concerns about adverse outcomes will puts patients at high risk of cardiovascular events caused by elevated heart rate.We investigated the status of restiong heart rate,usage rate of P-receptor blocker and achieved resting heart rate controlling in patients with hypertension in our country,which provided evidence for making clinical decision.MethodsA total of 8767 hypertensive patients were consecutively recruited from June 1st,2014 to June 1st,2015 in 20 secondary or tertiary hospitals of 18 cities for a cross-sectional study,and blood pressure,resting heart rate and medications were recorded.ResultsThe average resting heart rate of hypertensive patients was 75.1 beats/min.Hypertensive patients with heart rate greater than 80 beats/min accounted for 26.6%and the usage rate of P-blockers was 11.3%.The proportion of resting heart rate ?80 beats/min without receiving ?-blockers was 73.4%,23.6%of patients with resting heart rate>80 beats/min did not received ?-blockers and 3.0%with ?-blockers,but their heart rate remained more than 80 beats/min.Compared with elders,the average heart rate of young and middle-aged patients with hypertension is significantly higher(76.2 vs.73.7,P<0.05).Compared with young and middle-aged patients with hypertension,there was no difference in the treatment of ?-blockers in elders(10.9%vs.11.7%,P=0.23),but the proportion of resting heart rate?80 beats/min was significant higher in elders(77.9%vs.72.0%,P<0.01,P<0.01).ConclusionsThe achieved rate of resting heart rate was lower,probably due to the low usage rate of ?-receptor blocker.Section 4 Aspirin reduced long-term recurrent stroke in patients with lacunar strokeObjectivesLacunar stroke had an unfavorable prognosis in the long term with a high risk of recurrent stroke,aspirin has been widely used to prevent ischemic stroke,but data on the effect of antiplatelet therapy on lacunar infarction are limited.We investigated the long-term effect of aspirin treatment on stroke recurrence risk in patients with lacunar stroke in a multicenter prospective cohort.MethodsBetween November 2000 and November 2001,2000 consecutive stroke patients(age 35-74 years)were recruited from seven clinical centers.For the present study,a total of 544 patients with lacunar infarction were finally included in the analysis.The patients were divided into 2 groups(aspirin group,n=342 and non-aspirin group,n=202).The effect of aspirin on stroke recurrence was evaluated by using Kaplan-Meier analysis and Cox regression models.ResultsDuring a median 4.1-year follow-up for 544 patients with lacunar stroke,99 recurrent strokes,125 cardiovascular events(stroke,myocardial infarction,vascular death),31 vascular deaths and 59 all-cause deaths were identified.Kaplan-Meier analysis showed that aspirin nonusers had a higher risk of future recurrent stroke and of vascular events than did aspirin users(log-rank test,P=0.049,0.047,respectively).Aspirin significantly reduced the stroke recurrence in patients with lacunar stroke analyzed with multivariate stepwise analysis using model of Cox proportional hazards with backward elimination(HR=0.67,95%CI 0.45-0.99).ConclusionsWe concluded that aspirin significantly reduced stroke recurrence in patients with lacunar stroke.