Examinando por Autor "Zhu, Jun"
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- PublicaciónAcceso abiertoAntihypertensives and Statin Therapy for Primary Stroke Prevention: A Secondary Analysis of the HOPE-3 Tria(Stroke, 2021-05-14) Bosch, Jackie; Lonn, Eva; Dagenais, Gilles; Gao, Peggy; Lopez-Jaramillo, Patricio; Zhu, Jun; Pais, Prem; Avezum, Alvaro; Sliwa, Karen; Chazova, Irina E.; Peters, Ron; Held, Claes; Yusoff, Khalid; Lewis, Basil S.; Toff, William D.; Khunti, Kamlesh; Reid, Christopher M.; Leiter, Lawrence A.; Yusuf, Salim; Hart, Robert G.; The HOPE-3 Investigators; MasiraBackground and Purpose: The HOPE-3 trial (Heart Outcomes Prevention Evaluation–3) found that antihypertensive therapy combined with a statin reduced first stroke among people at intermediate cardiovascular risk. We report secondary analyses of stroke outcomes by stroke subtype, predictors, treatment effects in key subgroups. Methods: Using a 2-by-2 factorial design, 12 705 participants from 21 countries with vascular risk factors but without overt cardiovascular disease were randomized to candesartan 16 mg plus hydrochlorothiazide 12.5 mg daily or placebo and to rosuvastatin 10 mg daily or placebo. The effect of the interventions on stroke subtypes was assessed. Results: Participants were 66 years old and 46% were women. Baseline blood pressure (138/82 mm Hg) was reduced by 6.0/3.0 mm Hg and LDL-C (low-density lipoprotein cholesterol; 3.3 mmol/L) was reduced by 0.90 mmol/L on active treatment. During 5.6 years of follow-up, 169 strokes occurred (117 ischemic, 29 hemorrhagic, 23 undetermined). Blood pressure lowering did not significantly reduce stroke (hazard ratio [HR], 0.80 [95% CI, 0.59–1.08]), ischemic stroke (HR, 0.80 [95% CI, 0.55–1.15]), hemorrhagic stroke (HR, 0.71 [95% CI, 0.34–1.48]), or strokes of undetermined origin (HR, 0.92 [95% CI, 0.41–2.08]). Rosuvastatin significantly reduced strokes (HR, 0.70 [95% CI, 0.52–0.95]), with reductions mainly in ischemic stroke (HR, 0.53 [95% CI, 0.37–0.78]) but did not significantly affect hemorrhagic (HR, 1.22 [95% CI, 0.59–2.54]) or strokes of undetermined origin (HR, 1.29 [95% CI, 0.57–2.95]). The combination of both interventions compared with double placebo substantially and significantly reduced strokes (HR, 0.56 [95% CI, 0.36–0.87]) and ischemic strokes (HR, 0.41 [95% CI, 0.23–0.72]). Conclusions: Among people at intermediate cardiovascular risk but without overt cardiovascular disease, rosuvastatin 10 mg daily significantly reduced first stroke. Blood pressure lowering combined with rosuvastatin reduced ischemic stroke by 59%. Both therapies are safe and generally well tolerated.
- PublicaciónAcceso abiertoBlood-pressure and cholesterol lowering in persons without cardiovascular disease(2016-04-02) Yusuf, Salim; Lonn, Eva; Pais, Prem; Bosch, Jackie; Lopez-Jaramillo, Patricio; Zhu, Jun; Xavier, Denis; Avezum, Alvaro; Leiter, Lawrence A.; Piegas, Leopoldo S.; Parkhomenko, Alexander; Keltai, Matyas; Keltai, Katalin; Sliwa, Karen; Chazova, Irina; Peters, Ron J.G.; Held, Claes; Yusoff, Khalid; Lewis, Basil S.; Jansky, Petr; Khunti, Kamlesh; Toff, William D.; Reid, Christopher M.; Varigos, John; Accini, Jose Luis; McKelvie, Robert; Pogue, Janice; Jung, Hyejung; Liu, Lisheng; Diaz, Rafael; Dans, Antonio; Dagenais, Gilles; HOPE-3 InvestigatorsBACKGROUND Elevated blood pressure and elevated low-density lipoprotein (LDL) cholesterol increase the risk of cardiovascular disease. Lowering both should reduce the risk of cardiovascular events substantially. METHODS In a trial with 2-by-2 factorial design, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to rosuvastatin (10 mg perday) or placebo and to candesartan (16 mg per day) plus hydrochlorothiazide (12.5 mg per day) or placebo. In the analyses reported here, we compared the 3180 participants assigned to combined therapy (with rosuvastatin and the two antihypertensive agents) with the 3168 participants assigned to dual placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included heart failure, cardiac arrest, or revascularization. The median follow-up was 5.6 years. RESULTS The decrease in the LDL cholesterol level was 33.7 mg per deciliter (0.87 mmol per liter) greater in the combined-therapy group than in the dual-placebo group, and the decrease in systolic blood pressure was 6.2 mm Hg greater with combined therapy than with dual placebo. The first coprimary outcome occurred in 113 participants (3.6%) in the combined-therapy group and in 157 (5.0%) in the dual-placebo group (hazard ratio, 0.71; 95% confidence interval [CI], 0.56 to 0.90; P=0.005). The second coprimary outcome occurred in 136 participants (4.3%) and 187 participants (5.9%), respectively (hazard ratio, 0.72; 95% CI, 0.57 to 0.89; P=0.003). Muscle weakness and dizziness were more common in the combined-therapy group than in the dual-placebo group, but the overall rate of discontinuation of the trial regimen was similar in the two groups. CONCLUSIONS The combination of rosuvastatin (10 mg per day), candesartan (16 mg per day), and hydrochlorothiazide (12.5 mg per day) was associated with a significantly lower rate of cardiovascular events than dual placebo among persons at intermediate risk who did not have cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov number, NCT00468923.)
- PublicaciónAcceso abiertoBlood-pressure lowering in intermediate-risk persons without cardiovascular disease(2016-04-26) Lonn, Eva; Bosch, Jackie; Lopez-Jaramillo, Patricio; Zhu, Jun; Liu, Lisheng; Pais, Prem; Diaz, Rafael; Xavier, Denis; Sliwa, Karen; Dans, Antonio; Avezum, Alvaro; Leopoldo S., Piegas; Keltai, Katalin; Keltai, Matyas; Chazova, Irina; Peters, Ron J.G.; Held, Claes; Yusoff, Khalid; Lewis, Basil S.; Jansky, Petr; Parkhomenko, Alexander; Khunti, Kamlesh; Toff, William D.; Reid, Christopher M.; Varigos, John; Leiter, Lawrence A.; Molina, Dora I.; McKelvie, Robert; Pogue, Janice; Wilkinson, Joanne; Jung, Hyejung; Dagenais, Gilles; Yusuf, Salim; HOPE-3 InvestigatorsBACKGROUND Antihypertensive therapy reduces the risk of cardiovascular events among high-risk persons and among those with a systolic blood pressure of 160 mm Hg or higher, but its role in persons at intermediate risk and with lower blood pressure is unclear. METHODS In one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to receive either candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke; the second coprimary outcome additionally included resuscitated cardiac arrest, heart failure, and revascularization. The median follow-up was 5.6 years. RESULTS The mean blood pressure of the participants at baseline was 138.1/81.9 mm Hg; the decrease in blood pressure was 6.0/3.0 mm Hg greater in the active-treatment group than in the placebo group. The first coprimary outcome occurred in 260 participants (4.1%) in the active-treatment group and in 279 (4.4%) in the placebo group (hazard ratio, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P=0.40); the second coprimary outcome occurred in 312 participants (4.9%) and 328 participants (5.2%), respectively (hazard ratio, 0.95; 95% CI, 0.81 to 1.11; P=0.51). In one of the three prespecified hypothesis-based subgroups, participants in the subgroup for the upper third of systolic blood pressure (>143.5 mm Hg) who were in the active-treatment group had significantly lower rates of the first and second coprimary outcomes than those in the placebo group; effects were neutral in the middle and lower thirds (P=0.02 and P=0.009, respectively, for trend in the two outcomes). CONCLUSIONS Therapy with candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day was not associated with a lower rate of major cardiovascular events than placebo among persons at intermediate risk who did not have cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov number, NCT00468923.)
- PublicaciónAcceso abiertoCholesterol lowering in intermediate-risk persons without cardiovascular disease(2016-05-26) Yusuf, Salim; Bosch, Jackie; Dagenais, Gilles; Zhu, Jun; Xavier, Denis; Liu, Lisheng; Pais, Prem; Lopez-Jaramillo, Patricio; Leiter, Lawrence A.; Dans, Antonio; Avezum, Alvaro; Piegas, Leopoldo S.; Parkhomenko, Alexander; Keltai, Katalin; Keltai, Matyas; Sliwa, Karen; Peters, Ron J.G.; Held, Claes; Chazova, Irina; Yusoff, Khalid; Lewis, Basil S.; Jansky, Petr; Khunti, Kamlesh; Toff, William D.; Reid, Christopher M.; Varigos, John; Sánchez Vallejo, Gregorio; McKelvie, Robert; Pogue, Janice; Jung, Hyejung; Gao, Peggy; Diaz, Rafael; Lonn, Eva; The HOPE-3 InvestigatorsBACKGROUND Previous trials have shown that the use of statins to lower cholesterol reduces the risk of cardiovascular events among persons without cardiovascular disease. Those trials have involved persons with elevated lipid levels or inflammatory markers and involved mainly white persons. It is unclear whether the benefits of statins can be extended to an intermediate-risk, ethnically diverse population without cardiovascular disease. METHODS In one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participants in 21 countries who did not have cardiovascular disease and were at intermediate risk to receive rosuvastatin at a dose of 10 mg per day or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included revascularization, heart failure, and resuscitated cardiac arrest. The median follow-up was 5.6 years. RESULTS The overall mean low-density lipoprotein cholesterol level was 26.5% lower in the rosuvastatin group than in the placebo group. The first coprimary outcome occurred in 235 participants (3.7%) in the rosuvastatin group and in 304 participants (4.8%) in the placebo group (hazard ratio, 0.76; 95% confidence interval [CI], 0.64 to 0.91; P=0.002). The results for the second coprimary outcome were consistent with the results for the first (occurring in 277 participants [4.4%] in the rosuvastatin group and in 363 participants [5.7%] in the placebo group; hazard ratio, 0.75; 95% CI, 0.64 to 0.88; P<0.001). The results were also consistent in subgroups defined according to cardiovascular risk at baseline, lipid level, C-reactive protein level, blood pressure, and race or ethnic group. In the rosuvastatin group, there was no excess of diabetes or cancers, but there was an excess of cataract surgery (in 3.8% of the participants, vs. 3.1% in the placebo group; P=0.02) and muscle symptoms (in 5.8% of the participants, vs. 4.7% in the placebo group; P=0.005). CONCLUSIONS Treatment with rosuvastatin at a dose of 10 mg per day resulted in a significantly lower risk of cardiovascular events than placebo in an intermediate-risk, ethnically diverse population without cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; HOPE-3 ClinicalTrials.gov number, NCT00468923.
- PublicaciónAcceso abiertoCorrigendum to "Heart failure in low- and middle-income countries : Background, rationale, and design of the INTERnational Congestive Heart Failure Study (INTER-CHF)" (Am Heart J. (2015) 170:4 (627-634))(2016) Dokainish, Hisham; Teo, Koon; Zhu, Jun; Roy, Ambuj; AlHabib, Khalid F.; ElSayed, Ahmed; Palileo Villaneuva, Lia; Lopez-Jaramillo, Patricio; Karaye, Kamilu; Lanas, Fernando; Prabhakaran, Dorairaj; Huffman, Mark D.; Badr, Amr; Elmaghawry, Mohamed; Damasceno, Albertino; Belley Cote, Emilie; Grinvalds, Alex; Harkness, Karen; McKelvie, Robert; Yusuf, Salim
- PublicaciónAcceso abiertoFixed-dose combination therapies with and without aspirin for primary prevention of cardiovascular disease: an individual participant data meta-analysis(The Lancet, 2021-09-25) Joseph, Philip; Roshandel, Gholamreza; Gao, Peggy; Pais, Prem; Lonn, Eva; Xavier, Denis; Avezum, Alvaro; Zhu, Jun; Liu, Lisheng; Sliwa, Karen; Gamra, Habib; Bangdiwala, Shrikant I.; Teo, Koon; Diaz, Rafael; Dans, Antonio; Lopez-Jaramillo, Patricio; Prabhakaran, Dorairaj; Castellano, Jose Maria; Fuster, Valentin; Rodgers, Anthony; Huffman, Mark D.; Bosch, Jackie; Dagenais, Gilles R.; Malekzadeh, Reza; Yusuf, Salim; Polypill Trialists' Collaboration; MasiraBackground In randomised controlled trials, fixed-dose combination treatments (or polypills) have been shown to reduce a composite of cardiovascular disease outcomes in primary prevention. However, whether or not aspirin should be included, effects on specific outcomes, and effects in key subgroups are unknown. Methods We did an individual participant data meta-analysis of large randomised controlled trials (each with ≥1000 participants and ≥2 years of follow-up) of a fixed-dose combination treatment strategy versus control in a primary cardiovascular disease prevention population. We included trials that evaluated a fixed-dose combination strategy of at least two blood pressure lowering agents plus a statin (with or without aspirin), compared with a control strategy (either placebo or usual care). The primary outcome was time to first occurrence of a composite of cardiovascular death, myocardial infarction, stroke, or arterial revascularisation. Additional outcomes included individual cardiovascular outcomes and death from any cause. Outcomes were also evaluated in groups stratified by the inclusion of aspirin in the fixed-dose treatment strategy, and effect sizes were estimated in prespecified subgroups based on risk factors. Kaplan-Meier survival curves and Cox proportional hazard regression models were used to compare strategies. Findings Three large randomised trials were included in the analysis (TIPS-3, HOPE-3, and PolyIran), with a total of 18 162 participants. Mean age was 63·0 years (SD 7·1), and 9038 (49·8%) participants were female. Estimated 10-year cardiovascular disease risk for the population was 17·7% (8·7). During a median follow-up of 5 years, the primary outcome occurred in 276 (3·0%) participants in the fixed-dose combination strategy group compared with 445 (4·9%) in the control group (hazard ratio 0·62, 95% CI 0·53–0·73, p<0·0001). Reductions were also observed for the separate components of the primary outcome: myocardial infarction (0·52, 0·38–0·70), revascularisation (0·54, 0·36–0·80), stroke (0·59, 0·45–0·78), and cardiovascular death (0·65, 0·52–0·81). Significant reductions in the primary outcome and its components were observed in the analyses of fixed-dose combination strategies with and without aspirin, with greater reductions for strategies including aspirin. Treatment effects were similar at different lipid and blood pressure levels, and in the presence or absence of diabetes, smoking, or obesity. Gastrointestinal bleeding was uncommon but slightly more frequent in the fixed-dose combination strategy with aspirin group versus control (19 [0·4%] vs 11 [0·2%], p=0·15). The frequencies of haemorrhagic stroke (10 [0·2%] vs 15 [0·3%]), fatal bleeding (two [<0·1%] vs four [0·1%]), and peptic ulcer disease (32 [0·7%] vs 34 [0·8%]) were low and did not differ significantly between groups. Dizziness was more common with fixed-dose combination treatment (1060 [11·7%] vs 834 [9·2%], p<0·0001). Interpretation Fixed-dose combination treatment strategies substantially reduce cardiovascular disease, myocardial infarction, stroke, revascularisation, and cardiovascular death in primary cardiovascular disease prevention. These benefits are consistent irrespective of cardiometabolic risk factors.
- PublicaciónRestringidoGlobal mortality variations in patients with heart failure : Results from the International Congestive Heart Failure (INTER-CHF) prospective cohort study(2017-07-01) Lopez-Jaramillo, Patricio; Dokainish, Hisham; Teo, Koon; Zhu, Jun; Roy, Ambuj; AlHabib, Khalid F.; ElSayed, Ahmed; Palileo Villaneuva, Lia; Karaye, Kamilu; Yusoff, Khalid; Orlandini, Andres; Sliwa, Karen; Mondo, Charles; Lanas, Fernando; Prabhakaran, Dorairaj; Badr, Amr; Elmaghawry, Mohamed; Damasceno, Albertino; Tibazarwa, Kemi; Belley Cote, Emilie; Balasubramanian, Kumar; Islam, Shofiqul; Yacoub, Magdi H.; Huffman, Mark D.; Harkness, Karen; Grinvalds, Alex; McKelvie, Robert; Bangdiwala, Shrikant I.; Yusuf, Salim; On behalf of the INTER-CHF Investigators.Background Most data on mortality and prognostic factors in patients with heart failure come from North America and Europe, with little information from other regions. Here, in the International Congestive Heart Failure (INTERCHF) study, we aimed to measure mortality at 1 year in patients with heart failure in Africa, China, India, the Middle East, southeast Asia and South America; we also explored demographic, clinical, and socioeconomic variables associated with mortality. Methods We enrolled consecutive patients with heart failure (3695 [66%] clinic outpatients, 2105 [34%] hospital in patients) from 108 centres in six geographical regions. We recorded baseline demographic and clinical characteristics and followed up patients at 6 months and 1 year from enrolment to record symptoms, medications, and outcomes. Time to death was studied with Cox proportional hazards models adjusted for demographic and clinical variables, medications, socioeconomic variables, and region. We used the explained risk statistic to calculate the relative contribution of each level of adjustment to the risk of death. Findings We enrolled 5823 patients within 1 year (with 98% follow-up). Overall mortality was 16·5%: highest in Africa (34%) and India (23%), intermediate in southeast Asia (15%), and lowest in China (7%), South America (9%), and the Middle East (9%). Regional differences persisted after multivariable adjustment. Independent predictors of mortality included cardiac variables (New York Heart Association Functional Class III or IV, previous admission for heart failure, and valve disease) and non-cardiac variables (body-mass index, chronic kidney disease, and chronic obstructive pulmonary disease). 46% of mortality risk was explained by multivariable modelling with these variables; however, the remainder was unexplained. Interpretation Marked regional differences in mortality in patients with heart failure persisted after multivariable adjustment for cardiac and non-cardiac factors. Therefore, variations in mortality between regions could be the result of health-care infrastructure, quality and access, or environmental and genetic factors. Further studies in large, global cohorts are needed. Funding The study was supported by Novartis.
- PublicaciónAcceso abiertoHeart Failure in Africa, Asia, the Middle East and South America: The INTER-CHF study(2016-02) Dokainish, Hisham; Teo, Koon; Zhu, Jun; Roy, Ambuj; AlHabib, Khalid F.; ElSayed, Ahmed; Palileo Villaneuva, Lia; Lopez-Jaramillo, Patricio; Karaye, Kamilu; Yusoff, Khalid; Orlandini, Andres; Sliwa, Karen; Mondo, Charles; Lanas, Fernando; Prabhakaran, Dorairaj; Badr, Amr; Elmaghawry, Mohamed; Damasceno, Albertino; Tibazarwa, Kemi; Belley Cote, Emilie; Balasubramanian, Kumar; Yacoub, Magdi H.; Huffman, Mark D.; Harkness, Karen; Grinvalds, Alex; McKelvie, Robert; Yusuf, Salim; The INTER-CHF InvestigatorsBackground There are few data on heart failure (HF) patients from Africa, Asia, the Middle East and South America. Methods INTER-CHF is a prospective study that enrolled HF patients in 108 centers in 16 countries from 2012 to 2014. Consecutive ambulatory or hospitalized adult patients with HF were enrolled. Baseline data were recorded on sociodemographics, clinical characteristics, HF etiology and treatments. Age- and sex-adjusted results are reported. Results We recruited 5813 HF patients: mean(SE) age = 59(0.2) years, 39% female, 65% outpatients, 31% from rural areas, 26% with HF with preserved ejection fraction, with 1294 from Africa, 2661 from Asia, 1000 from the Middle-East, and 858 from South America. Participants from Africa—closely followed by Asians—were younger, had lower literacy levels, and were less likely to have health or medication insurance or be on beta-blockers compared with participants from other regions, but were most likely to be in NYHA class IV. Participants from South America were older, had higher insurance and literacy levels, and, along with Middle Eastern participants, were more likely to be on beta-blockers, but had the lowest proportion in NYHA IV. Ischemic heart disease was the most common HF etiology in all regions except Africa where hypertensive heart disease was most common. Conclusions INTER-CHF describes significant regional variability in socioeconomic and clinical factors, etiologies and treatments in HF patients from Africa, Asia, the Middle East and South America. Opportunities exist for improvement in health/medication insurance rates and proportions of patients on beta blockers, particularly in Africa and Asia.
- PublicaciónAcceso abiertoLong-term Effects of Statins, Blood Pressure-Lowering, and Both on Erectile Function in Persons at Intermediate Risk for Cardiovascular Disease : A Substudy of the Heart Outcomes Prevention Evaluation-3 (HOPE-3) Randomized Controlled Trial(2018-01) Joseph, Philip; Lonn, Eva; Bosch, Jackie; Lopez-Jaramillo, Patricio; Zhu, Jun; Keltai, Matyas; Dans, Antonio; Reid, Christopher M.; Khunti, Kamlesh; Toff, William D.; Piegas, Leopoldo S.; Kim, Jae Hyung; Swaminathan, Balakumar; Bohm, Michael; Yusuf, Salim; HOPE-3 InvestigatorsBackground: It is unclear whether modifying cholesterol, blood pressure, or both affect erectile dysfunction. Also, there are concerns that erectile dysfunction is worsened by common medications used to treat these risk factors. In this study, we evaluated the effect of: (1) cholesterol-lowering with a statin; (2) pharmacologic blood pressure reduction; and (3) their combination, on erectile function. Methods: A priori, this was a secondary analysis of the Heart Outcomes Prevention Evaluation-3 (HOPE-3) randomized controlled trial. Men were 55 years of age or older with at least 1 cardiovascular risk factor. Erectile function was measured using the erectile function domain of the International Index of Erectile Function (IIEF-EF) score. Men with incomplete scores, or who did not engage in sexual activity, were excluded. Using a 2 × 2 factorial design, participants were randomized to rosuvastatin (10 mg/d) or placebo, and to candesartan with hydrochlorothiazide (HCTZ; 16 mg/12.5 mg/d; Cand+HCTZ) or placebo. Primary outcome was change in IIEF-EF from baseline to end of study follow-up. Results: Two thousand one hundred fifty-three men were included; mean age was 61.5 years, and mean follow-up was 5.8 years. Mean IIEF-EF score at baseline was 23.0 (SD 5.6). Least square mean change in the IIEF-EF score did not differ with rosuvastatin compared with placebo (−1.4; standard error [SE], 0.3 vs −1.5; SE, 0.3; P = 0.74), Cand+HCTZ compared with placebo (−1.6; SE, 0.3 vs −1.3; SE, 0.3; P = 0.10), or combination therapy compared with double placebo (P = 0.35). Conclusions: Cholesterol-lowering using a statin, and blood pressure-lowering using Cand+HCTZ, either alone or in combination, do not improve or adversely affect erectile function.
- PublicaciónAcceso abiertoLowering cholesterol, blood pressure, or both to prevent cardiovascular events: Results of 8.7 years of follow-up of Heart Outcomes Evaluation Prevention (HOPE)-3 study participants(Oxford Academic, 2021-08-14) Bosch, Jackie; Lonn, Eva M.; Jung, Hyejung; Zhu, Jun; Liu, Lisheng; Lopez-Jaramillo, Patricio; Pais, Prem; Xavier, Denis; Diaz, Rafael; Dagenais, Gilles; Dans, Antonio; Avezum, Alvaro; Piegas, Leopoldo S.; Parkhomenko, Alexander; Keltai, Kati; Keltai, Matya; Sliwa, Karen; Held, Claus; Peters, Ronald J.G.; Lewis, Basil S.; Jansky, Petr; Yusoff, Khalid; Khunti, Kamlesh; Toff, William D.; Reid, Christopher M.; Varigos, John; Joseph, Philip; Leiter, Lawrence A.; Yusuf, Salim; The Heart Outcomes Prevention Evaluation (HOPE)-3 Investigators; MasiraAims. Rosuvastatin (10 mg per day) compared with placebo reduced major adverse cardiovascular (CV) events by 24% in 12 705 participants at intermediate CV risk after 5.6 years. There was no benefit of blood pressure (BP) lowering treatment in the overall group, but a reduction in events in the third of participants with elevated systolic BP. After cessation of all the trial medications, we examined whether the benefits observed during the active treatment phase were sustained, enhanced, or attenuated. Methods and results. After the randomized treatment period (5.6 years), participants were invited to participate in 3.1 further years of observation (total 8.7 years). The first co-primary outcome for the entire length of follow-up was the composite of myocardial infarction, stroke, or CV death [major adverse cardiovascular event (MACE)-1], and the second was MACE-1 plus resuscitated cardiac arrest, heart failure, or coronary revascularization (MACE-2). In total, 9326 (78%) of 11 994 surviving Heart Outcomes Prevention Evaluation (HOPE)-3 subjects consented to participate in extended follow-up. During 3.1 years of post-trial observation (total follow-up of 8.7 years), participants originally randomized to rosuvastatin compared with placebo had a 20% additional reduction in MACE-1 [95% confidence interval (CI), 0.64–0.99] and a 17% additional reduction in MACE-2 (95% CI 0.68–1.01). Therefore, over the 8.7 years of follow-up, there was a 21% reduction in MACE-1 (95% CI 0.69–0.90, P = 0.005) and 21% reduction in MACE-2 (95% CI 0.69–0.89, P = 0.002). There was no benefit of BP lowering in the overall study either during the active or post-trial observation period, however, a 24% reduction in MACE-1 was observed over 8.7 years. Conclusion. The CV benefits of rosuvastatin, and BP lowering in those with elevated systolic BP, compared with placebo continue to accrue for at least 3 years after cessation of randomized treatment in individuals without cardiovascular disease indicating a legacy effect
- PublicaciónAcceso abiertoNovel Approaches in Primary Cardiovascular Disease Prevention : The HOPE-3 Trial Rationale, Design, and Participants' Baseline Characteristics(2016-03) Lonn, Eva; Bosch, Jackie; Pogue, Janice; Avezum, Alvaro; Chazova, Irina; Dans, Antonio; Diaz, Rafael; Fodor, George J.; Held, Claes; Jansky, Petr; Keltai, Matyas; Keltai, Katalin; Kunti, Kamlesh; Kim, Jae Hyung; Leiter, Lawrence A.; Lewis, Basil S.; Liu, Lisheng; Lopez-Jaramillo, Patricio; Pais, Prem; Parkhomenko, Alexander; Peters, Ron J.G.; Piegas, Leopoldo S.; Reid, Christopher M.; Sliwa, Karen; Toff, William D.; Varigos, John; Xavier, Denis; Yusoff, Khalid; Zhu, Jun; Dagenais, Gilles; Yusuf, Salim; The HOPE-3 InvestigatorsRésumé Introduction Il est possible de faire baisser efficacement et en toute sécurité le cholestérol et la pression artérielle (PA) avec les statines et les antihypertenseurs tout en réduisant de 20 à 30 % les manifestations cardiovasculaires majeures en l’espace de cinq ans chez les personnes à risque élevé. Les données obtenues dans les populations exposées à un risque plus faible sont néanmoins limitées. L’essai HOPE-3 (Heart Outcomes Prevention Evaluation-3) tâche de déterminer si l’abaissement du cholestérol à l’aide d’une statine, l’abaissement de la pression artérielle à l’aide de deux agents antihypertenseurs administrés à raison d’une faible dose et leur association permettent de réduire en toute sécurité les manifestations cardiovasculaires majeures chez les personnes exposées à un risque intermédiaire qui n’ont pas d’antécédents d’événements vasculaires et dont le taux de cholestérol et la PA se situent dans la moyenne. Méthodes Au total, 12 705 femmes et hommes, les unes âgées de 65 ans et plus et les autres de 55 ans et plus, qui présentent au moins un facteur de risque cardiovasculaire et qui n’ont pas de maladie cardiovasculaire connue ni aucune indication ou contre-indication claires aux médicaments à l’étude, ont été répartis aléatoirement pour recevoir de la rosuvastatine à raison de 10 mg par jour ou un placebo et l’association candésartan/hydrochlorothiazide à raison de 16/12,5 mg par jour ou un placebo (plan factoriel 2 × 2). Ces patients seront suivis pendant une moyenne de 5,8 ans. Les principaux paramètres d’évaluation de l’étude combinent le décès d’origine cardiovasculaire, l’infarctus du myocarde non mortel et l’AVC non mortel d’une part, et le décès d’origine cardiovasculaire, l’infarctus du myocarde non mortel, l’AVC non mortel, la réanimation après arrêt cardiaque, l’insuffisance cardiaque et la revascularisation artérielle d’autre part. Résultats Les participants ont été recrutés dans 21 pays situés en Amérique du Nord, en Amérique du Sud, en Europe, en Asie et en Australie. L’âge moyen au moment de la répartition aléatoire était de 66 ans, et 46 % des sujets étaient des femmes. Conclusions L’essai HOPE-3 fournira de nouveaux renseignements sur l’abaissement du taux de cholestérol et de la PA dans des populations exposées à un risque intermédiaire dont le taux de cholestérol et la PA se situent dans la moyenne. Il devrait également fournir des données à l’appui des stratégies de prévention primaire mises en place partout dans le monde (HOPE-3 ClinicalTrials.gov NCT00468923).
- PublicaciónAcceso abiertoVariations in common diseases, hospital admissions, and deaths in middle-aged adults in 21 countries from five continents (PURE)(Elsevier Inc., 2019-09-03) Dagenais, Gilles R.; Leong, Darryl P.; Rangarajan, Sumathy; Lanas, Fernando; Lopez-Jaramillo, Patricio; Gupta, Rajeev; Diaz, Rafael; Avezum, Alvaro; Alhabib, Khalid F.; Temizhan, Ahmet; Ismail, Noorhassim; Chifamba, Jephat; Yeates, Karen; Khatib, Rasha; Rahman, Omar; Zatonska, Katarzyna; Kazmi, Khawar; Wei, Li; Zhu, Jun; Rosengren, Annika; Vijayakumar, K.; Kaur, Manmeet; Mohan, Viswanathan; Yusufali, AfzalHussein; Kelishadi, Roya; Teo, Koon K.; Joseph, Philip; Yusuf, Salim; Elsevier; EverestBackground To our knowledge, no previous study has prospectively documented the incidence of common diseases and related mortality in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) with standardised approaches. Such information is key to developing global and context-specific health strategies. In our analysis of the Prospective Urban Rural Epidemiology (PURE) study, we aimed to evaluate differences in the incidence of common diseases, related hospital admissions, and related mortality in a large contemporary cohort of adults from 21 HICs, MICs, and LICs across five continents by use of standardised approaches. Methods The PURE study is a prospective, population-based cohort study of individuals aged 35–70 years who have been enrolled from 21 countries across five continents. The key outcomes were the incidence of fatal and non-fatal cardiovascular diseases, cancers, injuries, respiratory diseases, and hospital admissions, and we calculated the age-standardised and sex-standardised incidence of these events per 1000 person-years. Findings This analysis assesses the incidence of events in 162 534 participants who were enrolled in the first two phases of the PURE core study, between Jan 6, 2005, and Dec 4, 2016, and who were assessed for a median of 9·5 years (IQR 8·5–10·9). During follow-up, 11 307 (7·0%) participants died, 9329 (5·7%) participants had cardiovascular disease, 5151 (3·2%) participants had a cancer, 4386 (2·7%) participants had injuries requiring hospital admission, 2911 (1·8%) participants had pneumonia, and 1830 (1·1%) participants had chronic obstructive pulmonary disease (COPD). Cardiovascular disease occurred more often in LICs (7·1 cases per 1000 person-years) and in MICs (6·8 cases per 1000 person-years) than in HICs (4·3 cases per 1000 person-years). However, incident cancers, injuries, COPD, and pneumonia were most common in HICs and least common in LICs. Overall mortality rates in LICs (13·3 deaths per 1000 person-years) were double those in MICs (6·9 deaths per 1000 person-years) and four times higher than in HICs (3·4 deaths per 1000 person-years). This pattern of the highest mortality in LICs and the lowest in HICs was observed for all causes of death except cancer, where mortality was similar across country income levels. Cardiovascular disease was the most common cause of deaths overall (40%) but accounted for only 23% of deaths in HICs (vs 41% in MICs and 43% in LICs), despite more cardiovascular disease risk factors (as judged by INTERHEART risk scores) in HICs and the fewest such risk factors in LICs. The ratio of deaths from cardiovascular disease to those from cancer was 0·4 in HICs, 1·3 in MICs, and 3·0 in LICs, and four upper-MICs (Argentina, Chile, Turkey, and Poland) showed ratios similar to the HICs. Rates of first hospital admission and cardiovascular disease medication use were lowest in LICs and highest in HICs. Interpretation Among adults aged 35–70 years, cardiovascular disease is the major cause of mortality globally. However, in HICs and some upper-MICs, deaths from cancer are now more common than those from cardiovascular disease, indicating a transition in the predominant causes of deaths in middle-age. As cardiovascular disease decreases in many countries, mortality from cancer will probably become the leading cause of death. The high mortality in poorer countries is not related to risk factors, but it might be related to poorer access to health care. Funding Full funding sources are listed at the end of the paper (see Acknowledgments).