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Salim Yusuf - One of the best experts on this subject based on the ideXlab platform.
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Incidence of Diabetes Following Ramipril or Rosiglitazone Withdrawal
Diabetes care, 2011Co-Authors: Rury R. Holman, Jackie Bosch, Salim Yusuf, Patrick Sheridan, B. Zinman, Sonia S. Anand, Ignacio Conget, Melanie J. Davies, Valdis Pirags, Gilles R. DagenaisAbstract:OBJECTIVE To examine the impact of withdrawing rosiglitazone and Ramipril medication on diabetes incidence after closeout of the Diabetes REduction Assessment with Ramipril and rosiglitazone Medication (DREAM) trial. RESEARCH DESIGN AND METHODS The 3,366 DREAM subjects at trial end who had not developed diabetes while taking double-blind study medication were transferred to single-blind placebo for 2 to 3 months before undergoing an oral glucose tolerance test. Glycemic status was analyzed for the trial plus washout period and for the washout period alone. RESULTS Following median (interquartile range) 71 (63–86) days drug withdrawal, overall glycemic status remained modestly improved in those allocated Ramipril during the trial with an 11% increase in regression to normoglycemia, compared with placebo. In those previously allocated rosiglitazone, glycemic status remained substantially improved with a 49% reduction of new-onset diabetes or death and a 22% increase in regression to normoglycemia, compared with placebo. However, during the washout phase alone the incidence of diabetes or death was identical for those allocated previously to Ramipril or placebo, or to rosiglitazone or placebo. CONCLUSIONS In people allocated to Ramipril compared with those not allocated Ramipril during the trial, the postwashout normoglycemia incidence was higher. In people allocated to rosiglitazone compared with those not allocated rosiglitazone during the trial, the postwashout incidence of diabetes was significantly lower and the incidence of normoglycemia was higher. During the washout period, diabetes incidence was the same for Ramipril versus placebo and for rosiglitazone versus placebo. Rosiglitazone delays disease progression during treatment but the process resumes at the placebo rate when the drug is stopped.
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in a subgroup of high risk asians telmisartan was non inferior to Ramipril and better tolerated in the prevention of cardiovascular events
PLOS ONE, 2010Co-Authors: Antonio L Dans, Koon K. Teo, Peggy Gao, Jyhhong Chen, Kim Jaehyung, Khalid Yusoff, Suphachai Chaithiraphan, Jun Zhu, Liu Lisheng, Salim YusufAbstract:Background and Objectives Results of the recently published ONTARGET study (The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial) showed that telmisartan (80 mg/day) was non-inferior to Ramipril (10 mg/day) in reducing cardiovascular events. Clinicians in Asia doubt tolerability of these doses for their patients. We therefore analyzed data from this study and a parallel study TRANSCEND (Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease). Our objectives were to compare Asians and non-Asians with respect to the following: 1) Effectiveness of telmisartan vs. Ramipril in reducing cardiovascular events; 2) Proportions who reached the full dose of telmisartan, Ramipril or placebo; and 3) Proportions of overall discontinuations, and discontinuations due to adverse effects. Method The ONTARGET study randomized 25,620 patients at risk of cardiovascular events to Ramipril, telmisartan, or their combination. The primary composite endpoint was death caused by cardiovascular disease, acute MI, stroke, and hospitalization because of congestive heart failure. TRANSCEND randomized 5926 high-risk patients with a history of intolerance to ACE-inhibitors to telmisartan or placebo. The primary outcome was the same. In this substudy, we compared Asians and non-Asians as to how well they tolerated telmisartan (given in both studies) and Ramipril (given in ONTARGET). Results 1) Telmisartan was non-inferior to Ramipril in lowering the primary endpoint among Asians (RR = 0.92; 95% CI: 0.74, 1.13); 2) more Asians achieved the full dose of either drug; 3) less withdrew (overall); and 4) less withdrew for adverse effects. Furthermore, telmisartan was better tolerated than Ramipril. This advantage was greater among Asians. Conclusion and Significance Although Asians had lower BMI than non-Asians, Asians tolerated both drugs better. Regulatory agencies require reporting of safety and effectiveness data by ethnicity, but few comply with this requirement. This study shows that safety data in ethnic subgroups can help assess applicability of results to specific populations. Trial Registration ClinicalTrials.gov NCT00153101
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Effect of Ramipril on the incidence of diabetes.
The New England journal of medicine, 2006Co-Authors: Jackie Bosch, Gilles R. Dagenais, Janice Pogue, Salim Yusuf, Hertzel C. Gerstein, Patrick Sheridan, Rafael Diaz, Alvaro Avezum, Fernando Lanas, Jeffrey L ProbstfieldAbstract:Background Previous studies have suggested that blockade of the renin–angiotensin system may prevent diabetes in people with cardiovascular disease or hypertension. Methods In a double-blind, randomized clinical trial with a 2-by-2 factorial design, we randomly assigned 5269 participants without cardiovascular disease but with impaired fasting glucose levels (after an 8-hour fast) or impaired glucose tolerance to receive Ramipril (up to 15 mg per day) or placebo (and rosiglitazone or placebo) and followed them for a median of 3 years. We studied the effects of Ramipril on the development of diabetes or death, whichever came first (the primary outcome), and on secondary outcomes, including regression to normoglycemia. Results The incidence of the primary outcome did not differ significantly between the Ramipril group (18.1%) and the placebo group (19.5%; hazard ratio for the Ramipril group, 0.91; 95% confidence interval [CI], 0.81 to 1.03; P = 0.15). Participants receiving Ramipril were more likely to have regression to normoglycemia than those receiving placebo (hazard ratio, 1.16; 95% CI, 1.07 to 1.27; P = 0.001). At the end of the study, the median fasting plasma glucose level was not significantly lower in the Ramipril group (102.7 mg per deciliter [5.70 mmol per liter]) than in the placebo group (103.4 mg per deciliter [5.74 mmol per liter], P = 0.07), though plasma glucose levels 2 hours after an oral glucose load were significantly lower in the Ramipril group (135.1 mg per deciliter [7.50 mmol per liter] vs. 140.5 mg per deciliter [7.80 mmol per liter], P = 0.01). Conclusions Among persons with impaired fasting glucose levels or impaired glucose tolerance, the use of Ramipril for 3 years does not significantly reduce the incidence of diabetes or death but does significantly increase regression to normoglycemia. (ClinicalTrials.gov number, NCT00095654.)
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effects of Ramipril on left ventricular mass and function in cardiovascular patients with controlled blood pressure and with preserved left ventricular ejection fraction a substudy of the heart outcomes prevention evaluation hope trial
Journal of the American College of Cardiology, 2004Co-Authors: Eva Lonn, Jackie Bosch, Salim Yusuf, Roya Shaikholeslami, Brian Sullivan, Paul H Tanser, Alison MagiAbstract:Abstract Objectives The purpose of this study was to assess the effects of Ramipril on left ventricular mass (LVM) and function in vascular disease patients with controlled blood pressure (BP) and with preserved left ventricular ejection fraction (LVEF). Background Increased LVM and left ventricular (LV) volume and decreased LVEF predict clinical events. Angiotensin-converting enzyme inhibitors reduce LVM and LV volume and preserve LVEF in patients with hypertension and/or LV dysfunction, but have not been studied in patients with controlled BP and preserved LVEF. Methods We compared the effects of two doses of Ramipril (10 mg/day and 2.5 mg/day) versus placebo in 506 patients with vascular disease on echocardiographic measures of LVM and LV function. Results Baseline BP and LVEF were similar, 131/76 mm Hg and 58%, in all treatment groups. After four years, LVM index increased by 3.98 ± 2.08 g/m2in the placebo and by 4.16 ± 1.86 g/m2in the Ramipril 2.5 mg/day groups and decreased by 2.02 ± 2.25 g/m2in the Ramipril 10 mg/day group (p = 0.02). The changes in LV end-diastolic and end-systolic volumes were 4.16 ± 2.55 ml and 5.31 ± 1.67 ml in the placebo, −0.43 ± 2.75 ml and 2.90 ± 1.45 ml in the Ramipril 2.5 mg/day, and −5.90 ± 2.93 ml and −1.90 ± 1.55 ml in the Ramipril 10 mg/day groups (p = 0.02 and p = 0.001). The changes in LVEF were −2.02 ± 0.72%, −1.54 ± 0.74%, and −0.17 ± 0.72%, respectively (p = 0.01). Conclusions Ramipril has beneficial effects on LV structure and function in vascular patients with controlled BP and with preserved LVEF.
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effect of long term therapy with Ramipril in high risk women
Journal of the American College of Cardiology, 2002Co-Authors: Eva Lonn, Gilles R. Dagenais, Peter Sleight, Jackie Bosch, Jeffrey L Probstfield, Rosa Roccaforte, Pamela Suhan, Mary Micks, Victoria Bernstein, Salim YusufAbstract:Abstract Objectives We evaluated the effects of long-term therapy with the angiotensin-converting enzyme (ACE) inhibitor Ramipril on major cardiovascular (CV) outcomes in high-risk women. Background The effect of long-term ACE inhibitor therapy in high-risk women without heart failure and with preserved left ventricular (LV) systolic function has not been previously reported. Methods The Heart Outcomes Prevention Evaluation (HOPE) trial is a large, randomized clinical trial that evaluated Ramipril and vitamin E in high-risk patients. We present the preplanned analysis of the effects of Ramipril in women in the HOPE study. The study randomized 2,480 women aged ≥55 years with vascular disease or diabetes and at least one additional CV risk factor and without heart failure or a known low LV ejection fraction to Ramipril (10 mg/day) or placebo. The primary outcome was the composite of myocardial infarction, stroke or CV death. Average follow-up was 4.5 years. Results Treatment with Ramipril resulted in reduced primary end point rates (11.3% vs. 14.9% in the placebo arm; relative risk [RR] 0.77, 95% confidence interval [CI] 0.62 to 0.96; p = 0.019), fewer strokes (3.1% vs. 4.8%; RR 0.64, 95% CI 0.43 to 0.96; p = 0.029) and fewer CV deaths (4.2% vs. 6.9%; RR 0.62, 95% CI 0.44 to 0.88; p = 0.0068). There were trends toward reduced rates of myocardial infarction, heart failure and all-cause death. The beneficial effect of Ramipril was similar in women and men. Conclusions Treatment with Ramipril reduces the CV risk in high-risk women without heart failure and with preserved LV systolic function.
M A Abounassif - One of the best experts on this subject based on the ideXlab platform.
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a stability indicating lc method for the simultaneous determination of Ramipril and hydrochlorothiazide in dosage forms
Journal of Pharmaceutical and Biomedical Analysis, 2001Co-Authors: F Belal, I A Alzaagi, Elrasheed A Gadkariem, M A AbounassifAbstract:Abstract A simple, rapid and sensitive HPLC method has been developed for the simultaneous determination of Ramipril and hydrochlorothiazide in their dosage forms. Acetonitrile: sodium perchlorate solution (0.1 M) adjusted to pH 2.5±0.2 with phosphoric acid (46:54 v/v), was used as the mobile phase, at a flow rate of 1.5 ml/min. A supelcosil™ LC-8 column (5 μm), 15 cm×4.6 mm i.d. was utilized as stationary phase. Detection was affected spectrophotometrically at 210 nm. Clobazam was used as an internal standard. The method was also applied for the determination of Ramipril in the presence of its degradation products. Linearity ranges for Ramipril and hydrochlorothiazide were 4.5–45 and 0.6–14 μg/ml, respectively. Minimum detection limits (S/N=2) obtained were 180 and 23 ng/ml for Ramipril and hydrochlorothiazide, respectively. The proposed method was further applied to the analysis of tablets containing the two drugs, the percentage recoveries±S.D. ( n =5) were 100.45%±0.63 and 99.55%±0.78 for Ramipril and hydrochlorothiazide, respectively.
Gilles R. Dagenais - One of the best experts on this subject based on the ideXlab platform.
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Incidence of Diabetes Following Ramipril or Rosiglitazone Withdrawal
Diabetes care, 2011Co-Authors: Rury R. Holman, Jackie Bosch, Salim Yusuf, Patrick Sheridan, B. Zinman, Sonia S. Anand, Ignacio Conget, Melanie J. Davies, Valdis Pirags, Gilles R. DagenaisAbstract:OBJECTIVE To examine the impact of withdrawing rosiglitazone and Ramipril medication on diabetes incidence after closeout of the Diabetes REduction Assessment with Ramipril and rosiglitazone Medication (DREAM) trial. RESEARCH DESIGN AND METHODS The 3,366 DREAM subjects at trial end who had not developed diabetes while taking double-blind study medication were transferred to single-blind placebo for 2 to 3 months before undergoing an oral glucose tolerance test. Glycemic status was analyzed for the trial plus washout period and for the washout period alone. RESULTS Following median (interquartile range) 71 (63–86) days drug withdrawal, overall glycemic status remained modestly improved in those allocated Ramipril during the trial with an 11% increase in regression to normoglycemia, compared with placebo. In those previously allocated rosiglitazone, glycemic status remained substantially improved with a 49% reduction of new-onset diabetes or death and a 22% increase in regression to normoglycemia, compared with placebo. However, during the washout phase alone the incidence of diabetes or death was identical for those allocated previously to Ramipril or placebo, or to rosiglitazone or placebo. CONCLUSIONS In people allocated to Ramipril compared with those not allocated Ramipril during the trial, the postwashout normoglycemia incidence was higher. In people allocated to rosiglitazone compared with those not allocated rosiglitazone during the trial, the postwashout incidence of diabetes was significantly lower and the incidence of normoglycemia was higher. During the washout period, diabetes incidence was the same for Ramipril versus placebo and for rosiglitazone versus placebo. Rosiglitazone delays disease progression during treatment but the process resumes at the placebo rate when the drug is stopped.
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Vascular protection: telmisartan in the ONTARGET Trial Programme
European Heart Journal Supplements, 2009Co-Authors: Gilles R. DagenaisAbstract:The ONTARGET Trial Programme includes the ONTARGET and TRANSCEND studies. In both studies, participants were at high cardiovascular risk because they had vascular disease without heart failure, or diabetes with end-organ damage. Participants also received proven therapies for cardiovascular risk reduction. In ONTARGET, telmisartan 80 mg was compared with Ramipril 10 mg, and the combination of telmisartan and Ramipril was compared with Ramipril alone. Telmisartan was as effective as Ramipril on the primary outcome and other cardiovascular events and was better tolerated, with fewer treatment discontinuations. In TRANSCEND, telmisartan and placebo, both added to background therapy, were compared in high-risk patients intolerant to angiotensin-converting enzyme-inhibitors. There was a lower incidence of cardiovascular events than assumed in power calculations probably due to higher use of background therapy than expected based upon the HOPE trial. This may explain why the reduction in the primary outcome associated with telmisartan was not statistically significant. Nevertheless, the results of TRANSCEND were consistent with the outcome of the HOPE trial, and the secondary endpoint in TRANSCEND, which was equal to the HOPE primary endpoint (cardiovascular death, myocardial infarction, and stroke), was indeed significant. Telmisartan plus Ramipril did not reduce the primary outcome compared with Ramipril alone and was associated with a greater likelihood of adverse events. The combination is not recommended for the prevention of cardiovascular events in this patient population. In summary, telmisartan was as effective as Ramipril on major vascular events in high-risk patients in ONTARGET but showed a non-significant benefit in TRANSCEND. In both studies, the lower rate of treatment discontinuations with telmisartan is important life-long adherence to therapy.
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Effect of Ramipril on the incidence of diabetes.
The New England journal of medicine, 2006Co-Authors: Jackie Bosch, Gilles R. Dagenais, Janice Pogue, Salim Yusuf, Hertzel C. Gerstein, Patrick Sheridan, Rafael Diaz, Alvaro Avezum, Fernando Lanas, Jeffrey L ProbstfieldAbstract:Background Previous studies have suggested that blockade of the renin–angiotensin system may prevent diabetes in people with cardiovascular disease or hypertension. Methods In a double-blind, randomized clinical trial with a 2-by-2 factorial design, we randomly assigned 5269 participants without cardiovascular disease but with impaired fasting glucose levels (after an 8-hour fast) or impaired glucose tolerance to receive Ramipril (up to 15 mg per day) or placebo (and rosiglitazone or placebo) and followed them for a median of 3 years. We studied the effects of Ramipril on the development of diabetes or death, whichever came first (the primary outcome), and on secondary outcomes, including regression to normoglycemia. Results The incidence of the primary outcome did not differ significantly between the Ramipril group (18.1%) and the placebo group (19.5%; hazard ratio for the Ramipril group, 0.91; 95% confidence interval [CI], 0.81 to 1.03; P = 0.15). Participants receiving Ramipril were more likely to have regression to normoglycemia than those receiving placebo (hazard ratio, 1.16; 95% CI, 1.07 to 1.27; P = 0.001). At the end of the study, the median fasting plasma glucose level was not significantly lower in the Ramipril group (102.7 mg per deciliter [5.70 mmol per liter]) than in the placebo group (103.4 mg per deciliter [5.74 mmol per liter], P = 0.07), though plasma glucose levels 2 hours after an oral glucose load were significantly lower in the Ramipril group (135.1 mg per deciliter [7.50 mmol per liter] vs. 140.5 mg per deciliter [7.80 mmol per liter], P = 0.01). Conclusions Among persons with impaired fasting glucose levels or impaired glucose tolerance, the use of Ramipril for 3 years does not significantly reduce the incidence of diabetes or death but does significantly increase regression to normoglycemia. (ClinicalTrials.gov number, NCT00095654.)
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effect of long term therapy with Ramipril in high risk women
Journal of the American College of Cardiology, 2002Co-Authors: Eva Lonn, Gilles R. Dagenais, Peter Sleight, Jackie Bosch, Jeffrey L Probstfield, Rosa Roccaforte, Pamela Suhan, Mary Micks, Victoria Bernstein, Salim YusufAbstract:Abstract Objectives We evaluated the effects of long-term therapy with the angiotensin-converting enzyme (ACE) inhibitor Ramipril on major cardiovascular (CV) outcomes in high-risk women. Background The effect of long-term ACE inhibitor therapy in high-risk women without heart failure and with preserved left ventricular (LV) systolic function has not been previously reported. Methods The Heart Outcomes Prevention Evaluation (HOPE) trial is a large, randomized clinical trial that evaluated Ramipril and vitamin E in high-risk patients. We present the preplanned analysis of the effects of Ramipril in women in the HOPE study. The study randomized 2,480 women aged ≥55 years with vascular disease or diabetes and at least one additional CV risk factor and without heart failure or a known low LV ejection fraction to Ramipril (10 mg/day) or placebo. The primary outcome was the composite of myocardial infarction, stroke or CV death. Average follow-up was 4.5 years. Results Treatment with Ramipril resulted in reduced primary end point rates (11.3% vs. 14.9% in the placebo arm; relative risk [RR] 0.77, 95% confidence interval [CI] 0.62 to 0.96; p = 0.019), fewer strokes (3.1% vs. 4.8%; RR 0.64, 95% CI 0.43 to 0.96; p = 0.029) and fewer CV deaths (4.2% vs. 6.9%; RR 0.62, 95% CI 0.44 to 0.88; p = 0.0068). There were trends toward reduced rates of myocardial infarction, heart failure and all-cause death. The beneficial effect of Ramipril was similar in women and men. Conclusions Treatment with Ramipril reduces the CV risk in high-risk women without heart failure and with preserved LV systolic function.
Jackie Bosch - One of the best experts on this subject based on the ideXlab platform.
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Incidence of Diabetes Following Ramipril or Rosiglitazone Withdrawal
Diabetes care, 2011Co-Authors: Rury R. Holman, Jackie Bosch, Salim Yusuf, Patrick Sheridan, B. Zinman, Sonia S. Anand, Ignacio Conget, Melanie J. Davies, Valdis Pirags, Gilles R. DagenaisAbstract:OBJECTIVE To examine the impact of withdrawing rosiglitazone and Ramipril medication on diabetes incidence after closeout of the Diabetes REduction Assessment with Ramipril and rosiglitazone Medication (DREAM) trial. RESEARCH DESIGN AND METHODS The 3,366 DREAM subjects at trial end who had not developed diabetes while taking double-blind study medication were transferred to single-blind placebo for 2 to 3 months before undergoing an oral glucose tolerance test. Glycemic status was analyzed for the trial plus washout period and for the washout period alone. RESULTS Following median (interquartile range) 71 (63–86) days drug withdrawal, overall glycemic status remained modestly improved in those allocated Ramipril during the trial with an 11% increase in regression to normoglycemia, compared with placebo. In those previously allocated rosiglitazone, glycemic status remained substantially improved with a 49% reduction of new-onset diabetes or death and a 22% increase in regression to normoglycemia, compared with placebo. However, during the washout phase alone the incidence of diabetes or death was identical for those allocated previously to Ramipril or placebo, or to rosiglitazone or placebo. CONCLUSIONS In people allocated to Ramipril compared with those not allocated Ramipril during the trial, the postwashout normoglycemia incidence was higher. In people allocated to rosiglitazone compared with those not allocated rosiglitazone during the trial, the postwashout incidence of diabetes was significantly lower and the incidence of normoglycemia was higher. During the washout period, diabetes incidence was the same for Ramipril versus placebo and for rosiglitazone versus placebo. Rosiglitazone delays disease progression during treatment but the process resumes at the placebo rate when the drug is stopped.
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Effect of Ramipril on the incidence of diabetes.
The New England journal of medicine, 2006Co-Authors: Jackie Bosch, Gilles R. Dagenais, Janice Pogue, Salim Yusuf, Hertzel C. Gerstein, Patrick Sheridan, Rafael Diaz, Alvaro Avezum, Fernando Lanas, Jeffrey L ProbstfieldAbstract:Background Previous studies have suggested that blockade of the renin–angiotensin system may prevent diabetes in people with cardiovascular disease or hypertension. Methods In a double-blind, randomized clinical trial with a 2-by-2 factorial design, we randomly assigned 5269 participants without cardiovascular disease but with impaired fasting glucose levels (after an 8-hour fast) or impaired glucose tolerance to receive Ramipril (up to 15 mg per day) or placebo (and rosiglitazone or placebo) and followed them for a median of 3 years. We studied the effects of Ramipril on the development of diabetes or death, whichever came first (the primary outcome), and on secondary outcomes, including regression to normoglycemia. Results The incidence of the primary outcome did not differ significantly between the Ramipril group (18.1%) and the placebo group (19.5%; hazard ratio for the Ramipril group, 0.91; 95% confidence interval [CI], 0.81 to 1.03; P = 0.15). Participants receiving Ramipril were more likely to have regression to normoglycemia than those receiving placebo (hazard ratio, 1.16; 95% CI, 1.07 to 1.27; P = 0.001). At the end of the study, the median fasting plasma glucose level was not significantly lower in the Ramipril group (102.7 mg per deciliter [5.70 mmol per liter]) than in the placebo group (103.4 mg per deciliter [5.74 mmol per liter], P = 0.07), though plasma glucose levels 2 hours after an oral glucose load were significantly lower in the Ramipril group (135.1 mg per deciliter [7.50 mmol per liter] vs. 140.5 mg per deciliter [7.80 mmol per liter], P = 0.01). Conclusions Among persons with impaired fasting glucose levels or impaired glucose tolerance, the use of Ramipril for 3 years does not significantly reduce the incidence of diabetes or death but does significantly increase regression to normoglycemia. (ClinicalTrials.gov number, NCT00095654.)
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effects of Ramipril on left ventricular mass and function in cardiovascular patients with controlled blood pressure and with preserved left ventricular ejection fraction a substudy of the heart outcomes prevention evaluation hope trial
Journal of the American College of Cardiology, 2004Co-Authors: Eva Lonn, Jackie Bosch, Salim Yusuf, Roya Shaikholeslami, Brian Sullivan, Paul H Tanser, Alison MagiAbstract:Abstract Objectives The purpose of this study was to assess the effects of Ramipril on left ventricular mass (LVM) and function in vascular disease patients with controlled blood pressure (BP) and with preserved left ventricular ejection fraction (LVEF). Background Increased LVM and left ventricular (LV) volume and decreased LVEF predict clinical events. Angiotensin-converting enzyme inhibitors reduce LVM and LV volume and preserve LVEF in patients with hypertension and/or LV dysfunction, but have not been studied in patients with controlled BP and preserved LVEF. Methods We compared the effects of two doses of Ramipril (10 mg/day and 2.5 mg/day) versus placebo in 506 patients with vascular disease on echocardiographic measures of LVM and LV function. Results Baseline BP and LVEF were similar, 131/76 mm Hg and 58%, in all treatment groups. After four years, LVM index increased by 3.98 ± 2.08 g/m2in the placebo and by 4.16 ± 1.86 g/m2in the Ramipril 2.5 mg/day groups and decreased by 2.02 ± 2.25 g/m2in the Ramipril 10 mg/day group (p = 0.02). The changes in LV end-diastolic and end-systolic volumes were 4.16 ± 2.55 ml and 5.31 ± 1.67 ml in the placebo, −0.43 ± 2.75 ml and 2.90 ± 1.45 ml in the Ramipril 2.5 mg/day, and −5.90 ± 2.93 ml and −1.90 ± 1.55 ml in the Ramipril 10 mg/day groups (p = 0.02 and p = 0.001). The changes in LVEF were −2.02 ± 0.72%, −1.54 ± 0.74%, and −0.17 ± 0.72%, respectively (p = 0.01). Conclusions Ramipril has beneficial effects on LV structure and function in vascular patients with controlled BP and with preserved LVEF.
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effect of long term therapy with Ramipril in high risk women
Journal of the American College of Cardiology, 2002Co-Authors: Eva Lonn, Gilles R. Dagenais, Peter Sleight, Jackie Bosch, Jeffrey L Probstfield, Rosa Roccaforte, Pamela Suhan, Mary Micks, Victoria Bernstein, Salim YusufAbstract:Abstract Objectives We evaluated the effects of long-term therapy with the angiotensin-converting enzyme (ACE) inhibitor Ramipril on major cardiovascular (CV) outcomes in high-risk women. Background The effect of long-term ACE inhibitor therapy in high-risk women without heart failure and with preserved left ventricular (LV) systolic function has not been previously reported. Methods The Heart Outcomes Prevention Evaluation (HOPE) trial is a large, randomized clinical trial that evaluated Ramipril and vitamin E in high-risk patients. We present the preplanned analysis of the effects of Ramipril in women in the HOPE study. The study randomized 2,480 women aged ≥55 years with vascular disease or diabetes and at least one additional CV risk factor and without heart failure or a known low LV ejection fraction to Ramipril (10 mg/day) or placebo. The primary outcome was the composite of myocardial infarction, stroke or CV death. Average follow-up was 4.5 years. Results Treatment with Ramipril resulted in reduced primary end point rates (11.3% vs. 14.9% in the placebo arm; relative risk [RR] 0.77, 95% confidence interval [CI] 0.62 to 0.96; p = 0.019), fewer strokes (3.1% vs. 4.8%; RR 0.64, 95% CI 0.43 to 0.96; p = 0.029) and fewer CV deaths (4.2% vs. 6.9%; RR 0.62, 95% CI 0.44 to 0.88; p = 0.0068). There were trends toward reduced rates of myocardial infarction, heart failure and all-cause death. The beneficial effect of Ramipril was similar in women and men. Conclusions Treatment with Ramipril reduces the CV risk in high-risk women without heart failure and with preserved LV systolic function.
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reduction of cardiovascular risk by regression of electrocardiographic markers of left ventricular hypertrophy by the angiotensin converting enzyme inhibitor Ramipril
Circulation, 2001Co-Authors: James Mathew, Peter Sleight, Eva Lonn, David E Johnstone, Janice Pogue, Qilong Yi, Jackie Bosch, Bruce Sussex, Jeffrey L Probstfield, Salim YusufAbstract:Background Electrocardiographic markers of left ventricular hypertrophy (LVH) predict poor prognosis. We determined whether the ACE inhibitor Ramipril prevents the development and causes regression of ECG-LVH and whether these changes are associated with improved prognosis independent of blood pressure reduction. Methods and Results In the Heart Outcomes Prevention Evaluation (HOPE) study, patients at high risk were randomly assigned to Ramipril or placebo and followed for 4.5years. ECGs were recorded at baseline and at study end. We compared prevention/regression and development/persistence of ECG-LVH in the two groups and related these changes to outcomes. At baseline, 676 patients had LVH (321 in the Ramipril group and 355 in the placebo group) and 7605 patients did not have LVH (3814 in the Ramipril group and 3791 in the placebo group). By study end, 336 patients in the Ramipril group (8.1%) compared with 406 in the placebo group (9.8%) had development/persistence of LVH; in contrast, 3799 patients in...
A. Breitstadt - One of the best experts on this subject based on the ideXlab platform.
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Combination of Ramipril and hydrochlorothiazide in the treatment of mild to moderate hypertension: Part 1--A double-blind, comparative, multicenter study in nonresponders to Ramipril monotherapy.
Clinical cardiology, 1992Co-Authors: D. Heidbreder, K.‐l. Froer, V. Cairns, A. Breitstadt, N. Bender, A. LangleyAbstract:In a parallel-group multicenter study, the efficacy and safety of combination therapy with Ramipril 5 mg plus hydrochlorothiazide 25 mg were compared double-blind with those of 5 mg and 10 mg Ramipril monotherapy in patients with mild to moderate hypertension who had not responded adequately to Ramipril 5 mg alone. Patients were initially treated single-blind for 1 week with Ramipril 2.5 mg and 3 weeks with Ramipril 5 mg. Of 240 patients enrolled, 165 were subsequently classed as nonresponders (diastolic blood pressure > 90 mmHg) and were randomized to one of the three double-blind treatments for a further 4 weeks. In the double-blind phase, the mean reductions in supine systolic and diastolic blood pressures at end point were significantly greater in the 5 mg plus 25 mg combination group (11.6/10.6 mmHg) than in the groups receiving Ramipril 5 mg (6.2/5.9 mmHg; both p < 0.01) and Ramipril 10 mg (7.4/7.1 mmHg; both p < 0.05). The proportion of responders at end point was also higher for combination therapy (72%) than for monotherapy (48% for Ramipril 5 mg and 62% for Ramipril 10 mg). All three treatments were well tolerated. Analysis of laboratory values revealed no clinically important changes.
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Efficacy and safety of Ramipril in combination with hydrochlorothiazide: results of a long-term study.
Journal of Cardiovascular Pharmacology, 1991Co-Authors: D. Heidbreder, K.‐l. Froer, B. Bauer, V. Cairns, A. BreitstadtAbstract:Hypertensive patients from a double-blind study comparing 5 mg of Ramipril, 10 mg of Ramipril, and 5 mg of Ramipril+25 mg of hydrochlorothiazide (HCTZ) were enrolled in an open 1-year extension study with Ramipril and concomitant HCTZ. The starting dose of Ramipril was 5 mg/day. Patients were given 25 mg of HCTZ in addition only if their diastolic blood pressure (DBP) was higher than 90 mm Hg. During treatment, the investigator was permitted to adjust the dosage of Ramipril and HCTZ according to BP response and tolerance
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Efficacy and safety of Ramipril in combination with hydrochlorothiazide: results of a long-term study.
Journal of cardiovascular pharmacology, 1991Co-Authors: D. Heidbreder, K.‐l. Froer, B. Bauer, V. Cairns, A. BreitstadtAbstract:Hypertensive patients from a double-blind study comparing 5 mg of Ramipril, 10 mg of Ramipril, and 5 mg of Ramipril + 25 mg of hydrochlorothiazide (HCTZ) were enrolled in an open 1-year extension study with Ramipril and concomitant HCTZ. The starting dose of Ramipril was 5 mg/day. Patients were given 25 mg of HCTZ in addition only if their diastolic blood pressure (DBP) was higher than 90 mm Hg. During treatment, the investigator was permitted to adjust the dosage of Ramipril and HCTZ according to BP response and tolerance. A total of 159 patients were included in the 1-year study (86 men, 73 women, mean age of 54 years). One hundred twenty-one of the 159 patients received the combination of Ramipril + HCTZ at some point in the study, 83 of them for more than 50 weeks. Thirty-eight patients were treated with Ramipril alone over the entire study. In patients treated with Ramipril monotherapy throughout the study, the largest drop in blood pressure occurred before visit 1. In patients treated with Ramipril + HCTZ for greater than or equal to 50 weeks, the mean blood pressure continued to fall up to around week 10, while the therapy was being adjusted. Subsequently, the mean blood pressures remained low and fairly stable in both treatment groups. Similar results were seen in patients treated with the combination for less than 50 weeks. Adverse events were reported in 11 of the 38 patients in the Ramipril group, in 22 of 83 patients treated with the combination for more than 50 weeks, and in 9 of 38 patients treated with the combination for 50 weeks or less. The analysis of the laboratory values revealed no general deterioration. It can be concluded that Ramipril alone and in combination with HCTZ is an effective and safe drug for the long-term treatment of essential hypertension.
