The Experts below are selected from a list of 174 Experts worldwide ranked by ideXlab platform

Arno W. Hoes - One of the best experts on this subject based on the ideXlab platform.

  • Sudden Cardiac Death in Patients with Hypertension
    Drug Safety, 1997
    Co-Authors: Arno W. Hoes, Diederick E. Grobbee, Jacobus Lubsen
    Abstract:

    The cornerstones of current antihypertensive treatment are Diuretics and β-blockers and the efficacy of these drugs in preventing cardiovascular disease is undisputed. This article focuses on the effect of these 2 drug classes on the incidence of sudden death. Numerous studies have shown that thiazide Diuretics have a strong, dosagedependent potassium-depleting effect, and it has been postulated that this may explain why the reduction in risk of coronary heart disease, observed in hypertension trials, was less pronounced than expected. In 7 trials that included sudden death as an end-point, a pooled risk-ratio of sudden death of 1.5 (95% confidence interval 1.1 to 2.0) was observed when non-Potassium-Sparing Diuretics were compared with placebo. Two recent case-control studies have also strongly indicated that the use of thiazides increases the risk of sudden death. Evidence from trials using Potassium-Sparing Diuretic combinations suggests that these may be better tolerated than thiazide monotherapy. Although it was suggested in the 2 recent case-control studies that recipients of β-blockers are also at an increased risk of sudden death, further studies are required to confirm this finding, particularly since these drugs have several well-documented cardioprotective effects.

  • Diuretics and risk of sudden death in hypertension--evidence and potential implications.
    Clinical and experimental hypertension (New York N.Y. : 1993), 1996
    Co-Authors: Arno W. Hoes, Diederick E. Grobbee
    Abstract:

    Randomized trials have produced solid evidence that non Potassium-Sparing Diuretic therapy in hypertension is beneficial, but the controversy regarding the possibility that these drugs may increase the risk of sudden death in some patients continues. Although few sudden deaths were reported in the trials, findings indicate that an excess risk of sudden death in users of these Diuretics exists (pooled risk ratio 1.5; 95%CI 1.1-2.0). Two recent case-control studies provide consistent evidence that non Potassium-Sparing Diuretics are associated with a twofold risk of sudden death compared to Potassium-Sparing Diuretic therapy. It is estimated that among the 400,000 men and 1,000,000 women treated for hypertension in the Netherlands, such an excess risk would lead to respectively 96 and 34 cases of sudden death. We conclude that the available evidence strongly suggests that hypertensive patients on non Potassium-Sparing Diuretic therapy are at an increased risk of sudden death. Concomitant prescription of pot...

  • Non-Potassium-Sparing Diuretics and risk of sudden cardiac death.
    Journal of Hypertension, 1995
    Co-Authors: Diederick E. Grobbee, Arno W. Hoes
    Abstract:

    Objective : To review current evidence for a possible association between the use of non-Potassium-Sparing Diuretics and the risk of sudden cardiac death in hypertension. Methods : Examination of published randomized trials and recent case-control studies. Results : Numerous studies have shown that the administration of non-Potassium-Sparing Diuretics causes a dose-dependent decrease in serum potassium levels in hypertensive patients. Although largely circumstantial, some evidence implies that Diuretic-induced electrolyte depletion leading to arrhythmias may be the mechanism involved in the association between Diuretics and sudden death. Published randomized trials on the efficacy of non-Potassium-Sparing Diuretic therapy have consistently failed to show a reduction in the incidence of sudden cardiac death, while findings from hypertension trials including Potassium-Sparing Diuretic combinations demonstrated an impressive decrease in coronary events. Two similar, recent case-control studies, together comprising 371 cases of sudden cardiac death in patients taking drug treatment for hypertension, indicated that hypertensive patients who were prescribed non-Potassium-Sparing Diuretics had approximately double the risk of sudden cardiac death compared with users of Potassium-Sparing Diuretic therapy. Although treatment allocation in these studies is, by definition, non-random, adequate measures were taken to reduce sources of bias. Conclusions : Current evidence supports the hypothesis that Diuretic-induced potassium loss causes sudden cardiac death in some hypertensive patients. It seems prudent to use thiazide Diuretics at a low dose only. Adding a Potassium-Sparing Diuretic drug may further reduce the mortality risk.

  • Non-Potassium-Sparing Diuretics and risk of sudden cardiac death.
    Journal of hypertension, 1995
    Co-Authors: Diederick E. Grobbee, Arno W. Hoes
    Abstract:

    To review current evidence for a possible association between the use of non-Potassium-Sparing Diuretics and the risk of sudden cardiac death in hypertension. Examination of published randomized trials and recent case-control studies. Numerous studies have shown that the administration of non-Potassium-Sparing Diuretics causes a dose-dependent decrease in serum potassium levels in hypertensive patients. Although largely circumstantial, some evidence implies that Diuretic-induced electrolyte depletion leading to arrhythmias may be the mechanism involved in the association between Diuretics and sudden death. Published randomized trials on the efficacy of non-Potassium-Sparing Diuretic therapy have consistently failed to show a reduction in the incidence of sudden cardiac death, while findings from hypertension trials including Potassium-Sparing Diuretic combinations demonstrated an impressive decrease in coronary events. Two similar, recent case-control studies, together comprising 371 cases of sudden cardiac death in patients taking drug treatment for hypertension, indicated that hypertensive patients who were prescribed non-Potassium-Sparing Diuretics had approximately double the risk of sudden cardiac death compared with users of Potassium-Sparing Diuretic therapy. Although treatment allocation in these studies is, by definition, non-random, adequate measures were taken to reduce sources of bias. Current evidence supports the hypothesis that Diuretic-induced potassium loss causes sudden cardiac death in some hypertensive patients. It seems prudent to use thiazide Diuretics at a low dose only. Adding a Potassium-Sparing Diuretic drug may further reduce the mortality risk.

Diederick E. Grobbee - One of the best experts on this subject based on the ideXlab platform.

  • Sudden Cardiac Death in Patients with Hypertension
    Drug Safety, 1997
    Co-Authors: Arno W. Hoes, Diederick E. Grobbee, Jacobus Lubsen
    Abstract:

    The cornerstones of current antihypertensive treatment are Diuretics and β-blockers and the efficacy of these drugs in preventing cardiovascular disease is undisputed. This article focuses on the effect of these 2 drug classes on the incidence of sudden death. Numerous studies have shown that thiazide Diuretics have a strong, dosagedependent potassium-depleting effect, and it has been postulated that this may explain why the reduction in risk of coronary heart disease, observed in hypertension trials, was less pronounced than expected. In 7 trials that included sudden death as an end-point, a pooled risk-ratio of sudden death of 1.5 (95% confidence interval 1.1 to 2.0) was observed when non-Potassium-Sparing Diuretics were compared with placebo. Two recent case-control studies have also strongly indicated that the use of thiazides increases the risk of sudden death. Evidence from trials using Potassium-Sparing Diuretic combinations suggests that these may be better tolerated than thiazide monotherapy. Although it was suggested in the 2 recent case-control studies that recipients of β-blockers are also at an increased risk of sudden death, further studies are required to confirm this finding, particularly since these drugs have several well-documented cardioprotective effects.

  • Diuretics and risk of sudden death in hypertension--evidence and potential implications.
    Clinical and experimental hypertension (New York N.Y. : 1993), 1996
    Co-Authors: Arno W. Hoes, Diederick E. Grobbee
    Abstract:

    Randomized trials have produced solid evidence that non Potassium-Sparing Diuretic therapy in hypertension is beneficial, but the controversy regarding the possibility that these drugs may increase the risk of sudden death in some patients continues. Although few sudden deaths were reported in the trials, findings indicate that an excess risk of sudden death in users of these Diuretics exists (pooled risk ratio 1.5; 95%CI 1.1-2.0). Two recent case-control studies provide consistent evidence that non Potassium-Sparing Diuretics are associated with a twofold risk of sudden death compared to Potassium-Sparing Diuretic therapy. It is estimated that among the 400,000 men and 1,000,000 women treated for hypertension in the Netherlands, such an excess risk would lead to respectively 96 and 34 cases of sudden death. We conclude that the available evidence strongly suggests that hypertensive patients on non Potassium-Sparing Diuretic therapy are at an increased risk of sudden death. Concomitant prescription of pot...

  • Non-Potassium-Sparing Diuretics and risk of sudden cardiac death.
    Journal of Hypertension, 1995
    Co-Authors: Diederick E. Grobbee, Arno W. Hoes
    Abstract:

    Objective : To review current evidence for a possible association between the use of non-Potassium-Sparing Diuretics and the risk of sudden cardiac death in hypertension. Methods : Examination of published randomized trials and recent case-control studies. Results : Numerous studies have shown that the administration of non-Potassium-Sparing Diuretics causes a dose-dependent decrease in serum potassium levels in hypertensive patients. Although largely circumstantial, some evidence implies that Diuretic-induced electrolyte depletion leading to arrhythmias may be the mechanism involved in the association between Diuretics and sudden death. Published randomized trials on the efficacy of non-Potassium-Sparing Diuretic therapy have consistently failed to show a reduction in the incidence of sudden cardiac death, while findings from hypertension trials including Potassium-Sparing Diuretic combinations demonstrated an impressive decrease in coronary events. Two similar, recent case-control studies, together comprising 371 cases of sudden cardiac death in patients taking drug treatment for hypertension, indicated that hypertensive patients who were prescribed non-Potassium-Sparing Diuretics had approximately double the risk of sudden cardiac death compared with users of Potassium-Sparing Diuretic therapy. Although treatment allocation in these studies is, by definition, non-random, adequate measures were taken to reduce sources of bias. Conclusions : Current evidence supports the hypothesis that Diuretic-induced potassium loss causes sudden cardiac death in some hypertensive patients. It seems prudent to use thiazide Diuretics at a low dose only. Adding a Potassium-Sparing Diuretic drug may further reduce the mortality risk.

  • Non-Potassium-Sparing Diuretics and risk of sudden cardiac death.
    Journal of hypertension, 1995
    Co-Authors: Diederick E. Grobbee, Arno W. Hoes
    Abstract:

    To review current evidence for a possible association between the use of non-Potassium-Sparing Diuretics and the risk of sudden cardiac death in hypertension. Examination of published randomized trials and recent case-control studies. Numerous studies have shown that the administration of non-Potassium-Sparing Diuretics causes a dose-dependent decrease in serum potassium levels in hypertensive patients. Although largely circumstantial, some evidence implies that Diuretic-induced electrolyte depletion leading to arrhythmias may be the mechanism involved in the association between Diuretics and sudden death. Published randomized trials on the efficacy of non-Potassium-Sparing Diuretic therapy have consistently failed to show a reduction in the incidence of sudden cardiac death, while findings from hypertension trials including Potassium-Sparing Diuretic combinations demonstrated an impressive decrease in coronary events. Two similar, recent case-control studies, together comprising 371 cases of sudden cardiac death in patients taking drug treatment for hypertension, indicated that hypertensive patients who were prescribed non-Potassium-Sparing Diuretics had approximately double the risk of sudden cardiac death compared with users of Potassium-Sparing Diuretic therapy. Although treatment allocation in these studies is, by definition, non-random, adequate measures were taken to reduce sources of bias. Current evidence supports the hypothesis that Diuretic-induced potassium loss causes sudden cardiac death in some hypertensive patients. It seems prudent to use thiazide Diuretics at a low dose only. Adding a Potassium-Sparing Diuretic drug may further reduce the mortality risk.

Darren C. Johnson - One of the best experts on this subject based on the ideXlab platform.

  • 6-Substituted Hexamethylene Amiloride (HMA) Derivatives as Potent and Selective Inhibitors of the Human Urokinase Plasminogen Activator for Use in Cancer.
    Journal of medicinal chemistry, 2018
    Co-Authors: Benjamin J. Buckley, Ashraf Abdel A Aboelela, Elahe Minaei, Longguang Jiang, Umar Ali, Karen Fildes, Chen-yi Cheung, Simon M. Cook, Darren C. Johnson
    Abstract:

    Metastasis is the cause of death in the majority (∼90%) of malignant cancers. The oral Potassium-Sparing Diuretic amiloride and its 5-substituted derivative 5-N,N-(hexamethylene)amiloride (HMA) rep...

  • 6‑Substituted Hexamethylene Amiloride (HMA) Derivatives as Potent and Selective Inhibitors of the Human Urokinase Plasminogen Activator for Use in Cancer
    2018
    Co-Authors: Benjamin J. Buckley, Elahe Minaei, Umar Ali, Karen Fildes, Chen-yi Cheung, Simon M. Cook, Ashraf Aboelela, Longguang X. Jiang, Darren C. Johnson
    Abstract:

    Metastasis is the cause of death in the majority (∼90%) of malignant cancers. The oral Potassium-Sparing Diuretic amiloride and its 5-substituted derivative 5-N,N-(hexamethylene)­amiloride (HMA) reportedly show robust antitumor/metastasis effects in multiple in vitro and animal models. These effects are likely due, at least in part, to inhibition of the urokinase plasminogen activator (uPA), a key protease determinant of cell invasiveness and metastasis. This study reports the discovery of 6-substituted HMA analogs that show nanomolar potency against uPA, high selectivity over related trypsin-like serine proteases, and minimal inhibitory effects against epithelial sodium channels (ENaC), the Diuretic and antikaliuretic target of amiloride. Reductions in lung metastases were demonstrated for two analogs in a late-stage experimental mouse metastasis model, and one analog completely inhibited formation of liver metastases in an orthotopic xenograft mouse model of pancreatic cancer. The results support further evaluation of 6-substituted HMA derivatives as uPA-targeting anticancer drugs

Jacobus Lubsen - One of the best experts on this subject based on the ideXlab platform.

  • Sudden Cardiac Death in Patients with Hypertension
    Drug Safety, 1997
    Co-Authors: Arno W. Hoes, Diederick E. Grobbee, Jacobus Lubsen
    Abstract:

    The cornerstones of current antihypertensive treatment are Diuretics and β-blockers and the efficacy of these drugs in preventing cardiovascular disease is undisputed. This article focuses on the effect of these 2 drug classes on the incidence of sudden death. Numerous studies have shown that thiazide Diuretics have a strong, dosagedependent potassium-depleting effect, and it has been postulated that this may explain why the reduction in risk of coronary heart disease, observed in hypertension trials, was less pronounced than expected. In 7 trials that included sudden death as an end-point, a pooled risk-ratio of sudden death of 1.5 (95% confidence interval 1.1 to 2.0) was observed when non-Potassium-Sparing Diuretics were compared with placebo. Two recent case-control studies have also strongly indicated that the use of thiazides increases the risk of sudden death. Evidence from trials using Potassium-Sparing Diuretic combinations suggests that these may be better tolerated than thiazide monotherapy. Although it was suggested in the 2 recent case-control studies that recipients of β-blockers are also at an increased risk of sudden death, further studies are required to confirm this finding, particularly since these drugs have several well-documented cardioprotective effects.

Benjamin J. Buckley - One of the best experts on this subject based on the ideXlab platform.