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COVID-19: U.S. cardiology groups reaffirm continued use of RAAS-active drugs
Controversy continued over the potential effect of drugs that interfere with the renin-angiotensin-aldosterone system via the angiotensin-converting enzymes (ACE) may have on exacerbating infection with the SARS-CoV-2 virus that causes COVID-19.
A joint statement from the American Heart Association, American College of Cardiology, and the Heart Failure Society of America on March 17 gave full, unqualified support to maintaining patients on drugs that work this way, specifically the ACE inhibitors and angiotensin-receptor blockers (ARBs), which together form a long-standing cornerstone of treatment for hypertension, heart failure, and ischemic heart disease.
The three societies “recommend continuation” of ACE inhibitors or ARBs “for all patients already prescribed.” The statement went on to say that patients already diagnosed with a COVID-19 infection “should be fully evaluated before adding or removing any treatments, and any changes to their treatment should be based on the latest scientific evidence and shared decision making with their physician and health care team.”
“We understand the concern – as it has become clear that people with cardiovascular disease are at much higher risk of serious complications including death from COVID-19. However, we have reviewed the latest research – the evidence does not confirm the need to discontinue ACE inhibitors or ARBs, and we strongly recommend all physicians to consider the individual needs of each patient before making any changes to ACE-inhibitor or ARB treatment regimens,” said Robert A. Harrington, MD, president of the American Heart Association and professor and chair of medicine at Stanford (Calif.) University, in the statement.
“There are no experimental or clinical data demonstrating beneficial or adverse outcomes among COVID-19 patients using ACE-inhibitor or ARB medications,” added Richard J. Kovacs, MD, president of the American College of Cardiology and professor of cardiology at Indiana University in Indianapolis.
The “latest research” referred to in the statement likely focuses on a report that had appeared less than a week earlier in a British journal that hypothesized a possible increase in the susceptibility of human epithelial cells of the lungs, intestine, kidneys, and blood vessels exposed to these or certain other drugs, like the thiazolidinedione oral diabetes drugs or ibuprofen, because they cause up-regulation of the ACE2 protein in cell membranes, and ACE2 is the primary cell-surface receptor that allows the SARS-CoV-2 virus to enter.
“We therefore hypothesize that diabetes and hypertension treatment with ACE2-stimulating drugs increases the risk of developing severe and fatal COVID-19,” wrote Michael Roth, MD, and his associates in their recent article (Lancet Resp Med. 2020 Mar 11. doi: 10.1016/S2213-2600[20]30116-8). While the potential clinical impact of an increase in the number of ACE2 molecules in a cell’s surface membrane remains uninvestigated, the risk this phenomenon poses should mean that patients taking these drugs should receive heightened monitoring for COVID-19 disease, suggested Dr. Roth, a professor of biomedicine who specializes in studying inflammatory lung diseases including asthma, and associates.
However, others who have considered the impact that ACE inhibitors and ARBs might have on ACE2 and COVID-19 infections have noted that the picture is not simple. “Higher ACE2 expression following chronically medicating SARS‐CoV‐2 infected patients with AT1R [angiotensin receptor 1] blockers, while seemingly paradoxical, may protect them against acute lung injury rather than putting them at higher risk to develop SARS. This may be accounted for by two complementary mechanisms: blocking the excessive angiotensin‐mediated AT1R activation caused by the viral infection, as well as up-regulating ACE2, thereby reducing angiotensin production by ACE and increasing the production” of a vasodilating form of angiotensin, wrote David Gurwitz, PhD, in a recently published editorial (Drug Dev Res. 2020 Mar 4. doi: 10.1002/ddr.21656). A data-mining approach may allow researchers to determine whether patients who received drugs that interfere with angiotensin 1 function prior to being diagnosed with a COVID-19 infection had a better disease outcome, suggested Dr. Gurwitz, a molecular geneticist at Tel Aviv University in Jerusalem.
The statement from the three U.S. cardiology societies came a few days following a similar statement of support for ongoing use of ACE inhibitors and ARBs from the European Society of Cardiology’s Council on Hypertension.
Dr. Harrington, Dr. Kovacs, Dr. Roth, and Dr. Gurwitz had no relevant disclosures.
Controversy continued over the potential effect of drugs that interfere with the renin-angiotensin-aldosterone system via the angiotensin-converting enzymes (ACE) may have on exacerbating infection with the SARS-CoV-2 virus that causes COVID-19.
A joint statement from the American Heart Association, American College of Cardiology, and the Heart Failure Society of America on March 17 gave full, unqualified support to maintaining patients on drugs that work this way, specifically the ACE inhibitors and angiotensin-receptor blockers (ARBs), which together form a long-standing cornerstone of treatment for hypertension, heart failure, and ischemic heart disease.
The three societies “recommend continuation” of ACE inhibitors or ARBs “for all patients already prescribed.” The statement went on to say that patients already diagnosed with a COVID-19 infection “should be fully evaluated before adding or removing any treatments, and any changes to their treatment should be based on the latest scientific evidence and shared decision making with their physician and health care team.”
“We understand the concern – as it has become clear that people with cardiovascular disease are at much higher risk of serious complications including death from COVID-19. However, we have reviewed the latest research – the evidence does not confirm the need to discontinue ACE inhibitors or ARBs, and we strongly recommend all physicians to consider the individual needs of each patient before making any changes to ACE-inhibitor or ARB treatment regimens,” said Robert A. Harrington, MD, president of the American Heart Association and professor and chair of medicine at Stanford (Calif.) University, in the statement.
“There are no experimental or clinical data demonstrating beneficial or adverse outcomes among COVID-19 patients using ACE-inhibitor or ARB medications,” added Richard J. Kovacs, MD, president of the American College of Cardiology and professor of cardiology at Indiana University in Indianapolis.
The “latest research” referred to in the statement likely focuses on a report that had appeared less than a week earlier in a British journal that hypothesized a possible increase in the susceptibility of human epithelial cells of the lungs, intestine, kidneys, and blood vessels exposed to these or certain other drugs, like the thiazolidinedione oral diabetes drugs or ibuprofen, because they cause up-regulation of the ACE2 protein in cell membranes, and ACE2 is the primary cell-surface receptor that allows the SARS-CoV-2 virus to enter.
“We therefore hypothesize that diabetes and hypertension treatment with ACE2-stimulating drugs increases the risk of developing severe and fatal COVID-19,” wrote Michael Roth, MD, and his associates in their recent article (Lancet Resp Med. 2020 Mar 11. doi: 10.1016/S2213-2600[20]30116-8). While the potential clinical impact of an increase in the number of ACE2 molecules in a cell’s surface membrane remains uninvestigated, the risk this phenomenon poses should mean that patients taking these drugs should receive heightened monitoring for COVID-19 disease, suggested Dr. Roth, a professor of biomedicine who specializes in studying inflammatory lung diseases including asthma, and associates.
However, others who have considered the impact that ACE inhibitors and ARBs might have on ACE2 and COVID-19 infections have noted that the picture is not simple. “Higher ACE2 expression following chronically medicating SARS‐CoV‐2 infected patients with AT1R [angiotensin receptor 1] blockers, while seemingly paradoxical, may protect them against acute lung injury rather than putting them at higher risk to develop SARS. This may be accounted for by two complementary mechanisms: blocking the excessive angiotensin‐mediated AT1R activation caused by the viral infection, as well as up-regulating ACE2, thereby reducing angiotensin production by ACE and increasing the production” of a vasodilating form of angiotensin, wrote David Gurwitz, PhD, in a recently published editorial (Drug Dev Res. 2020 Mar 4. doi: 10.1002/ddr.21656). A data-mining approach may allow researchers to determine whether patients who received drugs that interfere with angiotensin 1 function prior to being diagnosed with a COVID-19 infection had a better disease outcome, suggested Dr. Gurwitz, a molecular geneticist at Tel Aviv University in Jerusalem.
The statement from the three U.S. cardiology societies came a few days following a similar statement of support for ongoing use of ACE inhibitors and ARBs from the European Society of Cardiology’s Council on Hypertension.
Dr. Harrington, Dr. Kovacs, Dr. Roth, and Dr. Gurwitz had no relevant disclosures.
Controversy continued over the potential effect of drugs that interfere with the renin-angiotensin-aldosterone system via the angiotensin-converting enzymes (ACE) may have on exacerbating infection with the SARS-CoV-2 virus that causes COVID-19.
A joint statement from the American Heart Association, American College of Cardiology, and the Heart Failure Society of America on March 17 gave full, unqualified support to maintaining patients on drugs that work this way, specifically the ACE inhibitors and angiotensin-receptor blockers (ARBs), which together form a long-standing cornerstone of treatment for hypertension, heart failure, and ischemic heart disease.
The three societies “recommend continuation” of ACE inhibitors or ARBs “for all patients already prescribed.” The statement went on to say that patients already diagnosed with a COVID-19 infection “should be fully evaluated before adding or removing any treatments, and any changes to their treatment should be based on the latest scientific evidence and shared decision making with their physician and health care team.”
“We understand the concern – as it has become clear that people with cardiovascular disease are at much higher risk of serious complications including death from COVID-19. However, we have reviewed the latest research – the evidence does not confirm the need to discontinue ACE inhibitors or ARBs, and we strongly recommend all physicians to consider the individual needs of each patient before making any changes to ACE-inhibitor or ARB treatment regimens,” said Robert A. Harrington, MD, president of the American Heart Association and professor and chair of medicine at Stanford (Calif.) University, in the statement.
“There are no experimental or clinical data demonstrating beneficial or adverse outcomes among COVID-19 patients using ACE-inhibitor or ARB medications,” added Richard J. Kovacs, MD, president of the American College of Cardiology and professor of cardiology at Indiana University in Indianapolis.
The “latest research” referred to in the statement likely focuses on a report that had appeared less than a week earlier in a British journal that hypothesized a possible increase in the susceptibility of human epithelial cells of the lungs, intestine, kidneys, and blood vessels exposed to these or certain other drugs, like the thiazolidinedione oral diabetes drugs or ibuprofen, because they cause up-regulation of the ACE2 protein in cell membranes, and ACE2 is the primary cell-surface receptor that allows the SARS-CoV-2 virus to enter.
“We therefore hypothesize that diabetes and hypertension treatment with ACE2-stimulating drugs increases the risk of developing severe and fatal COVID-19,” wrote Michael Roth, MD, and his associates in their recent article (Lancet Resp Med. 2020 Mar 11. doi: 10.1016/S2213-2600[20]30116-8). While the potential clinical impact of an increase in the number of ACE2 molecules in a cell’s surface membrane remains uninvestigated, the risk this phenomenon poses should mean that patients taking these drugs should receive heightened monitoring for COVID-19 disease, suggested Dr. Roth, a professor of biomedicine who specializes in studying inflammatory lung diseases including asthma, and associates.
However, others who have considered the impact that ACE inhibitors and ARBs might have on ACE2 and COVID-19 infections have noted that the picture is not simple. “Higher ACE2 expression following chronically medicating SARS‐CoV‐2 infected patients with AT1R [angiotensin receptor 1] blockers, while seemingly paradoxical, may protect them against acute lung injury rather than putting them at higher risk to develop SARS. This may be accounted for by two complementary mechanisms: blocking the excessive angiotensin‐mediated AT1R activation caused by the viral infection, as well as up-regulating ACE2, thereby reducing angiotensin production by ACE and increasing the production” of a vasodilating form of angiotensin, wrote David Gurwitz, PhD, in a recently published editorial (Drug Dev Res. 2020 Mar 4. doi: 10.1002/ddr.21656). A data-mining approach may allow researchers to determine whether patients who received drugs that interfere with angiotensin 1 function prior to being diagnosed with a COVID-19 infection had a better disease outcome, suggested Dr. Gurwitz, a molecular geneticist at Tel Aviv University in Jerusalem.
The statement from the three U.S. cardiology societies came a few days following a similar statement of support for ongoing use of ACE inhibitors and ARBs from the European Society of Cardiology’s Council on Hypertension.
Dr. Harrington, Dr. Kovacs, Dr. Roth, and Dr. Gurwitz had no relevant disclosures.
PARAGON-HF: Optimal systolic pressure in HFpEF is 120-129 mm Hg
A target systolic blood pressure (SBP) of 120-129 mm Hg in patients with heart failure with preserved ejection fraction proved to be the sweet spot with the lowest rates of major adverse cardiovascular and renal events in a new analysis from the landmark PARAGON-HF trial.
This finding from the largest-ever randomized, controlled study in heart failure with preserved ejection fraction (HFpEF) strengthens support for current U.S. joint hypertension guidelines, which call for a target SBP less than 130 mm Hg in patients with HFpEF (J Am Coll Cardiol. 2017 Aug 8;70[6]:776-803), a recommendation based upon weak evidence until now. That’s because the SPRINT trial, the major impetus for adoption of intensive blood pressure control in the current guidelines, excluded patients with symptomatic HF, Scott D. Solomon, MD, and coinvestigators noted in their new analysis. The study was published in the Journal of the American College of Cardiology and had been planned for presentation during the joint scientific sessions of the American College of Cardiology and the World Heart Federation. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.
The new analysis from PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HFpEF) also ruled out the SBP-lowering effect of sacubitril/valsartan (Entresto) as the explanation for the combination drug’s demonstrated beneficial impact on outcomes in the subgroup with an SBP of 120-129 mm Hg. That wasn’t actually a surprise. Indeed, the new study had two hypotheses: one, that the relationship between SBP and cardiovascular and renal outcomes in HFpEF would follow a J-shaped curve, and two, that sacubitril/valsartan’s blood pressure–lowering effect would not account for the drug’s outcome benefits in the subset of HFpEF patients with an SBP in the sweet spot of 120-129 mm Hg. Both hypotheses were borne out, noted Dr. Solomon, professor of medicine at Harvard Medical School and director of noninvasive cardiology at Brigham and Women’s Hospital, both in Boston.
“These data strongly support that additional mechanisms other than blood pressure–lowering account for the benefit. But this is not surprising. The same can be said for most of the therapies that work in heart failure,” he said in an interview.
Take, for example, spironolactone. In TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist), another major trial in which Dr. Solomon played a leadership role, the beneficial effect of spironolactone on clinical outcomes also proved unrelated to the drug’s blood pressure–lowering effect.
Other known effects of sacubitril/valsartan, a novel angiotensin receptor–neprilysin inhibitor, or ARNI, might in theory account for the observed clinical benefits in ARNI-treated patients with an on-treatment SBP of 120-129 mm Hg in PARAGON-HF. These include improved left atrial remodeling, an increase in natriuretic peptides, and improved myocardial relaxation. However, the current lack of understanding of the basic mechanistic processes underlying the varied clinical expressions of HFpEF is a major factor contributing to the lack of any proven-effective therapy for this extremely common and costly disorder, according to Dr. Solomon and coinvestigators.
In contrast to HFpEF, for which to date there is no proven treatment, heart failure with reduced ejection fraction sacubitril/valsartan has a class I recommendation on the strength of its performance in significantly reducing cardiovascular deaths and heart failure hospitalizations in the PARADIGM-HF trial (N Engl J Med. 2014 Sep 11;371:993-1004).
PARAGON-HF included 4,822 patients with symptomatic HFpEF who were randomized to sacubitril/valsartan at 97/103 mg b.i.d. or valsartan at 160 mg b.i.d. As previously reported (N Engl J Med. 2019 Oct 24;381[17]:1609-20), at an average follow-up of 35 months, the primary outcome – a composite of total hospitalizations for heart failure and cardiovascular death – occurred at a rate of 12.8 events per 100 patient-years in the sacubitril/valsartan group and 14.6 per 100 patient-years in the valsartan arm, for a 13% relative risk reduction that narrowly missed statistical significance (P = .059).
However, sacubitril/valsartan showed significant benefit on some prespecified secondary endpoints, including worsening renal function, change in New York Heart Association class, and quality of life. Women, who notably accounted for 52% of study participants, appeared to benefit from sacubitril/valsartan more than men as evidenced by their 27% relative risk reduction in the primary endpoint. Also, in the roughly half of PARAGON-HF participants with a baseline left ventricular ejection fraction of 45%-57%, treatment with sacubitril/valsartan resulted in a statistically significant 22% relative risk reduction in the primary endpoint, compared with valsartan alone.
SBP and cardiovascular outcomes in HFpEF
In the new analysis, Dr. Solomon and coworkers examined outcomes based on baseline and mean achieved SBP quartiles regardless of treatment arm. In an unadjusted analysis, the primary composite endpoint occurred at a rate of 15.2 events/100 patient-years in HFpEF patients with an achieved SBP below 120 mm Hg, 11.4/100 patient-years at 120-129 mm Hg, 12.2/100 patient-years at 130-139 mm Hg, and 15.6/100 patient-years at 140 mm Hg or more. Further, in a multivariate regression analysis extensively adjusted for atrial fibrillation, sex, race, and numerous other potential confounders, the group with an achieved SBP of 120-129 mm Hg continued to fare best. The adjusted risks for the primary endpoint were 11% and 21% higher in patients in the first and third quartiles of achieved SBP, compared with those at 120-129 mm Hg, although neither trend reached statistical significance. But patients in the top quartile, with an achieved SBP of 140 mm Hg or more, had a highly significant 56% increase in risk, compared with patients in the second-lowest SBP quartile.
Change in blood pressure from baseline to week 48 had no impact on quality of life or high-sensitivity troponin T. However, each 10–mm Hg lowering of SBP was associated with a modest 2.1% reduction in log-transformed N-terminal of the prohormone brain natriuretic peptide.
Sacubitril/valsartan reduced SBP by an average of 5.2 mm Hg more than valsartan alone at 4 weeks regardless of baseline SBP. And the combo drug had a significantly greater SBP-lowering effect in women than men, by a margin of 6.3 mm Hg versus 4.0 mm Hg. But a Cox regression analysis showed that in women, as in the study population as a whole, sacubitril/valsartan’s SBP-lowering effects didn’t account for the drug’s impact on outcomes.
In an editorial accompanying publication of the new PARAGON-HF blood pressure analysis (J Am Coll Cardiol. 2020 Mar 16. doi: 10.1016/j.jacc.2020.02.024), Hector O. Ventura, MD, and colleagues at the Ochsner Clinic in New Orleans observed that the study results “lend some credence to the prognostic relationship of blood pressure in HFpEF, but whether they should serve as a therapeutic target or are merely a prognostic surrogate determined by other pathogenic factors, such as vascular ventricular uncoupling or aortic stiffness on one hand when blood pressure is greater than 140 mm Hg, or a reduced cardiac performance indicated by reduced blood pressure to less than 120 mm Hg, remains uncertain.”
“What is certain, however, is that the relationship and contributions of hypertension in manifest HFpEF are complex, multifactorial and likely go well beyond a simplistic framework of hemodynamic influences,” they added.
Dr. Solomon has received research grants from and serves as a consultant to Novartis, which funded PARAGON-HF, and has similar financial relationships with more than a dozen other pharmaceutical companies. Dr. Ventura reported having no relevant financial interests.
SOURCE: Solomon SD et al. J Am Coll Cardiol. 2020 Mar 16. doi: 10.1016/j.jacc.2020.02.009.
A target systolic blood pressure (SBP) of 120-129 mm Hg in patients with heart failure with preserved ejection fraction proved to be the sweet spot with the lowest rates of major adverse cardiovascular and renal events in a new analysis from the landmark PARAGON-HF trial.
This finding from the largest-ever randomized, controlled study in heart failure with preserved ejection fraction (HFpEF) strengthens support for current U.S. joint hypertension guidelines, which call for a target SBP less than 130 mm Hg in patients with HFpEF (J Am Coll Cardiol. 2017 Aug 8;70[6]:776-803), a recommendation based upon weak evidence until now. That’s because the SPRINT trial, the major impetus for adoption of intensive blood pressure control in the current guidelines, excluded patients with symptomatic HF, Scott D. Solomon, MD, and coinvestigators noted in their new analysis. The study was published in the Journal of the American College of Cardiology and had been planned for presentation during the joint scientific sessions of the American College of Cardiology and the World Heart Federation. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.
The new analysis from PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HFpEF) also ruled out the SBP-lowering effect of sacubitril/valsartan (Entresto) as the explanation for the combination drug’s demonstrated beneficial impact on outcomes in the subgroup with an SBP of 120-129 mm Hg. That wasn’t actually a surprise. Indeed, the new study had two hypotheses: one, that the relationship between SBP and cardiovascular and renal outcomes in HFpEF would follow a J-shaped curve, and two, that sacubitril/valsartan’s blood pressure–lowering effect would not account for the drug’s outcome benefits in the subset of HFpEF patients with an SBP in the sweet spot of 120-129 mm Hg. Both hypotheses were borne out, noted Dr. Solomon, professor of medicine at Harvard Medical School and director of noninvasive cardiology at Brigham and Women’s Hospital, both in Boston.
“These data strongly support that additional mechanisms other than blood pressure–lowering account for the benefit. But this is not surprising. The same can be said for most of the therapies that work in heart failure,” he said in an interview.
Take, for example, spironolactone. In TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist), another major trial in which Dr. Solomon played a leadership role, the beneficial effect of spironolactone on clinical outcomes also proved unrelated to the drug’s blood pressure–lowering effect.
Other known effects of sacubitril/valsartan, a novel angiotensin receptor–neprilysin inhibitor, or ARNI, might in theory account for the observed clinical benefits in ARNI-treated patients with an on-treatment SBP of 120-129 mm Hg in PARAGON-HF. These include improved left atrial remodeling, an increase in natriuretic peptides, and improved myocardial relaxation. However, the current lack of understanding of the basic mechanistic processes underlying the varied clinical expressions of HFpEF is a major factor contributing to the lack of any proven-effective therapy for this extremely common and costly disorder, according to Dr. Solomon and coinvestigators.
In contrast to HFpEF, for which to date there is no proven treatment, heart failure with reduced ejection fraction sacubitril/valsartan has a class I recommendation on the strength of its performance in significantly reducing cardiovascular deaths and heart failure hospitalizations in the PARADIGM-HF trial (N Engl J Med. 2014 Sep 11;371:993-1004).
PARAGON-HF included 4,822 patients with symptomatic HFpEF who were randomized to sacubitril/valsartan at 97/103 mg b.i.d. or valsartan at 160 mg b.i.d. As previously reported (N Engl J Med. 2019 Oct 24;381[17]:1609-20), at an average follow-up of 35 months, the primary outcome – a composite of total hospitalizations for heart failure and cardiovascular death – occurred at a rate of 12.8 events per 100 patient-years in the sacubitril/valsartan group and 14.6 per 100 patient-years in the valsartan arm, for a 13% relative risk reduction that narrowly missed statistical significance (P = .059).
However, sacubitril/valsartan showed significant benefit on some prespecified secondary endpoints, including worsening renal function, change in New York Heart Association class, and quality of life. Women, who notably accounted for 52% of study participants, appeared to benefit from sacubitril/valsartan more than men as evidenced by their 27% relative risk reduction in the primary endpoint. Also, in the roughly half of PARAGON-HF participants with a baseline left ventricular ejection fraction of 45%-57%, treatment with sacubitril/valsartan resulted in a statistically significant 22% relative risk reduction in the primary endpoint, compared with valsartan alone.
SBP and cardiovascular outcomes in HFpEF
In the new analysis, Dr. Solomon and coworkers examined outcomes based on baseline and mean achieved SBP quartiles regardless of treatment arm. In an unadjusted analysis, the primary composite endpoint occurred at a rate of 15.2 events/100 patient-years in HFpEF patients with an achieved SBP below 120 mm Hg, 11.4/100 patient-years at 120-129 mm Hg, 12.2/100 patient-years at 130-139 mm Hg, and 15.6/100 patient-years at 140 mm Hg or more. Further, in a multivariate regression analysis extensively adjusted for atrial fibrillation, sex, race, and numerous other potential confounders, the group with an achieved SBP of 120-129 mm Hg continued to fare best. The adjusted risks for the primary endpoint were 11% and 21% higher in patients in the first and third quartiles of achieved SBP, compared with those at 120-129 mm Hg, although neither trend reached statistical significance. But patients in the top quartile, with an achieved SBP of 140 mm Hg or more, had a highly significant 56% increase in risk, compared with patients in the second-lowest SBP quartile.
Change in blood pressure from baseline to week 48 had no impact on quality of life or high-sensitivity troponin T. However, each 10–mm Hg lowering of SBP was associated with a modest 2.1% reduction in log-transformed N-terminal of the prohormone brain natriuretic peptide.
Sacubitril/valsartan reduced SBP by an average of 5.2 mm Hg more than valsartan alone at 4 weeks regardless of baseline SBP. And the combo drug had a significantly greater SBP-lowering effect in women than men, by a margin of 6.3 mm Hg versus 4.0 mm Hg. But a Cox regression analysis showed that in women, as in the study population as a whole, sacubitril/valsartan’s SBP-lowering effects didn’t account for the drug’s impact on outcomes.
In an editorial accompanying publication of the new PARAGON-HF blood pressure analysis (J Am Coll Cardiol. 2020 Mar 16. doi: 10.1016/j.jacc.2020.02.024), Hector O. Ventura, MD, and colleagues at the Ochsner Clinic in New Orleans observed that the study results “lend some credence to the prognostic relationship of blood pressure in HFpEF, but whether they should serve as a therapeutic target or are merely a prognostic surrogate determined by other pathogenic factors, such as vascular ventricular uncoupling or aortic stiffness on one hand when blood pressure is greater than 140 mm Hg, or a reduced cardiac performance indicated by reduced blood pressure to less than 120 mm Hg, remains uncertain.”
“What is certain, however, is that the relationship and contributions of hypertension in manifest HFpEF are complex, multifactorial and likely go well beyond a simplistic framework of hemodynamic influences,” they added.
Dr. Solomon has received research grants from and serves as a consultant to Novartis, which funded PARAGON-HF, and has similar financial relationships with more than a dozen other pharmaceutical companies. Dr. Ventura reported having no relevant financial interests.
SOURCE: Solomon SD et al. J Am Coll Cardiol. 2020 Mar 16. doi: 10.1016/j.jacc.2020.02.009.
A target systolic blood pressure (SBP) of 120-129 mm Hg in patients with heart failure with preserved ejection fraction proved to be the sweet spot with the lowest rates of major adverse cardiovascular and renal events in a new analysis from the landmark PARAGON-HF trial.
This finding from the largest-ever randomized, controlled study in heart failure with preserved ejection fraction (HFpEF) strengthens support for current U.S. joint hypertension guidelines, which call for a target SBP less than 130 mm Hg in patients with HFpEF (J Am Coll Cardiol. 2017 Aug 8;70[6]:776-803), a recommendation based upon weak evidence until now. That’s because the SPRINT trial, the major impetus for adoption of intensive blood pressure control in the current guidelines, excluded patients with symptomatic HF, Scott D. Solomon, MD, and coinvestigators noted in their new analysis. The study was published in the Journal of the American College of Cardiology and had been planned for presentation during the joint scientific sessions of the American College of Cardiology and the World Heart Federation. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.
The new analysis from PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HFpEF) also ruled out the SBP-lowering effect of sacubitril/valsartan (Entresto) as the explanation for the combination drug’s demonstrated beneficial impact on outcomes in the subgroup with an SBP of 120-129 mm Hg. That wasn’t actually a surprise. Indeed, the new study had two hypotheses: one, that the relationship between SBP and cardiovascular and renal outcomes in HFpEF would follow a J-shaped curve, and two, that sacubitril/valsartan’s blood pressure–lowering effect would not account for the drug’s outcome benefits in the subset of HFpEF patients with an SBP in the sweet spot of 120-129 mm Hg. Both hypotheses were borne out, noted Dr. Solomon, professor of medicine at Harvard Medical School and director of noninvasive cardiology at Brigham and Women’s Hospital, both in Boston.
“These data strongly support that additional mechanisms other than blood pressure–lowering account for the benefit. But this is not surprising. The same can be said for most of the therapies that work in heart failure,” he said in an interview.
Take, for example, spironolactone. In TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist), another major trial in which Dr. Solomon played a leadership role, the beneficial effect of spironolactone on clinical outcomes also proved unrelated to the drug’s blood pressure–lowering effect.
Other known effects of sacubitril/valsartan, a novel angiotensin receptor–neprilysin inhibitor, or ARNI, might in theory account for the observed clinical benefits in ARNI-treated patients with an on-treatment SBP of 120-129 mm Hg in PARAGON-HF. These include improved left atrial remodeling, an increase in natriuretic peptides, and improved myocardial relaxation. However, the current lack of understanding of the basic mechanistic processes underlying the varied clinical expressions of HFpEF is a major factor contributing to the lack of any proven-effective therapy for this extremely common and costly disorder, according to Dr. Solomon and coinvestigators.
In contrast to HFpEF, for which to date there is no proven treatment, heart failure with reduced ejection fraction sacubitril/valsartan has a class I recommendation on the strength of its performance in significantly reducing cardiovascular deaths and heart failure hospitalizations in the PARADIGM-HF trial (N Engl J Med. 2014 Sep 11;371:993-1004).
PARAGON-HF included 4,822 patients with symptomatic HFpEF who were randomized to sacubitril/valsartan at 97/103 mg b.i.d. or valsartan at 160 mg b.i.d. As previously reported (N Engl J Med. 2019 Oct 24;381[17]:1609-20), at an average follow-up of 35 months, the primary outcome – a composite of total hospitalizations for heart failure and cardiovascular death – occurred at a rate of 12.8 events per 100 patient-years in the sacubitril/valsartan group and 14.6 per 100 patient-years in the valsartan arm, for a 13% relative risk reduction that narrowly missed statistical significance (P = .059).
However, sacubitril/valsartan showed significant benefit on some prespecified secondary endpoints, including worsening renal function, change in New York Heart Association class, and quality of life. Women, who notably accounted for 52% of study participants, appeared to benefit from sacubitril/valsartan more than men as evidenced by their 27% relative risk reduction in the primary endpoint. Also, in the roughly half of PARAGON-HF participants with a baseline left ventricular ejection fraction of 45%-57%, treatment with sacubitril/valsartan resulted in a statistically significant 22% relative risk reduction in the primary endpoint, compared with valsartan alone.
SBP and cardiovascular outcomes in HFpEF
In the new analysis, Dr. Solomon and coworkers examined outcomes based on baseline and mean achieved SBP quartiles regardless of treatment arm. In an unadjusted analysis, the primary composite endpoint occurred at a rate of 15.2 events/100 patient-years in HFpEF patients with an achieved SBP below 120 mm Hg, 11.4/100 patient-years at 120-129 mm Hg, 12.2/100 patient-years at 130-139 mm Hg, and 15.6/100 patient-years at 140 mm Hg or more. Further, in a multivariate regression analysis extensively adjusted for atrial fibrillation, sex, race, and numerous other potential confounders, the group with an achieved SBP of 120-129 mm Hg continued to fare best. The adjusted risks for the primary endpoint were 11% and 21% higher in patients in the first and third quartiles of achieved SBP, compared with those at 120-129 mm Hg, although neither trend reached statistical significance. But patients in the top quartile, with an achieved SBP of 140 mm Hg or more, had a highly significant 56% increase in risk, compared with patients in the second-lowest SBP quartile.
Change in blood pressure from baseline to week 48 had no impact on quality of life or high-sensitivity troponin T. However, each 10–mm Hg lowering of SBP was associated with a modest 2.1% reduction in log-transformed N-terminal of the prohormone brain natriuretic peptide.
Sacubitril/valsartan reduced SBP by an average of 5.2 mm Hg more than valsartan alone at 4 weeks regardless of baseline SBP. And the combo drug had a significantly greater SBP-lowering effect in women than men, by a margin of 6.3 mm Hg versus 4.0 mm Hg. But a Cox regression analysis showed that in women, as in the study population as a whole, sacubitril/valsartan’s SBP-lowering effects didn’t account for the drug’s impact on outcomes.
In an editorial accompanying publication of the new PARAGON-HF blood pressure analysis (J Am Coll Cardiol. 2020 Mar 16. doi: 10.1016/j.jacc.2020.02.024), Hector O. Ventura, MD, and colleagues at the Ochsner Clinic in New Orleans observed that the study results “lend some credence to the prognostic relationship of blood pressure in HFpEF, but whether they should serve as a therapeutic target or are merely a prognostic surrogate determined by other pathogenic factors, such as vascular ventricular uncoupling or aortic stiffness on one hand when blood pressure is greater than 140 mm Hg, or a reduced cardiac performance indicated by reduced blood pressure to less than 120 mm Hg, remains uncertain.”
“What is certain, however, is that the relationship and contributions of hypertension in manifest HFpEF are complex, multifactorial and likely go well beyond a simplistic framework of hemodynamic influences,” they added.
Dr. Solomon has received research grants from and serves as a consultant to Novartis, which funded PARAGON-HF, and has similar financial relationships with more than a dozen other pharmaceutical companies. Dr. Ventura reported having no relevant financial interests.
SOURCE: Solomon SD et al. J Am Coll Cardiol. 2020 Mar 16. doi: 10.1016/j.jacc.2020.02.009.
FROM ACC 2020
High CV event risk seen in SLE patients with ACC/AHA-defined hypertension
, results of a retrospective, single-center investigation suggest.
Risk of atherosclerotic vascular events was increased by 73% for patients with systemic lupus erythematosus (SLE) who sustained a mean blood pressure of 130/80 to 139/89 mm Hg over 2 years in the study, which included 1,532 patients treated at a clinic in Toronto.
Management of hypertension in SLE patients should start early, and should aim to achieve levels below 130/80 mm Hg, according to the investigators, led by Konstantinos Tselios, MD, PhD, of the Centre for Prognosis Studies in the Rheumatic Diseases at the University of Toronto.
“The findings of the present study support that the target BP should be less than 130/80 mm Hg in all patients with lupus in order to minimize their cardiovascular risk,” Dr. Tselios and coauthors said in their study, which appears in Annals of the Rheumatic Diseases.
Despite the limitations inherent in a retrospective, observational study, this work by Dr. Tselios and colleagues may help inform the care of patients with SLE, according to C. Michael Stein, MBChB, professor of medicine at Vanderbilt University in Nashville, Tenn.
“It’s really interesting data that’s important and helps us think in terms of figuring out what may be reasonable to do for a particular patient,” Dr. Stein said in an interview.
Starting antihypertensive management early and aiming at levels below 130/80 mm Hg is a strategy that should be “reasonable” for most patients with SLE, said Dr. Stein, adding that the approach specified in the 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guidelines are appropriate to follow. In those guidelines, the threshold for diagnosis of hypertension was lowered to 130/80 mm Hg.
“You can start with risk factor modification, in terms of losing weight, exercising, stopping alcohol, and decreasing salt in the diet to see if you can get the blood pressure down, though it may come down to drug therapy for many patients, I believe,” Dr. Stein said.
Authors of those 2017 ACC/AHA guidelines made no recommendations for patients with SLE or other connective tissue diseases, despite including a section devoted to specific patient subgroups and comorbidities of interest, Dr. Tselios and coauthors noted in their report.
Management of hypertension in patients with lupus may be “delayed” in patients with blood pressures reaching the current hypertension threshold, according to Dr. Tselios and colleagues, due in part to difficulties in cardiovascular risk calculation in SLE patients, as well as current risk considerations outlined in the guidelines.
“On the basis of the recent guidelines, the patient with typical lupus (young female with no traditional atherosclerotic risk factors) would be considered as a low-risk individual and not offered treatment for a BP of 130-139/80-89 mm Hg,” they said in their report.
Accordingly, Dr. Tselios and colleagues sought to determine whether the new hypertension definition predicted atherosclerotic vascular events, including new-onset angina, acute myocardial infarction, cerebrovascular events, revascularization procedures, heart failure, or peripheral vascular disease requiring angioplasty, in patients with SLE treated at a Canadian clinic.
Their analysis comprised 1,532 patients with SLE who had at least 2 years of follow-up and had no prior atherosclerotic events on record. Over a mean follow-up of nearly 11 years, there were 124 such events documented in those patients.
With a mean follow-up of nearly 11 years, the incidence of atherosclerotic events was 18.9 per 1,000 patient-years for patients with blood pressure ≥ 140/90 mm Hg, 11.5 per 1,000 patient-years for the 130-139/80-89 mm Hg group, and 4.5 per 1,000 patient-years for those with blood pressures of 130/80 mm Hg or lower, with differences that were statistically significant between groups, according to the report.
An adjusted blood pressure of 130-139/80-89 mm Hg over the first 2 years since enrollment in the clinic was independently associated with the occurrence of an atherosclerotic event, with a hazard ratio of 1.73 (95% confidence interval, 1.13-2.69, P = 0.011), according to results of a multivariable analysis.
Those findings support targeting a blood pressure below 130/80 mm Hg in all patients with lupus, according to Dr. Tselios and coauthors.
“It seems reasonable that clinicians should not rely on CV risk calculators in SLE and commence treatment as soon as possible in cases of sustained BP elevation above the threshold of 130/80 mm Hg,” they wrote in their report.
How low to go remains unclear, however, as targeting lower levels of blood pressure might be unsafe in certain groups, such as those SLE patients with prior heart disease or heart failure; nevertheless, recent observational data from non-SLE populations suggest that effective treatment to levels lower than 130/80 mm Hg would “further reduce the incidence of atherosclerotic events in SLE,” the authors said in a discussion of their results.
Dr. Tselios and coauthors said they had no competing interests relative to the study. They reported funding for the University of Toronto Lupus Clinic from the University Health Network, Lou & Marissa Rocca, Mark & Diana Bozzo, and the Lupus Foundation of Ontario.
SOURCE: Tselios K et al. Ann Rheum Dis. 2020 Mar 10. doi: 10.1136/annrheumdis-2019-216764
, results of a retrospective, single-center investigation suggest.
Risk of atherosclerotic vascular events was increased by 73% for patients with systemic lupus erythematosus (SLE) who sustained a mean blood pressure of 130/80 to 139/89 mm Hg over 2 years in the study, which included 1,532 patients treated at a clinic in Toronto.
Management of hypertension in SLE patients should start early, and should aim to achieve levels below 130/80 mm Hg, according to the investigators, led by Konstantinos Tselios, MD, PhD, of the Centre for Prognosis Studies in the Rheumatic Diseases at the University of Toronto.
“The findings of the present study support that the target BP should be less than 130/80 mm Hg in all patients with lupus in order to minimize their cardiovascular risk,” Dr. Tselios and coauthors said in their study, which appears in Annals of the Rheumatic Diseases.
Despite the limitations inherent in a retrospective, observational study, this work by Dr. Tselios and colleagues may help inform the care of patients with SLE, according to C. Michael Stein, MBChB, professor of medicine at Vanderbilt University in Nashville, Tenn.
“It’s really interesting data that’s important and helps us think in terms of figuring out what may be reasonable to do for a particular patient,” Dr. Stein said in an interview.
Starting antihypertensive management early and aiming at levels below 130/80 mm Hg is a strategy that should be “reasonable” for most patients with SLE, said Dr. Stein, adding that the approach specified in the 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guidelines are appropriate to follow. In those guidelines, the threshold for diagnosis of hypertension was lowered to 130/80 mm Hg.
“You can start with risk factor modification, in terms of losing weight, exercising, stopping alcohol, and decreasing salt in the diet to see if you can get the blood pressure down, though it may come down to drug therapy for many patients, I believe,” Dr. Stein said.
Authors of those 2017 ACC/AHA guidelines made no recommendations for patients with SLE or other connective tissue diseases, despite including a section devoted to specific patient subgroups and comorbidities of interest, Dr. Tselios and coauthors noted in their report.
Management of hypertension in patients with lupus may be “delayed” in patients with blood pressures reaching the current hypertension threshold, according to Dr. Tselios and colleagues, due in part to difficulties in cardiovascular risk calculation in SLE patients, as well as current risk considerations outlined in the guidelines.
“On the basis of the recent guidelines, the patient with typical lupus (young female with no traditional atherosclerotic risk factors) would be considered as a low-risk individual and not offered treatment for a BP of 130-139/80-89 mm Hg,” they said in their report.
Accordingly, Dr. Tselios and colleagues sought to determine whether the new hypertension definition predicted atherosclerotic vascular events, including new-onset angina, acute myocardial infarction, cerebrovascular events, revascularization procedures, heart failure, or peripheral vascular disease requiring angioplasty, in patients with SLE treated at a Canadian clinic.
Their analysis comprised 1,532 patients with SLE who had at least 2 years of follow-up and had no prior atherosclerotic events on record. Over a mean follow-up of nearly 11 years, there were 124 such events documented in those patients.
With a mean follow-up of nearly 11 years, the incidence of atherosclerotic events was 18.9 per 1,000 patient-years for patients with blood pressure ≥ 140/90 mm Hg, 11.5 per 1,000 patient-years for the 130-139/80-89 mm Hg group, and 4.5 per 1,000 patient-years for those with blood pressures of 130/80 mm Hg or lower, with differences that were statistically significant between groups, according to the report.
An adjusted blood pressure of 130-139/80-89 mm Hg over the first 2 years since enrollment in the clinic was independently associated with the occurrence of an atherosclerotic event, with a hazard ratio of 1.73 (95% confidence interval, 1.13-2.69, P = 0.011), according to results of a multivariable analysis.
Those findings support targeting a blood pressure below 130/80 mm Hg in all patients with lupus, according to Dr. Tselios and coauthors.
“It seems reasonable that clinicians should not rely on CV risk calculators in SLE and commence treatment as soon as possible in cases of sustained BP elevation above the threshold of 130/80 mm Hg,” they wrote in their report.
How low to go remains unclear, however, as targeting lower levels of blood pressure might be unsafe in certain groups, such as those SLE patients with prior heart disease or heart failure; nevertheless, recent observational data from non-SLE populations suggest that effective treatment to levels lower than 130/80 mm Hg would “further reduce the incidence of atherosclerotic events in SLE,” the authors said in a discussion of their results.
Dr. Tselios and coauthors said they had no competing interests relative to the study. They reported funding for the University of Toronto Lupus Clinic from the University Health Network, Lou & Marissa Rocca, Mark & Diana Bozzo, and the Lupus Foundation of Ontario.
SOURCE: Tselios K et al. Ann Rheum Dis. 2020 Mar 10. doi: 10.1136/annrheumdis-2019-216764
, results of a retrospective, single-center investigation suggest.
Risk of atherosclerotic vascular events was increased by 73% for patients with systemic lupus erythematosus (SLE) who sustained a mean blood pressure of 130/80 to 139/89 mm Hg over 2 years in the study, which included 1,532 patients treated at a clinic in Toronto.
Management of hypertension in SLE patients should start early, and should aim to achieve levels below 130/80 mm Hg, according to the investigators, led by Konstantinos Tselios, MD, PhD, of the Centre for Prognosis Studies in the Rheumatic Diseases at the University of Toronto.
“The findings of the present study support that the target BP should be less than 130/80 mm Hg in all patients with lupus in order to minimize their cardiovascular risk,” Dr. Tselios and coauthors said in their study, which appears in Annals of the Rheumatic Diseases.
Despite the limitations inherent in a retrospective, observational study, this work by Dr. Tselios and colleagues may help inform the care of patients with SLE, according to C. Michael Stein, MBChB, professor of medicine at Vanderbilt University in Nashville, Tenn.
“It’s really interesting data that’s important and helps us think in terms of figuring out what may be reasonable to do for a particular patient,” Dr. Stein said in an interview.
Starting antihypertensive management early and aiming at levels below 130/80 mm Hg is a strategy that should be “reasonable” for most patients with SLE, said Dr. Stein, adding that the approach specified in the 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guidelines are appropriate to follow. In those guidelines, the threshold for diagnosis of hypertension was lowered to 130/80 mm Hg.
“You can start with risk factor modification, in terms of losing weight, exercising, stopping alcohol, and decreasing salt in the diet to see if you can get the blood pressure down, though it may come down to drug therapy for many patients, I believe,” Dr. Stein said.
Authors of those 2017 ACC/AHA guidelines made no recommendations for patients with SLE or other connective tissue diseases, despite including a section devoted to specific patient subgroups and comorbidities of interest, Dr. Tselios and coauthors noted in their report.
Management of hypertension in patients with lupus may be “delayed” in patients with blood pressures reaching the current hypertension threshold, according to Dr. Tselios and colleagues, due in part to difficulties in cardiovascular risk calculation in SLE patients, as well as current risk considerations outlined in the guidelines.
“On the basis of the recent guidelines, the patient with typical lupus (young female with no traditional atherosclerotic risk factors) would be considered as a low-risk individual and not offered treatment for a BP of 130-139/80-89 mm Hg,” they said in their report.
Accordingly, Dr. Tselios and colleagues sought to determine whether the new hypertension definition predicted atherosclerotic vascular events, including new-onset angina, acute myocardial infarction, cerebrovascular events, revascularization procedures, heart failure, or peripheral vascular disease requiring angioplasty, in patients with SLE treated at a Canadian clinic.
Their analysis comprised 1,532 patients with SLE who had at least 2 years of follow-up and had no prior atherosclerotic events on record. Over a mean follow-up of nearly 11 years, there were 124 such events documented in those patients.
With a mean follow-up of nearly 11 years, the incidence of atherosclerotic events was 18.9 per 1,000 patient-years for patients with blood pressure ≥ 140/90 mm Hg, 11.5 per 1,000 patient-years for the 130-139/80-89 mm Hg group, and 4.5 per 1,000 patient-years for those with blood pressures of 130/80 mm Hg or lower, with differences that were statistically significant between groups, according to the report.
An adjusted blood pressure of 130-139/80-89 mm Hg over the first 2 years since enrollment in the clinic was independently associated with the occurrence of an atherosclerotic event, with a hazard ratio of 1.73 (95% confidence interval, 1.13-2.69, P = 0.011), according to results of a multivariable analysis.
Those findings support targeting a blood pressure below 130/80 mm Hg in all patients with lupus, according to Dr. Tselios and coauthors.
“It seems reasonable that clinicians should not rely on CV risk calculators in SLE and commence treatment as soon as possible in cases of sustained BP elevation above the threshold of 130/80 mm Hg,” they wrote in their report.
How low to go remains unclear, however, as targeting lower levels of blood pressure might be unsafe in certain groups, such as those SLE patients with prior heart disease or heart failure; nevertheless, recent observational data from non-SLE populations suggest that effective treatment to levels lower than 130/80 mm Hg would “further reduce the incidence of atherosclerotic events in SLE,” the authors said in a discussion of their results.
Dr. Tselios and coauthors said they had no competing interests relative to the study. They reported funding for the University of Toronto Lupus Clinic from the University Health Network, Lou & Marissa Rocca, Mark & Diana Bozzo, and the Lupus Foundation of Ontario.
SOURCE: Tselios K et al. Ann Rheum Dis. 2020 Mar 10. doi: 10.1136/annrheumdis-2019-216764
FROM ANNALS OF THE RHEUMATIC DISEASES
Trump to governors: Don’t wait for feds on medical supplies
President Donald Trump has advised state governors not to wait on the federal government when it comes to ensuring readiness for a surge in patients from the COVID-19 outbreak.
“If they are able to get ventilators, respirators, if they are able to get certain things without having to go through the longer process of federal government,” they should order on their own and bypass the federal government ordering system, the president stated during a March 16 press briefing.
That being said, he noted that the federal government is “ordering tremendous numbers of ventilators, respirators, [and] masks,” although he could not give a specific number on how much has been ordered or how many has already been stockpiled.
“It is always going to be faster if they can get them directly, if they need them, and I have given them authorization to order directly,” President Trump said.
The comments came as the White House revised recommendations on gatherings. The new guidelines now limit gatherings to no more than 10 people. Officials are further advising Americans to self-quarantine for 2 weeks if they are sick, if someone in their house is sick, or if someone in their house has tested positive for COVID-19.
Additionally, the White House called on Americans to limit discretionary travel and to avoid eating and drinking in restaurants, bars, and food courts during the next 15 days, even if they are feeling healthy and are asymptomatic.
“With several weeks of focused action, we can turn the corner and turn it quickly,” the president said.
In terms of testing, the Food and Drug Administration has granted emergency use authorization to two commercial diagnostic tests: Thermo Fisher for its TaqPath COVID-19 Combo Kit and Roche for its cobas SARS-CoV-2 test. White House officials said up to 1 million tests will be available this week, with 2 million next week.
The president also announced that phase 1 testing of a vaccine has begun. The test involves more than 40 healthy volunteers in the Seattle area who will receive three shots over the trial period. Phase 1 testing is generally conducted to determine safety of a new therapeutic.
President Donald Trump has advised state governors not to wait on the federal government when it comes to ensuring readiness for a surge in patients from the COVID-19 outbreak.
“If they are able to get ventilators, respirators, if they are able to get certain things without having to go through the longer process of federal government,” they should order on their own and bypass the federal government ordering system, the president stated during a March 16 press briefing.
That being said, he noted that the federal government is “ordering tremendous numbers of ventilators, respirators, [and] masks,” although he could not give a specific number on how much has been ordered or how many has already been stockpiled.
“It is always going to be faster if they can get them directly, if they need them, and I have given them authorization to order directly,” President Trump said.
The comments came as the White House revised recommendations on gatherings. The new guidelines now limit gatherings to no more than 10 people. Officials are further advising Americans to self-quarantine for 2 weeks if they are sick, if someone in their house is sick, or if someone in their house has tested positive for COVID-19.
Additionally, the White House called on Americans to limit discretionary travel and to avoid eating and drinking in restaurants, bars, and food courts during the next 15 days, even if they are feeling healthy and are asymptomatic.
“With several weeks of focused action, we can turn the corner and turn it quickly,” the president said.
In terms of testing, the Food and Drug Administration has granted emergency use authorization to two commercial diagnostic tests: Thermo Fisher for its TaqPath COVID-19 Combo Kit and Roche for its cobas SARS-CoV-2 test. White House officials said up to 1 million tests will be available this week, with 2 million next week.
The president also announced that phase 1 testing of a vaccine has begun. The test involves more than 40 healthy volunteers in the Seattle area who will receive three shots over the trial period. Phase 1 testing is generally conducted to determine safety of a new therapeutic.
President Donald Trump has advised state governors not to wait on the federal government when it comes to ensuring readiness for a surge in patients from the COVID-19 outbreak.
“If they are able to get ventilators, respirators, if they are able to get certain things without having to go through the longer process of federal government,” they should order on their own and bypass the federal government ordering system, the president stated during a March 16 press briefing.
That being said, he noted that the federal government is “ordering tremendous numbers of ventilators, respirators, [and] masks,” although he could not give a specific number on how much has been ordered or how many has already been stockpiled.
“It is always going to be faster if they can get them directly, if they need them, and I have given them authorization to order directly,” President Trump said.
The comments came as the White House revised recommendations on gatherings. The new guidelines now limit gatherings to no more than 10 people. Officials are further advising Americans to self-quarantine for 2 weeks if they are sick, if someone in their house is sick, or if someone in their house has tested positive for COVID-19.
Additionally, the White House called on Americans to limit discretionary travel and to avoid eating and drinking in restaurants, bars, and food courts during the next 15 days, even if they are feeling healthy and are asymptomatic.
“With several weeks of focused action, we can turn the corner and turn it quickly,” the president said.
In terms of testing, the Food and Drug Administration has granted emergency use authorization to two commercial diagnostic tests: Thermo Fisher for its TaqPath COVID-19 Combo Kit and Roche for its cobas SARS-CoV-2 test. White House officials said up to 1 million tests will be available this week, with 2 million next week.
The president also announced that phase 1 testing of a vaccine has begun. The test involves more than 40 healthy volunteers in the Seattle area who will receive three shots over the trial period. Phase 1 testing is generally conducted to determine safety of a new therapeutic.
ESC says continue hypertension meds despite COVID-19 concern
Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s Coronavirus Resource Center.
The European Society of Cardiology (ESC) has issued a statement urging physicians and patients to continue treatment with angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), in light of a newly described theory that those agents could increase the risk of developing COVID-19 and/or worsen its severity.
The concern arises from the observation that the new coronavirus SARS-CoV-2 causing COVID-19 binds to angiotensin-converting enzyme 2 (ACE2) to infect cells, and both ACE inhibitors and ARBs increase ACE2 levels.
This mechanism has been theorized as a possible risk factor for facilitating the acquisition of COVID-19 infection and worsening its severity. However, paradoxically, it has also been hypothesized to protect against acute lung injury from the disease.
Meanwhile, a Lancet Respiratory Medicine article was published March 11 entitled, “Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?”
“We ... hypothesize that diabetes and hypertension treatment with ACE2-stimulating drugs increases the risk of developing severe and fatal COVID-19,” said the authors.
This prompted some media coverage in the United Kingdom and “social media-related amplification,” leading to concern and, in some cases, discontinuation of the drugs by patients.
But on March 13, the ESC Council on Hypertension dismissed the concerns as entirely speculative, in a statement posted to the ESC website.
It said that the council “strongly recommend that physicians and patients should continue treatment with their usual antihypertensive therapy because there is no clinical or scientific evidence to suggest that treatment with ACE inhibitors or ARBs should be discontinued because of the COVID-19 infection.”
The statement, signed by Council Chair Professor Giovanni de Simone, MD, on behalf of the nucleus members, also says that in regard to the theorized protective effect against serious lung complications in individuals with COVID-19, the data come only from animal, and not human, studies.
“Speculation about the safety of ACE-inhibitor or ARB treatment in relation to COVID-19 does not have a sound scientific basis or evidence to support it,” the ESC panel concludes.
This article first appeared on Medscape.com.
Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s Coronavirus Resource Center.
The European Society of Cardiology (ESC) has issued a statement urging physicians and patients to continue treatment with angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), in light of a newly described theory that those agents could increase the risk of developing COVID-19 and/or worsen its severity.
The concern arises from the observation that the new coronavirus SARS-CoV-2 causing COVID-19 binds to angiotensin-converting enzyme 2 (ACE2) to infect cells, and both ACE inhibitors and ARBs increase ACE2 levels.
This mechanism has been theorized as a possible risk factor for facilitating the acquisition of COVID-19 infection and worsening its severity. However, paradoxically, it has also been hypothesized to protect against acute lung injury from the disease.
Meanwhile, a Lancet Respiratory Medicine article was published March 11 entitled, “Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?”
“We ... hypothesize that diabetes and hypertension treatment with ACE2-stimulating drugs increases the risk of developing severe and fatal COVID-19,” said the authors.
This prompted some media coverage in the United Kingdom and “social media-related amplification,” leading to concern and, in some cases, discontinuation of the drugs by patients.
But on March 13, the ESC Council on Hypertension dismissed the concerns as entirely speculative, in a statement posted to the ESC website.
It said that the council “strongly recommend that physicians and patients should continue treatment with their usual antihypertensive therapy because there is no clinical or scientific evidence to suggest that treatment with ACE inhibitors or ARBs should be discontinued because of the COVID-19 infection.”
The statement, signed by Council Chair Professor Giovanni de Simone, MD, on behalf of the nucleus members, also says that in regard to the theorized protective effect against serious lung complications in individuals with COVID-19, the data come only from animal, and not human, studies.
“Speculation about the safety of ACE-inhibitor or ARB treatment in relation to COVID-19 does not have a sound scientific basis or evidence to support it,” the ESC panel concludes.
This article first appeared on Medscape.com.
Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s Coronavirus Resource Center.
The European Society of Cardiology (ESC) has issued a statement urging physicians and patients to continue treatment with angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), in light of a newly described theory that those agents could increase the risk of developing COVID-19 and/or worsen its severity.
The concern arises from the observation that the new coronavirus SARS-CoV-2 causing COVID-19 binds to angiotensin-converting enzyme 2 (ACE2) to infect cells, and both ACE inhibitors and ARBs increase ACE2 levels.
This mechanism has been theorized as a possible risk factor for facilitating the acquisition of COVID-19 infection and worsening its severity. However, paradoxically, it has also been hypothesized to protect against acute lung injury from the disease.
Meanwhile, a Lancet Respiratory Medicine article was published March 11 entitled, “Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?”
“We ... hypothesize that diabetes and hypertension treatment with ACE2-stimulating drugs increases the risk of developing severe and fatal COVID-19,” said the authors.
This prompted some media coverage in the United Kingdom and “social media-related amplification,” leading to concern and, in some cases, discontinuation of the drugs by patients.
But on March 13, the ESC Council on Hypertension dismissed the concerns as entirely speculative, in a statement posted to the ESC website.
It said that the council “strongly recommend that physicians and patients should continue treatment with their usual antihypertensive therapy because there is no clinical or scientific evidence to suggest that treatment with ACE inhibitors or ARBs should be discontinued because of the COVID-19 infection.”
The statement, signed by Council Chair Professor Giovanni de Simone, MD, on behalf of the nucleus members, also says that in regard to the theorized protective effect against serious lung complications in individuals with COVID-19, the data come only from animal, and not human, studies.
“Speculation about the safety of ACE-inhibitor or ARB treatment in relation to COVID-19 does not have a sound scientific basis or evidence to support it,” the ESC panel concludes.
This article first appeared on Medscape.com.
CV health in pregnancy improves outcomes for mother and infant
PHOENIX – according to results from a multinational cohort study.
“Over the past 10 years, cardiovascular health [CVH] has been characterized across most of the life course and is associated with a variety of health outcomes, but CVH as a whole has not been well studied during pregnancy,” Amanda M. Perak, MD, said at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting.
In an effort to examine the associations of maternal gestational CVH with adverse maternal and newborn outcomes, Dr. Perak of the departments of pediatrics and preventive medicine at Northwestern University and Lurie Children’s Hospital, both in Chicago, and colleagues drew from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study, which examined pregnant women at a target of 28 weeks’ gestation and assessed the associations of glycemia with pregnancy outcomes. The researchers analyzed data from an ancillary study of 2,230 mother-child dyads to characterize clinical gestational CVH with use of five metrics: body mass index, blood pressure, cholesterol, glucose, and smoking. The study excluded women with prepregnancy diabetes, preterm births, and cases of fetal death/major malformations.
Each maternal CVH metric was classified as ideal, intermediate, or poor according to modified definitions based on pregnancy guidelines. “For lipids, it’s known that levels change substantially during pregnancy, but there are no pregnancy guidelines,” Dr. Perak said. “We and others have also shown that higher triglycerides in pregnancy are associated with adverse pregnancy outcomes. We selected thresholds of less than 250 mg/dL for ideal and at least 500 mg/dL for poor, based on triglyceride distribution and clinical relevance.”
Total CVH was scored by assigning 2 points for ideal, 1 for intermediate, and 0 for each poor metric, for a total possible 10 points, with 10 being most favorable. They also created four CVH categories, ranging from all ideal to two or more poor metrics. Maternal adverse pregnancy outcomes included preeclampsia and unplanned primary cesarean section. Newborn adverse pregnancy outcomes included birth weight above the 90th percentile and a cord blood insulin sensitivity index lower than the 10th percentile.
The researchers used logistic and multinomial logistic regression of pregnancy outcomes on maternal gestational CVH in two adjusted models. Secondarily, they examined associations of individual CVH metrics with outcomes, with adjustment for the other metrics.
The cohort comprised mother-child dyads from nine field centers in six countries: the United States (25%), Barbados (23%), United Kingdom (21%), China (18%), Thailand (7%), and Canada (7%). The mothers’ mean age was 30 years, and the mean gestational age was 28 weeks. The mean gestational CVH score was 8.8 out of 10. Nearly half of mothers (42%) had ideal metrics, while 4% had two or more poor metrics. Delivery occurred at a mean of 39.8 weeks, and adverse pregnancy outcomes occurred in 4.7%-17.9% of pregnancies.
In the fully adjusted model, which accounted for maternal age, height, alcohol use, gestational age at pregnancy exam, maternal parity, and newborn sex and race/ethnicity, odds ratios per 1-point higher (better) CVH score were 0.61 (95% confidence interval, 0.53-0.70) for preeclampsia, 0.85 (95% CI, 0.76-0.95) for unplanned primary cesarean section (among primiparous mothers), 0.83 (95% CI, 0.77-0.91) for large for gestational age infant, and 0.79 (95% CI, 0.72-0.87) for infant insulin sensitivity index below the 10th percentile. CVH categories were also associated with outcomes. For example, odds ratios for preeclampsia were 4.61 (95% CI, 2.13-11.14) for mothers with one or more intermediate metrics, 7.62 (95% CI, 3.60-18.13) for mothers with one poor metric, and 12.02 (95% CI, 4.70-32.50) for mothers with two or more poor metrics, compared with mothers with all metrics ideal.
“Except for smoking, each CVH metric was independently associated with adverse outcomes,” Dr. Perak said. “However, total CVH was associated with a wider range of outcomes than any single metric. This suggests that CVH provides health insights beyond single risk factors.”
Strengths of the study, she continued, included geographic and racial diversity of participants and high-quality research measurements of CVH. Limitations were that the cohort excluded prepregnancy diabetes and preterm births. “Diet and exercise data were not available, and CVH was measured once at 28 weeks,” she said. “Further study is needed across pregnancy and in other settings, but this study provides the first data on the relevance of gestational CVH for pregnancy outcomes.”
In an interview, Stephen S. Rich, PhD, who directs the Center for Public Health Genomics at the University of Virginia, said that the data “provide strong epidemiologic support to focus on the full range of cardiovascular health. In my view, the primary limitation of the study is that there may be significant differences in how one achieves ideal CHV across a single country, not to mention across the world, particularly in absence of a highly controlled, research environment. It is not clear that the approach used in this study at nine selected sites in six relatively highly developed countries could be translated into primary care – particularly in the U.S. with different regulatory and reimbursement plans and payers. Nonetheless, the evidence suggests a way to reduce adverse outcomes in pregnancy and the area deserves greater research.”
According to Dr. Perak, gestational diabetes is associated with a twofold higher maternal risk for cardiovascular disease (Diabetologia. 2019;62:905-14), while diabetes is also associated with higher offspring risk for CVD (BMJ. 2019;367:16398). However, a paucity of data exists on gestational CVH. In one report, better gestational CVH was associated with less subclinical CVD for the mother 10 years later (J Am Heart Assoc. 2019 Jul 23. doi:10.1161/JAHA.118.011394). In a separate analysis, Dr. Perak and her colleagues found that better gestational CVH was associated with better offspring CVH in childhood. “Unfortunately, we also reported that, among pregnant women in the United States, fewer than 1 in 10 had high CVH,” she said (J Am Heart Assoc. 2020 Feb 17. doi:10.1161/JAHA.119.015123). “However, the relevance of gestational CVH for pregnancy outcomes is unknown, but a it’s key question when considering CVH monitoring in prenatal care.”
Dr. Perak reported having received grant support from the National Heart, Lung, and Blood Institute, the American Heart Association, and Northwestern University. The HAPO Study was supported by NHLBI and the National Institute of Diabetes and Digestive and Kidney Diseases.
The meeting was sponsored by the American Heart Association.
SOURCE: Perak A et al. Epi/Lifestyle 2020, Abstract 33.
PHOENIX – according to results from a multinational cohort study.
“Over the past 10 years, cardiovascular health [CVH] has been characterized across most of the life course and is associated with a variety of health outcomes, but CVH as a whole has not been well studied during pregnancy,” Amanda M. Perak, MD, said at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting.
In an effort to examine the associations of maternal gestational CVH with adverse maternal and newborn outcomes, Dr. Perak of the departments of pediatrics and preventive medicine at Northwestern University and Lurie Children’s Hospital, both in Chicago, and colleagues drew from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study, which examined pregnant women at a target of 28 weeks’ gestation and assessed the associations of glycemia with pregnancy outcomes. The researchers analyzed data from an ancillary study of 2,230 mother-child dyads to characterize clinical gestational CVH with use of five metrics: body mass index, blood pressure, cholesterol, glucose, and smoking. The study excluded women with prepregnancy diabetes, preterm births, and cases of fetal death/major malformations.
Each maternal CVH metric was classified as ideal, intermediate, or poor according to modified definitions based on pregnancy guidelines. “For lipids, it’s known that levels change substantially during pregnancy, but there are no pregnancy guidelines,” Dr. Perak said. “We and others have also shown that higher triglycerides in pregnancy are associated with adverse pregnancy outcomes. We selected thresholds of less than 250 mg/dL for ideal and at least 500 mg/dL for poor, based on triglyceride distribution and clinical relevance.”
Total CVH was scored by assigning 2 points for ideal, 1 for intermediate, and 0 for each poor metric, for a total possible 10 points, with 10 being most favorable. They also created four CVH categories, ranging from all ideal to two or more poor metrics. Maternal adverse pregnancy outcomes included preeclampsia and unplanned primary cesarean section. Newborn adverse pregnancy outcomes included birth weight above the 90th percentile and a cord blood insulin sensitivity index lower than the 10th percentile.
The researchers used logistic and multinomial logistic regression of pregnancy outcomes on maternal gestational CVH in two adjusted models. Secondarily, they examined associations of individual CVH metrics with outcomes, with adjustment for the other metrics.
The cohort comprised mother-child dyads from nine field centers in six countries: the United States (25%), Barbados (23%), United Kingdom (21%), China (18%), Thailand (7%), and Canada (7%). The mothers’ mean age was 30 years, and the mean gestational age was 28 weeks. The mean gestational CVH score was 8.8 out of 10. Nearly half of mothers (42%) had ideal metrics, while 4% had two or more poor metrics. Delivery occurred at a mean of 39.8 weeks, and adverse pregnancy outcomes occurred in 4.7%-17.9% of pregnancies.
In the fully adjusted model, which accounted for maternal age, height, alcohol use, gestational age at pregnancy exam, maternal parity, and newborn sex and race/ethnicity, odds ratios per 1-point higher (better) CVH score were 0.61 (95% confidence interval, 0.53-0.70) for preeclampsia, 0.85 (95% CI, 0.76-0.95) for unplanned primary cesarean section (among primiparous mothers), 0.83 (95% CI, 0.77-0.91) for large for gestational age infant, and 0.79 (95% CI, 0.72-0.87) for infant insulin sensitivity index below the 10th percentile. CVH categories were also associated with outcomes. For example, odds ratios for preeclampsia were 4.61 (95% CI, 2.13-11.14) for mothers with one or more intermediate metrics, 7.62 (95% CI, 3.60-18.13) for mothers with one poor metric, and 12.02 (95% CI, 4.70-32.50) for mothers with two or more poor metrics, compared with mothers with all metrics ideal.
“Except for smoking, each CVH metric was independently associated with adverse outcomes,” Dr. Perak said. “However, total CVH was associated with a wider range of outcomes than any single metric. This suggests that CVH provides health insights beyond single risk factors.”
Strengths of the study, she continued, included geographic and racial diversity of participants and high-quality research measurements of CVH. Limitations were that the cohort excluded prepregnancy diabetes and preterm births. “Diet and exercise data were not available, and CVH was measured once at 28 weeks,” she said. “Further study is needed across pregnancy and in other settings, but this study provides the first data on the relevance of gestational CVH for pregnancy outcomes.”
In an interview, Stephen S. Rich, PhD, who directs the Center for Public Health Genomics at the University of Virginia, said that the data “provide strong epidemiologic support to focus on the full range of cardiovascular health. In my view, the primary limitation of the study is that there may be significant differences in how one achieves ideal CHV across a single country, not to mention across the world, particularly in absence of a highly controlled, research environment. It is not clear that the approach used in this study at nine selected sites in six relatively highly developed countries could be translated into primary care – particularly in the U.S. with different regulatory and reimbursement plans and payers. Nonetheless, the evidence suggests a way to reduce adverse outcomes in pregnancy and the area deserves greater research.”
According to Dr. Perak, gestational diabetes is associated with a twofold higher maternal risk for cardiovascular disease (Diabetologia. 2019;62:905-14), while diabetes is also associated with higher offspring risk for CVD (BMJ. 2019;367:16398). However, a paucity of data exists on gestational CVH. In one report, better gestational CVH was associated with less subclinical CVD for the mother 10 years later (J Am Heart Assoc. 2019 Jul 23. doi:10.1161/JAHA.118.011394). In a separate analysis, Dr. Perak and her colleagues found that better gestational CVH was associated with better offspring CVH in childhood. “Unfortunately, we also reported that, among pregnant women in the United States, fewer than 1 in 10 had high CVH,” she said (J Am Heart Assoc. 2020 Feb 17. doi:10.1161/JAHA.119.015123). “However, the relevance of gestational CVH for pregnancy outcomes is unknown, but a it’s key question when considering CVH monitoring in prenatal care.”
Dr. Perak reported having received grant support from the National Heart, Lung, and Blood Institute, the American Heart Association, and Northwestern University. The HAPO Study was supported by NHLBI and the National Institute of Diabetes and Digestive and Kidney Diseases.
The meeting was sponsored by the American Heart Association.
SOURCE: Perak A et al. Epi/Lifestyle 2020, Abstract 33.
PHOENIX – according to results from a multinational cohort study.
“Over the past 10 years, cardiovascular health [CVH] has been characterized across most of the life course and is associated with a variety of health outcomes, but CVH as a whole has not been well studied during pregnancy,” Amanda M. Perak, MD, said at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting.
In an effort to examine the associations of maternal gestational CVH with adverse maternal and newborn outcomes, Dr. Perak of the departments of pediatrics and preventive medicine at Northwestern University and Lurie Children’s Hospital, both in Chicago, and colleagues drew from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study, which examined pregnant women at a target of 28 weeks’ gestation and assessed the associations of glycemia with pregnancy outcomes. The researchers analyzed data from an ancillary study of 2,230 mother-child dyads to characterize clinical gestational CVH with use of five metrics: body mass index, blood pressure, cholesterol, glucose, and smoking. The study excluded women with prepregnancy diabetes, preterm births, and cases of fetal death/major malformations.
Each maternal CVH metric was classified as ideal, intermediate, or poor according to modified definitions based on pregnancy guidelines. “For lipids, it’s known that levels change substantially during pregnancy, but there are no pregnancy guidelines,” Dr. Perak said. “We and others have also shown that higher triglycerides in pregnancy are associated with adverse pregnancy outcomes. We selected thresholds of less than 250 mg/dL for ideal and at least 500 mg/dL for poor, based on triglyceride distribution and clinical relevance.”
Total CVH was scored by assigning 2 points for ideal, 1 for intermediate, and 0 for each poor metric, for a total possible 10 points, with 10 being most favorable. They also created four CVH categories, ranging from all ideal to two or more poor metrics. Maternal adverse pregnancy outcomes included preeclampsia and unplanned primary cesarean section. Newborn adverse pregnancy outcomes included birth weight above the 90th percentile and a cord blood insulin sensitivity index lower than the 10th percentile.
The researchers used logistic and multinomial logistic regression of pregnancy outcomes on maternal gestational CVH in two adjusted models. Secondarily, they examined associations of individual CVH metrics with outcomes, with adjustment for the other metrics.
The cohort comprised mother-child dyads from nine field centers in six countries: the United States (25%), Barbados (23%), United Kingdom (21%), China (18%), Thailand (7%), and Canada (7%). The mothers’ mean age was 30 years, and the mean gestational age was 28 weeks. The mean gestational CVH score was 8.8 out of 10. Nearly half of mothers (42%) had ideal metrics, while 4% had two or more poor metrics. Delivery occurred at a mean of 39.8 weeks, and adverse pregnancy outcomes occurred in 4.7%-17.9% of pregnancies.
In the fully adjusted model, which accounted for maternal age, height, alcohol use, gestational age at pregnancy exam, maternal parity, and newborn sex and race/ethnicity, odds ratios per 1-point higher (better) CVH score were 0.61 (95% confidence interval, 0.53-0.70) for preeclampsia, 0.85 (95% CI, 0.76-0.95) for unplanned primary cesarean section (among primiparous mothers), 0.83 (95% CI, 0.77-0.91) for large for gestational age infant, and 0.79 (95% CI, 0.72-0.87) for infant insulin sensitivity index below the 10th percentile. CVH categories were also associated with outcomes. For example, odds ratios for preeclampsia were 4.61 (95% CI, 2.13-11.14) for mothers with one or more intermediate metrics, 7.62 (95% CI, 3.60-18.13) for mothers with one poor metric, and 12.02 (95% CI, 4.70-32.50) for mothers with two or more poor metrics, compared with mothers with all metrics ideal.
“Except for smoking, each CVH metric was independently associated with adverse outcomes,” Dr. Perak said. “However, total CVH was associated with a wider range of outcomes than any single metric. This suggests that CVH provides health insights beyond single risk factors.”
Strengths of the study, she continued, included geographic and racial diversity of participants and high-quality research measurements of CVH. Limitations were that the cohort excluded prepregnancy diabetes and preterm births. “Diet and exercise data were not available, and CVH was measured once at 28 weeks,” she said. “Further study is needed across pregnancy and in other settings, but this study provides the first data on the relevance of gestational CVH for pregnancy outcomes.”
In an interview, Stephen S. Rich, PhD, who directs the Center for Public Health Genomics at the University of Virginia, said that the data “provide strong epidemiologic support to focus on the full range of cardiovascular health. In my view, the primary limitation of the study is that there may be significant differences in how one achieves ideal CHV across a single country, not to mention across the world, particularly in absence of a highly controlled, research environment. It is not clear that the approach used in this study at nine selected sites in six relatively highly developed countries could be translated into primary care – particularly in the U.S. with different regulatory and reimbursement plans and payers. Nonetheless, the evidence suggests a way to reduce adverse outcomes in pregnancy and the area deserves greater research.”
According to Dr. Perak, gestational diabetes is associated with a twofold higher maternal risk for cardiovascular disease (Diabetologia. 2019;62:905-14), while diabetes is also associated with higher offspring risk for CVD (BMJ. 2019;367:16398). However, a paucity of data exists on gestational CVH. In one report, better gestational CVH was associated with less subclinical CVD for the mother 10 years later (J Am Heart Assoc. 2019 Jul 23. doi:10.1161/JAHA.118.011394). In a separate analysis, Dr. Perak and her colleagues found that better gestational CVH was associated with better offspring CVH in childhood. “Unfortunately, we also reported that, among pregnant women in the United States, fewer than 1 in 10 had high CVH,” she said (J Am Heart Assoc. 2020 Feb 17. doi:10.1161/JAHA.119.015123). “However, the relevance of gestational CVH for pregnancy outcomes is unknown, but a it’s key question when considering CVH monitoring in prenatal care.”
Dr. Perak reported having received grant support from the National Heart, Lung, and Blood Institute, the American Heart Association, and Northwestern University. The HAPO Study was supported by NHLBI and the National Institute of Diabetes and Digestive and Kidney Diseases.
The meeting was sponsored by the American Heart Association.
SOURCE: Perak A et al. Epi/Lifestyle 2020, Abstract 33.
REPORTING FROM EPI/LIFESTYLE 2020
Risk factors for death from COVID-19 identified in Wuhan patients
Patients who did not survive hospitalization for COVID-19 in Wuhan were more likely to be older, have comorbidities, and elevated D-dimer, according to the first study to examine risk factors associated with death among adults hospitalized with COVID-19. “Older age, showing signs of sepsis on admission, underlying diseases like high blood pressure and diabetes, and the prolonged use of noninvasive ventilation were important factors in the deaths of these patients,” coauthor Zhibo Liu said in a news release. Abnormal blood clotting was part of the clinical picture too.
Fei Zhou, MD, from the Chinese Academy of Medical Sciences, and colleagues conducted a retrospective, observational, multicenter cohort study of 191 patients, 137 of whom were discharged and 54 of whom died in the hospital.
The study, published online today in The Lancet, included all adult inpatients with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital who had been discharged or died by January 31 of this year. Severely ill patients in the province were transferred to these hospitals until February 1.
The researchers compared demographic, clinical, treatment, and laboratory data from electronic medical records between survivors and those who succumbed to the disease. The analysis also tested serial samples for viral RNA. Overall, 91 (48%) of the 191 patients had comorbidity. Most common was hypertension (30%), followed by diabetes (19%) and coronary heart disease (8%).
The odds of dying in the hospital increased with age (odds ratio 1.10; 95% confidence interval, 1.03-1.17; per year increase in age), higher Sequential Organ Failure Assessment (SOFA) score (5.65, 2.61-12.23; P < .0001), and D-dimer level exceeding 1 mcg/L on admission. The SOFA was previously called the “sepsis-related organ failure assessment score” and assesses rate of organ failure in intensive care units. Elevated D-dimer indicates increased risk of abnormal blood clotting, such as deep vein thrombosis.
Nonsurvivors compared with survivors had higher frequencies of respiratory failure (98% vs 36%), sepsis (100%, vs 42%), and secondary infections (50% vs 1%).
The average age of survivors was 52 years compared to 69 for those who died. Liu cited weakening of the immune system and increased inflammation, which damages organs and also promotes viral replication, as explanations for the age effect.
From the time of initial symptoms, median time to discharge from the hospital was 22 days. Average time to death was 18.5 days.
Fever persisted for a median of 12 days among all patients, and cough persisted for a median 19 days; 45% of the survivors were still coughing on discharge. In survivors, shortness of breath improved after 13 days, but persisted until death in the others.
Viral shedding persisted for a median duration of 20 days in survivors, ranging from 8 to 37. The virus (SARS-CoV-2) was detectable in nonsurvivors until death. Antiviral treatment did not curtail viral shedding.
But the viral shedding data come with a caveat. “The extended viral shedding noted in our study has important implications for guiding decisions around isolation precautions and antiviral treatment in patients with confirmed COVID-19 infection. However, we need to be clear that viral shedding time should not be confused with other self-isolation guidance for people who may have been exposed to COVID-19 but do not have symptoms, as this guidance is based on the incubation time of the virus,” explained colead author Bin Cao.
“Older age, elevated D-dimer levels, and high SOFA score could help clinicians to identify at an early stage those patients with COVID-19 who have poor prognosis. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future,” the researchers conclude.
A limitation in interpreting the findings of the study is that hospitalized patients do not represent the entire infected population. The researchers caution that “the number of deaths does not reflect the true mortality of COVID-19.” They also note that they did not have enough genetic material to accurately assess duration of viral shedding.
This article first appeared on Medscape.com.
Patients who did not survive hospitalization for COVID-19 in Wuhan were more likely to be older, have comorbidities, and elevated D-dimer, according to the first study to examine risk factors associated with death among adults hospitalized with COVID-19. “Older age, showing signs of sepsis on admission, underlying diseases like high blood pressure and diabetes, and the prolonged use of noninvasive ventilation were important factors in the deaths of these patients,” coauthor Zhibo Liu said in a news release. Abnormal blood clotting was part of the clinical picture too.
Fei Zhou, MD, from the Chinese Academy of Medical Sciences, and colleagues conducted a retrospective, observational, multicenter cohort study of 191 patients, 137 of whom were discharged and 54 of whom died in the hospital.
The study, published online today in The Lancet, included all adult inpatients with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital who had been discharged or died by January 31 of this year. Severely ill patients in the province were transferred to these hospitals until February 1.
The researchers compared demographic, clinical, treatment, and laboratory data from electronic medical records between survivors and those who succumbed to the disease. The analysis also tested serial samples for viral RNA. Overall, 91 (48%) of the 191 patients had comorbidity. Most common was hypertension (30%), followed by diabetes (19%) and coronary heart disease (8%).
The odds of dying in the hospital increased with age (odds ratio 1.10; 95% confidence interval, 1.03-1.17; per year increase in age), higher Sequential Organ Failure Assessment (SOFA) score (5.65, 2.61-12.23; P < .0001), and D-dimer level exceeding 1 mcg/L on admission. The SOFA was previously called the “sepsis-related organ failure assessment score” and assesses rate of organ failure in intensive care units. Elevated D-dimer indicates increased risk of abnormal blood clotting, such as deep vein thrombosis.
Nonsurvivors compared with survivors had higher frequencies of respiratory failure (98% vs 36%), sepsis (100%, vs 42%), and secondary infections (50% vs 1%).
The average age of survivors was 52 years compared to 69 for those who died. Liu cited weakening of the immune system and increased inflammation, which damages organs and also promotes viral replication, as explanations for the age effect.
From the time of initial symptoms, median time to discharge from the hospital was 22 days. Average time to death was 18.5 days.
Fever persisted for a median of 12 days among all patients, and cough persisted for a median 19 days; 45% of the survivors were still coughing on discharge. In survivors, shortness of breath improved after 13 days, but persisted until death in the others.
Viral shedding persisted for a median duration of 20 days in survivors, ranging from 8 to 37. The virus (SARS-CoV-2) was detectable in nonsurvivors until death. Antiviral treatment did not curtail viral shedding.
But the viral shedding data come with a caveat. “The extended viral shedding noted in our study has important implications for guiding decisions around isolation precautions and antiviral treatment in patients with confirmed COVID-19 infection. However, we need to be clear that viral shedding time should not be confused with other self-isolation guidance for people who may have been exposed to COVID-19 but do not have symptoms, as this guidance is based on the incubation time of the virus,” explained colead author Bin Cao.
“Older age, elevated D-dimer levels, and high SOFA score could help clinicians to identify at an early stage those patients with COVID-19 who have poor prognosis. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future,” the researchers conclude.
A limitation in interpreting the findings of the study is that hospitalized patients do not represent the entire infected population. The researchers caution that “the number of deaths does not reflect the true mortality of COVID-19.” They also note that they did not have enough genetic material to accurately assess duration of viral shedding.
This article first appeared on Medscape.com.
Patients who did not survive hospitalization for COVID-19 in Wuhan were more likely to be older, have comorbidities, and elevated D-dimer, according to the first study to examine risk factors associated with death among adults hospitalized with COVID-19. “Older age, showing signs of sepsis on admission, underlying diseases like high blood pressure and diabetes, and the prolonged use of noninvasive ventilation were important factors in the deaths of these patients,” coauthor Zhibo Liu said in a news release. Abnormal blood clotting was part of the clinical picture too.
Fei Zhou, MD, from the Chinese Academy of Medical Sciences, and colleagues conducted a retrospective, observational, multicenter cohort study of 191 patients, 137 of whom were discharged and 54 of whom died in the hospital.
The study, published online today in The Lancet, included all adult inpatients with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital who had been discharged or died by January 31 of this year. Severely ill patients in the province were transferred to these hospitals until February 1.
The researchers compared demographic, clinical, treatment, and laboratory data from electronic medical records between survivors and those who succumbed to the disease. The analysis also tested serial samples for viral RNA. Overall, 91 (48%) of the 191 patients had comorbidity. Most common was hypertension (30%), followed by diabetes (19%) and coronary heart disease (8%).
The odds of dying in the hospital increased with age (odds ratio 1.10; 95% confidence interval, 1.03-1.17; per year increase in age), higher Sequential Organ Failure Assessment (SOFA) score (5.65, 2.61-12.23; P < .0001), and D-dimer level exceeding 1 mcg/L on admission. The SOFA was previously called the “sepsis-related organ failure assessment score” and assesses rate of organ failure in intensive care units. Elevated D-dimer indicates increased risk of abnormal blood clotting, such as deep vein thrombosis.
Nonsurvivors compared with survivors had higher frequencies of respiratory failure (98% vs 36%), sepsis (100%, vs 42%), and secondary infections (50% vs 1%).
The average age of survivors was 52 years compared to 69 for those who died. Liu cited weakening of the immune system and increased inflammation, which damages organs and also promotes viral replication, as explanations for the age effect.
From the time of initial symptoms, median time to discharge from the hospital was 22 days. Average time to death was 18.5 days.
Fever persisted for a median of 12 days among all patients, and cough persisted for a median 19 days; 45% of the survivors were still coughing on discharge. In survivors, shortness of breath improved after 13 days, but persisted until death in the others.
Viral shedding persisted for a median duration of 20 days in survivors, ranging from 8 to 37. The virus (SARS-CoV-2) was detectable in nonsurvivors until death. Antiviral treatment did not curtail viral shedding.
But the viral shedding data come with a caveat. “The extended viral shedding noted in our study has important implications for guiding decisions around isolation precautions and antiviral treatment in patients with confirmed COVID-19 infection. However, we need to be clear that viral shedding time should not be confused with other self-isolation guidance for people who may have been exposed to COVID-19 but do not have symptoms, as this guidance is based on the incubation time of the virus,” explained colead author Bin Cao.
“Older age, elevated D-dimer levels, and high SOFA score could help clinicians to identify at an early stage those patients with COVID-19 who have poor prognosis. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future,” the researchers conclude.
A limitation in interpreting the findings of the study is that hospitalized patients do not represent the entire infected population. The researchers caution that “the number of deaths does not reflect the true mortality of COVID-19.” They also note that they did not have enough genetic material to accurately assess duration of viral shedding.
This article first appeared on Medscape.com.
Know the 15% rule in scleroderma
MAUI, HAWAII – The 15% rule in scleroderma is a handy tool that raises awareness of the disease’s associated prevalence of various severe organ complications so clinicians can screen appropriately, Janet Pope, MD, said at the 2020 Rheumatology Winter Clinical Symposium.
Dr. Pope and colleagues in the Canadian Scleroderma Research Group developed the 15% rule because they recognized that scleroderma is rare enough that most physicians practicing outside of a few specialized centers don’t see many affected patients. The systemic autoimmune disease is marked by numerous possible expressions of vascular inflammation and malfunction, fibrosis, and autoimmunity in different organ systems.
“A lot of clinicians do not know how common this stuff is,” according to Dr. Pope, professor of medicine at the University of Western Ontario and head of the division of rheumatology at St. Joseph’s Health Center in London, Ont.
Basically, the 15% rule holds that, at any given time, a patient with scleroderma has roughly a 15% chance – or one in six – of having any of an extensive array of severe organ complications. That means a 15% chance of having prevalent clinically significant pulmonary hypertension as defined by a systolic pulmonary artery pressure of 45 mm Hg or more on Doppler echocardiography, a 15% likelihood of interstitial lung disease or clinically significant pulmonary fibrosis as suggested by a forced vital capacity less than 70% of predicted, a 15% prevalence of Sjögren’s syndrome, a 15% likelihood of having pulmonary artery hypertension upon right heart catheterization, a 15% chance of inflammatory arthritis, and a one-in-six chance of having a myopathy or myositis. Also, diastolic dysfunction, 15%. Ditto symptomatic arrhythmias.
“It’s a good little rule of thumb,” Dr. Pope commented.
The odds of having a current digital ulcer on any given day? Again, about 15%. In addition, scleroderma patients have a 15% lifetime risk of developing a complicated digital ulcer requiring hospitalization and/or amputation, she continued.
And while the prevalence of scleroderma renal crisis in the overall population with scleroderma is low, at 3%, in the subgroup with diffuse cutaneous systemic sclerosis, it climbs to 12%-15%.
Every rule has its exceptions. The 15% rule doesn’t apply to Raynaud’s phenomenon, which is present in nearly all patients with scleroderma, nor to gastroesophageal reflux disease or dysphagia, present in roughly 80% of patients.
Dr. Pope and coinvestigators developed the 15% rule pertaining to the prevalence of serious organ complications in scleroderma by conducting a systematic review of 69 published studies, each including a minimum of 50 scleroderma patients. The detailed results of the systematic review have been published.
Dr. Pope reported receiving research grants from and/or serving as a consultant to more than a dozen pharmaceutical companies.
MAUI, HAWAII – The 15% rule in scleroderma is a handy tool that raises awareness of the disease’s associated prevalence of various severe organ complications so clinicians can screen appropriately, Janet Pope, MD, said at the 2020 Rheumatology Winter Clinical Symposium.
Dr. Pope and colleagues in the Canadian Scleroderma Research Group developed the 15% rule because they recognized that scleroderma is rare enough that most physicians practicing outside of a few specialized centers don’t see many affected patients. The systemic autoimmune disease is marked by numerous possible expressions of vascular inflammation and malfunction, fibrosis, and autoimmunity in different organ systems.
“A lot of clinicians do not know how common this stuff is,” according to Dr. Pope, professor of medicine at the University of Western Ontario and head of the division of rheumatology at St. Joseph’s Health Center in London, Ont.
Basically, the 15% rule holds that, at any given time, a patient with scleroderma has roughly a 15% chance – or one in six – of having any of an extensive array of severe organ complications. That means a 15% chance of having prevalent clinically significant pulmonary hypertension as defined by a systolic pulmonary artery pressure of 45 mm Hg or more on Doppler echocardiography, a 15% likelihood of interstitial lung disease or clinically significant pulmonary fibrosis as suggested by a forced vital capacity less than 70% of predicted, a 15% prevalence of Sjögren’s syndrome, a 15% likelihood of having pulmonary artery hypertension upon right heart catheterization, a 15% chance of inflammatory arthritis, and a one-in-six chance of having a myopathy or myositis. Also, diastolic dysfunction, 15%. Ditto symptomatic arrhythmias.
“It’s a good little rule of thumb,” Dr. Pope commented.
The odds of having a current digital ulcer on any given day? Again, about 15%. In addition, scleroderma patients have a 15% lifetime risk of developing a complicated digital ulcer requiring hospitalization and/or amputation, she continued.
And while the prevalence of scleroderma renal crisis in the overall population with scleroderma is low, at 3%, in the subgroup with diffuse cutaneous systemic sclerosis, it climbs to 12%-15%.
Every rule has its exceptions. The 15% rule doesn’t apply to Raynaud’s phenomenon, which is present in nearly all patients with scleroderma, nor to gastroesophageal reflux disease or dysphagia, present in roughly 80% of patients.
Dr. Pope and coinvestigators developed the 15% rule pertaining to the prevalence of serious organ complications in scleroderma by conducting a systematic review of 69 published studies, each including a minimum of 50 scleroderma patients. The detailed results of the systematic review have been published.
Dr. Pope reported receiving research grants from and/or serving as a consultant to more than a dozen pharmaceutical companies.
MAUI, HAWAII – The 15% rule in scleroderma is a handy tool that raises awareness of the disease’s associated prevalence of various severe organ complications so clinicians can screen appropriately, Janet Pope, MD, said at the 2020 Rheumatology Winter Clinical Symposium.
Dr. Pope and colleagues in the Canadian Scleroderma Research Group developed the 15% rule because they recognized that scleroderma is rare enough that most physicians practicing outside of a few specialized centers don’t see many affected patients. The systemic autoimmune disease is marked by numerous possible expressions of vascular inflammation and malfunction, fibrosis, and autoimmunity in different organ systems.
“A lot of clinicians do not know how common this stuff is,” according to Dr. Pope, professor of medicine at the University of Western Ontario and head of the division of rheumatology at St. Joseph’s Health Center in London, Ont.
Basically, the 15% rule holds that, at any given time, a patient with scleroderma has roughly a 15% chance – or one in six – of having any of an extensive array of severe organ complications. That means a 15% chance of having prevalent clinically significant pulmonary hypertension as defined by a systolic pulmonary artery pressure of 45 mm Hg or more on Doppler echocardiography, a 15% likelihood of interstitial lung disease or clinically significant pulmonary fibrosis as suggested by a forced vital capacity less than 70% of predicted, a 15% prevalence of Sjögren’s syndrome, a 15% likelihood of having pulmonary artery hypertension upon right heart catheterization, a 15% chance of inflammatory arthritis, and a one-in-six chance of having a myopathy or myositis. Also, diastolic dysfunction, 15%. Ditto symptomatic arrhythmias.
“It’s a good little rule of thumb,” Dr. Pope commented.
The odds of having a current digital ulcer on any given day? Again, about 15%. In addition, scleroderma patients have a 15% lifetime risk of developing a complicated digital ulcer requiring hospitalization and/or amputation, she continued.
And while the prevalence of scleroderma renal crisis in the overall population with scleroderma is low, at 3%, in the subgroup with diffuse cutaneous systemic sclerosis, it climbs to 12%-15%.
Every rule has its exceptions. The 15% rule doesn’t apply to Raynaud’s phenomenon, which is present in nearly all patients with scleroderma, nor to gastroesophageal reflux disease or dysphagia, present in roughly 80% of patients.
Dr. Pope and coinvestigators developed the 15% rule pertaining to the prevalence of serious organ complications in scleroderma by conducting a systematic review of 69 published studies, each including a minimum of 50 scleroderma patients. The detailed results of the systematic review have been published.
Dr. Pope reported receiving research grants from and/or serving as a consultant to more than a dozen pharmaceutical companies.
REPORTING FROM RWCS 2020
Prescription cascade more likely after CCBs than other hypertension meds
Elderly adults with hypertension who are newly prescribed a calcium-channel blocker (CCB), compared to other antihypertensive agents, are at least twice as likely to be given a loop diuretic over the following months, a large cohort study suggests.
The likelihood remained elevated for as long as a year after the start of a CCB and was more pronounced when comparing CCBs to any other kind of medication.
“Our findings suggest that many older adults who begin taking a CCB may subsequently experience a prescribing cascade” when loop diuretics are prescribed for peripheral edema, a known CCB adverse effect, that is misinterpreted as a new medical condition, Rachel D. Savage, PhD, Women’s College Hospital, Toronto, Canada, told theheart.org/Medscape Cardiology.
Edema caused by CCBs is caused by fluid redistribution, not overload, and “treating euvolemic individuals with a diuretic places them at increased risk of overdiuresis, leading to falls, urinary incontinence, acute kidney injury, electrolyte imbalances, and a cascade of other downstream consequences to which older adults are especially vulnerable,” explain Savage and coauthors of the analysis published online February 24 in JAMA Internal Medicine.
However, 1.4% of the cohort had been prescribed a loop diuretic, and 4.5% had been given any diuretic within 90 days after the start of CCBs. The corresponding rates were 0.7% and 3.4%, respectively, for patients who had started on ACE inhibitors or angiotensin receptor blocker (ARB) rather than a CCB.
Also, Savage observed, “the likelihood of being prescribed a loop diuretic following initiation of a CCB changed over time and was greatest 61 to 90 days postinitiation.” At that point, it was increased 2.4 times compared with initiation of an ACE inhibitor or an ARB in an adjusted analysis and increased almost 4 times compared with starting on any non-CCB agent.
Importantly, the actual prevalence of peripheral edema among those started on CCBs, ACE inhibitors, ARBs, or any non-CCB medication was not available in the data sets.
However, “the main message for clinicians is to consider medication side effects as a potential cause for new symptoms when patients present. We also encourage patients to ask prescribers about whether new symptoms could be caused by a medication,” senior author Lisa M. McCarthy, PharmD, told theheart.org/Medscape Cardiology.
“If a patient experiences peripheral edema while taking a CCB, we would encourage clinicians to consider whether the calcium-channel blocker is still necessary, whether it could be discontinued or the dose reduced, or whether the patient can be switched to another therapy,” she said.
Based on the current analysis, if the rate of CCB-induced peripheral edema is assumed to be 10%, which is consistent with the literature, then “potentially 7% to 14% of people who develop edema while taking a calcium channel blocker may then receive a loop diuretic,” an accompanying editorial notes.
“Patients with polypharmacy are at heightened risk of being exposed to [a] series of prescribing cascades if their current use of medications is not carefully discussed before the decision to add a new antihypertensive,” observe Timothy S. Anderson, MD, Beth Israel Deaconess Medical Center, Boston, Massachusetts, and Michael A. Steinman, MD, San Francisco Veterans Affairs Medical Center and University of California, San Francisco.
“The initial prescribing cascade can set off many other negative consequences, including adverse drug events, potentially avoidable diagnostic testing, and hospitalizations,” the editorialists caution.
“Identifying prescribing cascades and their consequences is an important step to stem the tide of polypharmacy and inform deprescribing efforts.”
The analysis was based on administrative data from almost 340,000 adults in the community aged 66 years or older with hypertension and new drug prescriptions over 5 years ending in September 2016, the report notes. Their mean age was 74.5 years and 56.5% were women.
The data set included 41,086 patients who were newly prescribed a CCB; 66,494 who were newly prescribed an ACE inhibitor or ARB; and 231,439 newly prescribed any medication other than a CCB. The prescribed CCB was amlodipine in 79.6% of patients.
Although loop diuretics could possibly have been prescribed sometimes as a second-tier antihypertensive in the absence of peripheral edema, “we made efforts, through the design of our study, to limit this where possible,” Savage said in an interview.
For example, the focus was on loop diuretics, which aren’t generally recommended for blood-pressure lowering. Also, patients with heart failure and those with a recent history of diuretic or other antihypertensive medication use had been excluded, she said.
“As such, our cohort comprised individuals with new-onset or milder hypertension for whom diuretics would unlikely to be prescribed as part of guideline-based hypertension management.”
Although amlodipine was the most commonly prescribed CCB, the potential for a prescribing cascade seemed to be a class effect and to apply at a range of dosages.
That was unexpected, McCarthy observed, because “peripheral edema occurs more commonly in people taking dihydropyridine CCBs, like amlodipine, compared to non–dihydropyridine CCBs, such as verapamil and diltiazem.”
Savage, McCarthy, their coauthors, and the editorialists have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Elderly adults with hypertension who are newly prescribed a calcium-channel blocker (CCB), compared to other antihypertensive agents, are at least twice as likely to be given a loop diuretic over the following months, a large cohort study suggests.
The likelihood remained elevated for as long as a year after the start of a CCB and was more pronounced when comparing CCBs to any other kind of medication.
“Our findings suggest that many older adults who begin taking a CCB may subsequently experience a prescribing cascade” when loop diuretics are prescribed for peripheral edema, a known CCB adverse effect, that is misinterpreted as a new medical condition, Rachel D. Savage, PhD, Women’s College Hospital, Toronto, Canada, told theheart.org/Medscape Cardiology.
Edema caused by CCBs is caused by fluid redistribution, not overload, and “treating euvolemic individuals with a diuretic places them at increased risk of overdiuresis, leading to falls, urinary incontinence, acute kidney injury, electrolyte imbalances, and a cascade of other downstream consequences to which older adults are especially vulnerable,” explain Savage and coauthors of the analysis published online February 24 in JAMA Internal Medicine.
However, 1.4% of the cohort had been prescribed a loop diuretic, and 4.5% had been given any diuretic within 90 days after the start of CCBs. The corresponding rates were 0.7% and 3.4%, respectively, for patients who had started on ACE inhibitors or angiotensin receptor blocker (ARB) rather than a CCB.
Also, Savage observed, “the likelihood of being prescribed a loop diuretic following initiation of a CCB changed over time and was greatest 61 to 90 days postinitiation.” At that point, it was increased 2.4 times compared with initiation of an ACE inhibitor or an ARB in an adjusted analysis and increased almost 4 times compared with starting on any non-CCB agent.
Importantly, the actual prevalence of peripheral edema among those started on CCBs, ACE inhibitors, ARBs, or any non-CCB medication was not available in the data sets.
However, “the main message for clinicians is to consider medication side effects as a potential cause for new symptoms when patients present. We also encourage patients to ask prescribers about whether new symptoms could be caused by a medication,” senior author Lisa M. McCarthy, PharmD, told theheart.org/Medscape Cardiology.
“If a patient experiences peripheral edema while taking a CCB, we would encourage clinicians to consider whether the calcium-channel blocker is still necessary, whether it could be discontinued or the dose reduced, or whether the patient can be switched to another therapy,” she said.
Based on the current analysis, if the rate of CCB-induced peripheral edema is assumed to be 10%, which is consistent with the literature, then “potentially 7% to 14% of people who develop edema while taking a calcium channel blocker may then receive a loop diuretic,” an accompanying editorial notes.
“Patients with polypharmacy are at heightened risk of being exposed to [a] series of prescribing cascades if their current use of medications is not carefully discussed before the decision to add a new antihypertensive,” observe Timothy S. Anderson, MD, Beth Israel Deaconess Medical Center, Boston, Massachusetts, and Michael A. Steinman, MD, San Francisco Veterans Affairs Medical Center and University of California, San Francisco.
“The initial prescribing cascade can set off many other negative consequences, including adverse drug events, potentially avoidable diagnostic testing, and hospitalizations,” the editorialists caution.
“Identifying prescribing cascades and their consequences is an important step to stem the tide of polypharmacy and inform deprescribing efforts.”
The analysis was based on administrative data from almost 340,000 adults in the community aged 66 years or older with hypertension and new drug prescriptions over 5 years ending in September 2016, the report notes. Their mean age was 74.5 years and 56.5% were women.
The data set included 41,086 patients who were newly prescribed a CCB; 66,494 who were newly prescribed an ACE inhibitor or ARB; and 231,439 newly prescribed any medication other than a CCB. The prescribed CCB was amlodipine in 79.6% of patients.
Although loop diuretics could possibly have been prescribed sometimes as a second-tier antihypertensive in the absence of peripheral edema, “we made efforts, through the design of our study, to limit this where possible,” Savage said in an interview.
For example, the focus was on loop diuretics, which aren’t generally recommended for blood-pressure lowering. Also, patients with heart failure and those with a recent history of diuretic or other antihypertensive medication use had been excluded, she said.
“As such, our cohort comprised individuals with new-onset or milder hypertension for whom diuretics would unlikely to be prescribed as part of guideline-based hypertension management.”
Although amlodipine was the most commonly prescribed CCB, the potential for a prescribing cascade seemed to be a class effect and to apply at a range of dosages.
That was unexpected, McCarthy observed, because “peripheral edema occurs more commonly in people taking dihydropyridine CCBs, like amlodipine, compared to non–dihydropyridine CCBs, such as verapamil and diltiazem.”
Savage, McCarthy, their coauthors, and the editorialists have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Elderly adults with hypertension who are newly prescribed a calcium-channel blocker (CCB), compared to other antihypertensive agents, are at least twice as likely to be given a loop diuretic over the following months, a large cohort study suggests.
The likelihood remained elevated for as long as a year after the start of a CCB and was more pronounced when comparing CCBs to any other kind of medication.
“Our findings suggest that many older adults who begin taking a CCB may subsequently experience a prescribing cascade” when loop diuretics are prescribed for peripheral edema, a known CCB adverse effect, that is misinterpreted as a new medical condition, Rachel D. Savage, PhD, Women’s College Hospital, Toronto, Canada, told theheart.org/Medscape Cardiology.
Edema caused by CCBs is caused by fluid redistribution, not overload, and “treating euvolemic individuals with a diuretic places them at increased risk of overdiuresis, leading to falls, urinary incontinence, acute kidney injury, electrolyte imbalances, and a cascade of other downstream consequences to which older adults are especially vulnerable,” explain Savage and coauthors of the analysis published online February 24 in JAMA Internal Medicine.
However, 1.4% of the cohort had been prescribed a loop diuretic, and 4.5% had been given any diuretic within 90 days after the start of CCBs. The corresponding rates were 0.7% and 3.4%, respectively, for patients who had started on ACE inhibitors or angiotensin receptor blocker (ARB) rather than a CCB.
Also, Savage observed, “the likelihood of being prescribed a loop diuretic following initiation of a CCB changed over time and was greatest 61 to 90 days postinitiation.” At that point, it was increased 2.4 times compared with initiation of an ACE inhibitor or an ARB in an adjusted analysis and increased almost 4 times compared with starting on any non-CCB agent.
Importantly, the actual prevalence of peripheral edema among those started on CCBs, ACE inhibitors, ARBs, or any non-CCB medication was not available in the data sets.
However, “the main message for clinicians is to consider medication side effects as a potential cause for new symptoms when patients present. We also encourage patients to ask prescribers about whether new symptoms could be caused by a medication,” senior author Lisa M. McCarthy, PharmD, told theheart.org/Medscape Cardiology.
“If a patient experiences peripheral edema while taking a CCB, we would encourage clinicians to consider whether the calcium-channel blocker is still necessary, whether it could be discontinued or the dose reduced, or whether the patient can be switched to another therapy,” she said.
Based on the current analysis, if the rate of CCB-induced peripheral edema is assumed to be 10%, which is consistent with the literature, then “potentially 7% to 14% of people who develop edema while taking a calcium channel blocker may then receive a loop diuretic,” an accompanying editorial notes.
“Patients with polypharmacy are at heightened risk of being exposed to [a] series of prescribing cascades if their current use of medications is not carefully discussed before the decision to add a new antihypertensive,” observe Timothy S. Anderson, MD, Beth Israel Deaconess Medical Center, Boston, Massachusetts, and Michael A. Steinman, MD, San Francisco Veterans Affairs Medical Center and University of California, San Francisco.
“The initial prescribing cascade can set off many other negative consequences, including adverse drug events, potentially avoidable diagnostic testing, and hospitalizations,” the editorialists caution.
“Identifying prescribing cascades and their consequences is an important step to stem the tide of polypharmacy and inform deprescribing efforts.”
The analysis was based on administrative data from almost 340,000 adults in the community aged 66 years or older with hypertension and new drug prescriptions over 5 years ending in September 2016, the report notes. Their mean age was 74.5 years and 56.5% were women.
The data set included 41,086 patients who were newly prescribed a CCB; 66,494 who were newly prescribed an ACE inhibitor or ARB; and 231,439 newly prescribed any medication other than a CCB. The prescribed CCB was amlodipine in 79.6% of patients.
Although loop diuretics could possibly have been prescribed sometimes as a second-tier antihypertensive in the absence of peripheral edema, “we made efforts, through the design of our study, to limit this where possible,” Savage said in an interview.
For example, the focus was on loop diuretics, which aren’t generally recommended for blood-pressure lowering. Also, patients with heart failure and those with a recent history of diuretic or other antihypertensive medication use had been excluded, she said.
“As such, our cohort comprised individuals with new-onset or milder hypertension for whom diuretics would unlikely to be prescribed as part of guideline-based hypertension management.”
Although amlodipine was the most commonly prescribed CCB, the potential for a prescribing cascade seemed to be a class effect and to apply at a range of dosages.
That was unexpected, McCarthy observed, because “peripheral edema occurs more commonly in people taking dihydropyridine CCBs, like amlodipine, compared to non–dihydropyridine CCBs, such as verapamil and diltiazem.”
Savage, McCarthy, their coauthors, and the editorialists have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
FDA promises rigorous review of new renal denervation trials
NATIONAL HARBOR, MD. – Just a month before results from the first of several new pivotal trials with a renal denervation device are to be presented, a Food and Drug Administration medical officer speaking at CRT 2020 sponsored by MedStar Heart & Vascular Institute explained which data will most attract the scrutiny of regulators.
“The FDA is very interested in these devices. We recognize that there is a clinical need, but a reasonable benefit-to-risk relationship has to be established,” said Meir Shinnar, MD, PhD, who works in the division of cardiac devices in the FDA’s Office of Device Evaluation.
The field of renal denervation is expected to heat up again if the results of the SPYRAL HTN OFF MED pivotal trial, planned as a late-breaking presentation at the annual meeting of the American College of Cardiology in March 2020, are positive. However, long-term safety will remain a concern, and positive results will not diminish the rigor with which the relative safety and efficacy of other devices in late stages of clinical testing are evaluated.
“The safety profile is unique to the device design and the procedural technique,” Dr. Shinnar said. For example, vascular injury from the energy employed for denervation, whether radiofrequency or another modality, is an important theoretical risk. A minor initial injury might have no immediate consequences but pose major risks if it leads to altered kidney function over time.
“Most of the follow-up data we have now [with renal denervation devices] is about 1-3 years, but I think long-term safety requires a minimum of 5 years of safety data,” Dr. Shinnar said. “We do not expect all that data to be available at the time of approval, but postmarketing studies will be needed.”
Almost 6 years after the SYMPLICITY HTN-3 trial failed to show a significant reduction in blood pressure among patients with resistant hypertension treated with renal denervation rather than a sham procedure (N Engl J Med 2014;370:1393-401), this treatment is again considered promising. The surprising SYMPLICITY HTN-3 result led to several revisions in technique based on the suspicion that denervation was inadequate.
However, the basic principles remain unchanged. For renal denervation, SPYRAL HTN OFF MED, like the SYMPLICITY HTN 3 study, is employing the Symplicity (Medtronic) device, which has been approved in 50 countries but not in the United States, Canada, or Japan.
SPYRAL HTN OFF MED is designed to provide a very straightforward test of efficacy. Unlike SYMPLICITY HTN-3, which permitted patients to remain on their antihypertensive medications, patients in SPYRAL HTN OFF MED will be tested in the absence of drug therapy (a trial with adjunctive antihypertensive drugs, SPYRAL HTN ON MED, is ongoing). This is a design feature that is relevant to regulatory evaluation.
Although not speaking about the SPYRAL HTN OFF MED trial specifically, Dr. Shinnar noted that “the bar is considered to be higher for a first-line indication than when a device is used as an adjunctive to drug therapy.”
Whether used with or without medications, devices are not likely to receive approval without showing a durable benefit. Dr. Shinnar, citing the surgical studies in which blood pressure control was lost 1-2 years after denervation, said 12 months is now considered a “preferred” length of follow-up to confirm efficacy.
If renal denervation moves forward as a result of the new wave of phase 3 trials, there will still be many unanswered questions, according to Dr. Shinnar, who noted that the FDA convened an advisory committee in December 2018 to gather expert opinion about meaningful safety as well as efficacy endpoints for this modality. One will be determining which populations, defined by age, gender, or phenotype, most benefit.
It also remains unclear whether the first approval will create a standard to which subsequent devices should be compared, according to Dr. Shinnar. Although the FDA recognizes blood pressure reductions as an acceptable endpoint, he believes that documentation of the impact on clinical events will be sought in postmarketing analyses.
“All of the denervation modalities involve class 3 devices that require significant data,” Dr. Shinnar cautioned.
Even if the SPYRAL HTN OFF MED trial is positive on the basis of efficacy, it does not guarantee regulatory approval. Dr. Shinnar described a multifaceted approach to defining an acceptable risk-to-benefit ratio from approved devices, and warned that several points regarding the evaluation of renal denervation devices by the FDA are still being debated internally.
Dr. Shinnar reported no potential financial conflicts of interest.
NATIONAL HARBOR, MD. – Just a month before results from the first of several new pivotal trials with a renal denervation device are to be presented, a Food and Drug Administration medical officer speaking at CRT 2020 sponsored by MedStar Heart & Vascular Institute explained which data will most attract the scrutiny of regulators.
“The FDA is very interested in these devices. We recognize that there is a clinical need, but a reasonable benefit-to-risk relationship has to be established,” said Meir Shinnar, MD, PhD, who works in the division of cardiac devices in the FDA’s Office of Device Evaluation.
The field of renal denervation is expected to heat up again if the results of the SPYRAL HTN OFF MED pivotal trial, planned as a late-breaking presentation at the annual meeting of the American College of Cardiology in March 2020, are positive. However, long-term safety will remain a concern, and positive results will not diminish the rigor with which the relative safety and efficacy of other devices in late stages of clinical testing are evaluated.
“The safety profile is unique to the device design and the procedural technique,” Dr. Shinnar said. For example, vascular injury from the energy employed for denervation, whether radiofrequency or another modality, is an important theoretical risk. A minor initial injury might have no immediate consequences but pose major risks if it leads to altered kidney function over time.
“Most of the follow-up data we have now [with renal denervation devices] is about 1-3 years, but I think long-term safety requires a minimum of 5 years of safety data,” Dr. Shinnar said. “We do not expect all that data to be available at the time of approval, but postmarketing studies will be needed.”
Almost 6 years after the SYMPLICITY HTN-3 trial failed to show a significant reduction in blood pressure among patients with resistant hypertension treated with renal denervation rather than a sham procedure (N Engl J Med 2014;370:1393-401), this treatment is again considered promising. The surprising SYMPLICITY HTN-3 result led to several revisions in technique based on the suspicion that denervation was inadequate.
However, the basic principles remain unchanged. For renal denervation, SPYRAL HTN OFF MED, like the SYMPLICITY HTN 3 study, is employing the Symplicity (Medtronic) device, which has been approved in 50 countries but not in the United States, Canada, or Japan.
SPYRAL HTN OFF MED is designed to provide a very straightforward test of efficacy. Unlike SYMPLICITY HTN-3, which permitted patients to remain on their antihypertensive medications, patients in SPYRAL HTN OFF MED will be tested in the absence of drug therapy (a trial with adjunctive antihypertensive drugs, SPYRAL HTN ON MED, is ongoing). This is a design feature that is relevant to regulatory evaluation.
Although not speaking about the SPYRAL HTN OFF MED trial specifically, Dr. Shinnar noted that “the bar is considered to be higher for a first-line indication than when a device is used as an adjunctive to drug therapy.”
Whether used with or without medications, devices are not likely to receive approval without showing a durable benefit. Dr. Shinnar, citing the surgical studies in which blood pressure control was lost 1-2 years after denervation, said 12 months is now considered a “preferred” length of follow-up to confirm efficacy.
If renal denervation moves forward as a result of the new wave of phase 3 trials, there will still be many unanswered questions, according to Dr. Shinnar, who noted that the FDA convened an advisory committee in December 2018 to gather expert opinion about meaningful safety as well as efficacy endpoints for this modality. One will be determining which populations, defined by age, gender, or phenotype, most benefit.
It also remains unclear whether the first approval will create a standard to which subsequent devices should be compared, according to Dr. Shinnar. Although the FDA recognizes blood pressure reductions as an acceptable endpoint, he believes that documentation of the impact on clinical events will be sought in postmarketing analyses.
“All of the denervation modalities involve class 3 devices that require significant data,” Dr. Shinnar cautioned.
Even if the SPYRAL HTN OFF MED trial is positive on the basis of efficacy, it does not guarantee regulatory approval. Dr. Shinnar described a multifaceted approach to defining an acceptable risk-to-benefit ratio from approved devices, and warned that several points regarding the evaluation of renal denervation devices by the FDA are still being debated internally.
Dr. Shinnar reported no potential financial conflicts of interest.
NATIONAL HARBOR, MD. – Just a month before results from the first of several new pivotal trials with a renal denervation device are to be presented, a Food and Drug Administration medical officer speaking at CRT 2020 sponsored by MedStar Heart & Vascular Institute explained which data will most attract the scrutiny of regulators.
“The FDA is very interested in these devices. We recognize that there is a clinical need, but a reasonable benefit-to-risk relationship has to be established,” said Meir Shinnar, MD, PhD, who works in the division of cardiac devices in the FDA’s Office of Device Evaluation.
The field of renal denervation is expected to heat up again if the results of the SPYRAL HTN OFF MED pivotal trial, planned as a late-breaking presentation at the annual meeting of the American College of Cardiology in March 2020, are positive. However, long-term safety will remain a concern, and positive results will not diminish the rigor with which the relative safety and efficacy of other devices in late stages of clinical testing are evaluated.
“The safety profile is unique to the device design and the procedural technique,” Dr. Shinnar said. For example, vascular injury from the energy employed for denervation, whether radiofrequency or another modality, is an important theoretical risk. A minor initial injury might have no immediate consequences but pose major risks if it leads to altered kidney function over time.
“Most of the follow-up data we have now [with renal denervation devices] is about 1-3 years, but I think long-term safety requires a minimum of 5 years of safety data,” Dr. Shinnar said. “We do not expect all that data to be available at the time of approval, but postmarketing studies will be needed.”
Almost 6 years after the SYMPLICITY HTN-3 trial failed to show a significant reduction in blood pressure among patients with resistant hypertension treated with renal denervation rather than a sham procedure (N Engl J Med 2014;370:1393-401), this treatment is again considered promising. The surprising SYMPLICITY HTN-3 result led to several revisions in technique based on the suspicion that denervation was inadequate.
However, the basic principles remain unchanged. For renal denervation, SPYRAL HTN OFF MED, like the SYMPLICITY HTN 3 study, is employing the Symplicity (Medtronic) device, which has been approved in 50 countries but not in the United States, Canada, or Japan.
SPYRAL HTN OFF MED is designed to provide a very straightforward test of efficacy. Unlike SYMPLICITY HTN-3, which permitted patients to remain on their antihypertensive medications, patients in SPYRAL HTN OFF MED will be tested in the absence of drug therapy (a trial with adjunctive antihypertensive drugs, SPYRAL HTN ON MED, is ongoing). This is a design feature that is relevant to regulatory evaluation.
Although not speaking about the SPYRAL HTN OFF MED trial specifically, Dr. Shinnar noted that “the bar is considered to be higher for a first-line indication than when a device is used as an adjunctive to drug therapy.”
Whether used with or without medications, devices are not likely to receive approval without showing a durable benefit. Dr. Shinnar, citing the surgical studies in which blood pressure control was lost 1-2 years after denervation, said 12 months is now considered a “preferred” length of follow-up to confirm efficacy.
If renal denervation moves forward as a result of the new wave of phase 3 trials, there will still be many unanswered questions, according to Dr. Shinnar, who noted that the FDA convened an advisory committee in December 2018 to gather expert opinion about meaningful safety as well as efficacy endpoints for this modality. One will be determining which populations, defined by age, gender, or phenotype, most benefit.
It also remains unclear whether the first approval will create a standard to which subsequent devices should be compared, according to Dr. Shinnar. Although the FDA recognizes blood pressure reductions as an acceptable endpoint, he believes that documentation of the impact on clinical events will be sought in postmarketing analyses.
“All of the denervation modalities involve class 3 devices that require significant data,” Dr. Shinnar cautioned.
Even if the SPYRAL HTN OFF MED trial is positive on the basis of efficacy, it does not guarantee regulatory approval. Dr. Shinnar described a multifaceted approach to defining an acceptable risk-to-benefit ratio from approved devices, and warned that several points regarding the evaluation of renal denervation devices by the FDA are still being debated internally.
Dr. Shinnar reported no potential financial conflicts of interest.
EXPERT ANALYSIS FROM CRT 2020