Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The identification and treatment of high-risk patients for cardiovascular disease reduces the risk of morbidity and mortality. Significant risk factors for cardiovascular events in hypertensive patients over and above dyslipidemia, smoking, and obesity include coronary heart disease, peripheral arterial disease, cerebrovascular/carotid artery disease, and diabetes. Treatment options for the reduction of cardiovascular events in hypertensive patients include diuretics, beta-blockers, alpha-blockers, calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and aldosterone antagonists. All of these agents, in various combinations, have been found to reduce the risk of cardiovascular events, even in high-risk patients. The use of ACE inhibitors or ARBs (usually in combination with a diuretic) has proven especially effective in reducing cardiovascular events in diabetes and, although both classes of drugs target the renin-angiotensin-aldosterone system, each has a different mechanism of action. Some investigators believe that combination therapy with an ACE inhibitor and ARB, usually given with other medications, may be more effective than either agent alone with other drugs. The Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET) is evaluating the cardioprotective effect of an ACE inhibitor (ramipril) plus an ARB (telmisartan) in high-risk patients.
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PMID:Evolving treatment options for prevention of cardiovascular events in high-risk hypertensive patients. 1797 96

The Heart Outcomes Prevention Evaluation study established the angiotensin-converting enzyme inhibitor ramipril, versus placebo, for prevention of cardiovascular events in high-risk patients. The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) was later conducted in similar high-risk patients using multifactorial treatment to control hypertension, platelet aggregation, and dyslipidemia, while comparing ramipril, telmisartan, or their combination, without placebo. In ONTARGET, the first angiotensin II receptor blocker-based study to be performed in a broader population of patients without congestive heart failure and/or left ventricular hypertrophy/dysfunction, telmisartan provided cardiovascular protection that was noninferior to ramipril. However, greater blockade of the renin-angiotensin system, using their combination, was not superior to ramipril alone. Telmisartan was better tolerated than ramipril in this high-risk population: notably, the incidence of cough and angioedema was significantly lower with telmisartan alone. Thus, telmisartan provides comparable efficacy to ramipril with less adverse events, which may encourage patient compliance.
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PMID:Clinical evidence from ONTARGET: the value of an angiotensin II receptor blocker and an angiotensin-converting enzyme inhibitor. 1958 51

Bardoxolone methyl is an antioxidant inflammation modulator acting through induction of Keap1-Nrf2 pathway. Results from a recent phase IIb clinical trial reported that bardoxolone methyl was associated with improvement in the estimated glomerular filtration rate in patients with advanced chronic kidney disease and Type 2 diabetes. However, increases in albuminuria, serum transaminase, and frequency of adverse events were noted. We studied the effect of 3-mo treatment with RTA 405, a synthetic triterpenoid analog of bardoxolone methyl in Zucker diabetic fatty rats with overt Type 2 diabetes. Rats were treated from 3 mo of age with vehicle, RTA 405, ramipril, or RTA 405 plus ramipril. RTA 405 caused severe changes in food intake and diuresis with decline in body weight, worsening of dyslipidemia, and increase in blood pressure. Early elevation in serum transaminase was followed by liver injury. RTA 405 worsened proteinuria, glomerulosclerosis, and tubular damage. Ramipril was renoprotective, but when given with RTA 405 it was not able to limit its worsening effects. These data could be due to degradation products in the drug substance used, as disclosed by the company once the study was concluded. To overcome such a drawback, the company offered to test dh404, a variant of RTA 405, in Zucker diabetic fatty rats. The dh404 did not display beneficial effects on proteinuria, glomerulosclerosis, and interstitial inflammation. Rather, kidneys from three rats receiving dh404 showed the presence of a granulomatous and inflammatory process reminiscent of a pseudotumor. Altogether these data raise serious concerns on the use of bardoxolone analogs in Type 2 diabetic nephropathy.
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PMID:Analogs of bardoxolone methyl worsen diabetic nephropathy in rats with additional adverse effects. 2326 42