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Effect of rosiglitazone/ramipril on preclinical vasculopathy in newly diagnosed, untreated diabetes and IGT patients: 1-year randomised, double-blind, placebo-controlled study

Rahman S, Ismail AA, Ismail SB, Naing NN, Abdul Rahman AR

Eur J Clin Pharmacol, 2007 Aug;63(8):733-41.
PMID: 17565489 DOI: 10.1007/s00228-007-0315-3

OBJECTIVE: To investigate whether pharmacological interventions with rosiglitazone/ramipril can reverse preclinical vasculopathy in newly diagnosed untreated patients with type 2 diabetes (T2DM) and impaired glucose tolerance (IGT).

METHODS: In this randomised, double-blind, placebo-controlled study, 33 T2DM and 33 IGT patients were randomised to 4 mg rosiglitazone or 5 mg ramipril or placebo for 1 year. The subjects were newly diagnosed, untreated, normotensive, nonobese, nonsmoker, and nonhyperlipidaemic. Haemodynamic variables were measured at three treatment phases and pulse wave velocity (PWV) and augmentation index (AI) were measured throughout the treatment period.

RESULTS: Rosiglitazone showed a significant reduction in PWV (p=0.039) and AI (p=0.031) and ramipril demonstrated a significant reduction of AI (p=0.025) in IGT in comparison to placebo on the 12th month of treatment. No significant difference was observed in PWV and AI in T2DM with rosiglitazone/ramipril in comparison to placebo during overall treatment period.

CONCLUSIONS: Rosiglitazone significantly reversed preclinical vasculopathy in IGT as evident by significant decrease in PWV and AI after 1 year of treatment. Ramipril also reduced large artery stiffness as shown by significant decrease of AI after 1 year of treatment in IGT. Further trials are needed for a longer period of time, maybe with higher doses, to show whether rosiglitazone/ramipril can reverse preclinical vasculopathy in T2DM.

Matched MeSH terms: Ramipril/administration & dosage; Ramipril/pharmacology; Ramipril/therapeutic use*
Fulltext Using primary care prescribing databases to determine drug switching and continuation of care

Mohamed IN, Helms PJ, McLay JS

Basic Clin Pharmacol Toxicol, 2012 Dec;111(6):396-401.
PMID: 22734606 DOI: 10.1111/j.1742-7843.2012.00917.x

Drug switching is a common medical practice. It indicates continuation of treatment regardless of the reason why the original therapy was stopped and switched. Therefore, the aims of this study were to develop a novel method for determining drug switching from routinely acquired NHS health data and to explore the aspect of continuation of care for patients. Patients who were first prescribed ramipril, simvastatin and an angiotensin receptor blocker (ARB) between 1 March 2004 and 28 February 2007 and discontinued their medication within 6 months of the index prescription were identified from the PTI database. The identified patients were then categorized into three groups: i) patients who were switched to a different drug for the same medical condition, ii) patients who were being prescribed with other types of antihypertensive/lipid-regulating drug prior to the initiation of study; and iii) patients who were without any continuation of care or therapy. Twenty percent (808), 29%(1429) and 14%(455) of the identified patients discontinued ramipril, simvastatin and ARB, respectively, within 6 months of an index prescription. Among the ramipril discontinuation group, 36.4% of the patients were switched to another antihypertensive, while another 31.6% of them were without continuation of care. In patients discontinuing ARB, 30.6% were switched, while another 30.1% were without continuation of treatment. In patients discontinuing simvastatin, 28.8% were switched to another lipid-regulating medicine, while another 63.1% of them were without continuation of care. The results of this study confirm that primary care prescribing databases can be used to determine drug-switching information and continuation of care/therapy.

Matched MeSH terms: Ramipril/therapeutic use
Association of egg intake with blood lipids, cardiovascular disease, and mortality in 177,000 people in 50 countries

Dehghan M, Mente A, Rangarajan S, Mohan V, Lear S, Swaminathan S, et al.

Am J Clin Nutr, 2020 04 01;111(4):795-803.
PMID: 31965140 DOI: 10.1093/ajcn/nqz348

BACKGROUND: Eggs are a rich source of essential nutrients, but they are also a source of dietary cholesterol. Therefore, some guidelines recommend limiting egg consumption. However, there is contradictory evidence on the impact of eggs on diseases, largely based on studies conducted in high-income countries.
OBJECTIVES: Our aim was to assess the association of egg consumption with blood lipids, cardiovascular disease (CVD), and mortality in large global studies involving populations from low-, middle-, and high-income countries.
METHODS: We studied 146,011 individuals from 21 countries in the Prospective Urban Rural Epidemiology (PURE) study. Egg consumption was recorded using country-specific validated FFQs. We also studied 31,544 patients with vascular disease in 2 multinational prospective studies: ONTARGET (Ongoing Telmisartan Alone and in Combination with Ramipril Global End Point Trial) and TRANSCEND (Telmisartan Randomized Assessment Study in ACEI Intolerant Subjects with Cardiovascular Disease). We calculated HRs using multivariable Cox frailty models with random intercepts to account for clustering by study center separately within each study.
RESULTS: In the PURE study, we recorded 14,700 composite events (8932 deaths and 8477 CVD events). In the PURE study, after excluding those with history of CVD, higher intake of egg (≥7 egg/wk compared with <1 egg/wk intake) was not significantly associated with blood lipids, composite outcome (HR: 0.96; 95% CI: 0.89, 1.04; P-trend = 0.74), total mortality (HR: 1.04; 95% CI: 0.94, 1.15; P-trend = 0.38), or major CVD (HR: 0.92; 95% CI: 0.83, 1.01; P-trend = 0.20). Similar results were observed in ONTARGET/TRANSCEND studies for composite outcome (HR 0.97; 95% CI: 0.76, 1.25; P-trend = 0.09), total mortality (HR: 0.88; 95% CI: 0.62, 1.24; P-trend = 0.55), and major CVD (HR: 0.97; 95% CI: 0.73, 1.29; P-trend = 0.12).
CONCLUSIONS: In 3 large international prospective studies including ∼177,000 individuals, 12,701 deaths, and 13,658 CVD events from 50 countries in 6 continents, we did not find significant associations between egg intake and blood lipids, mortality, or major CVD events. The ONTARGET and TRANSCEND trials were registered at clinicaltrials.gov as NCT00153101. The PURE trial was registered at clinicaltrials.gov as NCT03225586.

Matched MeSH terms: Ramipril/administration & dosage
The superoxide dismutase mimetic tempol blunts diabetes-induced upregulation of NADPH oxidase and endoplasmic reticulum stress in a rat model of diabetic nephropathy

De Blasio MJ, Ramalingam A, Cao AH, Prakoso D, Ye JM, Pickering R, et al.

Eur J Pharmacol, 2017 Jul 15;807:12-20.
PMID: 28438648 DOI: 10.1016/j.ejphar.2017.04.026

Endoplasmic reticulum (ER) stress contributes to progression of diabetic nephropathy, which promotes end-stage renal failure in diabetic patients. This study was undertaken to investigate the actions of tempol and ramipril, pharmacological agents that target the consequences of NADPH oxidase, on diabetic nephropathy in a rat model of type 1 diabetes, with an emphasis on markers of ER stress. Male Sprague-Dawley rats were injected intravenously with a single bolus of streptozotocin (55mg/kg) to induce type 1 diabetes. An additional age-matched group of rats was administered with citrate vehicle as controls. After 4 weeks of untreated diabetes, rats received tempol (1.5mM/kg/day subcutaneously, n=8), ramipril (1mg/kg/day in drinking water, n=8) or remained untreated for an additional 4 weeks (n=7). After 8 weeks of diabetes in total, kidneys were collected for histological analysis, gene expression and protein abundance. Tempol and ramipril blunted diabetes-induced upregulation of NADPH oxidase isoforms (Nox4, Nox2, p47phox), accompanied by an amelioration of diabetes-induced glomerular injury (podocin, nephrin, Kim-1), tubulo-interstitial fibrosis (TGFβ1, TGFβ-R2, pSMAD3, α-SMA) and pro-inflammatory cytokines (TNFα, MCP-1, ANX-A1, FPR2) expression. In addition, the diabetes-induced renal ER stress, evidenced by increased expression of GRP-78 chaperone and stress-associated markers ATF4, TRB3, as well as XBP1s, phospho-p38 mitogen-activated protein kinase (MAPK) and 3-nitrotyrosination, were all attenuated by tempol and ramipril. These observations suggest that antioxidant approaches that blunt NADPH upregulation may attenuate diabetic nephropathy, at least in part by negatively regulating ER stress and inflammation, and hence ameliorating kidney damage.

Matched MeSH terms: Ramipril/pharmacology
Fulltext The International Polycap Study-3 (TIPS-3): Design, baseline characteristics and challenges in conduct

Joseph P, Pais P, Dans AL, Bosch J, Xavier D, Lopez-Jaramillo P, et al.

Am Heart J, 2018 Dec;206:72-79.
PMID: 30342297 DOI: 10.1016/j.ahj.2018.07.012

BACKGROUND: It is hypothesized that in individuals without clinical cardiovascular disease (CVD), but at increased CVD risk, a 50% to 60% reduction in CVD risk could be achieved using fixed dose combination (FDC) therapy (usually comprised of multiple blood-pressure agents and a statin [with or without aspirin]) in a single "polypill". However, the impact of a polypill in preventing clinical CV events has not been evaluated in a large randomized controlled trial.
METHODS: TIPS-3 is a 2x2x2 factorial randomized controlled trial that will examine the effect of a FDC polypill on major CV outcomes in a primary prevention population. This study aims to determine whether the Polycap (comprised of atenolol, ramipril, hydrochlorothiazide, and a statin) reduces CV events in persons without a history of CVD, but who are at least at intermediate CVD risk. Additional interventions in the factorial design of the study will compare the effect of (1) aspirin versus placebo on CV events (and cancer), (2) vitamin D versus placebo on the risk of fractures, and (3) the combined effect of aspirin and the Polycap on CV events.
RESULTS: The study has randomized 5713 participants across 9 countries. Mean age of the study population is 63.9 years, and 53% are female. Mean INTERHEART risk score is 16.8, which is consistent with a study population at intermediate CVD risk.
CONCLUSION: Results of the TIP-3 study will be key to determining the appropriateness of FDC therapy as a strategy in the global prevention of CVD.

Matched MeSH terms: Ramipril/administration & dosage*