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    • Introduction Cardiovascular disease is the principal cause o

    2023-01-30

    Introduction Cardiovascular disease is the principal cause of morbidity and mortality in patients with bifonazole synthesis (1). Comprehensive management of these patients includes not only adequate glycemic control but also attention to additional recognized risk factors. Hypertension is a cardiovascular risk factor with very high prevalence in people with diabetes, and several clinical trials have demonstrated improved cardiovascular or renal outcomes with blood pressure (BP) control in patients with diabetes (2). The hallmark trial demonstrating improved clinical outcomes with BP reduction was the United Kingdom Prospective Diabetes Study, which enrolled 1,148 patients who had hypertension with diabetes and randomized them to achieve a BP target of below 150/85 mmHg (intensive arm) or below 180/105 mmHg (control arm) by using captopril or atenolol. The primary outcome, a composite of any diabetes-related complication, was reduced by 24% in the intensive arm over a mean follow-up period of 8.4 years (3). Microvascular and macrovascular complications were reduced by 37% and 34%, respectively.
    Cardiovascular Outcomes with ARBs in Patients with Diabetes When ARBs became available, several trials evaluated their efficacy in cardiovascular outcomes in the general population and in various patient subgroups. The Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) program was the first to assess efficacy of an ARB in patients with heart failure and included 3 independent randomized controlled trials (4). A total of 28% of patients in the CHARM program had diabetes. The primary endpoint for each of the 3 CHARM trials was time to cardiovascular death or hospital admission for heart failure. It occurred in 30% of patients in the candesartan arm and in 35% of patients in the placebo arm; adjusted hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.77 to 0.91. Candesartan was also associated with reduction in all-cause mortality (adjusted HR 0.90, 95% CI 0.82 to 0.99), driven by reduction of cardiovascular mortality, particularly in patients with heart failure involving reduced left ventricular ejection fraction (<40%). The Losartan Intervention For Endpoint reduction study enrolled patients with hypertension and left ventricular hypertrophy on electrocardiogram and randomized them to receive either a losartan-based or an atenolol-based antihypertensive regimen. A prespecified subgroup analysis included the 1,195 patients who had diabetes at the beginning of the study (5). The primary composite endpoint of cardiovascular mortality, stroke or myocardial infarction occurred in 18% of patients in the losartan group vs. 23% of patients in the atenolol group (adjusted HR, 0.76, 95% CI 0.58 to 0.98). Patients in the losartan group also had lower incidences of all cause-mortality and heart failure compared with patients in the atenolol group. These results were obtained despite a similar BP decrease in both arms throughout the follow-up period. The Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND) Trials evaluated the efficacy of telmisartan vs. placebo in patients with established cardiovascular disease or diabetes with end-organ damage who were intolerant to ACEIs (6). More than 35% of the 5,926 patients enrolled had diabetes. The primary outcome, a composite of cardiovascular death, myocardial infarction, stroke or hospitalization for heart failure, occurred in 15.7% of patients in the telmisartan group vs. 17.0% of patients in the placebo group (HR 0.92, 95% CI 0.81 to 1.05). The secondary outcome of cardiovascular death, myocardial infarction or stroke occurred in 13.0% of patients in the telmisartan group vs. 14.8% of patients in the placebo group (HR 0.87, 95% CI 0.76 to 1.00). These important outcomes trended in favour of a benefit from telmisartan but did not reach statistical significance due to an event rate that was too low for the power of the study and that could be attributed to improved standard-of-care baseline treatment (55% of patients were taking statins, 58% were taking beta blockers and 85% were taking antiplatelet agents). Despite these limitations, another secondary outcome, hospitalizations for any cardiovascular cause, was statistically significantly lower (p=0.025) in favour of the telmisartan group (30.3%) vs. the placebo group (33.0%). Importantly, the proportion of patients who discontinued telmisartan for the same reason they were intolerant to ACEIs was low and was similar to that of the placebo group.