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Benefits of intensive lipid lowering in patients with stable CHD and systolic blood pressure above or below 140 mmHg: A post hoc analysis of the TNT study
... Furthermore, a post hoc analysis of TNT showed that the best results in terms of risk reduction were achieved in patients who not only received intensive LDL-lowering therapy but who also had their BP levels managed (systolic BP <140 mm Hg). 27 Patients with a mean LDL-C level of 60 mg/dL and a mean systolic BP of 122 mm Hg had an event rate of 7.2%, whereas those with an LDL-C level of 132 mg/dL and a systolic BP of 122 mm Hg had an event rate of 11% (P <.0001). ...
... Further clinical evidence for the benefit of combined blood pressure and lipid-lowering therapy is provided by a subanalysis of the Comparison of Amlodipine Versus Enalapril to Limit Occurrences of Thrombosis (CAMELOT) trial, which found that CVoutcomes were reduced by amlodipine as compared with both placebo and enalapril (Nissen et al., 2004); this effect was greater in the subgroup of patients receiving statin therapy than in those who were not receiving a statin (Baghdasarian et al., 2006). Conversely, in patients receiving atorvastatin in the Treating to New Targets (TNT) trial, the lowest incidence of adverse CV events was observed in the subgroup of patients with systolic blood pressure b 140 mm Hg and the lowest LDL-cholesterol levels as compared with patients with higher blood pressure and LDL-cholesterol levels (Kostis et al., 2006). Consistent with these findings, combined treatment with antihypertensive agents and statins has been found to exert beneficial effects at the cellular level that are superior to those for each agent in isolation. ...
Hypertension, a prevalent risk factor for cardiovascular disease, frequently occurs in conjunction with metabolic disturbances and in particular with dyslipidaemia; such comorbidity presents in more than one-third of hypertensive patients. Moreover, hypertension and dyslipidaemia often manifest concomitantly in the clinical context of obesity and insulin resistance. In this setting, distinct metabolic anomalies may account for the development of both conditions, and may equally act to exacerbate their effects on vascular dysfunction. Significantly, hypertension and dyslipidaemia are linked mechanistically and may act in synergy at the arterial wall to enhance atherosclerosis. In this review, we identify potential mechanisms underlying the pathophysiological interaction between hypertension and dyslipidaemia at the cellular and molecular levels, and which may underlie elevated cardiovascular risk in obesity and insulin resistance. Finally, the clinical evidence supporting the beneficial effects of an integrated pharmacotherapeutic strategy to the reduction of cardiovascular risk in patients with insulin resistance, type 2 diabetes and the metabolic syndrome is critically discussed.
Atorvastatin is one of the most widely prescribed drugs and the most widely prescribed statin in the world. It is therefore important to know the dose-related magnitude of effect of atorvastatin on blood lipids.
To quantify the dose-related effects of atorvastatin on blood lipids and withdrawals due to adverse effects (WDAE).
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library Issue 4, 2011, MEDLINE (1966 to November 2011), EMBASE (1980 to November 2011), ISI Web of Science (1899 to November 2011) and BIOSIS Previews (1969 to November 2011). No language restrictions were applied.
Randomised controlled and uncontrolled before-and-after trials evaluating the dose response of different fixed doses of atorvastatin on blood lipids over a duration of 3 to 12 weeks.
Two review authors independently assessed trial quality and extracted data. WDAE information was collected from the placebo-controlled trials.
Two hundred fifty-four trials evaluated the dose-related efficacy of atorvastatin in 33,505 participants. Log dose-response data revealed linear dose-related effects on blood total cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides. Combining all the trials using the generic inverse variance fixed-effect model for doses of 10 to 80 mg/day resulted in decreases of 36% to 53% for LDL-cholesterol. There was no significant dose-related effects of atorvastatin on blood high-density lipoprotein (HDL)-cholesterol. WDAE were not statistically different between atorvastatin and placebo for these short-term trials (risk ratio 0.99; 95% confidence interval 0.68 to 1.45).
Blood total cholesterol, LDL-cholesterol and triglyceride lowering effect of atorvastatin was dependent on dose. Log dose-response data was linear over the commonly prescribed dose range. Manufacturer-recommended atorvastatin doses of 10 to 80 mg/day resulted in 36% to 53% decreases of LDL-cholesterol. The review did not provide a good estimate of the incidence of harms associated with atorvastatin because of the short duration of the trials and the lack of reporting of adverse effects in 37% of the placebo-controlled trials.
Clinical management of two key modifiable risk factors for cardiovascular disease (CVD), hypertension and dyslipidemia, has evolved considerably over the past 40 years, in terms of the focus of therapy, available pharmacologic agents, and therapeutic targets.
A brief review of the epidemiology of hypertension and hyperlipidemia and of controlled clinical trials of pharmacologic therapy of these conditions in decreasing cardiovascular events is presented.
Risk factors for CVD generally do not occur in isolation, and the co-occurrence of hypertension and dyslipidemia, with or without other additional risk factors, greatly increases the risk of CVD. Clinical trials performed in the last 40 years have demonstrated the clinical benefit of treating hypertension and dyslipidemia. Recent trials have shown that intensive, early management of these risk factors provide the greatest clinical benefits. Emerging evidence suggests that lipid management provides clinical benefit in patients at high risk of CVD, regardless of their baseline cholesterol levels, and that lipid-lowering with statin therapy provides additional benefits over antihypertensive therapy alone in high-risk patients with hypertension. It has become evident that the most effective means of reducing CVD risk is the simultaneous management of all modifiable risk factors. Treatment of an individual risk factor can reduce CVD events by approximately 30%, whereas treatment of multiple risk factors can reduce the risk of CVD by more than 50%. However, a large number of patients are not treated or receive suboptimal treatment.
Overwhelming controlled clinical trial evidence supports the clinical benefit of treating hypertension and hypercholesterolemia. Fixed-dose combination medications for hypertension, and integrative combination therapies containing antihypertensive and lipid-lowering medications in a single pill contribute to better risk factor management with the potential for greater adherence and improved clinical outcomes.
To investigate the efficacy and safety of single-pill amlodipine/atorvastatin therapy for the simultaneous treatment of hypertension (HTN) and dyslipidemia in African Americans.
Conducted between July 19, 2004, and August 9, 2005, the Clinical Utility of Caduet in Simultaneously Achieving Blood Pressure and Lipid End Points trial was a 20-week, open-label, noncomparative, multicenter trial of the efficacy and safety of single-pill amlodipine/atorvastatin in controlling elevated blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) in African Americans with concomitant HTN and dyslipidemia and either no additional risk factors, 1 or more cardiovascular risk factors, or coronary heart disease or a risk equivalent. Eight dosage strengths of single-pill amlodipine/atorvastatin were flexibly titrated. The primary efficacy assessment of the main trial was the percentage of patients who attained the LDL-C treatment goals of both the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure and the National Cholesterol Education Program Adult Treatment Panel III.
Of the 1170 African American patients screened, 501 were enrolled in the study and 499 received drug therapy. At end point, 236 (48.3%) of 489 patients reached both their BP and LDLC goals (vs 4 [0.8%] of 484 at baseline); 280 (56.8%) of 493 reached BP goals (vs 7 [1.4%] of 494 at baseline); and 361 (73.7%) of 490 reached LDL-C goals (vs 138 [28.5%] of 484 at baseline). Among the 499 patients receiving drug therapy, common treatment-related adverse events were peripheral edema (17 patients [3.4%]), headache (11 [2.2%]), myalgia (11 [2.2%]), and constipation (10 [2.0%]).
Single-pill amlodipine/atorvastatin therapy was well tolerated and effectively targeted HTN and dyslipidemia in this population of African Americans who were at risk of cardiovascular disease.
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