Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Co-administration of antihypertensive drug therapy and hormonal replacement therapy (HRT) is frequent in postmenopausal women but it is not known whether HRT interacts with concomitant antihypertensive therapy. The present study was designed to investigate efficacy and safety of the ACE inhibitor moexipril in comparison to placebo in hypertensive, postmenopausal women on HRT. After a 4-week placebo run-in phase, 95 postmenopausal women (35-74 years of age) who had a sitting diastolic blood pressure (BP) of 95-114 mm Hg and were treated with HRT were randomised to a 12-week treatment with moexipril 15 mg or placebo. Efficacy and safety were assessed by measuring changes in sitting BP and metabolic parameters associated with cardiovascular disease including triglycerides, total cholesterol, HDL, LDL, total cholesterol/HDL ratio and glucose. Adverse events were recorded continuously. After 12 weeks of treatment, moexipril 15 mg was significantly more effective in reducing sitting systolic and diastolic BP from baseline than placebo (-12.2/-9.9 mm Hg vs -1.6/-4.3 mm Hg, P < 0.001). Metabolic parameters were not affected by treatment with moexipril: mean levels of triglycerides, total cholesterol, HDL, LDL, total cholesterol/HDL ratio and glucose remained unchanged throughout the study. Fibrinogen, an independent cardiovascular risk factor, increased after placebo (+35.0 mg/dl) and decreased after treatment with moexipril (-33.6 mg/dl), the difference, however, was not statistically significant. Moexipril was well-tolerated by postmenopausal women using HRT. The most frequent adverse events included headache (21.3%), cough (12.8%) and rhinitis (10.6%) and there were no significant differences in the number and severity of adverse events between the moexipril and placebo groups. This study indicates that moexipril is effective and well tolerated in the treatment of hypertensive, postmenopausal women and can safely be co-administered to HRT.
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PMID:Co-administration of an ACE-inhibitor (moexipril) and hormonal replacement therapy in postmenopausal women. 1037 52

Elevated levels of serum lipids and lipoproteins are known to play a major role in the development of atherosclerosis and subsequent coronary heart disease (CHD). In controlled clinical studies, atorvastatin (Sortis), a new 3-hydroxy-3-methyl-glutaryl-coenzyme-A (HMG-CoA)-reductase inhibitor, proved to be a very effective and safe lipid-lowering agent. The aim of this open-label, multicentre study (without a control group) was to confirm the efficacy and safety of atorvastatin in a private practice group, including 181 Swiss cardiologists, internists, and general practitioners. A total of 877 hyperlipidaemic patients requiring treatment participated in this study. To evaluate the effectiveness of the treatment with atorvastatin over a period of 12 weeks, total plasma cholesterol (TC), HDL cholesterol, LDL cholesterol and triglycerides (TG) were determined every 4 weeks. The initial atorvastatin dose was 10 mg in 78% of patients and 20 mg in 22%. The dose was doubled every 4 weeks until the target values of TC < or = 5.2 mmol/l and TC/HDL < or = 5 were reached. After 12 weeks of treatment with atorvastatin the mean reduction in TC, TC/HDL, LDL and TG compared to baseline levels was 33, 37, 42, and 25% respectively. At the same time the HDL concentration was increased by 9%. These results were evidenced in patients with existing coronary heart disease, in high risk patients without manifest coronary heart disease and in patients with significantly elevated lipid levels (TC > 7.8 mmol/l, TC/HDL > 6.5). After treatment with atorvastatin for 12 weeks, 59% of patients had reached the therapeutic target of TC < or = 5.2 mmol/l. The target of TC/HDL < or = 5 was reached by 79%. Atorvastatin was almost without exception well tolerated, the most frequently reported side effects being nausea, myalgia, and headache. In this open-label multicentre study atorvastatin was found to be effective and well tolerated. The observed reduction in the lipid and lipoprotein concentration is in accordance with the results of published controlled studies. The lipid and lipoprotein concentrations were decreased significantly in patients with slight to moderate elevation of lipid levels as well as in those with significantly raised values.
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PMID:[Evaluating the efficacy and tolerance of atorvastatin in hyperlipidemia in general practice (SWITCH Study)]. 1089 90

This pivotal, multicentre, double-blind, parallel-group study evaluated the efficacy and safety of cerivastatin 0.8 mg. Patients with primary hypercholesterolaemia were randomized, after 10 weeks' dietary stabilization on an American Heart Association (AHA) Step I diet, to treatment with cerivastatin 0.8 mg (n = 776), cerivastatin 0.4 mg (n = 195) or placebo (n = 199) once daily for 8 weeks. Cerivastatin 0.8 mg reduced mean low density lipoprotein-cholesterol (LDL-C) by 41.8% compared with cerivastatin 0.4 mg (-35.6%, P < 0.0001) or placebo. In 90% of patients receiving cerivastatin 0.8 mg LDL-C was reduced by 23.9 -58.4% (6th - 95th percentile). Overall attainment of the National Cholesterol Education Program (NCEP) goal was achieved by 84% of patients receiving cerivastatin 0.8 mg and by 59% of those with coronary heart disease (CHD). In the sub-population meeting the NCEP criteria for pharmacological therapy for LDL-C reduction, 74.6% of patients, including the 59% with CHD, reached the goal with cerivastatin 0.8 mg. Cerivastatin 0.8 mg also reduced mean total cholesterol by 29.9%, apolipoprotein B by 33.2% and median triglycerides by 22.9% (all P < 0.0001). Mean high density lipoprotein-cholesterol (HDL-C) and apolipoprotein A1 were elevated 8.7% (P < 0.0001) and 4.5% (P < 0.0001), respectively, by cerivastatin 0.8 mg. Reductions of triglyceride and elevation in HDL-C were dependent upon triglyceride baseline levels; in patients having baseline triglyceride levels 250 - 400 mg/dl, cerivastatin 0.8 mg reduced median triglycerides by 29.5% and elevated HDL-C by 13.2%. Cerivastatin 0.8 mg was well tolerated. The most commonly reported adverse events included headache, pharyngitis and rhinitis (4 - 6%). Symptomatic creatine kinase elevations > 10 times upper limit of normal occurred in 0%, 1% and 0.9% of patients receiving placebo, cerivastatin 0.4 mg or cerivastatin 0.8 mg, respectively. Cerivastatin 0.8 mg is an effective and safe treatment for patients with primary hypercholesterolaemia who need aggressive LDL-C lowering in order to achieve NCEP-recommended levels.
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PMID:Efficacy and safety of cerivastatin 0.8 mg in patients with hypercholesterolaemia: the pivotal placebo-controlled clinical trial. Cerivastatin Study Group. 1089 18

Cilostazol (Pletal), a quinolinone derivative, has been approved in the U.S. for the treatment of symptoms of intermittent claudication (IC) since 1999 and for related indications since 1988 in Japan and other Asian countries. The vasodilatory and antiplatelet actions of cilostazol are due mainly to the inhibition of phosphodiesterase 3 (PDE3) and subsequent elevation of intracellular cAMP levels. Recent preclinical studies have demonstrated that cilostazol also possesses the ability to inhibit adenosine uptake, a property that may distinguish it from other PDE3 inhibitors, such as milrinone. Elevation of interstitial and circulating adenosine levels by cilostazol has been found to potentiate the cAMP-elevating effect of PDE3 inhibition in platelets and smooth muscle, thereby augmenting antiplatelet and vasodilatory effects of the drug. In contrast, elevation of interstitial adenosine by cilostazol in the heart has been shown to reduce increases in cAMP caused by the PDE3-inhibitory action of cilostazol, thus attenuating the cardiotonic effects. Cilostazol has also been reported to inhibit smooth muscle cell proliferation in vitro and has been demonstrated in a clinical study to favorably alter plasma lipids: to decrease triglyceride and to increase HDL-cholesterol levels. One, or a combination of several of these effects may contribute to the clinical benefits and safety of this drug in IC and other disease conditions secondary to atherosclerosis. In eight double-blind randomized placebo-controlled trials, cilostazol significantly increased maximal walking distance, or absolute claudication distance on a treadmill. In addition, cilostazol improved quality of life indices as assessed by patient questionnaire. One large randomized, double-blinded, placebo-controlled, multicenter competitor trial demonstrated the superiority of cilostazol over pentoxifylline, the only other drug approved for IC. Cilostazol has been generally well-tolerated, with the most common adverse events being headache, diarrhea, abnormal stools and dizziness. Studies involving off-label use of cilostazol for prevention of coronary thrombosis/restenosis and stroke recurrence have also recently been reported.
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PMID:Cilostazol (pletal): a dual inhibitor of cyclic nucleotide phosphodiesterase type 3 and adenosine uptake. 1183 Jul 53

71 Egyptian women using Norplant contraceptive implants for 1 year were followed with laboratory testing of carbohydrate, lipid and protein metabolism, liver and kidney function tests, serum iron and iron binding capacity and pituitary response to GnRH. The subjects were normal, healthy fertile, non-pregnant, non-lactating women who had not used hormone for 6 months. There were no pregnancies. Most women complained of altered menstrual patterns. Some reported headache, dizziness, increased vaginal discharge, nausea, and pain at the insertion site. There was no significant change in fasting or post-prandial glucose, or kidney function. Cholesterol decreased significantly at 3 months, triglycerides fell at 3 and 12 months, and HDL rose significantly at 3 and 12 months. SGPT fell significantly at 3 and 12 months. Total protein and albumin was significantly lower at 12 months. Serum iron and total iron binding capacity were significantly elevated at 3 and 12 months. Secretion of LH and FSH fluctuated around normal limits. The lipoprotein findings are discrepant from those reported from other developing countries in Norplant trials.
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PMID:Clinical chemistry and pituitary response changes in Egyptian acceptors of L. Norgestrel six rods implants during the first year of use. 1228 53

New progestin molecules have been synthesized for the purpose of maintaining the antiovulatory and antiestrogenic effects of existing progestins while suppressing their undesirable androgenic effects. Desogestrel, gestodene, and norgestimate are 3 third generation progestins now available in Europe in combined oral contraceptives (OCs) containing ethinyl estradiol. The 3 gonane molecules all result from modifications in the structure of levonorgestrel which neutralize its androgenic activity. The 3 molecules maintain their affinity for the androgen receptors. A review of the literature suggests that the third generation OCs have no major disadvantages compared to other low dose preparations now being marketed. Among the fundamental differences between levonorgestrel and the 3 new gonanes, the absence of the androgenic effect reveals the predominant estrogenic effect on HDL cholesterol and sex hormone binding globulin (SHBG). It appears however that the absence of androgenic effect does not affect the antiestrogenic power of the molecule at the level of the target cells such as the endometrium, or at the level of the pituitary cells. As with all low-dose formulations, a nonnegligible percentage of patients conserves ovarian activity with follicular maturation and estrogen secretion. It remains to be demonstrated whether the 2-10% of users reporting undesirable effects such as breast tenderness, swelling, headaches, and irritability are those in whom ovarian activity is not completely suppressed. The percentage of women using the third generation gonanes who conserve ovarian activity seems to be lower than that of users of the older low-dose formulations. Carbohydrate tolerance differs little from that observed with levonorgestrel. Modifications of coagulation factors reflect the estrogen content and do not differ in the third generation gonanes and older low-dose formulations. It is difficult to identify major clinical advantages of any 1 of the new preparations because of the minor differences between them. Prospective, longterm epidemiologic studies will be needed to confirm possible cardiovascular benefits and the absence of increased mammary pathology.
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PMID:[Disadvantages of third generation progestins]. 1231 28

Pharmacotherapy is limited for the relief of intermittent claudication (IC), a common manifestation of peripheral arterial disease (PAD). Pentoxyfylline, the only current pharmacological therapy for IC, has been shown to have similar efficacy as placebo. Cilostazol, a new phosphodiesterase III (PDE III) inhibitor, is a potent inhibitor of platelet aggregation with vasodilatory, antithrombotic, antiproliferative and positive lipid-altering effects. To evaluate the efficacy and safety of cilostazol for the treatment of IC in Indian patients, 123 patients were selected from 6 centres in India. The patients, aged 58-73 years, with the diagnosis of stable moderate-to-severe IC received cilostazol 100/50 mg twice daily for a period of 12 weeks. Primary efficacy measures included initial claudication distance (ICD) and absolute walking distance (ACD) by treadmill testing and ankle-brachial index (ABI) using Doppler ultrasonography-measured systolic pressures. Secondary efficacy outcomes included subjective assessment of symptom improvement by patient and investigator and estimation of lipid values. Adverse events were monitored throughout the study. Laboratory investigations were carried out at baseline and end of study. At the end of week 12 of cilostazol therapy, there was a significant improvement in the raw walking distances (ICD and ACD). Percentage change in ICD and ACD was 46.77% and 64.5%, respectively, at the end of study. There was a significant increase (32.7%) in the ABI by the end of study period. According to patient and investigator assessment of symptoms, 58-60% of the subjects showed significant improvement to complete resolution of claudication symptoms by the end of 12 weeks of therapy. In addition, there was a significant increase of 20.24% in the mean plasma HDL-cholesterol levels and a decrease of 29.55% in the mean plasma triglyceride concentrations by the end of study period. Headache, diarrhoea, palpitation and dizziness were the commonly reported adverse effects during the study. No adverse effect led to discontinuation of therapy. The present study suggests that cilostazol is an effective therapeutic option with an acceptable tolerability profile for the treatment of IC in patients with PAD.
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PMID:Efficacy and safety of cilostazol, a novel phosphodiesterase inhibitor in patients with intermittent claudication. 1516 99

Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects. The present study was undertaken to compare the effects of policosanol and ticlopidine in patients with moderately severe intermittent claudication (IC). The study had a 4-week baseline step, followed by a 20-week double-blinded, randomized treatment period. Twenty-eight eligible patients were randomized to policosanol 10 mg or ticlopidine 250 mg tablets twice daily (bid). Walking distances in a treadmill (constant speed 3.2 km/hr, slope 10 degrees, temperature 25 degrees C) were assessed before and after 20 weeks of treatment. Both groups were similar at baseline. Compared with baseline, policosanol significantly increased (p < 0.01) mean values of initial (ICD) and absolute (ACD) claudication distances from 162.1 to 273.2 m and from 255.8 to 401.0 m, respectively. Ticlopidine also raised significantly (p < 0.01) ICD (166.2 to 266.3 m) and ACD (252.9 to 386.4 m). Comparisons between groups did not show significant differences. Policosanol, but not ticlopidine, significantly (p < 0.05), but modestly, increased the ankle/arm pressure ratio. After 10 weeks, policosanol significantly (p < 0.001) lowered low-density lipoprotein-cholesterol (LDL-C), total cholesterol (TC) (p < 0.01), and TC/HDL-C and raised (p < 0.05) high-density lipoprotein-cholesterol (HDL-C). At study completion, policosanol lowered (p < 0.001) LDL-C (30.2%), TC (16.9%), and TC/HDL-C (33.9%), increased (p < 0.01) HDL-C (+31.7%), and left triglycerides unchanged. Ticlopidine did not affect the lipid profile variable. Policosanol induced modest, but significant, reductions (p < 0.01) of fibrinogen levels compared with baseline and ticlopidine. Treatments were well tolerated and did not impair safety indicators. Three ticlopidine patients (21.4%) withdrew from the trial, only 1 owing to a serious adverse experience (AE) (unstable angina). Three other ticlopidine patients experienced mild AE (headache, diarrhea, and acidity). It is concluded that policosanol (10 mg bid) can be as effective as ticlopidine (250 mg bid) for improving walking distances of claudicant patients, and it could be advantageous for the global risk of these individuals owing to its cholesterol-lowering effects. This study is, however, just a pilot comparison, so that further studies in larger sample sizes are needed for definitive conclusions of the comparative effects of both drugs on patients with IC.
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PMID:Effects of policosanol and ticlopidine in patients with intermittent claudication: a double-blinded pilot comparative study. 1525 82

Migraine has been associated with an unfavourable cardiovascular risk profile and with increased risk of cardiovascular disease. In a cross-sectional analysis of 27,626 women aged >or=45 years, we evaluated the association of migraine and migraine aura status with elevated levels of total cholesterol, low- and high-density lipoprotein cholesterol (HDL-C), non-HDL-C, apolipoprotein (Apo) A-1 and B(100), lipoprotein (a), C-reactive protein (CRP), fibrinogen, intercellular adhesion molecule-1, homocysteine and creatinine. A total of 5087 (18.4%) women reported any history of migraine. Compared with women with no migraine history, women who reported any history of migraine had modestly increased adjusted odds ratios (95% confidence interval) of 1.09 (1.01, 1.18) for elevated total cholesterol, 1.14 (1.05, 1.23) for non-HDL-C, 1.09 (1.01, 1.18) for Apo B(100) and 1.13 (1.05, 1.22) for CRP. The increase did not meaningfully differ according to migraine aura status and migraine frequency. In this large cohort of women, only a modest association was found between migraine and adverse levels of certain cardiovascular biomarkers.
Cephalalgia 2008 Jan
PMID:Migraine and biomarkers of cardiovascular disease in women. 1798 70

We investigated tolerability and efficacy of ezetimibe treatment (10 mg/d) in 25 heart allograft recipients already on stable statin therapy. Total cholesterol (TC), low-density cholesterol (LDL-C), high-density cholesterol (HDL-C), triglycerides (TG), immunosuppressant drug levels, laboratory and clinical parameters were assessed before, four months and one yr after initiation of ezetimibe treatment. Mean equivalent statin dose was 53.5 +/- 12.3 mg of pravastatin, remaining unchanged throughout the study period. Ezetimibe was generally well tolerated, only two patients (8%) discontinued ezetimibe due to stomach pain or headache. Mean TC decreased from 231.8 +/- 6.4 mg/dL before therapy to 202.2 +/- 8.8 mg/dL after four months and 192.9 +/- 7.0 mg/dL after one yr (p < 0.001). Mean LDL-C decreased from 143.1 +/- 5.4 mg/dL to 121.4 +/- 7.9 mg/dL (month 4; p < 0.05) and 107.1 +/- 5.6 mg/dL (one yr; p < 0.001). TG decreased from 182 +/- 14.3 mg/dL to 173.3 +/- 17.5 mg/dL after one yr (p < 0.05), whereas HDL-C was unchanged. Initial LDL-C and cardiac diagnosis before transplantation were identified as predictors of absolute LDL-C reduction. Immunosuppressant drug doses and blood concentrations were unchanged as well as other laboratory and clinical parameters. Ezetimibe appears safe and effective for further reduction of TC and LDL-C in heart allograft recipients already on stable statin therapy. Extent of pre-treatment LDL-C and cardiac disorder prior to transplantation appear to correlate with the efficacy of ezetimibe therapy.
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PMID:Ezetimibe effectively lowers LDL-cholesterol in cardiac allograft recipients on stable statin therapy. 1849 70


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