Doxazosin and hydrochlorothiazide equally affect arterial wall thickness in hypertensive males with hypercholesterolaemia (the DAPHNE study). Doxazosin Atherosclerosis Progression Study in Hypertensives in the Netherlands. Effect of high dose verapamil on restenosis after peripheral angioplasty. Impact of ramipril in patients with evidence of clinical or subclinical peripheral arterial disease. ACE-inhibition with perindopril in essential hypertensive patients with concomitant diseases. The Perindopril Therapeutic Safety Collaborative Research Group.
Observational studies suggest a synergistic effect of hypertension and hyperlipidaemia on the progression of atherosclerosis. The alpha-blocker doxazosin has favourable effects on plasma lipids, insulin resistance and blood pressure, while the diuretic hydrochlorothiazide (HCTZ) principally affects blood pressure and increases insulin resistance.
                A randomised double-blind study over 36 months was performed to compare the effects of doxazosin and HCTZ on fasting lipids and on progression of peripheral atherosclerosis. Eighty males (45 to 70 years) with peripheral atherosclerotic disease and increased cholesterol levels (5.2-8.0 mmol/l) were treated for essential hypertension with either doxazosin (n = 41) or HCTZ (n = 39). Main outcome measures were arterial intima-media thickness (IMT) of the carotid and femoral arteries and fasting lipid parameters.
                In the doxazosin-treated group, significant changes were observed in the concentration of triglycerides (-13.7%, p < 0.01), HDLc (+25.7%, p < 0.05) and IDLc (-30.1%, P < 0.05). In the HCTZ-treated group no significant changes in plasma lipid levels were observed. On follow-up visits systolic blood pressure in the doxazosin-treated group was 6 mm higher than in the HCTZ group. Nevertheless, the groups treated with doxazosin or HCTZ showed no differential effect on IMT after three years of treatment (p = 0.8). A significant reduction of the IMT of combined carotid and femoral arterial walls was shown in both treatment groups (p < 0.005).
                Hypertension treatment with doxazosin or HCTZ resulted in a comparable change in arterial IMT after three years, in spite of differences in effect on plasma lipids. The study emphasises the importance of blood pressure control in patients with peripheral vascular disease and hypercholesterolaemia. We sought to determine whether treatment with high dose verapamil prevents restenosis in patients at high risk for reoccurrence after successful percutaneous transluminal coronary angioplasty (PTCA).
                Restenosis is the major limitation of PTCA. Calcium antagonists have demonstrated some potential as inhibitors of this process.
                A total of 98 patients with peripheral occlusive arterial disease (POAD), stable angina pectoris, mild hypertension and at least one additional risk factor increasing the likelihood of restenosis after angioplasty were selected for this placebo-controlled, double-blind, randomized trial. Verapamil (240 mg twice daily) or placebo was taken for 6 months. Efficacy variables assessed before and after angioplasty and at 6 weeks and 6 months after PTCA included thickness of the intima/media complex degree of stenosis, interventricular septal thickness, crurobrachial pressure ratios of dorsalis pedis and posterior tibial arteries, distance to claudication and total vessel diameter.
                No significant intergroup differences emerged before or immediately after PTCA. Six weeks after angioplasty, a significant thickening of the intima/media complex in the treated vascular segment of 14.3% occurred in the placebo group versus 0% among verapamil patients (p < 0.01). At 6 months, the intima/media thickness was 35.7% greater in the placebo group but had decreased by 14.3% in the verapamil group (p < 0.001). At 6 months, a marked reduction in septal thickness was observed in the verapamil group versus that in the placebo group (p < 0.001). The rate of restenosis was also significantly lower in the verapamil group (p < 0.001). Few minor side effects were reported.
                In patients with POAD at increased risk for restenosis, the administration of high dose verapamil prevented recurrent stenosis for 6 months after successful peripheral angioplasty and was well tolerated. The aim of this study was to assess the prognostic importance of peripheral arterial disease (PAD) as evaluated by ankle blood pressure index (ABI), and the impact of ramipril on the prevention of major cardiovascular events in PAD patients included in the Heart Outcomes Prevention Evaluation (HOPE) study.
                Patients were randomized to treatment with ramipril or placebo and followed for 4.5 years. Ankle brachial blood pressure index was measured, mainly by digital palpation of the foot pulse, at baseline in 8986 patients. The ABI was subnormal (< or =0.9) in 3099 patients and normal in 5887 patients. A low ABI was a strong predictor of morbidity and mortality during the follow-up even in patients with no clinical symptoms of PAD (n=6769). This was so for the primary outcome of the study; ABI>0.9:13.1%, 0.6-0.9: 18.2% and <0.6: 18.0% (P<0.0001) and for mortality from all causes: in those with a normal ABI it was 8.5%, in those with ABI >0.6-0.9, 12.4% and 14.2% in those with an ABI lower than 0.6 (P<0.0001). Ramipril reduced the risk of clinical outcomes in those with a clinical history of PAD as well as in the patients with subclinical PAD.
                The ABI even if measured simply by palpation of the foot arteries is a strong predictor for future cardiovascular events and for all-cause mortality. Ramipril prevented major cardiovascular events in patients with clinical as well as subclinical PAD. Many hypertensive patients have other, usually long-term diseases. Antihypertensive therapy may interfere with these diseases and their therapies. In the present study, the possible interactions of the ACE-inhibitor perindopril with several of the most common long-term diseases was evaluated.
                In a multicenter, double-blind, randomized, placebo-controlled trial, the effect of perindopril was evaluated in 490 patients with mild essential hypertension and any one of the following concomitant diseases: hyperlipidemia, type II diabetes mellitus, ischemic heart disease, cardiac arrhythmia, peripheral arterial occlusive disease, nephropathy with proteinuria, chronic obstructive pulmonary disease, or degenerative joint disease treated with nonsteroidal anti-inflammatory drugs (NSAIDs). After a 3-week single-blind placebo run-in, the patients received either perindopril (4 mg/d) or matching placebo for 6 weeks.
                Blood pressure was effectively reduced by perindopril irrespective of the associated disease. The rate of spontaneously reported side effects was low. Treatment with perindopril was free from adverse interactions with the concomitant diseases and therapies. Moreover, favorable actions could be observed in patients with ischemic heart disease (reduction of maximal ST-segment depression during peak exercise and decrease in the number of angina attacks), in patients with proteinuria (decrease in albuminuria in patients with normal serum creatinine levels), and in patients with NSAID-treatment (increase in prostaglandin E2 concentration in gastric mucosa suggesting gastric cytoprotection).
                This trial shows that ACE-inhibition with perindopril represents a simple, safe, and effective short-term therapeutic option for the large proportion of patients with mild essential hypertension and concomitant diseases and therapies.