A Phase I, double-blind, randomized, crossover study in healthy males (N=106) was conducted between March 21, 2004, and May 17, 2004, to determine the magnitude and duration of the hemodynamic interaction of avanafil (a phosphodiesterase type-5 inhibitor for treating males with erectile dysfunction) when coadministered with glyceryl trinitrate (NTG) compared with sildenafil and placebo. Subjects received avanafil (200 mg), sildenafil (100 mg), and placebo (on separate days) via the oral route followed by NTG (0.4 mg) 12, 8, 4, 1, or 0.5 hours post-dose via the sublingual route. Blood pressure (BP) and heart rate (HR) were assessed at defined intervals.Throughout the study (after administration of the study drug, and including the period after NTG administration), the effects of avanafil and sildenafil on BP and HR were significantly greatest overall, at the shortest (0.5-hour) time interval compared with placebo. By the 8- and 12-hour time intervals, no significant difference in BP or HR was observed for avanafil (8 and 12 hours) or sildenafil (12 hours) (p>0.05, compared with placebo). Compared with avanafil, sildenafil had a significantly greater effect when dosed 0.5 hours before NTG on standing HR (p=0.05); 1 hour before NTG on standing systolic blood pressure (SBP) (p<0.05), sitting SBP (p=0.01) and standing HR (p<0.01); and 12 hours before NTG on standing SBP (p=0.05). Throughout the study, symptomatic hypotension adverse events occurred in 27%, 29%, and 12%, and clinically significant reductions in standing SBP (≥30 mmHg) occurred in 15%, 29%, and 12% of subjects dosed with avanafil, sildenafil, and placebo, respectively (overall treatment differences: p<0.01 and p<0.05, respectively).These data show that avanafil and sildenafil have no significant effect on BP and HR if administered to healthy males ≥8 hours (avanafil) or ≥12 hours (sildenafil) before a sublingual dose of NTG. However, results may differ in populations with known vascular disease, especially those using other concurrent pharmacotherapy. These findings may be of interest to clinicians who treat patients with erectile dysfunction and who also have a cardiovascular condition. Of note, the applicability of these results in such patients may be limited because the enrollment comprised healthy, normal subjects.
Cardiovascular disease mortality in the Philippines was studied from the existing vital statistics for 1963-76. Death rates from rheumatic fever and rheumatic heart disease remained unchanged, those for cerebrovascular diseases decreased, whereas mortality rates of ischaemic heart disease (IHD) and hypertensive disease (HPN) increased enormously both in men and women. This increase in IHD and HPN mortality was seen in all age groups. The age-standardized IHD mortality rate in men rose from 33.3 in 1964 to 78.0 in 1976, and that of women from 15.4 to 34.5. The age-standardized HPN mortality rate in men rose from 21.0 in 1964 to 45.6 in 1976, and that of women from 15.6 to 25.5. The male to female ratios in the age-standardized death rates for IHD, HPN and also for all causes increased during this 12-year period. Age-standardized all causes mortality increased clearly in the male population but decreased in the female population of the Philippines. This excess mortality in males is mostly due to the increased cardiovascular disease death rate. This is a clear example of how chronic non-communicable diseases are becoming major health problems in countries where they previously have not been prevalent. Immediate preventive measures are needed in order to control cardiovascular diseases in these countries where disease rates are rapidly increasing.
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