Effects of isradipine sustained release on platelet function and fibrinolysis in essential hypertensives with or without other risk factors

Abstract

The aim of this study was to assess the chronic effects of a highly selective dihydropiridine calcium channel blocker, israpidine, in its sustained release form (I-SRO), on platelet functions and fibrinolytic parameters in subjects with essential hypertension (EH) combined or not with other well-known cardiovascular risk factors, such as cigarette smoking (EH+S) and type II diabetes mellitus (EH+DM). Thirty-six patients with essential hypertension with sitting diastolic blood pressures of 96-104 mmHg without (EH, n = 12) or with other risk factors (EH+S, n = 12, EH+DM, n = 12) were enrolled. After a 4-week, single-blind, placebo run-in period, the subjects received I-SRO 5 mg once daily for 18 weeks. After both placebo and 6 and 18 weeks of I-SRO treatment, the following parameters were measured: sitting blood pressure by mercury sphygmomanometer; platelet aggregation, plasma beta-thromboglobulin (BTG), platelet factor-4 (PF4), and plasminogen activator inhibitor 1 (PAI-1) by means of ELISA methods; and euglobulin lysis time before (ELT) and after standardized (10 min) venous occlusion (ELT-VO). In the group of patients as a whole compared with placebo, I-SRO significantly reduced SBP/DBP platelet aggregation, BTG, PF4, ELT, and ELT-VO. Significant reductions in these parameters were also observed in each group. In addition to the antihypertensive effect, I-SRO chronic treatment may favorably affect the platelet function and fibrinolytic system in essential hypertension with or without other cardiovascular risk factors.

Dihydropyridine Calcium Antagonists Increase Fibrinolytic Activity: A Systematic Review

“…The search resulted in 26 studies investigating the effect of calcium antagonists on fibrinolytic parameters Winther 1989, 1991;Gleerup et al, , 1995Ahaneku et al, 2000a, b, c;Fogari et al, 2003Fogari et al, , 2004De Luca et al, 2000;Pahor et al, 2002;Sengeløv and Winther, 1989;Raccah et al, 1994;Ranieri et al, 1996;Smith et al, 1997;Fujinishi et al, 1997;Held et al, 1997;Yin et al, 1998;Sakata et al, 1999;Candela et al, 2001;Chi et al, 2002;Turchetti et al, 2002;Mugellini et al, 2004;Ishikawa et al, 2005;Ruilope et al, 2005;Roos et al, 2001). Fifteen studies were randomized studies (De Luca et al, 2000;Pahor et al, 2002;Winther 1989, 1991;Held et al, 1997;Yin et al, 1998;Sakata et al, 1999;Fogari et al, 2003Fogari et al, , 2004Mugellini et al, 2004;Roos et al, 2001;Sengelov and Winther, 1989;Ranieri et al, 1996;Fujinishi et al, 1997;Chi et al, 2002;Turchetti et al, 2002;Ishikawa et al, 2005), and the remaining were longitudinal cohort studies (Ahaneku et al, 2000a, b, c).…”

“…Fifteen studies were randomized studies (De Luca et al, 2000;Pahor et al, 2002;Winther 1989, 1991;Held et al, 1997;Yin et al, 1998;Sakata et al, 1999;Fogari et al, 2003Fogari et al, , 2004Mugellini et al, 2004;Roos et al, 2001;Sengelov and Winther, 1989;Ranieri et al, 1996;Fujinishi et al, 1997;Chi et al, 2002;Turchetti et al, 2002;Ishikawa et al, 2005), and the remaining were longitudinal cohort studies (Ahaneku et al, 2000a, b, c). One longitudinal cohort study and three randomized trials were excluded afterwards because of insufficient data presented (Raccah et al, 1994;Smith et al, 1997;Ishikawa et al, 2005;Ruilope et al, 2005).…”

“…The fibrinolytic effect of calcium antagonists was most often studied in patients with hypertension (Gleerup et al, , 1995Ranieri et al, 1996;Chi et al, 2002) (15 studies, 406 patients) (De Luca et al, 2000;Pahor et al, 2002;Gleerup and Winther, 1989;Ahaneku et al, 2000a, b, c;Sakata et al, 1999;Fogari et al, 2003Fogari et al, , 2004Mugellini et al, 2004). Other investigations were performed in patients with angina pectoris (one study, 301 patients) (Held et al, 1997), SAH (one study, 27 patients) (Roos et al, 2001), preeclampsia (one study, 14 patients) (Yin et al, 1998), coronary artery disease (one study, 11 patients) (Fujinishi et al, 1997), congestive heart failure (one study, 10 patients) (Turchetti et al, 2002), and systemic sclerosis (one study, seven patients) (Candela et al, 2001).…”

“…In 21 studies (501 patients), the following calcium antagonists from the dihydropyridine group were studied: isradipine (n = 6) Winther 1989, 1991;Gleerup et al, , 1995Ranieri et al, 1996;Yin et al, 1998), amlodipine (n = 6) (Fogari et al, 2003Turchetti et al, 2002;De Luca et al, 2000;Pahor et al, 2002;Ahaneku et al, 2000a), nifedipine (n = 2) (Candela et al, 2001;Chi et al, 2002), cilnidipine (n = 2) (Ahaneku et al, 2000b, c), nimodipine (n = 1) (Roos et al, 2001), felodipine (n = 1) (Sengeløv and Winther, 1989), manidipine (n = 1) , nitrendipine (n = 1) (Sakata et al, 1999), and nisoldipine (n = 1) (Fujinishi et al, 1997). In one study (301 patients), the Dihydropyridines enhance fibrinolysis -review MDI Vergouwen et al See appendix for abbreviations.…”

“…(D) Methodology: The methodological quality of the included studies was sufficient in 16 studies (De Luca et al, 2000;Pahor et al, 2002;Gleerup and Winther, 1989;Sengeløv and Winther, 1989;Ahaneku et al, 2000a, b, c;Held et al, 1997;Yin et al, 1998;Sakata et al, 1999;Candela et al, 2001;Fogari et al, 2003Fogari et al, , 2004Turchetti et al, 2002;Mugellini et al, 2004;Roos et al, 2001), and insufficient in six studies (Gleerup et al, , 1995Ranieri et al, 1996;Fujinishi et al, 1997;Chi et al, 2002). The median score was 5 (range 1 to 7).…”