Jack Zhang

Università degli Studi di Sassari, Sassari, Sardinia, Italy

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Publications (9)97.63 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: J Clin Hypertens (Greenwich). 2012; 14:821-827. ©2012 Wiley Periodicals, Inc. Combination antihypertensive therapies are recommended to attain blood pressure (BP) targets especially in high-risk patients in whom rapid and pronounced BP control is essential. This 28- to 54-week, open-label, multicenter study evaluated the safety and efficacy of a triple combination, aliskiren with amlodipine and hydrochlorothiazide (HCTZ), in patients with moderate to severe hypertension. Following a washout period of up to 4 weeks, patients received aliskiren/HCTZ 300/12.5 mg for 1 week, followed by add-on amlodipine 5 mg for 1 week. Thereafter, the doses of amlodipine and HCTZ were doubled. The first 206 of 564 patients who completed 28 weeks of study continued for an additional 26 weeks. Safety was assessed by recording all adverse events. Efficacy variables included changes in BP from baseline to endpoint and BP control rate. Of 564 patients, 493 completed the study. Peripheral edema (9.4%), headache (5.7%), nasopharyngitis (4.1%), and bronchitis (3.7%) were reported frequently. Clinically significant reductions in mean sitting systolic BP/mean sitting diastolic BP from baseline (-34.2/-20.3 mm Hg and -37.3/-21.8 mm Hg at weeks 28 and 54, respectively) were observed. Corresponding BP control rates were 69.1% and 77.1%. The aliskiren/amlodipine/HCTZ combination in patients with moderate to severe hypertension was well tolerated and provided clinically significant BP reductions and effective BP control.
    Journal of Clinical Hypertension 12/2012; 14(12):821-7. · 2.36 Impact Factor
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    ABSTRACT: Many patients with hypertension will require multiple antihypertensive drugs to achieve blood pressure (BP) control. This double-blind study evaluated the efficacy and safety of aliskiren/amlodipine single-pill combinations (SPCs) in patients with mild-to-moderate hypertension who were non-responsive to aliskiren monotherapy. After a 4-week run-in with aliskiren 300 mg, patients with mean sitting diastolic BP (msDBP) ≥90 and <110 mmHg were randomized to once-daily aliskiren/amlodipine 300/10 mg or 300/5 mg, or aliskiren 300 mg for 8 weeks. Aliskiren/amlodipine SPCs provided significantly greater mean reductions in mean sitting systolic BP/msDBP (300/10 mg, 18.0/13.1 mmHg; 300/5 mg, 14.4/10.5 mmHg) than aliskiren 300 mg (6.4/5.8 mmHg) at week 8 endpoint. This represents additional mean reductions of 11.6/7.2 mmHg (300/10 mg) and 8.0/4.7 mmHg (300/5 mg) over aliskiren alone (both p<0.0001). Significantly more patients achieved BP control (<140/90 mmHg) with aliskiren/amlodipine 300/10 mg (65.5%) and 300/5 mg (56.6%) than with aliskiren (31.5%; both p<0.0001). Aliskiren, alone and in combination with amlodipine, was well tolerated, with a slightly higher incidence of adverse events with SPCs (29.0-30.1%) than with monotherapy (22.7%). In conclusion, aliskiren/amlodipine SPCs offer an effective next step for patients who have an inadequate BP response to aliskiren alone.
    Current Vascular Pharmacology 02/2012; · 2.91 Impact Factor
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    ABSTRACT: To assess the long-term safety and antihypertensive efficacy of aliskiren/valsartan 300/320 mg combination. This was a 54-week, multicenter, open-label study (core phase), followed by a 26-week extension phase. Efficacy variables were change in msDBP and msSBP from baseline to endpoint (54-week and 80-week). Safety was assessed by monitoring and recording adverse events (AEs). ClinicalTrials.gov Identifier: NCT00386607 A total of 601 patients (msDBP ≥ 90 and <110 mmHg) entered the 54-week core study. Optional add-on HCT was allowed at week 10 onwards if BP was ≥ 140/90 mmHg at two consecutive visits. Of the 486 patients completed the core study, 180 patients entered the extension phase and received aliskiren/valsartan and add-on HCT (12.5 or 25 mg). Overall the combination of aliskiren/valsartan was well-tolerated and the majority of AEs were mild-to-moderate in severity. The incidence of SAEs was low (core phase: n = 22 [3.7%]; extension phase: n = 4 [2.2%]). Elevated serum potassium (>5.5 mmol/L at any time during the study) was observed in 21 (3.6%) patients. The majority of these elevations were transient and returned to normal in subsequent visits, and the discontinuation rate due to elevated serum potassium was low (0.3% [n = 2]). Decreased serum potassium levels (<3.5 mmol/L at any time during the study) was observed in 26 (4.4%) patients, mainly in patients receiving aliskiren/valsartan/HCT (n = 22; 7.1%). At the 54-week endpoint, a mean BP reduction of 20.5/13.4 mmHg from baseline (baseline BP: 152.9/97.0 mmHg) was observed and 66.9% (n = 398/595) of patients achieved BP control with aliskiren/valsartan with or without HCT. At the end of the extension phase (80-week endpoint), additional reduction in BP was obtained (overall, 28.8/18.3 mmHg) and 86.6% (n = 155/179) of patients achieved BP control with aliskiren/valsartan/HCT. A limitation is the absence of an active comparator group. Conclusion: Long-term treatment with the combination of aliskiren/valsartan with or without HCT provided clinically meaningful BP reductions and high rates of BP control and was well-tolerated.
    Current Medical Research and Opinion 11/2010; 26(12):2841-9. · 2.37 Impact Factor
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    ABSTRACT: Patients with stage 2 hypertension require large absolute reductions in blood pressure (BP) to achieve recommended BP goals. Combination therapy with the direct renin inhibitor, aliskiren, and the angiotensin receptor blocker, valsartan, has been shown to produce greater BP reductions than either agent alone in a double-blind study in 1797 hypertensive patients. This post-hoc analysis evaluated the BP-lowering efficacy of aliskiren in combination with valsartan in a subset of patients (n=581) with stage 2 hypertension (baseline mean sitting systolic BP [msSBP] > or =160 mmHg). Patients were randomized to receive aliskiren/valsartan 150/160 mg, aliskiren 150 mg, valsartan 160 mg, or placebo once daily for 4 weeks followed by 4 weeks at double the initial dose. Mean changes from baseline in msSBP and mean sitting diastolic BP were assessed at week-8 endpoint (intent-to-treat population). Aliskiren/valsartan 300/320 mg reduced BP from baseline by 22.5/11.4 mmHg at week-8 endpoint. BP reductions with combination therapy were significantly greater than with aliskiren 300 mg (17.3/8.9 mmHg, P<0.05), valsartan 320 mg (15.5/8.3 mmHg, P<0.01), or with placebo (7.9/3.7 mmHg, P<0.0001). BP control rates (<140/90 mmHg) were also significantly higher (P<0.05) with aliskiren/valsartan 300/320 mg (29.8%) compared with either aliskiren 300 mg (19.0%) or valsartan 320 mg (13.8%) monotherapy, or placebo (8.9%). All treatments were generally well tolerated. Combination therapy with aliskiren and valsartan provided significantly greater BP reductions over aliskiren or valsartan monotherapy and is an appropriate option for management of BP in patients with stage 2 hypertension.
    Advances in Therapy 01/2009; 25(12):1288-302. · 2.44 Impact Factor
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    ABSTRACT: Renin-angiotensin system (RAS) blockade with ACE inhibitor and/or angiotensin receptor blocker therapy can lead to increased potassium levels, hence the need to assess dual blockade involving a direct renin inhibitor. Here we report the results of a pre-planned 6-month interim analysis of a long-term, open-label study examining the safety, tolerability and efficacy of the aliskiren/valsartan 300/320-mg combination in patients with hypertension. A total of 601 patients with hypertension (msDBP > or = 90 and < 110 mmHg) received a combination of aliskiren/valsartan 150/160 mg for 2 weeks followed by forced titration to aliskiren/valsartan 300/320 mg once daily for a targeted duration of 52 weeks. Optional hydrochlorothiazide (HCTZ) addition was allowed from week 8 for inadequate BP control (> or = 140/90 mmHg). The primary objective was to assess the safety of combination therapy; potassium elevations were a predefined safety outcome. BP was measured at regular intervals during the study. At the 6-month cut-off date, 512 patients (85.2%) were still ongoing with study treatment, and 192 patients had received at least one dose of HCTZ add-on during this period. Combination therapy was generally well-tolerated; the most commonly reported adverse events were headache (7.5%), dizziness (7.3%) and nasopharyngitis (7.2%). Ten patients (2.5%) receiving aliskiren/valsartan and two patients (1.0%) receiving aliskiren/valsartan/HCTZ had serum potassium elevations > 5.5 mmol/L. Only one patient (0.2%) exhibited potassium levels > or = 6.0 mmol/L during this period and the patient was treated with aliskiren/valsartan. Mean msSBP/DBP reductions of 22.3/14.4 mmHg were observed at 6-month endpoint (LOCF analysis) and 73.4% of patients achieved BP control (< 140/90 mmHg; LOCF). Although lack of an active comparator group is a limitation of the study, our findings show that long-term treatment with the aliskiren/valsartan 300/320-mg combination provided clinically significant BP lowering, was well-tolerated and was associated with a very low rate of potassium elevations in patients with hypertension.
    Current Medical Research and Opinion 04/2008; 24(4):1039-47. · 2.37 Impact Factor
  • The Lancet 10/2007; 370(9593):1126-7. · 39.06 Impact Factor
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    ABSTRACT: The aim of this study was to assess dual renin system intervention with the maximum recommended doses of aliskiren and valsartan, compared with each drug alone in patients with hypertension. In this double-blind study, 1797 patients with hypertension (mean sitting diastolic blood pressure 95-109 mm Hg and 8-h daytime ambulatory diastolic blood pressure > or =90 mm Hg) were randomly assigned to receive once-daily aliskiren 150 mg (n=437), valsartan 160 mg (455), a combination of aliskiren 150 mg and valsartan 160 mg (446), or placebo (459) for 4 weeks, followed by forced titration to double the dose to the maximum recommended dose for another 4 weeks. The primary endpoint was change in mean sitting diastolic blood pressure from baseline to week 8 endpoint. Analyses were done by intention to treat. This trial is registered at ClinicalTrials.gov with the number NCT00219180. 196 (11%) patients discontinued study treatment before the end of the trial (63 in the placebo group, 53 in the aliskiren group, 43 in the valsartan group, and 37 in the aliskiren/valsartan group), mainly due to lack of therapeutic effect. At week 8 endpoint, the combination of aliskiren 300 mg and valsartan 320 mg lowered mean sitting diastolic blood pressure from baseline by 12.2 mm Hg, significantly more than either monotherapy (aliskiren 300 mg 9.0 mm Hg decrease, p<0.0001; valsartan 320 mg, 9.7 mm Hg decrease, p<0.0001), or with placebo (4.1 mm Hg decrease, p<0.0001). Rates of adverse events and laboratory abnormalities were similar in all groups. The combination of aliskiren and valsartan at maximum recommended doses provides significantly greater reductions in blood pressure than does monotherapy with either agent in patients with hypertension, with a tolerability profile similar to that with aliskiren and valsartan alone.
    The Lancet 07/2007; 370(9583):221-9. · 39.06 Impact Factor
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    ABSTRACT: Aliskiren is a novel, orally active renin inhibitor. Its antihypertensive efficacy and safety, alone and in combination with hydrochlorothiazide (HCTZ), were investigated in an 8-week, double-blind, placebo-controlled trial in hypertensive patients. The effects of these treatments on plasma renin activity (PRA) were also assessed. A total of 2776 patients aged >or=18 years with mean sitting diastolic blood pressure (MSDBP) 95-109 mmHg were randomized to receive once-daily treatment with aliskiren (75, 150 or 300 mg), HCTZ (6.25, 12.5 or 25 mg), the combination of aliskiren and HCTZ, or placebo, in a factorial design. The primary endpoint was the change in MSDBP from baseline to week 8. PRA was assessed at these timepoints at selected study centers. Aliskiren monotherapy was superior to placebo (P < 0.001; overall Dunnett's test) in reducing MSDBP and mean sitting systolic blood pressure (MSSBP). Combination treatment was superior to both component monotherapies in reducing BP (maximum MSSBP/MSDBP reduction of 21.2/14.3 mmHg from baseline with aliskiren/HCTZ 300/25 mg), and resulted in more responders (patients with MSDBP < 90 mmHg and/or >or=10 mmHg reduction) and better control rates (patients achieving MSSBP/MSDBP < 140/90 mmHg) than either monotherapy. Aliskiren monotherapy reduced PRA by up to 65% from baseline. Although HCTZ monotherapy increased PRA by up to 72%, PRA decreased in all of the combination therapy groups. All active treatments were well tolerated. Aliskiren monotherapy demonstrated significant BP lowering, and its effect was considerably greater when combined with HCTZ. Renin inhibition with aliskiren neutralized the compensatory rise in PRA induced by HCTZ.
    Journal of Hypertension 02/2007; 25(1):217-26. · 4.22 Impact Factor
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    ABSTRACT: The antihypertensive efficacy and safety of the direct renin inhibitor aliskiren were assessed in a pooled analysis of data from seven randomized, multicenter studies. Data were available for 7,045 patients (mean age 52.5 to 59.8 years, 50.2 to 72.5% men) with mild-to-moderate hypertension (mean sitting diastolic blood pressure [msDBP] 95 to 109 mm Hg) over treatment durations of 6 to 8 weeks. In placebo-controlled trials, aliskiren reduced mean sitting systolic blood pressure/msDBP from baseline by 8.6 to 12.1/7.2 to 10.3 mm Hg (75 mg), 8.7 to 13.0/7.8 to 10.3 mm Hg (150 mg), 14.1 to 15.8/10.3 to 12.3 mm Hg (300 mg), and 15.7 to 15.8/11.5 to 12.5 mm Hg (600 mg), compared with 2.9 to 10.0/3.3 to 8.6 mm Hg for placebo. Aliskiren demonstrated comparable efficacy in men and women, in patients aged <65 years or >/=65 years, and lowered blood pressure (BP) effectively in all racial subgroups. Combination of aliskiren 150 mg or 300 mg with ramipril, amlodipine, or hydrochlorothiazide provided significant additional BP reductions compared with the respective monotherapies. The overall incidence of adverse events with aliskiren monotherapy was similar to placebo (39.8% vs. 40.2%, respectively). The incidence of diarrhea with aliskiren was higher than placebo due to a significantly higher rate with aliskiren 600 mg (P < .0001 vs. placebo). In conclusion, aliskiren 150 mg or 300 mg provides highly effective and consistent BP lowering with placebo-like tolerability in patients with mild-to-moderate hypertension.
    Journal of the American Society of Hypertension 01/2007; 1(4):264-77. · 2.84 Impact Factor

Publication Stats

555 Citations
97.63 Total Impact Points

Institutions

  • 2012
    • Università degli Studi di Sassari
      Sassari, Sardinia, Italy
    • Hospital Universitario La Paz
      Madrid, Madrid, Spain
  • 2008–2010
    • Oklahoma City University
      Oklahoma City, Oklahoma, United States
  • 2007
    • University of Alabama at Birmingham
      • Department of Medicine
      Birmingham, AL, United States
    • IntraMed
      Buenos Aires, Buenos Aires F.D., Argentina
    • University of Maryland, Baltimore
      • Division of Nephrology
      Baltimore, MD, United States