Safety of the Up-titration of Nifedipine GITS and Valsartan or Low-dose Combination in Uncontrolled Hypertension: the FOCUS Study.

PURPOSE: Doubling the dose of antihypertensive drugs is necessary to manage hypertension in patients whose disease is uncontrolled. However, this strategy can result in safety issues. This study compared the safety and efficacy of up-titration of the nifedipine gastrointestinal therapeutic system (GITS) with up-titration of valsartan monotherapy; these were also compared with low-dose combinations of the two therapies. METHODS: This prospective, open-label, randomized, active-controlled, multicenter study lasted 8 weeks. If patients did not meet the target blood pressure (BP) after 4 weeks of treatment with low-dose monotherapy, they were randomized to up-titration of the nifedipine GITS dose from 30 mg (N30) to 60 mg or valsartan from 80 mg to 160 mg or they were randomized to receive a low-dose combination of N30 and valsartan 80 mg for another 4 weeks. BP variability was assessed by using the SD or the %CV of the short-term BP measured at clinic. FINDINGS: Of the 391 patients (20~70 years with stage II or higher hypertension) screened for study inclusion, 362 patients who had 3 BP measurements were enrolled. The reduction in the mean systolic/diastolic BP from baseline to week 4 was similar in both low-dose monotherapy groups with either N30 or valsartan 80 mg. BP variability (SD) was unchanged with either therapy, but the %CV was slightly increased in the N30 group. There was no significant difference in BP variability either in SD or %CV between responders and nonresponders to each monotherapy despite the significant difference in the mean BP changes. The up-titration effect of nifedipine GTS from 30 to 60 mg exhibited an additional BP reduction, but this effect was not shown in the up-titration of valsartan from 80 to 160 mg. Although the difference in BP was obvious between high-dose nifedipine GTS and valsartan, the BP variability was unchanged between the 2 drugs and was similar to the low-dose combinations. There was a low rate of adverse events in all treatment groups. In addition, escalating the dose of either nifedipine GITS or valsartan revealed a similar occurrence of adverse effects with low-dose monotherapy or the low-dose combination. IMPLICATIONS: Compared with up-titration of the angiotensin receptor blocker valsartan, up-titration of the calcium channel blocker nifedipine GITS provided no additional increased safety concerns and revealed better mean reductions in BP without affecting short-term BP variability. ClinicalTrials.gov identifier: NCT01071122.

High-dose atorvastatin for preventing contrast-induced nephropathy in primary percutaneous coronary intervention.

AIMS: To evaluate the efficacy of high-dose atorvastatin on contrast-induced nephropathy (CIN) occurrence in patients with ST-elevation myocardial infarction undergoing primary angioplasty. METHODS: We studied whether 80  mg atorvastatin loading and its subsequent use for 5 days (high-dose group) could prevent CIN as compared to those who received 10  mg atorvastatin (regular-dose group) in patients with ST-elevation myocardial infarction undergoing primary angioplasty. The primary endpoint was incidence of CIN, defined as an at least 25% or at least 0.5  mg/dl increase in baseline serum creatinine within 5 days after contrast administration. The secondary endpoint was an in-hospital 1 and 6-month renal function change, and a composite of all-cause mortality, myocardial infarction, renal failure requiring dialysis, heart failure, and target vessel revascularization. RESULTS: One hundred and ten patients were allocated to high dose and 108 to regular dose from August 2007 to February 2009. CIN incidence was 5.5% (6/110) in the high-dose group and 10.2% (11/108) in the regular-dose group, which is a nonsignificant difference (P = 0.193). CIN occurred significantly less in the high-dose than in the regular-dose group in subgroups of renal insufficiency (creatinine clearance ≤60  ml/min) [0% (0/28) vs. 16.7% (5/30); P = 0.024] and in the elderly patients who were at least 70 years old [4% (1/25) and 23.1% (6/26); P = 0.048]. Serum creatinine level tended to decrease in the high-dose group and increase in the regular-dose group, but the change was not statistically different (P = 0.093). The composite of clinical outcomes at 6 months was comparable in the high-dose and regular-dose groups (7.9 and 13.1%; P = 0.26). CONCLUSION: High-dose atorvastatin pretreatment does not seem to prevent CIN in patients receiving primary angioplasty. However, it has the potential to lower CIN in patients with renal insufficiency and in the elderly.