Effects Of Long-acting Nifedipine Research Articles

Abstract 13344: Beneficial Effects of Long-acting Nifedipine on Coronary Vasomotion Abnormalities After Drug-Eluting Stent Implantation -The NOVEL Study

Introduction: It is widely known that drug-eluting stents (DES) induce coronary vasomotion abnormalities. We have previously demonstrated that chronic treatment with long-acting nifedipine, which exerts cardiovascular protective effects through inhibition of vascular inflammation, suppresses DES-induced abnormal coronary vasoconstriction in pigs. In order to test whether this is also the case in humans, we performed a prospective, randomized, multicenter trial, termed as the NOVEL Study. Methods and Results: We enrolled 146 patients with stable angina pectoris who underwent elective implantation of everolimus-eluting stents (EES) in the left coronary arteries. They were randomly assigned to receive either conventional treatments alone (aspirin, clopidogrel, renin-angiotensin system inhibitor and statin) or additionally long-acting nifedipine (10-60 mg/day) (n=73 each). After 8-10 months, 53 patients in the control and 57 in the nifedipine group were finally examined for coronary reactivity to intracoronary acetylcholine (ACh) by quantitative coronary angiography after 48-hour withdrawal of nifedipine. Baseline patient characteristics and procedural profiles were comparable between the two groups. Coronary vasoconstricting responses to ACh were significantly enhanced at the distal segment adjacent to EES as compared with non-stented vessel (P<0.001) and were significantly inhibited in the nifedipine group (P<0.01) (Figure). Furthermore, the inflammatory profiles, including serum levels of high-sensitivity CRP and adiponectin, were improved only in the nifedipine group (P<0.05) (Figure). Conclusions: These results indicate that DES-induced coronary vasomotion abnormalities still remain an important clinical issue even with the second-generation of DES, for which long-acting nifedipine exerts beneficial effects associated with its anti-inflammatory effects.

Amlodipine Better Than Lisinopril?

The Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT) compared in >30 000 high-risk hypertensive patients the effects on coronary heart disease of 3 treatment strategies: (1) based on the diuretic chlorthalidone, (2) the calcium-channel blocker (CCB) amlodipine, and (3) the angiotensin converting-enzyme (ACE) inhibitor lisinopril, respectively.1 Sponsored by the National Heart, Lung, and Blood Institute, ALLHAT stands out because no differences occurred in the incidence of the primary end point that consisted of the combination of fatal coronary heart disease and acute myocardial infarction.1 Not surprisingly, the attention of the ALLHAT consortium shifted to secondary end points, such as stroke, or to loosely defined2 components of secondary end points, such as heart failure. At the end of the line, the ALLHAT investigators based their main conclusions on events that, at the initiation of the trial, they regarded as “soft data that will at best confirm or supplement the primary endpoint.”3 More importantly, what was not identical in the 3 treatment groups was the on-treatment blood pressure despite vigorous attempts to titrate and combine the study medications to achieve a blood pressure of <140 mm Hg systolic and 90 mm Hg diastolic.1 These salient features of ALLHAT should be kept in mind whenever one attempts to interpret the findings of this landmark trial. In this issue of Hypertension , Leenen et al4 published a post hoc analysis, in which they made a direct comparison of cardiovascular and other outcomes among the 18 102 ALLHAT participants randomly assigned to amlodipine or lisinopril. In line with previous reports,1 the incidence of the primary coronary end point and total and cardiovascular mortality were similar in both groups. However, the patients randomly assigned to lisinopril experienced higher risks of stroke, combined cardiovascular disease, gastrointestinal bleeding, …

Effect of Long-Acting Nifedipine on Mortality and Cardiovascular Morbidity in Patients With Symptomatic Stable Angina and Hypertension: The ACTION Trial

Effect of Long-Acting Nifedipine on Mortality and Cardiovascular Morbidity in Patients With Symptomatic Stable Angina and Hypertension: The ACTION Trial

An Updated Meta-Analysis With a Few Surprises

The meta-regression analysis by Verdecchia et al in this issue of Hypertension 1 updates the 2003 analyses of Staessen et al2 and the Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC).3 It includes the 5 trials published after those 2003 manuscripts were composed. All 5 of the additional studies were secondary prevention trials, all on patients with known coronary heart disease (CHD).4–8 In 4 of the 5, either an angiotensin-converting enzyme inhibitor (ACEI) or a calcium channel blocker (CCB) was compared with a placebo, providing an additional 3.0 to 6.1 mm Hg further reduction in the mean systolic blood pressure. In all of these 4 trials of ACEI or CCB versus placebo, patients were also receiving other antihypertensive drugs, mainly directly toward their coronary disease. The new analysis1 confirms …

Effect of long-acting nifedipine on blood pressure control and clinical outcome in patients with stable angina: The action study

Effect of long-acting nifedipine on blood pressure control and clinical outcome in patients with stable angina: The action study

Effect of long-acting nifedipine on mortality and cardiovascular morbidity in patients with symptomatic stable angina and hypertension: the ACTION trial

To examine the effects of nifedipine GITS on clinical outcome in patients with concurrent stable angina and hypertension. Data from the double-blind placebo-controlled ACTION trial was stratified for hypertension (blood pressure > or = 140/90 mmHg), at baseline. A total of 52% of 7665 ACTION patients were hypertensive. Some 80% were on a beta blocker; hypertensives were more often treated with other blood pressure-lowering drugs. Mean baseline blood pressure was 122/74 mmHg among normotensives and 151/85 mmHg among hypertensives. Follow-up blood pressures were reduced by nifedipine (P < 0.001) on the average by 3.9/2.4 and 6.6/3.5 mmHg among normotensives and hypertensives, respectively. Nifedipine GITS significantly (P < 0.05) reduced the combined incidence of all-cause mortality, myocardial infarction, refractory angina, heart failure, stroke and peripheral revascularization by 13% in hypertensives only. Nifedipine significantly reduced the incidence of any stroke or transient ischemic attack by almost 30% in both subgroups and the need for coronary angiography by 21% in normotensives and 16% in hypertensives. Among hypertensives, the incidence of new overt heart failure was significantly reduced by 38% and of debilitating stroke by 33%. Among normotensives, the need for coronary bypass grafting was significantly reduced by 32%. Nifedipine did not affect all-cause death, cardiovascular death and myocardial infarction in either normo- or hypertensives, but increased the need for peripheral revascularization. The salutary effects of the addition of nifedipine GITS to the basic regimen of patients with concurrent stable symptomatic coronary artery disease and hypertension emphasize the need for blood pressure control.

Effect of long-acting nifedipine on mortality and cardiovascular morbidity in patients with stable angina requiring treatment (ACTION trial): Randomised controlled trial

Irritable bowel syndrome (IBS) is one of the most common disorders seen by gastroenterologists. Visceral hypersensitivity is now well recognized as a clinical marker for the disease. Intrarectal lidocaine has been previously shown to decrease pain report from rectal distension in patients with IBS without any significant serum lidocaine levels. We conducted a prospective, double-blind, crossover trial on 10 patients with IBS to evaluate the effects of 300 mg intrarectal lidocaine jelly on abdominal pain. Ten Caucasian premenopausal women who met the Rome II criteria for diarrhea-predominant IBS were recruited into the study. All of the patients that participated had intermittent left lower quadrant pain and diarrhea. Each patient participated in 2 sessions in which saline jelly (placebo) and lidocaine jelly was administered on a double-blind, crossover basis. Patients participated in these sessions at a time when their ongoing pain was at least 3 on a 0 to 10 visual analogue scale. In comparison to placebo saline jelly, lidocaine jelly significantly decreased abdominal pain (P < .02) for at least 4 hours. None of the patients experienced any side effects. Intrarectal lidocaine may be a potentially useful treatment for chronic abdominal pain in IBS.The possible presence of abnormal sodium channels in the rectal and or colonic visceral afferents of patients with IBS might serve as a clue as to the effectiveness of rectal lidocaine. The dose of lidocaine used in this study may be of sufficient strength to normalize aberrant sodium channels that may be present in the colon of patients with IBS without affecting normal sodium channels of either IBS or control subjects.

Effect of long-acting nifedipine on mortality and cardiovascular morbidity in patients with stable angina requiring treatment (ACTION trial): randomised controlled trial

Calcium antagonists are widely prescribed for angina pectoris but their effect on clinical outcome is controversial. We aimed to investigate the effect of the calcium antagonist nifedipine on long-term outcome in patients with stable angina pectoris. We randomly assigned 3825 patients with treated stable symptomatic coronary disease to double-blind addition of nifedipine GITS (gastrointestinal therapeutic system) 60 mg once daily and 3840 to placebo. The primary endpoint was the combination of death, acute myocardial infarction, refractory angina, new overt heart failure, debilitating stroke, and peripheral revascularisation. Mean follow-up was 4.9 years (SD 1.1). Analysis was by intention to treat. 310 patients allocated nifedipine died (1.64 per 100 patient-years) compared with 291 people allocated placebo (1.53 per 100 patient-years; hazard ratio 1.07 [95% CI 0.91-1.25], p=0.41). Primary endpoint rates were 4.60 per 100 patient-years for nifedipine and 4.75 per 100 patient-years for placebo (0.97 [0.88-1.07], p=0.54). With nifedipine, rate of death and any cardiovascular event or procedure was 9.32 per 100 patient-years versus 10.50 per 100 patient-years for placebo (0.89 [0.83-0.95], p=0.0012). The difference was mainly attributable to a reduction in the need for coronary angiography and interventions in patients assigned nifedipine, despite an increase in peripheral revascularisation. Nifedipine had no effect on the rate of myocardial infarction. Addition of nifedipine GITS to conventional treatment of angina pectoris has no effect on major cardiovascular event-free survival. Nifedipine GITS is safe and reduces the need for coronary angiography and interventions.

Mortality in the Jerusalem 70-year-olds longitudinal study: does nifedipine have a role?

Short-acting nifedipine was found to be associated with increased mortality in elderly patients in some studies. We examined effects of long-acting nifedipine in a longitudinal study of Jerusalem 70 year olds (448 participants). After follow-up of 6.5 years (1990-1996) 70 subjects died. We examined the effects of baseline variables on total mortality. Hypertensives had higher mortality than normotensives, 21.2% versus 13.8%, p = 0.01. Diuretic-treated patients (n = 72), mostly hypertensive (n = 71), had significantly higher mortality than non-diuretic-treated patients (n = 375), 45.5% versus 14.1%; p < 0.001. Although nifedipine-treated patients had a higher prevalence of coronary heart disease diagnosis than diuretic-treated patients (52% versus 35%), their relative risk of mortality was 0.8 (CI 0.4-1.4) of that of diuretic-treated patients. A multiple logistic regression model, including gender, systolic blood pressure, creatinine, cholesterol, diagnosis of congestive heart failure, cardiovascular arrest, diabetes, previous myocardial infarction, physical activity, nifedipine, other calcium channel and beta blockers and diuretics, found only serum creatinine and diuretic therapy associated with total mortality, p = 0.004 and p < 0.02, respectively. When interaction terms were added to account for drug combinations, diuretic therapy lost significance, but the combination of diuretics and beta blockers (probably representing a more severe form of hypertension) became significant, p = 0.03. Long acting nifedipine is not associated with increased mortality in elderly hypertensives.

Effects of long-acting nifedipine on casual office blood pressure measurements, 24-hour ambulatory blood pressure profiles, exercise parameters and left ventricular mass and function in black patients with mild to moderate systemic hypertension

Thirty-nine black patients with mild to moderate hypertension were treated for 1 year with various long-acting preparations of nifedipine, during which time serial changes in 24-hour ambulatory blood pressure (BP), exercise performance, left ventricular (LV) mass index and LV systolic function were evaluated. Mean 24-hour ambulatory BP decreased from 156 ± 15 99 ± 8 to 125 ± 10 79 ± 6 mm Hg at 1 year (p <0.0001). LV mass index decreased from 130 ± 40 to 114 ± 39 g/m 2 at 6 weeks (p <0.005) and to 95 ± 32 at 1 year (p <0.0001). There was a significant reduction in septal and posterior wall thickness from 11.0 ± 2.0 to 9.3 ± 2.0 mm (p <0.0001) and from 10.9 ± 2.0 to 9.3 ± 2.0 mm (p <0.005), respectively. Cardiac index and fractional shortening changed insignificantly from 2.9 ± 0.7 to 2.9 ± 0.6 liters/min/m 2, and from 35 ± 5 to 36 ± 6%, respectively. At 1 year, using a modified Bruce protocol, exercise time increased from 691 ± 138 to 845 ± 183 seconds (p <0.05); peak exercise and 1 minute post-effort systolic BP decreased from 240 ± 26 to 200 ± 21 mm Hg and from 221 ± 27 to 169 ± 32 mm Hg (p <0.05), respectively. It is concluded that in the treatment of black patients with mild to moderate hypertension, the marked and sustained antihypertensive action of long-acting nifedipine documented by 24-hour ambulatory BP monitoring is associated with LV mass regression with no adverse effect on cardiac function together with a reduction in exercise systolic BP and a prolongation of exercise time.