Blood pressure lowering efficacy of renin inhibitors for primary hypertension: a Cochrane systematic review.

We conducted a systematic review and meta-analysis of double-blind randomized controlled trials to quantify the dose-related systolic (SBP) and diastolic blood pressure (DBP) lowering efficacy of renin inhibitors vs placebo in the treatment of adults with primary hypertension. Databases searched were Medline (1966-March 2008), EMBASE (1988-March 2008) and Cochrane Central Register of Controlled Trials (CENTRAL). Six trials in 3694 patients met the inclusion criteria. All examined aliskiren, the only renin inhibitor licensed for marketing in Canada and the United States. Aliskiren caused a dose-related SBP/DBP lowering effect compared to placebo: weighted mean difference with 95% CI: aliskiren 75 mg, -2.9 (-4.6, -1.3)/-2.3 (-3.3, -1.3) mm Hg; aliskiren 150 mg, -5.5 (-6.5, -4.4)/-3.0 (-3.7, -2.3) mm Hg; aliskiren 300 mg, -8.7 (-9.7,-7.6)/-5.0 (-5.6, -4.3) and aliskiren 600 mg, -11.4 (-13.5, -9.2)/-6.6 (-7.9, -5.2) mm Hg. Aliskiren 300 mg significantly lowered both SBP -3.0 (-4.0, -2.0) and DBP -1.7 (-2.3, -1.0) as compared to aliskiren 150 mg. Aliskiren has no effect on blood pressure variability. No data were available to assess the effect of aliskiren on heart rate or pulse pressure. This review found weak evidence that during 4- to 8-week use, aliskiren did not increase withdrawals due to adverse effects as compared to placebo. We concluded that aliskiren has a dose-related blood pressure lowering effect better than placebo and magnitude of effect is similar to that determined for angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.

Pharmacological interventions for hypertensive emergencies: a Cochrane systematic review.

Hypertensive emergencies occur when high blood pressure is associated with the presence of acute end-organ damage, such as hypertensive encephalopathy. There is controversy as to when and which antihypertensive drugs to use in these situations. Using a comprehensive search strategy in electronic sources, MEDLINE, EMBASE and Cochrane clinical trial register, we conducted a systematic review to look all randomized control trials (RCTs) that compare an antihypertensive drug versus placebo, no treatment or another antihypertensive drug. Fifteen RCTs (representing 869 patients) met the inclusion criteria. Two trials included a placebo arm. All studies (except one) were open-label trials. Seven drug classes were evaluated in those trials: nitrates (nine trials), angiotensin-converting enzyme inhibitors (seven), diuretics (three), calcium channel blockers (six), alpha-1 adrenergic antagonists (four), direct vasodilators (two) and dopamine agonists (one). Mortality event data were reported in seven trials. Due to insufficient data, no meta-analysis was performed for clinical outcomes. Differences in blood pressure changes between antihypertensives were minor. There is no RCT evidence demonstrating that antihypertensive drugs reduce mortality or morbidity in patients with hypertensive emergencies. Furthermore, there is insufficient RCT evidence to determine which drug or drug class is most effective in reducing mortality and morbidity. There were some minor differences in the degree of blood pressure lowering when one class of antihypertensive drug is compared to another. However, the clinical significance is unknown. RCTs are needed to assess different drug classes to determine initial and longer-term mortality and morbidity outcomes.

Pharmacological interventions for hypertensive emergencies.

BACKGROUND: Hypertensive emergencies, marked hypertension associated with acute end-organ damage, are life-threatening conditions. Many anti-hypertensive drugs have been used in these clinical settings. The benefits and harms of such treatment and the best first-line treatment are not known. OBJECTIVES: To answer the following two questions using randomized controlled trials (RCTs): 1) does anti-hypertensive drug therapy as compared to placebo or no treatment affect mortality and morbidity in patients presenting with a hypertensive emergency? 2) Does one first-line antihypertensive drug class as compared to another antihypertensive drug class affect mortality and morbidity in these patients? SEARCH STRATEGY: Electronic sources: MEDLINE, EMBASE, Cochrane clinical trial register. In addition, we searched for references in review articles and trials. We attempted to contact trialists. Most recent search August 2007. SELECTION CRITERIA: All unconfounded, truly randomized trials that compare an antihypertensive drug versus placebo, no treatment, or another antihypertensive drug from a different class in patients presenting with a hypertensive emergency. DATA COLLECTION AND ANALYSIS: Quality of concealment allocation was scored. Data on randomized patients, total serious adverse events, all-cause mortality, non-fatal cardiovascular events, withdrawals due to adverse events, length of follow-up, blood pressure and heart rate were extracted independently and cross checked. MAIN RESULTS: Fifteen randomized controlled trials (representing 869 patients) met the inclusion criteria. Two trials included a placebo arm. All studies (except one) were open-label trials. Seven drug classes were evaluated in those trials: nitrates (9 trials), ACE-inhibitors (7), diuretics (3), calcium channel blockers (6), alpha-1 adrenergic antagonists (4), direct vasodilators (2) and dopamine agonists (1). Mortality event data were reported in 7 trials. No meta-analysis was performed for clinical outcomes, due to insufficient data. The pooled effect of 3 different anti-hypertensive drugs in one placebo-controlled trial showed a statistically significant greater reduction in both systolic [WMD -13, 95%CI -19,-7] and diastolic [WMD -8, 95%CI, -12,-3] blood pressure with antihypertensive therapy. AUTHORS' CONCLUSIONS: There is no RCT evidence demonstrating that anti-hypertensive drugs reduce mortality or morbidity in patients with hypertensive emergencies. Furthermore, there is insufficient RCT evidence to determine which drug or drug class is most effective in reducing mortality and morbidity. There were some minor differences in the degree of blood pressure lowering when one class of antihypertensive drug is compared to another. However, the clinical significance is unknown. RCTs are needed to assess different drug classes to determine initial and longer term mortality and morbidity outcomes.

Placental pathology in relation to the White's classification of diabetes mellitus.

The objective of this study was to investigate various macroscopic and microscopic features of the placenta in pregnancies complicated by diabetes according to White's classification. A total of 148 placentas were studied. Sixty-five were from control patients and 83 from diabetic mothers. The diabetic mothers were further divided into three groups according to White's classification. There were 40 cases in White's group A and 36 cases in White's group B. There were 7 cases in White's groups C and D combined. Advanced maternal age and grandmultiparity were significantly higher in White A, White B and White C&D compared to the normal group. Mean weight of the mother was higher in White group A and group B compared to the control group and group C&D. The placental weight and neonatal weight were increased provided the diabetes was not complicated by vascular disease. With accompanying vascular disease the placental weight and neonatal weight were reduced compared to the controls. As a result of increased perinatal jeopardy the rate of operative delivery was higher in diabetic mothers. No major difference was observed in microscopic changes of placentas in different groups according to White's classification and the normal group.

Post-invasion change in the trend of complications and outcome of pregnancy in Maternity Hospital Kuwait from 1981 to 1995.

To assess the trend in the complications and outcome of pregnancy in Maternity Hospital, Kuwait, a retrospective analysis of yearly hospital statistics books and labour ward records of patients delivering in Maternity Hospital Kuwait was carried out for the period 1981 to 1995. In the post-invasion period there is a significant rise in: primiparity; mothers aged 35 years or older; Kuwaiti mothers; and in multiple pregnancy. The incidence of pregnancy-induced hypertension, pre-eclampsia, and hysterectomy for postpartum haemorrhage also increased. There was a significant increase in spontaneous abortions and low birth weight babies. The incidence of hydatidiform mole has significantly decreased. Still birth rate shows a decreasing trend in the study period. The significant change in the age and parity of the mothers delivering in the post-invasion period might partly explain the above changes. However, the effect of environmental pollution, social and psychological stress, and anxiety due to war may have also contributed to an increase in the complications and adverse outcomes of pregnancy.

Influence of seasonal variation on pregnancy-induced hypertension and/or preeclampsia.

Seasonal variation of temperature and humidity are said to influence the incidence of hypertensive disorders of pregnancy. The aim of this study was to determine if temperature and humidity exert any influence on the incidence of pregnancy-induced hypertension and preeclampsia in Kuwait. This is a retrospective study performed in the Maternity Hospital, Kuwait (MHK) in the years 1992-1994. Monthly distribution of all deliveries and those in which the patients had pregnancy-induced hypertension and preeclampsia were recorded. There are some studies including ours which do not show any significant correlation between meteorological factors and hypertensive disorders of pregnancy. We found that the incidence of pregnancy-induced hypertension per 1,000 deliveries was high in June when the temperature was very high and the humidity at its lowest. The reverse was true for the incidence of preeclampsia per 1,000 deliveries, which was high in November when the temperature was low and the humidity high.

Clinical presentation of eclampsia in a Maternity Hospital, Kuwait.

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Eclampsia in Kuwait 1981-1993.

The aim of this study is to investigate the maternal and fetal outcome and the risk factors for developing eclampsia in Kuwait. The study includes all patients with eclampsia observed at the Maternity Hospital, Kuwait during the period from 1981 to 1993. It revealed that the risk factors predisposing to eclampsia were primiparity, a maternal age below 30 years, multiple pregnancy and the presence of preeclampsia. The pregnancy outcome in terms of the stillbirth rate, neonatal death rate and low birth-weight babies was significantly higher in mothers with eclampsia than in noneclamptic mothers. The operative delivery and maternal mortality rates were also significantly higher in these patients.

PIP: Data from 1981 to 1993 (excluding 1990-1991 due to Iraqi invasion) obtained from the Maternity Hospital in Kuwait were analyzed to examine pregnancy outcomes of eclamptic women and the risk factors for eclampsia in Kuwait. During the study period, 101 of 167,080 mothers had eclampsia for an incidence rate of 6/10,000. Eclampsia incidence did not change significantly during the study period. The incidence was 33/1000 for preeclampsia and 32/1000 for hypertension. Strong, significant risk factors for eclampsia included primiparity (relative risk [RR] = 8.93), age 30 years or younger (RR = 3.86), multiple pregnancy (RR = 4.15), preeclampsia (RR = 8.69), and low birth weight of 2500 g or less (RR = 13.96). Eclamptic women were significantly more likely to experience stillbirth, early neonatal death, and cesarean section. Maternal complications included need for intubation, disseminated intravascular coagulation, postpartum hemorrhage, maternal death, persistent increase in blood pressure, and proteinuria 1 week postpartum. One woman died from eclampsia for a maternal mortality rate of 0.99%, which is significantly higher than that for preeclampsia and for hypertension (0.0405 and 0.0396%, respectively). These findings show that risk factors for eclampsia are primiparity, young maternal age, multiple pregnancy, and presence of preeclampsia, and that eclamptic mothers experienced poorer pregnancy outcomes than other mothers.

Post-war changes in the outcome of pregnancy in Maternity Hospital, Kuwait.

To analyse the pre- and post-Gulf War changes in the outcome of pregnancy and to explore the possible causes that could have affected these changes, a retrospective analysis of medical records of patients delivering in Maternity Hospital Kuwait (MHK) was carried out for the period 1987-89 (pre-Gulf-War) and 1992 (post-Gulf War). The records of 1991 were used when adequate information was available. The normal z test was used to assess the significance between two proportions. There is a significant rise in abortion, low birth weight babies, triplet pregnancies, and major congenital anomalies in the post-war period. The still-birth rate, early neonatal mortality rate and perinatal mortality rate significantly increased in the immediate post-war period in 1991, but decreased to levels below the pre-war period in 1992. It should be investigated whether these changes are secondary to the changes in the population structure; the effects of war in terms of deterioration of health care services; environmental pollution caused by oil well fires, oil spills; or the psychological trauma, anxiety and stress caused by the Iraqi invasion of Kuwait.